Datasets:

---

kejian

/

SciRIFF-4096-0214-v1

like 0

[ { "content": "Find entities of these types in the text: [\"Participant\", \"Outcome\", \"Intervention\"].\n\nOutput a JSON object with entity types as keys and lists of found entities as values.\n\nText:\nAlternative voice after laryngectomy using a sound-producing voice prosthesis . OBJECTIVE To improve the voice quality of female laryngectomees and/or laryngectomees with a hypotonic pharyngoesophageal ( PE ) segment by means of a pneumatic artificial source of voice incorporated in a regular tracheoesophageal ( TE ) shunt valve . STUDY DESIGN Experimental , randomized , crossover trial . METHODS The new sound source consists of a single silicone lip , which performs an oscillatory movement driven by expired pulmonary air flowing along the outward-striking lip through the TE shunt valve . A prototype of this pneumatic sound source is evaluated in vitro and in six laryngectomees . In vivo evaluation includes speech rate , maximal phonation time , perceptual voice evaluation of read-aloud prose by an expert listener , speech intelligibility measurements with 12 listeners , and self-assessment by the patients . Moreover , extensive acoustical and aerodynamic in vivo registrations are performed using a newly developed data acquisition system . RESULTS The current prototype seems beneficial in female laryngectomees with a hypotonic PE segment only . For them the sound-producing voice prosthesis improves voice quality and increases the average pitch of voice , without decreasing intelligibility or necessitating other pressure and airflow rates than regular TE shunt speech . Pitch regulation of this prosthetic voice is possible , yet limited . CONCLUSIONS The mechanism is feasible and does not result in unacceptable airflow resistance . For this new mechanism of alaryngeal voice to become an established technique for postlaryngectomy voice restoration , a voice suitably pitched for male laryngectomees has to be generated and a large part of the melodic and dynamic range of the sound source has to be attainable within physiological airflow rates .", "role": "user" }, { "content": "{\"Intervention\": [\"laryngectomy\", \"sound-producing voice prosthesis\", \"pneumatic sound source\", \"pneumatic artificial source of voice incorporated in a regular tracheoesophageal ( TE ) shunt valve\"], \"Outcome\": [\"speech rate , maximal phonation time , perceptual voice evaluation of read-aloud prose by an expert listener , speech intelligibility measurements with 12 listeners , and self-assessment by the patients .\", \"aerodynamic in vivo registrations\", \"improves voice quality and increases the average pitch of voice , without decreasing intelligibility or necessitating other pressure and airflow rates than regular TE shunt speech . Pitch regulation\", \"improve the voice quality\", \"pneumatic artificial source of voice incorporated in a regular tracheoesophageal ( TE ) shunt valve .\", \"feasible\", \"extensive acoustical and\", \"newly developed data acquisition system .\"], \"Participant\": [\"laryngectomy\", \"male\", \"laryngectomees\", \"laryngectomees with a hypotonic PE segment\", \"six\", \"laryngectomees with a hypotonic pharyngoesophageal ( PE ) segment\", \"female\", \"speech intelligibility measurements\"]}", "role": "assistant" } ]

[ { "content": "Find entities of these types in the text: [\"Participant\", \"Outcome\", \"Intervention\"].\n\nOutput a JSON object with entity types as keys and lists of found entities as values.\n\nText:\nEffects of fatty and lean fish intake on blood pressure in subjects with coronary heart disease using multiple medications . BACKGROUND Intake of fish and long-chain n-3 fatty acids has been of wide interest due to their beneficial effects on cardiovascular risk factors and lower coronary heart disease ( CHD ) risk . AIM OF THE STUDY The aim of this pilot study was to examine the effects of fatty fish and lean ( white ) fish on fatty acid composition of serum lipids and cardiovascular risk factors in subjects with CHD using multiple drugs for this condition . METHODS The study was an 8-week controlled , parallel intervention . Inclusion criteria were myocardial infarction or unstable ischemic attack , age under 70 years , use of betablockers and presence of sinus rhythm . The subjects were randomized to one of the following groups : 4 meals/week fatty fish ( n = 11 ) , 4 meals/week lean fish ( n = 12 ) and control diet including lean meat ( n = 10 ) . RESULTS The mean ( +/-SD ) of reported fish meals per week was 4.3 +/- 0.4 , 4.7 +/- 1.1 and 0.6 +/- 0.4 in the groups , respectively . The proportions of eicosapentaenoic and docosahexaenoic acids in serum lipids increased in the fatty fish group only ( P < 0.05 ) . Systolic and diastolic blood pressure levels decreased in the lean fish group ( 0 vs. 8 week : 3.5 +/- 3.2 and 4.6 +/- 3.6 % , respectively , P < 0.05 ) . Serum total triglyceride concentration did not significantly change . HDL cholesterol concentration change differed among groups but without significant post hoc differences . Apolipoprotein A-1 concentration decreased in the control group ( 0 vs. 8 week , P < 0.05 ) . Coagulation factors , 25-hydroxy vitamin D , and heart rate variability ( 24 h Holter ) did not change among the groups . CONCLUSIONS Our results suggest that intake of lean fish at least four times per week could reduce blood pressure levels in CHD patients .", "role": "user" }, { "content": "{\"Intervention\": [\"4 meals/week\", \"lean ( white ) fish\", \"( n = 11 ) , 4 meals/week\", \"fatty fish\", \"lean fish\", \"( n = 12 ) and\", \"including lean meat ( n = 10 ) .\", \"control diet\", \"fatty and lean fish intake\"], \"Outcome\": [\"Systolic and diastolic blood pressure\", \"fatty acid composition of serum lipids\", \"Apolipoprotein A-1 concentration\", \"proportions of eicosapentaenoic and docosahexaenoic acids in serum lipids\", \"Serum total triglyceride concentration\", \"HDL cholesterol concentration\", \"cardiovascular risk factors\", \"blood pressure\", \"Coagulation factors , 25-hydroxy vitamin D , and heart rate variability ( 24 h Holter )\"], \"Participant\": [\"Inclusion criteria were myocardial infarction\", \"subjects with CHD using multiple drugs for this condition\", \"unstable ischemic attack\", \"use of betablockers and presence of sinus rhythm\", \"coronary heart disease ( CHD )\", \"subjects with coronary heart disease using multiple medications\", \"age under 70 years\", \"CHD patients\"]}", "role": "assistant" } ]

[ { "content": "Extract all unique entities of these types from the text: [\"Gene\"].\n\nOutput a JSON object of the format: {\"Gene\": [\"SSX\", ...]}.\n\nText:\nLEC induces chemotaxis and adhesion by interacting with CCR1 and CCR8. Liver-expressed chemokine (LEC) is an unusually large CC chemokine, which is also known as LMC, HCC-4, NCC-4, and CCL16. Previously, LEC was shown to induce leukocyte migration but the responsible signaling receptors were not characterized. We report chemotaxis and competitive binding studies that show LEC binds to and activates CCR1 and CCR8 transfected HEK-293 cells. LEC induced maximal migration of CCR1 and CCR8 transfected cells at 89.3 nmol/L and cell adhesion at 5.6 nmol/L. The molar concentration of LEC required to induce maximum cell migration is 20- to 200-fold greater than that required for RANTES or I309, respectively. All 3 chemokines induced maximal static adhesion at 5 to 7 nmol/L. A neutralizing polyclonal antibody to LEC was developed to demonstrate that the unusually high concentration of LEC required to induce chemotaxis was a property of LEC and not as a result of an irrelevant protein contamination. This study suggests that LEC may be a more effective inducer of cell adhesion than cell migration.", "role": "user" }, { "content": "{\"Gene\": [\"CC chemokine\", \"NCC-4\", \"LEC\", \"RANTES\", \"CCR8\", \"Liver-expressed chemokine\", \"I309\", \"HCC-4\", \"LMC\", \"CCR1\", \"CCL16\"]}", "role": "assistant" } ]

[ { "content": "Summarize the article in an uncomplicated manner.\n\nTitle: The Majority of Primate-Specific Regulatory Sequences Are Derived from Transposable Elements\nArticle:\nAbstract:\nAlthough emerging evidence suggests that transposable elements( TEs) have contributed novel regulatory elements to the human genome, their global impact on transcriptional networks remains largely uncharacterized. Here we show that TEs have contributed to the human genome nearly half of its active elements. Using DNase I hypersensitivity data sets from ENCODE in normal, embryonic, and cancer cells, we found that 44% of open chromatin regions were in TEs and that this proportion reached 63% for primate-specific regions. We also showed that distinct subfamilies of endogenous retroviruses( ERVs) contributed significantly more accessible regions than expected by chance, with up to 80% of their instances in open chromatin. Based on these results, we further characterized 2, 150 TE subfamily–transcription factor pairs that were bound in vivo or enriched for specific binding motifs, and observed that TEs contributing to open chromatin had higher levels of sequence conservation. We also showed that thousands of ERV–derived sequences were activated in a cell type–specific manner, especially in embryonic and cancer cells, and we demonstrated that this activity was associated with cell type–specific expression of neighboring genes. Taken together, these results demonstrate that TEs, and in particular ERVs, have contributed hundreds of thousands of novel regulatory elements to the primate lineage and reshaped the human transcriptional landscape.\nIntroduction:\nNearly half of human DNA is derived from sequences known as TEs that have successfully replicated in the genome during the evolution of our species[1]. Although the parasitic behavior of TEs was initially put forward as a sufficient explanation for their maintenance within genomes[2],[3] there is growing evidence to support the alternative view that TEs have facilitated genomic innovations[4],[5] and contributed critical regulatory elements to their host[6]. Indeed, a number of studies have shown recently that TEs have been the source of binding sites for various mammalian transcription factors( TFs)[7]–[9] and that they have rewired different developmental regulatory networks[10]–[12]. However, given that previous studies were limited either by the number of TFs they surveyed[7]–[10],[13],[14] or by the cell types they explored[10],[11],[15], a key question that remains is to what extent have TEs globally contributed to human transcriptional networks in undifferentiated and differentiated cells. The importance of characterizing the functional role of TEs and other repetitive regions in the human genome is accentuated by the facts that these sequences constitute most of the sequence diversity between mammalian species[16] and are a significant source of human polymorphisms[17] and of somatic mutations in healthy and disease tissues[18]–[20]. To systematically survey the contribution of TEs to human regulatory networks across a range of cell types, we made use of DNase I hypersensitive sites( DHS) data generated at the University of Washington( UW) and Duke as part of ENCODE[21],[22]. The benefit of using these chromatin accessibility maps is that they highlight active DNA sequences[23],[24] independently of a selected set of TFs. Although accessibility does not equate regulatory function, we build upon these data sets to measure the global activity profile of all classes of transposon-derived sequences and systematically characterize the impact that ancient and recent TEs expansions have had on the human chromatin landscape.\nDiscussion:\nIn summary, we found that TEs have contributed nearly half of the open chromatin regions of the human genome and the majority of primate-specific elements. This estimate is a lower bound that is likely to grow given that better strategies using longer and paired-end reads will be needed to measure the contribution of young repeat subfamilies and polymorphic sites( Figure S3). An example is the L1PA2 repeat subfamily where, despite the fact that the mappability ratio is 0. 08, 117 and 257 of the 4904 L1PA2 instances contributed to the H1 and H7 DHSs respectively. This finding is consistent with previous observations[7],[15],[34],[35] but greatly expands on our understanding of the repeat families contributing to open chromatin in the human genome. To better understand the regulatory functions that could have been retained in exapted TEs beyond the ones that have already been studied( e. g.[8]–[11],[14]), we predicted a total of 2150 TF-repeat subfamily associations and confirmed that a broad range of functional proteins are targeting these regions( Figure 2 and Tables S3, S4). This resource will be useful to provide insights into the regulation of some of the TE-derived loci that have already been implicated in disease[36]. There is an important distinction between biochemical activity and functional relevance to the host. To help confirm the importance of these regions, we also showed that repeat instances contributing to open chromatin were more conserved than expected by chance( Figure 2F). Next, we demonstrated that LTR/ERV repeats have contributed a disproportionate fraction of cell type-specific accessible chromatin regions especially in embryonic and cancer cell lines( Figure 3). This is interesting given that network rewiring using ERV elements has already been described in ESCs[10]–[12] and that it has been shown that stem cell potency fluctuates with endogenous retrovirus activity in mouse[37]. The level of activity observed in ERV sequences is likely a consequence of the permissive chromatin state found in ESCs that it sometimes reinstated in cancer[38]. There is fine balance between the successful replication of endogenous retroviruses, from which these repeats are derived, and retrotransposition control in the host[39]. One intriguing possibility is that the manipulations that were initially exerted by the ancestral viruses on their host to by-pass these control mechanisms have also facilitated co-option[40]. Finally, we also reported that repeat subfamilies activated in a cell type-specific manner were also frequently associated with higher expression of neighboring genes. This result corroborates the fact that at the level of expression, TE-derived transcripts, including lincRNAs[41], are also usually tissue-specific[42]. Interestingly, this pattern was observed not only in ESCs but also in differentiated and cancer cells( Figure 4 and Table S6). Taken together, these results demonstrate that TEs, and in particular endogenous retroviruses, have considerably transformed the transcriptional landscape during primate evolution.", "role": "user" }, { "content": "Nearly half of the human genome is composed of repetitive sequences , most of which were derived from transposable elements that have replicated in the genome during the evolution of our species . There is growing evidence showing that some of these transposon-derived sequences have been a source of new binding sites for various mammalian transcription factors . Considering that previous studies were targeting only few transcription factors and cell types , a key question that remains is to what extent the transposable elements have contributed to human transcriptional networks . To systematically survey this contribution , we used datasets generated by the international Encyclopedia of DNA Elements ( ENCODE ) consortium , identifying the location of active regulatory elements in more than 40 distinct human cell types . Using this resource we measured the contribution of all classes of repetitive sequences and systematically characterized the impact that transposable elements have had on the human chromatin landscape . Our results demonstrate that transposon-derived sequences have contributed hundreds of thousands of novel regulatory elements to the primate lineage and reshaped the human transcriptional landscape .", "role": "assistant" } ]

[ { "content": "Summarize the article in an uncomplicated manner.\n\nTitle: TLR2 Signaling Decreases Transmission of Streptococcus pneumoniae by Limiting Bacterial Shedding in an Infant Mouse Influenza A Co-infection Model\nArticle:\nAbstract:\nWhile the importance of transmission of pathogens is widely accepted, there is currently little mechanistic understanding of this process. Nasal carriage of Streptococcus pneumoniae( the pneumococcus) is common in humans, especially in early childhood, and is a prerequisite for the development of disease and transmission among hosts. In this study, we adapted an infant mouse model to elucidate host determinants of transmission of S. pneumoniae from inoculated index mice to uninfected contact mice. In the context of co-infection with influenza A virus, the pneumococcus was transmitted among wildtype littermates, with approximately half of the contact mice acquiring colonization. Mice deficient for TLR2 were colonized to a similar density but transmitted S. pneumoniae more efficiently( 100% transmission) than wildtype animals and showed decreased expression of interferon α and higher viral titers. The greater viral burden in tlr2−/− mice correlated with heightened inflammation, and was responsible for an increase in bacterial shedding from the mouse nose. The role of TLR2 signaling was confirmed by intranasal treatment of wildtype mice with the agonist Pam3Cys, which decreased inflammation and reduced bacterial shedding and transmission. Taken together, these results suggest that the innate immune response to influenza virus promotes bacterial shedding, allowing the bacteria to transit from host to host. These findings provide insight into the role of host factors in the increased pneumococcal carriage rates seen during flu season and contribute to our overall understanding of pathogen transmission.\nIntroduction:\nThe bacterial pathogen Streptococcus pneumoniae( the pneumococcus) robustly colonizes the upper respiratory tract of humans and is commonly carried asymptomatically. Colonization rates are highest in early childhood, where they can exceed 80%[1]; in crowded environments such as daycare centers[2]; and when viral respiratory infections are prevalent[3]. From its niche in the nasopharynx, the bacterium can invade other host sites, and as a result the pneumococcus is a leading cause of otitis media, pneumonia, and septicemia. Importantly, colonization of the nasopharynx is the reservoir for pneumococcal disease[4]–[7] and transmission between hosts[8],[9]. While pneumococcal colonization and disease have been well-studied using animal models( for review see[10],[11]), transmission of the bacterium remains poorly understood. In humans, close contact is required for transmission, which is thought to occur via respiratory secretions, but the specific host and bacterial factors contributing to this process have not been elucidated[12],[13]. Recently, an infant mouse model of pneumococcal transmission has been described[14]. In this model, ‘index’ mice are given Streptococcus pneumoniae intranasally and co-housed with uninoculated ‘contact’ littermates. Subsequently, all pups are inoculated with influenza A virus and, following an exposure period, transmission from index to contact mice is assessed by enumerating bacteria in the nasopharynx. Using this model, this group demonstrated that both increasing the bacterial titer in the index mice and inducing inflammation in the contact mice led to more efficient transmission[15]. Given the timing of these experiments, these studies suggest a role for the innate immune response in the setting of co-infection in transmission of the pneumococcus from host to host. The host immune response to influenza has been extensively reviewed[16],[17] and is briefly summarized here to highlight key elements. After passing through the mucus layer lining the respiratory tract, influenza A virus is recognized by several pattern recognition receptors( PRRs) expressed by epithelial cells, including the Toll-like receptors( TLRs), nucleotide oligomerization domain-like receptors( NLRs), and retinoic acid-inducible gene-I receptors( RIG-I). Engagement of these receptors induces a signaling cascade that culminates in expression of interferons( IFNs) and pro-inflammatory cytokines and chemokines, resulting in recruitment and activation of immune cells, such as neutrophils and macrophages. A recent study has shown that influenza infection also leads to increased mucin expression by epithelial cells in the respiratory tract[18]. TLR2 has been implicated in promoting clearance of the pneumococcus[19],[20], and stimulation of this receptor has been shown to protect against influenza infection[21]. Additionally, recent work has shown that signaling through TLR2 can induce anti-viral responses after stimulation by viral and synthetic ligands.[22],[23] Thus, we hypothesized that mice deficient for TLR2 would display altered transmission of the bacterium in this model. We found that mice deficient in TLR2 show heightened acute inflammation in index mice and enhanced transmission due to an increase in number of bacteria shed via nasal secretions. This model recapitulates many facets of human-to-human transmission of pneumococcal carriage, such as concurrent viral infection and close contact between infants/children, and these findings provide insight into how innate immune responses to infection promote the spread of pathogens from host to host.\nDiscussion:\nThis study aimed to expand existing knowledge of the transmission of respiratory bacterial pathogens by specifically analyzing spread of Streptococcus pneumoniae in an infant mouse model. Transmission of bacterial pathogens is critical to their success but has long been a black box in the study of pathogenesis due to a lack of tractable animal models. An infant mouse model utilizing influenza co-infection has been recently introduced[14],[15]. These studies have established a preliminary link between inflammation induced by infection and spread of the bacterium. Here, we sought to identify specific host factors that contribute to this process and to gain further insight into the mechanisms responsible for transmission in this model. Our results demonstrate a role for the innate immune receptor TLR2 in transmission of the pneumococcus in a flu-dependent manner. The findings in our report are consistent with previous studies in adult mice, which suggested that TLR2 stimulation by either commensal bacteria[26] or a synthetic agonist[21] is protective against flu infection. Previous in vitro studies have also demonstrated a role for TLR2-mediated signaling in induction of type I IFNs[22],[23]. Our work adds in vivo data to this model, demonstrating that expression of IFN α, a key component of the anti-viral response, was diminished in tlr2−/− mice compared to wildtype mice. These findings solidify a link between TLR2 activity and type 1 IFN expression. Importantly, influenza co-infection was required for transmission to occur; this was true for both wildtype and tlr2−/− experimental groups. Both infection with influenza alone and co-infection resulted in a significant inflammatory influx to the nasopharynx, with the largest proportion of the cellular infiltrate comprised of neutrophils. In tlr2−/− mice, this response was even more pronounced, with a significantly higher percentage of neutrophils present than in the wildtype samples, while we did not observe any differences in macrophages or other cell types recruited. The host response to increased viral titers also correlated with higher expression of the mucin Muc5ac. We hypothesize that these higher levels of virus stimulate an exaggerated acute inflammatory response that drives an increase in nasal secretions, consisting of mucus and inflammatory cells, providing an exit vehicle for the pneumococcus. As the presence of pneumococcus adds relatively little to inflammation, our findings suggest that it is primarily the host response to the virus that provides this vehicle for shedding, with the bacterium acting as a passenger. The pneumococcus can thus take advantage of the heightened inflammatory state present in co-infected index animals. The observation that there is very little inflammation seen in the context of a pneumococcal single infection explains why transmission is not detected when the animals are not given influenza. The few neutrophils that are recruited to the airway lumen in response to pneumococcal colonization have a limited ability to take up the organism in the absence of specific antibody, and depletion of neutrophils has no effect on bacterial clearance in adult singly infected mice[27]. Additionally, the neutrophil influx observed in influenza-infected lavages did not appear to be effective at lysing the bacterium, as indicated by the predominance of intact bacterial cells in immunofluorescence images. Thus, the secretions resulting from robust inflammation are required for transmission, but this inflammatory response must also be ineffective at killing the bacterium. We also demonstrate here that the inflammation induced by influenza infection promotes bacterial shedding from index mice at or above a level sufficient to infect uninoculated contact mice. Transmission could be a consequence of bacterial shedding above this threshold level. We conclude that the increased inflammation in tlr2−/− mice is due mostly to diminished sensing of the virus and inability to control viral infection. Another consideration is that while tlr2−/− genotype itself does not bias the composition of the host microbiota[28], it likely causes differences in sensing of the flora. Although previous studies have shown that the microbiota can affect the immune response to influenza, the contribution of the colonizing pneumococci to the inflammatory response was small in comparison to influenza. This was the case even though pneumococcal colonization itself stimulates TLR2 signaling[19]. Thus, it appears that the increased viral load observed in tlr2−/− mice was sufficient to lead to a heightened inflammatory response through sensing by other viral PRRs resulting in more copious purulent mucus secretions. These secretions carry live bacteria, which are then shed in increased numbers. As the nursing mother piles infant mice in close proximity to one another, there are thus ample opportunities for the bacteria to spread from one host to another. These studies also help to explain the transmission differences between adult and infant mice, namely that transmission has not been observed in similarly treated adults because of the higher inoculum required to establish robust colonization in adults. This is the first study to implicate a specific host factor in transmission of the bacterial pathogen S. pneumoniae. While stimulation of TLR2 limits transmission, approximately half of wildtype contact mice acquire the bacterium, indicating that other components of the innate immune system must contribute to the inflammation and shedding necessary for this process. For instance, stimulation of other pattern recognition receptors that respond to influenza, such as TLR3, TLR7, and RIG-I, could affect pneumococcal transmission, as shown for TLR2. Signaling downstream of other viral PRRs has yet to be fully explored in the context of transmission. The model detailed here thus shows much promise for investigating these additional microbial and host factors to determine the complete mechanism behind bacterial shedding and its consequences for host-to-host transmission.", "role": "user" }, { "content": "In this study , we sought to identify factors contributing to the transmission of the bacterial pathogen Streptococcus pneumoniae ( the pneumococcus ) , a major cause of otitis media , pneumonia , and septicemia . Often found as a co-infection with other bacterial and viral pathogens , the pneumococcus is commonly carried by young children and is spread by close human contact , most likely through large droplet respiratory secretions . The specific determinants of bacterial transmission , however , have not been identified . This report details our use of an infant mouse model of transmission , which includes influenza A co-infection , to elucidate the mechanism of host-to-host transmission . We found that the inflammatory response to influenza , which is aggravated in the context of weakened host defense , promotes transmission by inducing bacterial shedding from the mouse nose . These results show how a bacterial pathogen exploits the host immune response to spread from one host to the next .", "role": "assistant" } ]

[ { "content": "Write an abstract for this chemistry paper.\n\nTitle:\nOrganofluorine chemistry: Difluoromethylene motifs spaced 1,3 to each other imparts facial polarity to a cyclohexane ring\n\nPaper sections:\nIntroduction\n<p>Selective incorporation of fluorine atoms is a powerful strategy for modulating the properties of organic compounds [1][2][3]. For instance, the replacement of hydrogen by fluorine is commonly practised in medicinal [4,5] and agrochemical [6,7] research programmes. The dipole moment associated with the C-F bond has also rendered fluorine containing compounds important in the development of organic materials such as liquid crystals [8,9]. Strategic fluorination can add polarity to a molecule, however, such compounds do not generally increase in their hydrophilic capacity, thus selective fluorination leads to polarhydrophobic properties [10]. Although selective mono-fluori-nation and CF 3 incorporation have had wide currency, the difluoromethylene (CF 2 ) motif has received relatively less attention despite possessing unique properties [11][12][13][14]. For example CH 2 F 2 shows the highest molecular dipole (1.97 D) of the fluoromethane series, relative to CH 3 F (1.87 D) or CHF 3 (1.65 D) [15,16]. Also (poly)vinylidine fluoride (~CF 2 CH 2 ~) is the prototypical piezoelectric polymer, when the CF 2 group are orientated (poled) in the melt [17].</p><p>The search for new and more diverse polar hydrophobic scaffolds is attractive for drug discovery research and new materi-Scheme 2: Preparation of starting materials 5c and 6a-c. als [18]. In our own lab we have been exploring the synthesis and properties of differently fluorinated aliphatic structures based on the cyclopentane (1) and cyclohexane (2 and 3) rings, compounds which can show quite large dipole moments depending on the stereochemistry [19,20] (Figure 1). All-syn 1,2,3,4,5,6-hexafluorocyclohexane, which was prepared recently, emerges as among the most polar aliphatic compounds reported in the literature [21]. The specific arrangement with all of the fluorines \"up\" induces a facial polarisation to the cyclohexane, a unique phenomenon which may have unexplored utility in organic chemistry. For example derivatives of these compounds could be potentially useful as polar hydrophobic substituents in drug discovery that will simultaneously contact both electropositive and electronegative domains within a target protein. In this paper, we now report the design, synthesis and characterisation of a novel tetrafluorocyclohexane structure 4, rendered polar by placing two CF 2 groups located 1,3 from each other (Scheme 1). This forces two C-F bonds to lie 1,3-diaxial to each other while the cyclohexane adopts the classic chair conformation. To the best of our knowledge, 2,2,6,6-tetrafluorocyclohexanol is the only derivative containing this feature re-ported so far. It was prepared in an eight step synthesis [22]. At the outset we explored a more direct synthesis of this arrangement based on deoxofluorination of 1,3-diketones 5 with DAST or Deoxo-Fluor ® [23] (Scheme 1). An alternative route envisaged a fluorodesulfurisation using 1,3-bis-dithianes 6 as substrates [24] (Scheme 1). Both synthetic approaches have been widely used for the introduction of the CF 2 group in open-chain and (macro)cyclic systems [23,24], but not in a 1,3 relationship.</p>\n\nResults and Discussion\n<p>The preparation of diketones 5a-c and bis-dithianes 6a-c was carried out by previously described methods. The dimethyldiketone 5c was prepared by double methylation of 5b [25] (Scheme 2). Two different O-alkylated products 7 and 8 were also obtained as significant byproducts.</p><p>The reaction of ketones 5a-c with 1,2-ethanedithiol in the presence of catalytic BF 3 •OEt 2 afforded the corresponding bis-dithianes 6a-c in moderate to good yields [26] (Scheme 2). The reaction of diketone 5c also afforded the monoderivatised ketone 9 as a minor product. Direct fluorination of diketones 5a-c was explored with DAST or Deoxo-Fluor ® (Scheme 3). When diketones 5a and 5b were treated with DAST or Deoxo-Fluor ® , either neat or in DCM as a solvent, only complex and intractable products were obtained. These highly enolisable diketones [27,28] were incompatible with deoxyfluorination. In order to block enolisation, diketone 5c containing two methyl groups α to the ketones was subject to fluorination with DAST and Deoxo-Fluor ® . In this case the reaction was successful and the desired tetrafluorocyclohexane 4c could be obtained, most preferably with DAST although in a low overall yield (Scheme 3). The presence of the gem-dimethyl motif renders the carbonyl groups independent of each other and this facilitates the difluorination process relative to 5a and 5b. Nevertheless, other unidentified byproducts were also obtained, which made purification of 4c by column chromatography difficult and compromised the yield. Treatment of bis-dithianes 6 with NIS and HF•Py as previously described for linear systems [28] proved unsuccessful (Scheme 4) and did not offer a way forward. Tetrafluorocyclohexane 4c was a crystalline solid (mp 70 ºC). The structure of this compound was established by NMR, showing a AB system in 19 F NMR for axial/equatorial fluorines, and a triplet ( 1 J CF = 250 Hz) in 13 C NMR for the CF 2 group. In addition, single crystal X-ray diffraction data were obtained for 4c which confirmed the structure (Figure 2). The C-CF 2 -C angles in the cyclohexane ring are considerably wider (≈116°) than that of the C-CH 2 -C angles (≈112°), which is now recognised as a general phenomenon of the CF 2 group in an aliphatic chain/ring [10][11][12][13]. The two axial fluorines flex away from each other with widened right angles of 96.3°, distorting a co-parallel orientation. This distortion is also observed for the 1,3-diaxial C-F bonds in the solid state structures of 2 [20] and 3 [21] consistent with electrostatic dipolar repulsion between these C-F bonds and indicative of the origin of the polarity of these molecules. In terms of intermolecular packing in the solid state there are interactions between the non-fluorine face of the cyclohexyl ring and the phenyl group of a neighbouring molecule (Figure 2). These C-H•••π interactions are a feature of the solid state packing found in phenyl derivatives of 2 [29]. This electrostatic ordering was reinforced by an NMR shift experiment in different solvents. Selected 1 H NMR signals of 4c showed a very clear upfield shift in [ 2 H 8 ]-toluene when compared with the spectrum obtained in chloroform (CDCl 3 ) (Figure 3). In particular, the two axial protons H-3 and the axial methyl group at C-4 display higher upfield shifts in toluene (Δδ ≈ 0.5 ppm and Δδ ≈ 0.3 ppm, respectively), whereas that of the equatorial protons H-2, the equatorial methyl group at C-5 and the axial proton H-1 do not experience shifts of the same magnitude (Δδ ≈ 0.2 ppm, Δδ ≈ −0.1 ppm and Δδ ≈ 0.1 ppm, respectively). These observations are consistent with the anisotropic influence of the electronegative aromatic solvent (toluene) interacting with the more electropositive (non-fluorine) face of the cyclohexane ring (Figure 3).</p><p>To extend these experimental observations, a DFT computational study, at the B3LYP-D3/6-311+G(d,p) level, was carried out in order to obtain an electrostatic potential map of cyclohexane 4c. The profile confirms the presence of an electronegative face (in red) determined by the two 1,3-diaxial C-F bonds and an electropositive face (dark blue), which is most intense at the hydrogens of the diaxial C-H bonds pointing antiperiplanar to the diaxial C-F bonds (Figure 4). A molecular dipole moment for compound 4c was calculated at 3.1 D can be compared for example to 1,2,4,5-tetrafluorocyclohexane (2, 5.2 D) [18].</p>\n\nConclusion\n<p>In this study we have prepared a novel polar aliphatic structure 4c based on the 1,1,3,3-tetrafluorocyclohexyl motif. The compound was prepared by direct difluorination of the corresponding α,α-dimethylated 1,3-diketone with DAST. The presence of the two 1,3-diaxial fluorine atoms in structure 4c is responsible for the facial polarisation on the cyclohexane ring. We have demonstrated the intermolecular electrostatic interaction of the positive non-fluorous face with the π-system of an aromatic ring by single crystal X-ray diffraction and NMR experiments. Additionally, the polarity of 4c has been calculated by computational optimisations. It follows that functionalised cyclohexanes containing the 1,3-di-CF 2 motif would offer new possibilities for the design of performance molecules extending from organic materials research to medicinal chemistry.</p>\n\nSupporting Information Supporting Information File 1\n<p>Experimental part and NMR spectra of new synthesised compounds.</p><p>[http://www.beilstein-journals.org/bjoc/content/ supplementary/1860-5397-12-281-S1.pdf]</p>", "role": "user" }, { "content": "2,2-Dimethyl-5-phenyl-1,1,3,3-tetrafluororocyclohexane has been prepared and characterised as an example of a facially polarised cyclohexane containing 1,3 related CF 2 groups. The dipolar nature of the ring arises from the axial orientation of two of the C-F bonds pointing in the same direction, and set by the chair conformation of the cyclohexane. This electrostatic profile is revealed experimentally both in the solid-state (X-ray) packing of the rings and by solution (NMR) in different solvents. A computationally derived electrostatic profile of this compound is consistent with a more electronegative and a more electropositive face of the cyclohexane ring. This placing of CF 2 groups 1,3 to each other in a cyclohexane ring is introduced as a new design strategy which could be applicable to the preparation of polar hydrophobic cyclohexane motifs.", "role": "assistant" } ]

[ { "content": "Find entities of these types in the text: [\"Participant\", \"Outcome\", \"Intervention\"].\n\nOutput a JSON object with entity types as keys and lists of found entities as values.\n\nText:\nDisclosure of HSV-2 serological test results in the context of an adolescent HIV prevention trial in Kenya . OBJECTIVES Herpes simplex virus type 2 ( HSV-2 ) biomarkers are often used in adolescent sub-Saharan HIV prevention studies , but evaluations of test performance and disclosure outcomes are rare in the published literature . Therefore , we investigated the proportion of ELISA-positive and indeterminate samples confirmed by western blot ( WB ) , the psychosocial response to disclosure and whether reports of sexual behaviour and HSV-2 symptoms are consistent with WB confirmatory results among adolescent orphans in Kenya . METHODS In 2011 , 837 Kenyan orphan youth in grades 7 and 8 enrolled in an HIV prevention clinical trial with HSV-2 biomarker outcomes . We used a modified algorithm for the Kalon HSV-2 ELISA to improve specificity ; positive and indeterminate results were WB tested . We developed culturally sensitive protocols for disclosing positive results , and documented psychosocial responses , reports of sexual contact and HSV-2 symptoms . RESULTS 28 adolescents ( 3.3 % ) were identified as HSV-2 seropositive , six as indeterminate . Of these , 22 positive and all indeterminates were WB tested ; 20 and 5 , respectively , were confirmed positive . Most youth reported moderate brief stress after disclosure ; 22 % reported longer and more severe distress . Boys were more likely to be in the latter category . Self-reported virginity was highly inconsistent with WB-confirmed positives . CONCLUSIONS The higher than manufacturer 's cut-off for Kalon ELISA modestly reduced the rate of false-positive test results , but also increased false negatives . Investigators should consider the risk : benefit ratio in deciding whether or not to disclose HSV-2 results to adolescent participants under specific field conditions . TRIAL REGISTRATION NUMBER NCT01501864 .", "role": "user" }, { "content": "{\"Intervention\": [\"western blot\"], \"Outcome\": [\"moderate brief stress after disclosure\", \"false negatives\", \"longer and more severe distress\", \"Self-reported virginity\", \"WB-confirmed positives\", \"false-positive test results\"], \"Participant\": [\"HIV\", \"837\", \"adolescent participants\", \"28\", \"youth\", \"adolescent\"]}", "role": "assistant" } ]

[ { "content": "Write an abstract for this chemistry paper.\n\nTitle:\nA sudden creatinine increase: A case report\n\nPaper sections:\nIntroduction\n<p>Biomarkers, such as cystatin C (cysC), creatinine, and estimated glomerular filtration rate (eGFR), represent the commonly approved laboratory basis program in the assessment of patients' renal status. Comparing creatinine and cysC, different physiological functions and metabolisms could be distinguished, which further explain slight differences in their use as laboratory biomarkers. Naturally, both molecules are predominantly eliminated by the kidneys.</p><p>Creatinine is the end product of muscle catabolism. The biosynthesis of creatine originates from the amino acids arginine, glycine, and methionine in an initial enzymatic reaction. Creatine is a nitrogenous organic acid preferentially generated in the liver but also in the kidneys and pancreas. It is then further processed to creatinine; in the skeletal and heart muscles, creatine is converted to creatine phosphate, which acts as an important energy source for muscular contractions. In addition, in the muscle cells, creatine is irreversibly converted to creatinine, which is finally eliminated by the kidneys. Beyond that endogenous production, creatinine can also be alimentarily ingested because it is specifically found in dietary proteins (1).</p><p>In contrast to creatinine, cysC is a ubiquitously expressed molecule of nucleated cells with specific immune-modulatory functions. As a cysteine protease inhibitor, it is essentially responsible for protecting cells from protease degradation. CysC is freely filtered and mostly reabsorbed in the proximal tubule; consequently, cysC represents another suitable renal biomarker, although its international standardization is yet to be definitively accomplished (2, 3).</p>\n\nLaboratory analyses\n<p>Here, we report a 61-year-old patient who is essentially healthy according to his age. Although his medical records showed no indicators of renal impairment, he was interested in an outlined preventive medical examination and asked for an analysis of relevant biomarkers that reflect on his kidney function. We consequently analysed his creatinine and cysC and obtained non-pathological results. One hour later, we decided to control our results by taking a new sample for reanalysis and surprisingly received conspicuously elevated creatinine levels in combination with cysC results within the reference interval as it is demonstrated in Table 1.</p>\n\nFurther investigations\n<p>We primarily suspected haemolysis, lipaemia, or bilirubin as potential interference factors because many studies have already described artificially increased creatinine results in that context (4-6). However, macroscopic inspections could not corroborate that suspicion, and the haemolysis, icterus, and lipaemia indices yielded very low counts in both samples.</p>\n\nWhat happened\n<p>At lunchtime, our patient had previously eaten boiled beef for dinner. The second blood sample was taken too early after food intake (one hour postprandial) and altered the creatinine analysis without influencing the cysC concentration in repeat testing.</p>\n\nDiscussion\n<p>The analytical variability of creatinine is relatively high compared to cysC. Because cysC is continuously released from nucleated cells, it is almost invariably independent of muscle mass, gender, age, and ethnicity (7). In our case, food ingestion was the incriminated confounder that led to the false pathological creatinine results. Previous studies have already demonstrated this effect in depth. For reproducible reasons, this analysis error was described in different analytical laboratory systems, not only in the Jaffe method but also in approaches using alkaline picrate or enzymatic methods. Importantly, creatine-rich foods such as beef or fish are the main contributors to such falsely elevated results because creatine is converted to creatinine during the cooking process (8, 9). Interestingly, the impact of creatine intake on creatinine mismeasurement seems to be higher in patients with chronic kidney diseases. Nair et al. further demonstrated a creatinine peak after two hours in healthy individuals and after four hours in patients with advanced chronic kidney disease after consuming a cooked meat meal (10). Jacobsen et al. also reported that when six volunteers ate a beef-containing meal, their subsequent creatinine levels did not recover to their initial creatinine levels within 20 hours (11). However, limitations of their study included small sample size, unknown methodology for creatinine analysis, and unknown renal status of the volunteers (specifically, whether or not any participants had impaired renal function). These factors are important to consider when questioning the amount of time, it takes to regain uninfluenced results. In addition, individuals' constitutions may differ with regards to absorption and metabolization rates. Suggesting a general timeframe post food ingestion would thus be non-definitive, and it would be more rational to comply with fasting recommendations to avoid the detection of artificially higher creatinine levels (11).</p><p>Translating those findings into our case, we concluded that the second postprandial analysis was performed significantly too early in order to generate correct creatinine results. The working group on the preanalytical phase of the European Federation of Clinical Chemistry and Laboratory Medicine (EFCC) recommended a food fasting period of 12 hours and alcohol abstinence of 24 hours before blood samples are taken.</p><p>It has also been postulated that a worldwide standardization of blood sampling and patient preparation, respectively, is necessary. For example, specialists in laboratory medicine have been encouraged to elaborate on acceptance criteria related to fasting issues and to contemplate sample rejections in cases of non-compliance (12).</p><p>The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and the EFCC published a consensus paper on performance specifications for the extra-analytical phase. In this paper, they focused on harmonizing quality indicators of the laboratory process and identified inappropriate or unintelligible test requests as important quality indicators of the preanalytical phase (13). Correspondingly, Mrazek et al. published a report on overutilization as a relevant preanalytical problem (14). Among other things, this problem can be traced back to non-adherence with regards to retesting intervals. This study group suggested that specialists in laboratory medicine should proactively participate in the preanalytical phase of test ordering to prevent inappropriate test requests. They also published strategies and solutions to reduce test-overutilization (i.e., starting with educational feedback, interpretive comments and automated flags, gate-keeping strategies over to implemented algorithms and reflex criteria, and the establishment of diagnostic management teams) (14).</p><p>In our case, apart from non-compliance to an appropriate fasting period, a further preanalytical error existed in that the second creatinine analysis was not required. According to the recommendations listed above, we reanalysed creatinine levels on the next day under strict adherence to the fasting period and obtained results close to the baseline creatinine measurement of the day before (96.8 µmol/L) prior to food ingestion. This finding supported the suggestion of alimentary influence on consecutive mismeasurement of creatinine.</p><p>Moreover, in our case, the cysC remained stable at the baseline level in repeat analysis. However, there are still a few circumstances associated with cysC mismeasurement removing that biomarker out of an exclusively unfailing state. There is broad evidence that cysC is relevantly influenced by thyroid function. Patients with a hyperthyroid state commonly display higher cysC levels, whereas patients with a hypothyroid state tend to present with lower cysC levels. Therefore, in patients with thyroid dysfunction, the use of cysC for renal assessment should be avoided (15). Apart from thyroid hormones, corticosteroids can also be responsible for false cysC elevations without reflecting the actual renal state (16). In this context, it should be mentioned that cysC and creatinine alterations also affect the corresponding respective eGFR results. In our case, cysC mismeasurements due to the aforementioned causes could be excluded because our patient had neither endocrinological diseases nor had taken medications affecting the corticotropic or thyrotrophic axis and decisively obtained non-pathological results in both cysC analyses.</p>\n\nWhat you can do in your laboratory to prevent such errors\n<p>Postprandial laboratory assessment of renal status should be performed by the analysis of cysC with subsequent eGFR calculation instead of creatinine measurement. In elective settings, blood samples should be taken after an appropriate fasting time of 12 hours. Furthermore, repeat testing should not be performed without a reflected indication.</p>\n\n\n<p>Potential conflict of interest</p><p>None declared.</p>", "role": "user" }, { "content": "Creatinine and estimated glomerular filtration rate (eGFR) are first-line laboratory parameters in the diagnosis of various renal diseases. In recent decades, cystatin C (cysC) has furthered the laboratory repertoire regarding renal status assessment and has been implemented in many clinical guidelines. Accordingly, with the establishment of cysC as a renal routine biomarker, further opportunities for assessing eGFR have been attained. Nevertheless, various limitations are still associated with cysC and creatinine analysis. Preanalytical errors could cause false results in both biomarkers. In our case, we were confronted with implausibly elevated creatinine levels due to preanalytical errors.", "role": "assistant" } ]

[ { "content": "Given the full text of a scientific research paper, write an abstract section for the paper. Your response should contain only the abstract without any other text.\n\nArticle text:\nthe hamiltonian of the @xmath2 spin chain is given by @xmath6\\ ; . \\label{xxz}\\ ] ] here @xmath7 is the exchange coupling , @xmath8 the anisotropy , @xmath9 a magnetic field and @xmath10 the number of sites .\nthe isotropic model ( @xmath11 ) has direct applications to compounds like sr@xmath12cuo@xmath13 where copper - oxygen chains form along one crystal axis and the coupling between these chains is very weak making them effectively one dimensional .\nfurthermore , the system ( [ xxz ] ) can be mapped exactly onto interacting spinless fermions using the jordan - wigner transformation . in this language\n@xmath8 parametrizes a nearest - neighbor density - density interaction and @xmath9 becomes the chemical potential . the fermionic version of ( [ xxz ] ) is often used as a simple model for quantum wires @xcite .\nthe @xmath2 model is exactly solvable by means of bethe ansatz ( ba ) .\nhowever , the calculation of correlation function by ba is a difficult task and only limited results have been obtained so far . on the other hand , it is known that the low - energy effective theory for the hamiltonian ( [ xxz ] ) is just a free boson model .\nthis so called luttinger liquid hamiltonian @xmath14 is obtained by linearizing the dispersion around the two fermi points , going to the continuum limit and reexpressing the right- and left - moving fermions by bosons . ignoring irrelevant operators this leads to @xmath15 \\ , .\n\\label{hll}\\ ] ] here , @xmath16 is a bosonic field and @xmath17 its conjugated momentum satisfying @xmath18=i\\delta(x - y)$ ] . as a consequence of the linearized dispersion\nthe hamiltonian ( [ hll ] ) is lorentz invariant and a boson with momentum @xmath19 always carries energy @xmath20 . in the following\nwe will investigate corrections to ( [ hll ] ) due to band curvature and consequences for the lineshape of the dynamical structure factor .\nthe longitudinal dynamical structure factor is defined by @xmath21 here @xmath22 and @xmath23 is an eigenstate with energy @xmath24 above the ground state energy . for a finite system , @xmath25 at fixed @xmath26\nis a sum of @xmath27-peaks at the energies of the eigenstates . in the thermodynamic limit @xmath28 , the spectrum is continuous and\n@xmath25 becomes a smooth function of @xmath29 and @xmath26 .\ndue to lorentz invariance @xmath30 for the luttinger model ( [ hll ] ) . for @xmath31\nparticle - hole symmetry is broken and the leading irrelevant operators allowed by symmetry are the dimension - three operators @xmath32 .\nmore precisely , we consider the following correction to ( [ hll ] ) @xmath33 \\\\ & + & \\eta_{+}\\left[\\left(\\partial_{x}\\phi_{l}\\right)^{2}\\partial_{x}\\phi_{r}-\\left(\\partial_{x}\\phi_{r}\\right)^{2}\\partial_{x}\\phi_{l}\\right]\\bigg\\ } \\nonumber \\ ; , \\end{aligned}\\ ] ] where @xmath34 are the right- and left - moving components of the bosonic field with @xmath35 .\nthis correction is the bosonized form of the leading band curvature term @xmath36 .\nnote , that ( [ correct ] ) corresponds to interaction vertices allowing a boson to decay into two bosons .\nthe @xmath37-interaction allows for intermediate states with one right- and one left - moving boson , which together can carry small momentum but high energy @xmath38 thus giving rise to a high - energy tail in @xmath0 .\nthe @xmath39-interaction , on the other hand , will influence the on - shell part @xmath40 .\nif @xmath41 , where @xmath3 is the width if the on - shell peak , then the terms in ( [ correct ] ) can be treated in perturbation theory and we find a high - frequency tail @xcite @xmath42 the parameters @xmath43 can be related to the change in the velocity @xmath44 and the luttinger parameter @xmath45 when varying @xmath9 and we find @xmath46 and @xmath47 where @xmath48 and @xmath49 , @xmath50 for all anisotropies and fields by ba so that ( [ ff_tail ] ) does not contain any free parameters . in fig .\n[ fig1 ] this analytical result is compared to a ba calculation for a chain with @xmath51 sites . )\n( black solid line ) compared to a ba calculation for a chain with @xmath51 ( red dots ) .\nhere @xmath52 and the magnetization @xmath53 . ]\nperturbation theory in @xmath54 , on the other hand , produces terms which become increasingly singular at @xmath40 .\ntherefore the whole series has to be summed up to produce a finite result @xcite .\nhere we only present ba results for the form factors @xmath55 ( see ( [ strucfac ] ) ) for @xmath40 in fig .\n[ fig2 ] . at the free fermion point @xmath56 compared to numerical ba data at @xmath52 for different finite size systems with @xmath53 in both cases .\nthe effective mass in the free fermion case is given by @xmath57 where @xmath58 is the fermi momentum .\nfor small finite @xmath8 the effective mass can be obtained by ba and is given by @xmath59 @xcite . ] note that the width @xmath3 of the on - shell peak for finite @xmath8 is @xmath60 as in the free fermion case ( @xmath61 ) but the effective mass is renormalized . for finite @xmath62 ,\npustilnik _ et al .\n_ @xcite have shown that @xmath0 exhibits power laws at the upper and lower threshold of the on - shell peak with exponents depending on @xmath8 _ and _ @xmath26 .\ntheir results are consistent with our numerical data shown in fig .\nthis research was supported by cnpq through grant no . 200612/2004 - 2 ( r.g.p ) , the dfg ( j.s .\n) , fom ( j .- s.c . ) , cnrs and the euclid network ( j.m.m . ) , the nsf under dmr 0311843 ( s.r.w . ) , and nserc ( j.s . , i.a . ) and the ciar ( i.a . ) .\nm. pustilnik , e. g. mishenko , l. i. glazman , and a. v. andreev , phys .\n* 91 * ( 2003 ) 126805 .\nr. g. pereira , j. sirker , j .- s .\ncaux , r. hagemans , j. m. maillet , s. r. white , and i. affleck , phys .\n* 96 * ( 2006 ) 257202 .\nr. g. pereira , j. sirker , j .- s .\ncaux , r. hagemans , j. m. maillet , s. r. white , and i. affleck , in preparation .\nm. pustilnik , m. khodas , a. kamenev , and l. i. glazman , phys .\n* 96 * ( 2006 ) 196405 .", "role": "user" }, { "content": "we study the longitudinal dynamical structure factor @xmath0 for the anisotropic spin-@xmath1 ( @xmath2 ) chain at finite magnetic field using bosonization . \n the leading irrelevant operators in the effective bosonic model stemming from band curvature describe boson decay processes and lead to a high - frequency tail and a finite width @xmath3 of the on - shell peak for @xmath0 . \n we use the bethe ansatz to show that @xmath4 for @xmath5 and to calculate the amplitudes of the leading irrelevant operators in the effective field theory . , , , , , , spin chains ; structure factor ; bosonization ; bethe ansatz 75.10.jm , 75.10.pq , 02.30.ik", "role": "assistant" } ]

[ { "content": "Output a JSON object with \"verdict\" and \"evidence\" fields based on the claim and abstract below.\n\nClaim: Low protein blood levels is the main cause of death from the new coronavirus.\n\nAbstract:\nBACKGROUND: The 2019 novel coronavirus has caused the outbreak of the acute respiratory disease in Wuhan, Hubei Province of China since December 2019.\nThis study was performed to analyze the clinical characteristics of patients who succumbed to and who recovered from 2019 novel coronavirus disease (COVID-19).\nMETHODS: Clinical data were collected from two tertiary hospitals in Wuhan.\nA retrospective investigation was conducted to analyze the clinical characteristics of fatal cases of COVID-19 (death group) and we compare them with recovered patients (recovered group).\nContinuous variables were analyzed using the Mann-Whitney U test.\nCategorical variables were analyzed by &#967; test or Fisher exact test as appropriate.\nRESULTS: Our study enrolled 109 COVID-19 patients who died during hospitalization and 116 recovered patients.\nThe median age of the death group was older than the recovered group (69 [62, 74] vs. 40 [33, 57] years, Z = 9.738, P < 0.001).\nMore patients in the death group had underlying diseases (72.5% vs. 41.4%, &#967; = 22.105, P < 0.001).\nPatients in the death group had a significantly longer time of illness onset to hospitalization (10.0 [6.5, 12.0] vs. 7.0 [5.0, 10.0] days, Z = 3.216, P = 0.001).\nOn admission, the proportions of patients with symptoms of dyspnea (70.6% vs. 19.0%, &#967; = 60.905, P < 0.001) and expectoration (32.1% vs. 12.1%, &#967; = 13.250, P < 0.001) were significantly higher in the death group.\nThe blood oxygen saturation was significantly lower in the death group (85 [77, 91]% vs. 97 [95, 98]%, Z = 10.625, P < 0.001).\nThe white blood cell (WBC) in death group was significantly higher on admission (7.23 [4.87, 11.17] vs. 4.52 [3.62, 5.88] ×10/L, Z = 7.618, P < 0.001).\nPatients in the death group exhibited significantly lower lymphocyte count (0.63 [0.40, 0.79] vs. 1.00 [0.72, 1.27] ×10/L, Z = 8.037, P < 0.001) and lymphocyte percentage (7.10 [4.45, 12.73]% vs. 23.50 [15.27, 31.25]%, Z = 10.315, P < 0.001) on admission, and the lymphocyte percentage continued to decrease during hospitalization (7.10 [4.45, 12.73]% vs. 2.91 [1.79, 6.13]%, Z = 5.242, P < 0.001).\nAlanine transaminase (22.00 [15.00, 34.00] vs. 18.70 [13.00, 30.38] U/L, Z = 2.592, P = 0.010), aspartate transaminase (34.00 [27.00, 47.00] vs. 22.00 [17.65, 31.75] U/L, Z = 7.308, P < 0.001), and creatinine levels (89.00 [72.00, 133.50] vs. 65.00 [54.60, 78.75] µmol/L, Z = 6.478, P < 0.001) were significantly higher in the death group than those in the recovered group.\nC-reactive protein (CRP) levels were also significantly higher in the death group on admission (109.25 [35.00, 170.28] vs. 3.22 [1.04, 21.80] mg/L, Z = 10.206, P < 0.001) and showed no significant improvement after treatment (109.25 [35.00, 170.28] vs. 81.60 [27.23, 179.08] mg/L, Z = 1.219, P = 0.233).\nThe patients in the death group had more complications such as acute respiratory distress syndrome (ARDS) (89.9% vs. 8.6%, &#967; = 148.105, P < 0.001), acute cardiac injury (59.6% vs. 0.9%, &#967; = 93.222, P < 0.001), acute kidney injury (18.3% vs. 0%, &#967; = 23.257, P < 0.001), shock (11.9% vs. 0%, &#967; = 14.618, P < 0.001), and disseminated intravascular coagulation (DIC) (6.4% vs. 0%, &#967; = 7.655, P = 0.006).\nCONCLUSIONS: Compared to the recovered group, more patients in the death group exhibited characteristics of advanced age, pre-existing comorbidities, dyspnea, oxygen saturation decrease, increased WBC count, decreased lymphocytes, and elevated CRP levels.\nMore patients in the death group had complications such as ARDS, acute cardiac injury, acute kidney injury, shock, and DIC.", "role": "user" }, { "content": "{\"verdict\": \"CONTRADICT\", \"evidence\": [\"CONCLUSIONS: Compared to the recovered group, more patients in the death group exhibited characteristics of advanced age, pre-existing comorbidities, dyspnea, oxygen saturation decrease, increased WBC count, decreased lymphocytes, and elevated CRP levels.\"]}", "role": "assistant" } ]

[ { "content": "Write an abstract for this chemistry paper.\n\nTitle:\nAnalysis of gut microbiota in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)\n\nPaper sections:\nIntroduction\n<p>Drowing evidence supports the potential roles of gut microbiota in human health and diseases, including Parkinson's disease, multiple sclerosis, and atherosclerotic disease.(1,2) It may be difficult to clarify the influence of gut microbiota on sporadic cerebral infarction because stroke patients show different conventional risk factors, including hypertension, smoking, diabetes, hyperlipidemia, and aging. In contrast, patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a major hereditary small vessel disease caused by mutations in NOTCH3,(3) generally have no common vascular risk factors. Typical clinical characteristics of CADASIL patients are migraines, recurrent ischemic strokes, vascular dementia, and specific white matter lesions with multiple lacunar infarcts.(4) It is well-known that the progression and severity of CADASIL show both inter- and intra-familial variations among patients. Age at onset of the first stroke ranges from 20–70 years old, and moreover, some patients remain asymptomatic even after 70 years old.(4,5) These suggest that the CADASIL phenotype is modified by some genetic or environmental factors in addition to NOTCH3 mutation. To clarify the contribution of gut microbiota to cerebral infarction, we focused on the profile of fecal microbiota in CADASIL patients.</p>\n\nParticipants\n<p>We recruited nineteen Japanese CADASIL patients who visited our outpatient clinic at University Hospital, Kyoto Prefectural University of Medicine from January to November 2017. Eighteen of their family members (15 spouses, 2 siblings, and a child) were recruited as controls. Nutrition survey during the one month before and up to fecal sampling, using the brief-type self-administered diet history questionnaire (BDHQ).(6) Four CADASIL patients and 2 controls were excluded from the analysis because of taking medication that may interfere with gut microbiota (antibiotics: n = 1, proton pump inhibitors: n = 4, Metformin: n = 1). We finally analyzed fecal samples from 15 CADASIL patients and 16 controls. CADASIL patients were divided into two subgroups: those with a history of symptomatic ischemic stroke (n = 7) and those without it (n = 8). The Ethics Committee of Kyoto Prefectural University of Medicine approved the research protocol (permission No. ERB-C-725-1), and all participants provided written informed consent prior to enrollment.</p>\n\nMeta16S analysis of gut microbiota\n<p>Meta16S analysis of gut microbiota was performed according to Takagi et al.(7) In brief, fecal sampling was performed using a sampling kit (Techno Suruga Lab., Shizuoka, Japan). Meta16S analysis of fecal DNA was performed at the Biomedical Center, Takara Bio. PCR for DNA extracted from fecal samples was comprised of two steps. In the first step, PCR was performed to amplify with primers of 341F (5'-TCGTCGGCAGCGTCAGATGTGTATAAGAGACAGCCTACGGGNGGCWGCAG-3') and 806R (5'-GTCTCGTGGGCTC GGAGATGTGTATAAGAGACAGGGACTACHVGGGTWTCTAAT-3') corresponding to the V3–V4 region of the 16S rRNA gene. In the second PCR step, the index sequences for Illumina sequencer were added. Then, the libraries were subjected to the sequencing of paired-end 300 bases on MiSeq (Illumina).</p><p>Processing of sequence data, operational taxonomic unit (OTU) definition, and taxonomy assignment were performed using QIIME ver. 1.9, USEARCH ver. 8.0, and UCHIME ver. 4.2.40, respectively. Singletons were removed in the present study. Taxonomy assignment of the resulting OTU was completed using RDP classifier ver. 2.10.2 with the Greengenes database (May 2013).</p><p>Microbiota diversity within a sample (α-diversity) was evaluated as the Chao1 index (OTU richness estimation) and Shannon index (OTU evenness estimation) calculated by the R \"phyloseq\" package. Differences in diversity between samples (β-diversity) was estimated using the UniFrac metric by quantitative (weighted) or qualitative (unweighted) analysis, and the distances between the samples were visualized by principal coordinate analysis (PCoA) plotting, using the software QIIME (ver. 1.9.0).</p>\n\nStatistical analysis\n<p>Data were compared between groups (CADASIL patients vs controls, and CADASIL patients with and without stroke). Nutrition intake profiles were compared by the Mann-Whitney U test using SPSS 17.0. The relative abundance of bacterial genera, OTU, and α-diversity were compared with a Wilcoxon rank sum test using JMP14.0.0. Clustering on PCoA plot (β-diversity) and was statistically analyzed using permutational multivariate analysis of variance (PERMANOVA). Values of p<0.05 were considered significant.</p>\n\nBackgrounds and nutrition survey\n<p>There was no significant difference in backgrounds and vascular risk factors between CADASIL patients and controls, or CADASIL subgroups, except for weak difference in gender between CADASIL patients with stroke and those without stroke (p = 0.04) (Table 1).</p><p>The nutrition survey was performed using a BDHQ.(6) Between CADASIL patients and controls, there was no significant difference in 97 nutrition items. Between CADASIL subgroups, no significant difference was noted except for the daily intake of arachidonic acid (patients with stroke: 22.28 mg/day vs patients without it: 29.39 mg/day; p = 0.028).</p>\n\nAnalysis of gut microbiota diversity\n<p>In total, seven hundred ninety OTUs were detected after the removal of singletons in this study. No significant difference in α-diversity was observed between the CADASIL patients and controls, or between the patients with and without stroke (Fig. 1). As for β-diversity, PCoA plots showed no significant difference in clusters between CADASIL patients and controls, or between CADASIL patients with and without stroke (Fig. 2).</p>\n\nTaxonomic microbial analysis\n<p>The taxonomic change in the microbiota was assessed at genus and OTU levels. In CADASIL patients compared with controls, there was a significant increase in abundance of 6 genera (Lachnospira, Odoribacter, Parvimonas, unclassified genus belonging to Barnesiellaceae and Lachnospiraceae, unclassified genus belonging to order SHA-98), and a significant decrease in 2 genera (Megasphaera and Acidaminococcus) (Table 2). Regarding the OTU level, there was a significant increase in abundance of 24 OTUs and significant decrease in 4 OTUs in CADASIL patients compared with controls (Supplemental Table 1*).</p><p>In the CADASIL patients with compared with those without stroke, there was a significant decrease in abundance of 2 genera, Phascolarctobacterium and Paraprevotella (Table 2).</p><p>Regarding the OTU level, a significant increase in abundance of 13 OTUs and significant decrease in 3 OTUs were observed in CADASIL patients with compared with those without stroke (Supplemental Table 1*).</p>\n\nDiscussion\n<p>To our knowledge, this is the first study addressing the possibility of gut microbiota contributing to the development of CADASIL. The major finding of this study was identification of significant taxonomic differences in gut microbiota between CADASIL patients and controls, and also between patients with and without previous ischemic stroke. These suggest the role of gut microbiota as modifiers of the onset and progression of CADASIL.</p><p>Taxonomic analysis showed significant differences in abundances of some bacteria between CADASIL patients and controls. According to previous reports, some of the representative bacteria shown in Table 1 might be associated with stroke onset in CADASIL patients. Firstly, Goodrich et al.(8) reported that the abundance of SHA-98, a member of the Christensenellaceae consortium, was associated with a gene encoding aldehyde dehydrogenase (ALDH1L1). Interestingly, an SNP in ALDH1L1 was reported to be associated with ischemic stroke in the Framingham Heart Study.(9) Secondly, Parvimonas, a Gram-positive anaerobic coccus, was also of interest according to recent knowledge on the association between periodontal disease and ischemic stroke.(10) Fak et al.(11) reported that bacteria from the oral cavity and gut can be recovered from atherosclerotic plaque, and that the abundance of oral Parvimonas was positively associated with c-reactive protein (CRP) in atherosclerotic patients. Thirdly, the family Lachnospiraceae has been reported to facilitate Treg differentiation and stimulate TGF-β and IL-10 production by immune cells.(12) TGF-β is a key molecule in the pathogenesis of CARASIL, an autosomal recessive small vessel disease caused by HTRA1 mutations.(13) Dysregulation of TGF-β signaling may also be associated with CADASIL according to a report that latent TGF-β binding protein 1 was sequestrated into CADASIL-related NOTCH3 extracellular domain deposits.(14) Taken together, the increase of Lachnospiraceae in CADASIL patients is of interest.</p><p>In recent gut microbial taxonomic studies, other bacteria were reported to be associated with ischemic stroke in sporadic patients.(15) In this study, however, we did not replicate any of these findings.</p><p>On the other hand, on taxonomic analysis in association with stroke among CADASIL patients, two genera, Phascolarctobacterium and Paraprevotella, showed a significant difference. Based on our search, however, no previous report addressed the association of these genera with cerebrovascular dysfunction.</p><p>A major limitation of our study was the small number of participants, due to the fact that CADASIL is a rare hereditary disease. In this regard, it is of note that Inoue et al.(16) reported robust evaluation of gut dysbiosis in type 2 diabetic patients even though the sample size, 12 patients and 10 controls, was as small as our study. By using 16S rRNA metagenomic analysis in combination with functional prediction software Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database, they identified not only composition but also functional profiles of gut microbiota associated with diabetes pathophysiology.(16) Then, we additionally performed similar analysis. Although there was no significant difference between CADASIL patients and normal controls, we found 32 KEGG pathways of which abundances were significantly different between CADASIL patients with and without stroke (Supplemental Fig. 1*). To interpret these findings, further studies including fecal metabolome analysis should be necessary. However, of the 32 pathways, lipid metabolism seems of note, because Žitňanová et al.(17) recently reported that subfractions of plasma lipid were significantly altered in acute phase of stroke, another limitation was that we did not adjust background factors to compare gut microbiota between groups. Previous report showed that several changes in gut microbiota were associated with age and sex, by analyzing 277 healthy individuals.(18) Moreover, it cannot be concluded whether taxonomic changes between CADASIL and controls or between CADASIL patients with and without stroke were causes or results of the disease. To address these issues, increasing the number of participants and longitudinal analysis of each patient are necessary.</p><p>In conclusion, this is the first study on CADASIL focusing on gut microbiota. Significant differences in taxonomy were noted between CADASIL patients and controls, and between CADASIL patients with and without stroke, suggesting that gut microbiota modifies the onset and progression of CADASIL.</p>\n\nAuthor Contributions\n<p>TM and YN supervised and designed the study; JM and TM collected feces; JM, AW, TK, MM, IM and TM collected the clinical information; JM, RI, TT, IM, YN and TM analyzed and interpreted the gut microbiota data; JM, SW and TM analyzed and interpreted the nutrition data; JM, RI and SW performed the statistical analysis. All authors drafted and edited the manuscript, and discussed the results and commented on the manuscript.</p>", "role": "user" }, { "content": "Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a major hereditary small vessel disease caused by mutations in NOTCH3. The variations in progression and severity among patients suggest that the CADASIL phenotype is modified by some genetic and environmental factors. Recent studies have shown the potential roles of gut microbiota in human diseases. We hypothesized that gut microbiota modifies the disease phenotype. We performed gut microbial meta 16S rRNA analysis of fecal samples from 15 CADASIL patients and 16 controls. The microbial α- and β-diversities and taxonomy were compared between CADASIL patients and controls and between CADASIL patients with and without an ischemic stroke history. No significant difference in α- or β-diversity was observed in either case-control or subgroup comparisons. In the taxonomic microbial analysis, there was a significant increase in abundance of 6 genera and significant decrease in 2 genera in CADASIL patients compared with controls. There was a significant decrease in abundance of 2 genera in CADASIL patients with compared with those without stroke. This is the first study on CADASIL focusing on gut microbiota. Our findings suggest that gut microbiota modifies the onset and progression of CADASIL.", "role": "assistant" } ]

[ { "content": "Write a Related Work section based on these abstracts. Use numerical citations like [1], [2], etc.\n\nMain Abstract:\nIn this paper, we propose effective channel assignment algorithms for network utility maximization in a cellular network with underlaying device-to-device (D2D) communications. A major innovation is the consideration of partial channel state information (CSI), i.e., the base station (BS) is assumed to be able to acquire partial' instantaneous CSI of the cellular and D2D links, as well as, the interference links. In contrast to existing works, multiple D2D links are allowed to share the same channel, and the quality of service (QoS) requirements for both the cellular and D2D links are enforced. We first develop an optimal channel assignment algorithm based on dynamic programming (DP), which enjoys a much lower complexity compared to exhaustive search and will serve as a performance benchmark. To further reduce complexity, we propose a cluster-based sub-optimal channel assignment algorithm. New closed-form expressions for the expected weighted sum-rate and the successful transmission probabilities are also derived. Simulation results verify the effectiveness of the proposed algorithms. Moreover, by comparing different partial CSI scenarios, we observe that the CSI of the D2D communication links and the interference links from the D2D transmitters to the BS significantly affects the network performance, while the CSI of the interference links from the BS to the D2D receivers only has a negligible impact.\n\nCited Abstract(s):\n[1]: Device-to-device communication is likely to be added to LTE in 3GPP Release 12. In principle, exploiting direct communication between nearby mobile devices will improve spectrum utilization, overall throughput, and energy consumption, while enabling new peer-to-peer and location-based applications and services. D2D-enabled LTE devices can also become competitive for fallback public safety networks, which must function when cellular networks are not available or fail. Introducing D2D poses many challenges and risks to the long-standing cellular architecture, which is centered around the base station. We provide an overview of D2D standardization activities in 3GPP, identify outstanding technical challenges, draw lessons from initial evaluation studies, and summarize \"best practices\" in the design of a D2D-enabled air interface for LTE-based cellular networks\n\n[2]: In this paper, we investigate Device-to-Device (D2D) communication underlaying cellular networks to provide spectrally efficient support of local services. Since in underlay mode, D2D communications share resources in the time and frequency domains with cellular system, it will introduce potentially severe interference to the cellular users and accordingly presents a challenge in radio resource management. In order to avoid generating interference to the high-priority users (cellular users) operating on the same time-frequency resources and to optimize the throughput over the shared resources under the transmit power and the quality of service (QoS) constraints, we propose an interference alignment-based resource sharing scheme for D2D communication underlaying cellular networks. The simulation results demonstrate that by using the proposed scheme, D2D communication can effectively improve the total throughput without generating harmful interference to cellular networks.", "role": "user" }, { "content": "Resource allocation in D2D networks faces two main challenges. Firstly, when multiple D2D links are allowed to access the same channel, the dynamic resource allocation problem becomes an NP-hard problem [2] . Secondly, in cellular networks with underlaying D2D communications, the total number of links, especially interference links, is usually very large. As a result, overwhelming overheads will be incurred for collecting the channel state information (CSI) of all these links [1] . Therefore, the commonly considered full CSI scenario is not practical, and the partial CSI case, where instantaneous CSI of part of the communication and interference links is unknown at the BS, should be considered. In this paper, we will develop effective channel assignment algorithms for D2D communications with partial CSI.", "role": "assistant" } ]

[ { "content": "Write a Related Work section based on these abstracts. Use numerical citations like [1], [2], etc.\n\nMain Abstract:\nAutomatic language identification is a natural language processing problem that tries to determine the natural language of a given content. In this paper we present a statistical method for automatic language identification of written text using dictionaries containing stop words and diacritics. We propose different approaches that combine the two dictionaries to accurately determine the language of textual corpora. This method was chosen because stop words and diacritics are very specific to a language, although some languages have some similar words and special characters they are not all common. The languages taken into account were romance languages because they are very similar and usually it is hard to distinguish between them from a computational point of view. We have tested our method using a Twitter corpus and a news article corpus. Both corpora consists of UTF-8 encoded text, so the diacritics could be taken into account, in the case that the text has no diacritics only the stop words are used to determine the language of the text. The experimental results show that the proposed method has an accuracy of over 90 for small texts and over 99.8 for large texts.\n\nCited Abstract(s):\n[1]: Introduction.- Within-Language Information Retrieval.- Cross-Language Information Retrieval.- Interaction and User Interfaces.- Evaluation for Multilingual Information Retrieval Systems.- Applications of Multilingual Information Access.", "role": "user" }, { "content": "Stop words, from the point of view of LID, are defined as the most frequently terms as determined by a representative language sample. This list of words has been shown to be effective for language identification because these terms are very specific to a language [1] .", "role": "assistant" } ]

[ { "content": "Extract all chemical entities (ChEBI) from this biomedical text. Output as JSON array.\n\nText: Themajorityexhibitedthecharacteristic9+0doublets(arrowhead2and3inFigure3AandFigure3B).", "role": "user" }, { "content": "[]", "role": "assistant" } ]

[ { "content": "Write an abstract for this chemistry paper.\n\nTitle:\nFast and efficient synthesis of microporous polymer nanomembranes via light-induced click reaction\n\nPaper sections:\nIntroduction\n<p>The synthesis of microporous organic and inorganic materials such as zeolites [1], mesoporous silica [2] as well as metalorganic frameworks (MOF) [3,4] and covalent organic frameworks (COF) [5][6][7] attracted large attention because of their high potential in catalysis, gas storage and separation as well as in organic electronics [8]. Among the microporous materials, conjugated microporous polymers (CMPs) [9,10] or porous aromatic frameworks (PAF) [11] have favorable properties for many applications, since they combine a high chemical and thermal stability, which is comparable to inorganic materials, with the variability of organic compounds.</p><p>Nevertheless, their insoluble nature has so far greatly limited their processing and integration into functional devices, since CMPs and PAF are usually synthesized as highly crosslinked interconnected and insoluble powders [12]. Only few examples of soluble and therefore processable CMP materials are known, all limited to linear CMPs [13,14].</p><p>To overcome the issue of low processability, recently the group of Jiang and our group introduced the interfacial synthesis using an electro-activated approach [15] and a copper catalyzed azide-alkyne cycloaddition (CuAAC) approach, respectively [16]. These procedures are still limited to conductive substrates or associated with long reaction times.</p><p>In this work, we present a novel strategy for the LbL synthesis of CMP thin films and nanomembranes, using the light-induced and catalyst-free thiol-yne coupling (TYC) reaction.</p><p>TYC has gained large attention as a representative of the click chemistry concept [17]. In the TYC reaction, usually a photoinitiator creates thiyl radicals [18][19][20], which react with nearby alkyne moieties to form covalent sulfur-carbon bonds and vinyl radicals. Additional thiol moieties can undergo hydrogen transfer to the vinyl radical leading to thiyl radicals and vinyl sulfides. The vinyl sulfides can then undergo a thiol-ene coupling (TEC) reaction, leading to bis-sulfide species. TYC has been used for surface modification [21,22], biofunctionalization [23,24] and fabrication of 3D structures via direct laser writing (DLW) [25].</p>\n\nSynthesis of CMP thin films\n<p>We prepared the CMP nanomembranes in a LbL approach using the thiol-yne coupling (TYC) reaction. In order to perform the reaction on surfaces, we first functionalized the substrates with an alkyne terminated self-assembled monolayer, which presents initial groups for the stepwise growing of the CMPs using the TYC reaction.</p><p>In the first step, we immersed the functionalized surface in a solution of the tetra-topic thiol building block (tetrakis(4sulfanylphenyl)methane, TPM-SH) and a small amount of photoinitiator (2-hydroxy-1-[4-(2-hydroxyethoxy)phenyl]-2methylpropan-1-one) [26]. Afterwards we irradiated the substrate using a standard UV lamp at a wavelength of 365 nm for 3 minutes. We then rinsed the substrate thoroughly with absolute THF and immersed the substrate in a solution of the tetra-topic alkyne building block (tetrakis(4-ethynylphenyl)methane, TPM-alkyne), again with a small amount of photoinitiator. Then we irradiated the substrate for 3 minutes and rinsed the substrate thoroughly with absolute THF.</p><p>Figure 1 shows the LbL synthesis procedure as well as the molecular structures of the reactants used in the described reaction.</p><p>We repeated the described reaction cycle 20 times to obtain CMPs thin films on functionalized gold wafers.</p>\n\nCharacterization of CMP thin films\n<p>We characterized the reaction using infrared reflection absorption spectroscopy (IRRAS). Figure 2 shows the IRRA spectrum of the CMP thin film after 20 reaction cycles and the corresponding band assignments.</p><p>The absence of bands associated to alkyne and thiol functional groups in the IRRA-spectra suggest an almost quantitative reaction. (For IRRA-spectra of the starting materials, see Supporting Information File 1, Figures S1-S3.)</p><p>We evaluated the thickness of the CMP thin film using ellipsometry. The measurements show an average thickness of about 25.1 ± 0.1 nm with a mean squared error (MSE) value of 5.69 after fitting with Cauchy mode with the parameters A n = 1.399, B n = 0.051, C n = −0.0026, k-amplitude = 0 and exponent = 1.5 suggesting a very low surface roughness. To further confirm the thickness we performed the LbL synthesis on a sacrificial substrate [27,28]. Prior to the dissolution of the substrate, we coated the CMP thin film with a stabilizing layer of poly(methyl methacrylate) (PMMA). Upon substrate dissolution, we transferred the PMMA stabilized CMP thin film to a fresh gold substrate. After drying, we dissolved the PMMA layer in acetone, leaving only the CMP thin film. We then investigated the thickness of the film by an atomic force microscope (AFM) line scan along the edge of the film. Figure 3 shows the AFM image and the line-scan across the edge of the CMP thin film.</p><p>The AFM investigation also suggests a homogeneous thickness of the CMP thin film and the line-scan across the edge confirms a thickness of roughly 20 nm after 20 reaction cycles. The growth rate of roughly 1 nm per reaction cycle is in the same order as the previously described LbL synthesis of CMP nanomembranes using CuAAC click chemistry [16].</p>\n\nSynthesis of freestanding CMP nanomembranes\n<p>In order to produce freestanding CMP nanomembranes, we coated the CMP thin films on sacrificial substrates with a stabi- lizing layer of PMMA containing large holes [29]. This stabilizing layer was spin-coated from a dichloromethane (DCM) solution containing PMMA and polystyrene (PS) in a weight ratio of PMMA/PS = 4:1. During spin-coating, the PS phase separates into islands, which then were selectively dissolved using cyclohexane. Afterwards we dissolved the sacrificial substrate to obtain the freestanding CMP membranes. To investigate the freestanding CMP nanomembrane we transferred it to a copper grid and recorded scanning electron microscopy (SEM) images. Figure 4 shows the SEM images of the CMP nanomembrane.</p>\n\nConclusion\n<p>We described a new synthesis of CMP thin films and nanomembranes using a thiol-yne coupling (TYC) reaction. The TYC reaction allows a rapid synthesis of homogeneous thin films with a thickness of about 1 nm per reaction cycle as confirmed by ellipsometry and AFM investigations. The thin films show high mechanical stability as evidenced by the possibility to create feestanding membranes across holes of about 3-5 µm diameter. The rapid and scalable synthetic method for CMP nanomembranes described in this article, along with the possibility to transfer the nanomembranes to virtually any support, allows the integration of TYC based CMP materials in functional devices for applications in organic electronics or gas and liquid phase separation.</p>\n\nExperimental\n<p>Chemicals: All chemicals were purchased from commercial sources and used without further purification if not stated otherwise. Cyclohexane, dichloromethane and dry tetrahydrofuran (THF) were purchased from Merck Millipore; acetone was purchased from VWR Chemicals. Dry THF was degassed three times via freeze-pump-thaw prior to use. PMMA average M w ≈120.000, PS average M w ≈170.000, 2-hydroxy-1-[4-(2hydroxyethoxy)phenyl]-2-methylpropan-1-one), iodine and potassium iodide were purchased from Sigma-Aldrich. TPM-SH [30] and TPM-alkyne [31] were synthesized as described in the literature.</p>\n\nSubstrates:\n<p>The sacrificial substrate consists of a 150 nm gold film on mica. For analytical measurements, we transferred the membrane to a Si(100) wafer, coated with 5 nm titanium and 100 nm gold (Au/Ti/Si). The substrates were obtained from Georg-Albert-PVD, Germany and stored under an argon atmosphere prior to use.</p>\n\nInfrared reflection absorption spectroscopy (IRRAS):\n<p>The IRRA-spectra were recorded on a Bruker Vertex 80 purged with dried air. The IRRAS accessory (A518) has a fixed angle of incidence of 80°. The data were collected on a middle band liquid nitrogen cooled MCT detector. Perdeuterated hexadecanethiol-SAMs on Au/Ti/Si were used for reference measurements [32]. The absorption band positions are given in wavenumbers (cm −1 ).</p>\n\nScanning electron microscopy (SEM):\n<p>We recorded SEM images using a FEI Philips XL30 (FEI Co., Eindhoven, NL), a field emission gun environmental scanning electron microscope (FEG-ESEM). Samples have been coated with a thin layer (about 5 nm) of a gold/palladium film in order to avoid charging and improve samples conductivity. All specimen were imaged under high-vacuum conditions (1.0 Torr), using an acceleration voltage of 20 keV.</p><p>Atomic force microscopy (AFM): AFM-imaging was performed using an Asylum Research Atomic Force Microscope, MFP-3D BIO. The AFM was operated at 25 °C in an isolated chamber in alternating current mode (AC mode). AFM cantilevers were purchased from Ultrasharptm MikroMasch. Three types of AFM-cantilevers were used, an NSC-35 (resonance frequency 315 kHz; spring constant 14 N/m), an NSC-36 (resonance frequency: 105 KHz; spring constant: 0.95 N/m) and an NSC-18 (resonance frequency: 75 kHz; spring constant: 3.5 N/m).</p>\n\nSelf-assembled monolayer (SAM) preparation:\n<p>For SAM formation, a clean gold substrate (2.2 cm × 2.2 cm) was rinsed with absolute ethanol and then immersed in a solution of S- [11oxo-11-(propargylamino)undecyl] thioacetate (AcSC 10 H 20 -C(O)NHCH 2 C≡CH) (with a concentration of 1 mmol/L) in ethanol for 18 h. Afterwards the substrate was taken out, rinsed thoroughly with ethanol and dried in a nitrogen stream [33].</p><p>Preparation of conjugated microporous polymer (CMP) films: 6.7 mg of TPM-SH (15.0 µmol, 1.00 equiv), 6.3 mg of TPM-alkyne (15.0 µmol, 1.00 equiv) and 1.1 mg of 2-hydroxy-1-[4-(2-hydroxyethoxy)phenyl]-2-methylpropan-1-one) (5 µmol, 0.333 equiv) as photoinitiator were separately dissolved in 20 mL abs. THF. The synthesis was carried out under inert conditions using an argon atmosphere. At first, 1 mL of TPM-SH solution and 0.5 mL of the photoinitiator solution were added to the SAM coated substrate and stirred gently to ensure proper mixing. Then the mixture was exposed to 365 nm UV-light for 3 minutes. Afterwards, the substrate was rinsed with dry THF. Subsequently, 1 mL of TPM-alkyne solution and 0.5 mL of the photoinitiator solution were added to the substrate and stirred gently to ensure proper mixing. Then the mixture was exposed to 365 nm UV-light for 3 minutes. Then, the substrate was again rinsed with dry THF. The procedure was then repeated for the next reactant 20 times each. After the cycles were completed, the wafer was taken out of the inert environment, washed thoroughly with dry THF and ethanol and dried using a nitrogen stream.</p>\n\nTransfer of CMP nanomembranes:\n<p>To obtain freestanding nanomembranes, the CMP-films were grown on sacrificial substrates using the above-described procedure. The membrane was then obtained by following a procedure described in literature [28]. First, PMMA was spin coated as a supporting layer. Then, the mica was removed by floating in solutions of I 2 /KI/H 2 O; KI/H 2 O and in the last step by immersing the substrate in H 2 O. The retaining gold film was etched in a solution of I 2 /KI/H 2 O. The membrane was washed 3 times with water [28]. Then the membrane was transferred to Cu-TEM grids. The obtained membrane size was 0.3 cm × 0.3 cm.</p>\n\nPreparation of freestanding nanomembranes:\n<p>To obtain freestanding nanomembranes, the CMP-films were grown on sacrificial substrates using the above-described procedure. The membrane was then obtained by following a procedure described in literature [29]: First PMMA/PS was spin coated as a supporting layer and afterwards rinsed overnight in cyclohexane to remove the PS. Then, the mica was removed by floating in solutions of I 2 /KI/H 2 O; KI/H 2 O and in the last step by immersing the substrate in H 2 O. The retaining gold film was etched in a solution of I 2 /KI/H 2 O. The membrane was washed 3 times with water [28]. Afterwards the membrane was transferred to either a glass slide or a gold coated Si-wafer. The obtained membrane size was 2 cm × 2 cm.</p>", "role": "user" }, { "content": "Conjugated microporous polymers (CMPs) are materials of low density and high intrinsic porosity. This is due to the use of rigid building blocks consisting only of lightweight elements. These materials are usually stable up to temperatures of 400 °C and are chemically inert, since the networks are highly crosslinked via strong covalent bonds, making them ideal candidates for demanding applications in hostile environments. However, the high stability and chemical inertness pose problems in the processing of the CMP materials and their integration in functional devices. Especially the application of these materials for membrane separation has been limited due to their insoluble nature when synthesized as bulk material. To make full use of the beneficial properties of CMPs for membrane applications, their synthesis and functionalization on surfaces become increasingly important. In this respect, we recently introduced the solid liquid interfacial layer-by-layer (LbL) synthesis of CMP-nanomembranes via Cu catalyzed azide-alkyne cycloaddition (CuAAC). However, this process featured very long reaction times and limited scalability. Herein we present the synthesis of surface grown CMP thin films and nanomembranes via light induced thiol-yne click reaction. Using this reaction, we could greatly enhance the CMP nanomembrane synthesis and further broaden the variability of the LbL approach.", "role": "assistant" } ]

[ { "content": "Answer the following question using the provided context. Only provide the answer without any additional text.\n\nQuestion: Describe the usefulness of MiRduplexSVM.\nContext: MiRduplexSVM: A High-Performing MiRNA-Duplex Prediction and Evaluation Methodology.\nOur method combines a unique problem representation and an unbiased optimization protocol to learn from mirBase19.0 an accurate predictive model, termed MiRduplexSVM. This is the first model that provides precise information about all four ends of the miRNA duplex.\nIn relation with recent confidence evaluation methods used in miRBase, MiRduplexSVM was successful in identifying high confidence potential miRNAs.\nOur method combines a unique problem representation and an unbiased optimization protocol to learn from mirBase19.0 an accurate predictive model, termed MiRduplexSVM.\n(b) In all comparisons, MiRduplexSVM shows superior performance, achieving up to a 60% increase in prediction accuracy for mammalian hairpins and can generalize very well on plant hairpins, without any special optimization.\nMiRduplexSVM: A High-Performing MiRNA-Duplex Prediction and Evaluation Methodology.\nIn relation with recent confidence evaluation methods used in miRBase, MiRduplexSVM was successful in identifying high confidence potential miRNAs.\nOur method combines a unique problem representation and an unbiased optimization protocol to learn from mirBase19.0 an accurate predictive model, termed MiRduplexSVM.\n(b) In all comparisons, MiRduplexSVM shows superior performance, achieving up to a 60% increase in prediction accuracy for mammalian hairpins and can generalize very well on plant hairpins, without any special optimization.", "role": "user" }, { "content": "MiRduplexSVM is a high-performing miRNA-duplex prediction and evaluation methodology. It's a method that combines a unique problem representation and an unbiased optimization protocol to learn from mirBase19.0 an accurate predictive model. It is the first model that provides precise information about all four ends of the miRNA duplex.", "role": "assistant" } ]

[ { "content": "Classify the intent of this citation sentence by choosing from: [\"Method\", \"Background\", \"Result\"].\n\nMethod: Cites for methodology\nBackground: Cites for background information\nResult: Cites for findings\n\nCitation: 8 illustrates a summary for the comparison with the existing bit-split string matching approaches described in [8], [10], and [4].", "role": "user" }, { "content": "Background", "role": "assistant" } ]

[ { "content": "Write a Related Work section based on these abstracts. Use numerical citations like [1], [2], etc.\n\nMain Abstract:\nThe block Kaczmarz method is an iterative scheme for solving overdetermined least-squares problems. At each step, the algorithm projects the current iterate onto the solution space of a subset of the constraints. This paper describes a block Kaczmarz algorithm that uses a randomized control scheme to choose the subset at each step. This algorithm is the first block Kaczmarz method with an (expected) linear rate of convergence that can be expressed in terms of the geometric properties of the matrix and its submatrices. The analysis reveals that the algorithm is most effective when it is given a good row paving of the matrix, a partition of the rows into well-conditioned blocks. The operator theory literature provides detailed information about the existence and construction of good row pavings. Together, these results yield an efficient block Kaczmarz scheme that applies to many overdetermined least-squares problem.\n\nCited Abstract(s):\n[1]: Spring balance apparatus including a weighing lever supported on a knife edge balance point with one side of the lever acted on by a mass to be weighed against a weighing spring coupled with the other side of the weighing lever, and including an arrangement for the compensation of a measuring error due to temperature change by modifying the ratio of transmission of forces applied to the weighing lever by means of a bimet allic element in which the inventive improvement comprises a knife edge member transferring the forces of the weighing spring to the other side of the weighing lever which knife-edge member has connected rigidly to it an actuating lever coupled to the bimet allic element to alter responsive to temperature changes the orientation of the knife edge member relative to the other side of the weighing lever and thereby modify the ratio of transmission of forces to compensate for measuring error that would otherwise occur due to temperature change.\n\n[2]: Algebraic reconstruction techniques (ART) are iterative procedures for recovering objects from their projections. It is claimed that by a careful adjustment of the order in which the collected data are accessed during the reconstruction procedure and of the so-called relaxation parameters that are to be chosen in an algebraic reconstruction technique, ART can produce high-quality reconstructions with excellent computational efficiency. This is demonstrated by an example based on a particular (but realistic) medical imaging task, showing that ART can match the performance of the standard expectation-maximization approach for maximizing likelihood (from the point of view of that particular medical task), but at an order of magnitude less computational cost. >", "role": "user" }, { "content": "The classical variants of the Kaczmarz method rely on deterministic mechanisms for selecting a row at each iteration. Indeed, the simplest version just cycles through the rows in order. It has long been known that the cyclic control scheme performs badly when the rows are arranged in an unhappy order [1] . The literature contains empirical evidence [2] that control mechanisms may be more effective, but until recently there was no compelling theoretical analysis to support this observation.", "role": "assistant" } ]

[ { "content": "Write a Related Work section based on these abstracts. Use numerical citations like [1], [2], etc.\n\nMain Abstract:\nRecently, there has been a surge in interest in safe and robust techniques within reinforcement learning (RL). Current notions of risk in RL fail to capture the potential for systemic failures such as abrupt stoppages from system failures or surpassing of safety thresholds and the appropriate responsive controls in such instances. We propose a novel approach to risk minimisation within RL in which, in addition to taking actions that maximise its expected return, the controller learns a policy that is robust against stoppages due to an adverse event such as an abrupt failure. The results of the paper cover fault-tolerant control in worst-case scenarios under random stopping and optimal stopping, all in unknown environments. By demonstrating that the class of problems is represented by a variant of stochastic games, we prove the existence of a solution which is a unique fixed point equilibrium of the game and characterise the optimal controller behaviour. We then introduce a value function approximation algorithm that converges to the solution through simulation in unknown environments.\n\nCited Abstract(s):\n[1]: The authors develop a theory characterizing optimal stopping times for discrete-time ergodic Markov processes with discounted rewards. The theory differs from prior work by its view of per-stage and terminal reward functions as elements of a certain Hilbert space. In addition to a streamlined analysis establishing existence and uniqueness of a solution to Bellman's equation, this approach provides an elegant framework for the study of approximate solutions. In particular, the authors propose a stochastic approximation algorithm that tunes weights of a linear combination of basis functions in order to approximate a value function. They prove that this algorithm converges (almost surely) and that the limit of convergence has some desirable properties. The utility of the approximation method is illustrated via a computational case study involving the pricing of a path dependent financial derivative security that gives rise to an optimal stopping problem with a 100-dimensional state space.", "role": "user" }, { "content": "There is a plethora of work on OSPs in continuous and discrete-time . [1] use approximate dynamic programming methods to construct an iterative scheme to compute the solution of an OSP. Our results generalise existing analyses to strategic settings with both a controller and an adversarial stopper which tackles risk within OSPs. OSPs have been extended to games where each player chooses one of two actions; to stop the game or continue. .", "role": "assistant" } ]

[ { "content": "Write an abstract for the research paper below.\n\nPaper text:\namong non - viral diarrhea , causing agents giardia lamblia infection is very prevalent ( 1 ) .\nmicroscopy is the usual method has been used for diagnosis of g. lamblia infections by using stool samples ; closely rely upon times of sampling , application of concentration methods and how much expertise and experience has the technician performing the test . consequently , microscopic test for the diagnosis of g. lamblia in stool samples is behind hand and uneconomical ( 2 ) , due to expensiveness of hand working in comparison to machine work in the developed countries . over light microscopy\n, there are some immunological methods for the diagnosis of g. lamblia cysts or trophozoites in biological samples .\none is the detection of giardia antigens in the stool of patient ( 3 ) .\napplication of enzyme immunoassay for antigen detection does not eliminate the need to analyze multiple stool specimens for accurate detection of parasite ( 4 ) . in general , conventional methods using microscopy , biochemistry and immunological approaches have serious restrictions such as essential need to a high degree of expertise and experience in the diagnosis of giardia ( 5 ) .\ntherefore , molecular techniques with high sensitivity , specify and workable there have been in demand . in recent for the detection of diarrhea causing agents such as viruses and bacteria\nmany pcr based methods have been published but for the diagnosis of parasites it seems to be less addressed and , application of these methods for the diagnosis of parasitic diseases in routine laboratories is still very limited ( 2 ) .\nnowadays , there are some methods for nucleic acids isolation from biological samples , which could remove pcr inhibitors ( 6 )\n. combination of simple and quick dna isolation methods with easy genome amplification and detection techniques lets us to use these techniques in routine laboratory platforms for the detection of parasites . in this regard\n, we developed a pcr for the detection of g. lamblia genome in stool samples in comparison with microscopy , which is the gold standard .\nmore than 500 stool samples in the years 2012 to 2013 were examined , among which 22 positive samples and 47 negative samples were used .\nthe samples from different parts of iran such as tehran and bandar abbas were collected . a standard diagnostic method in this study ( golden standard ) was parasitological method , which is describing as follow .\nloose , soft and formed specimens formal - ether concentration was performed , then , wet mount prepared slides stained with temporary iodine stain and investigate for cyst and/or trophozoite of giardia using 400 magnifications . for watery and dysenteric samples , iodine\nstained wet mount preparation had done also without a formal - ether concentration for the detection of active trophozoites .\nwe used qiaamp dna stool mini kit ( qiagen , germany ) for dna extraction from feces , 180 to 220 mg feces suspended in 1.4 ml of lsa buffer provided in kit and following the other commands recommended by manufacturer , dna was isolated with qiaamp dna stool mini kit spin columns .\nit uses primer3 to design pcr primers and then uses blast and global alignment algorithm to design specific primers ( ncbi / primer - blast ) ( 7 ) , based on the g. lamblia cathepsin l - like protease gene sequence for g. lamblia ( genbank accession no .\nxm_001706220.1 ) that g. lamblia dna should be detected specifically . the g. lamblia specific primers consisted of forward primer glf ( 5- aatctgttgacttaagggagta-3 ; positions 185206 ) , reverse primer glr ( 5-attgagtcattatagggattgt-3 ; positions 647626 ) , product length : 463 base pairs ( fig .\n1% agarosegel stained by ethidiumbromid shows pcr product by gl f&gl r primers m : size marker , lane 1 : g. lamblia dna , lane 2 : negative control the specificity of the pcr was checked out by a range of dna extracted of various microorganisms includeing e. histolytica , e. dispar , entamoeba coli , blastocystishominis , cryptosporidum spp . and from escherichia coli , vibrio cholerae , and c. albicans .\nin dnase and rnase free pcr tubes amplification reactions were performed in a volume of 50 ml with 10x pcr buffer , 1 mm mgcl2 , 5 l of the dna template from the stool samples , 1 unit/l taq dna polymerase and 20 pmol/l of each specific primer .\npcr was carried out by using a peqstar thermocycler ( peqlab , germany ) under the following conditions : 5 min at 94c followed by 35 cycles of 60 s at 94 c , 90 s at 55 c , and 2 min at 72 c followed by 10 min at 72 c .\ndna of 47 stool samples , which were negative for parasitic infections in microscopy , had tested .\nsequencing had done on the amplicon produced from giardia samples achieved of culture for analyzing , and verified to present image of the accurate sequence of the targeted dna .\nsensitivity of the pcr was done with 100% ( 95%ci : 84.56100 ) for the detection of g. lamblia dna isolated from patients stool samples which were positive for g. lamblia cysts and/or trophozoites using microscopy as gold standard . in comparison with microscopy\n, pcr showed 1 false positive of 47 samples which were negative by microscopy in which the specificity of the test calculated to be 97.87% ( 95%ci : 88.7199.95 ) .\nthus , positive predictive value ( ppv ) of the pcr was achieved of 95.65% ( 95%ci : 78.0599.89 ) , and the assay negative predictive value ( npv ) was 100% ( 95%ci : 92.29100 ) .\nprevalence of g. lamblia in developed countries is 2 to 7% and in developing countries is about 20 to 30% ( 11 , 12 ) .\nmolecular methods have high sensitivity against conventional methods ( 13 ) , among these approaches , pcr have been used in studies for molecular epidemiology assessments and understanding about zoonotic transmission possibility of giardia ( 14 ) .\n, we used well - marked positive and negative stool samples as controls . in comparison with microscopy\nas the gold standard designed pcr results showed a sensitivity of 100% ( 95%ci : 84.56100 ) , the g. lamblia pcr achieved specificity of 97.87% ( 95%ci : 88.7199.95 ) for g. lamblia .\npcr showed the positive predictive value ( ppv ) , and the negative predictive value ( npv ) of 95.65% ( 95%ci : 78.0599.89 ) and 100% ( 95%ci : 92.29100 ) respectively .\ngold standard in the studies like our study ( 2 ) , but scientists stated that , microscopy is still the gold standard for the detection of many protozoan parasites ( 8) . in this way , we used the microscopy as gold standard and compared our pcr with it .\ntherefore , pcr showed high sensitivity and specificity in comparison with microscopy for the diagnoses of g. lamblia infections .\n( 2 ) who used a real - time pcr for the diagnoses of g. lamblia infections .\none false positive result was observed by the pcr , occurrence of false positive results can be due to many various causes such as contamination which could happen accidentally during the procedure or can occurs due to usage of previously contaminated reagents , even it could happen because of aerosol contamination . however , contamination is the achilles heel in the open tube system tests like pcr in contrast to those with closed tube systems such as real - time pcr .\nthere were no false negative results achieved by the pcr , the main reason for this as the case may be the existence of appropriate dna template in the reaction which we had used .\nas it proved there were many pcr inhibition factors in the stool samples which in this study using the qiaamp dna stool mini kit pcr inhibitors removed as manufacturer described . in the clinical laboratory , giardia diagnosis may face various problems , in some cases where giardia is not seen in feces but clinical symptoms are suspecting , in such cases duodenal sampling by a string test for microscopic examination is recommended ( 9 ) , but it is unpleasant for patient and slightly could be an invasive procedure . in situations like these a test which is potent to track parasites footprint like pcr will have a higher value .\nimmunological tests like direct fluorescent antibody ( dfa ) test are commercially available but limitation is requirement of laboratories access to a fluorescence microscope ( 10 ) . anyway , with consideration to the routine diagnosis techniques in medical parasitology and their limitations such as ; time consuming , laborious , less sensitivity etc .\n, this g. lamblia pcr is a sensitive and specific application for the diagnosis of g. lamblia and provide us a reliable method in the routine intestinal parasitic infection laboratory diagnosis .\nas well as possible , pcr proffer multiplex characterization of various objects in the same sample .\ntherefore , in subsequent steps authors will try to develop a multiplex pcr with using this g. lamblia pcr in combination with pcr assays for other pathogens like e. histolytica and c. parvum .\nthis pcr showed reliable sensitivity and specificity for the detection of g. lamblia in stool samples and has capability to perform in the routine diagnostic laboratories .", "role": "user" }, { "content": "background : among the most important parasitic disease , causing diarrhea , giardia lamblia is noteworthy . nowadays \n detection methods for these parasites include parasitological methods such as microscopic examination . \n the sensitivity of these methods relies on the expertise and experience of examiners . \n in contrast , molecular methods such as pcr are less dependent on the expertise of the examiner . \n here we developed a pcr for the detection of g. lamblia genome in stool samples in comparison with microscopy , which is the gold standard.methods:for the evaluation of primers , 22 positive samples and 47 negative samples were used . \n qiaamp dna stool mini kit ( qiagen , germany ) was used for dna extraction from feces . \n primers for pcr were designed using primer - blast which uses primer 3 to designing specific primers ( ncbi / primer - blast).results : sensitivity of the pcr was done with 100% ( 95%ci : 84.56100 ) for the detection of g. lamblia dna isolated from patients stool samples which were positive for g. lamblia cysts and/or trophozoites using microscopy as gold standard . in comparison with microscopy , pcr had showed the specificity of 97.87% ( 95%ci : 88.7199.95).conclusion : we designed new primers for the giardia , and pcr method for the rapid and accurate identification of giardia parasites established . \n with consideration to the routine diagnosis techniques in medical parasitology and their limitations such as time consuming , laborious , less sensitivity etc . \n this g. lamblia pcr is a sensitive and specific application for the diagnosis of g. lamblia and provides us a reliable method in the routine intestinal parasitic infection laboratory diagnosis .", "role": "assistant" } ]

[ { "content": "Summarize the article in an uncomplicated manner.\n\nTitle: The genotype-phenotype map of an evolving digital organism\nArticle:\nAbstract:\nTo understand how evolving systems bring forth novel and useful phenotypes, it is essential to understand the relationship between genotypic and phenotypic change. Artificial evolving systems can help us understand whether the genotype-phenotype maps of natural evolving systems are highly unusual, and it may help create evolvable artificial systems. Here we characterize the genotype-phenotype map of digital organisms in Avida, a platform for digital evolution. We consider digital organisms from a vast space of 10141 genotypes( instruction sequences), which can form 512 different phenotypes. These phenotypes are distinguished by different Boolean logic functions they can compute, as well as by the complexity of these functions. We observe several properties with parallels in natural systems, such as connected genotype networks and asymmetric phenotypic transitions. The likely common cause is robustness to genotypic change. We describe an intriguing tension between phenotypic complexity and evolvability that may have implications for biological evolution. On the one hand, genotypic change is more likely to yield novel phenotypes in more complex organisms. On the other hand, the total number of novel phenotypes reachable through genotypic change is highest for organisms with simple phenotypes. Artificial evolving systems can help us study aspects of biological evolvability that are not accessible in vastly more complex natural systems. They can also help identify properties, such as robustness, that are required for both human-designed artificial systems and synthetic biological systems to be evolvable.\nIntroduction:\nIn natural and artificial systems that undergo Darwinian evolution by random mutation and selection, a central distinction is that between a genotype( the entire set of genetic material or a digital organism’s set of instructions, respectively) and a phenotype( the set of observable traits encoded by the genotype). This distinction is important for two main reasons. First, genotypic change causes heritable variation, whereas the phenotypic change it brings forth is the substrate of natural selection. Second, phenotypes form through complex processes such as protein folding and embryonic development. These processes influence how genotypic variation is translated into phenotypic variation. Specifically, they influence what kind of variation becomes available to natural selection. They thus also constrain the directions of evolutionary change. Most importantly, they affect the likelihood that new and beneficial phenotypes—evolutionary adaptations and innovations—originate in the first place[1–5]. To understand the biases and constraints in the production of novel phenotypes, it is necessary to understand how genotypic change translates into phenotypic change. The concept of genotype-phenotype mapping was introduced by Pere Alberch in 1991 as a framework for integrating genetics and developmental biology[6]. However, there is no universal definition of the genotype-phenotype map. We refer to the genotype-phenotype map of natural systems as a( mathematical) function from a space of genotypes to a space of phenotypes, which determines how genotypic information specifies phenotypes through processes such as protein folding and embryonic development. Genotype-phenotype maps have been studied in multiple biological systems, including proteins and RNA molecules[7–12], genome-scale metabolism[13, 14], as well as biological circuits that regulate gene activity[15–17]. These studies have revealed a number of commonalities among otherwise very different systems. One of them is that such systems are to some extent robust to genotypic change[7–21]. Another is that this robustness leads to the existence of genotype networks[9, 10, 14, 15, 17, 22, 23], i. e., networks of genotypes that share the same phenotype, and that can be converted into one another by a series of phenotype-preserving small genetic changes( point mutations). Such networks can facilitate the origins of novel phenotypes because they help populations explore many different regions in genotype space that may harbor such phenotypes[24–26]. A third commonality is pervasive epistasis—non-additive interactions among individual mutations—which makes the phenotypic effects of individual mutations highly dependent on the genetic background on which they occur[27–29]. In addition to naturally evolving systems, researchers are exploring an increasing number of synthetic or artificial evolving systems[30–36] that range from minor modifications of natural systems, such as proteins with non-natural amino acids[37–41], to completely artificial systems such as digital organisms and computer viruses[31, 33, 34]. We know little about the genotype-phenotype maps of such artificial systems. Specifically, we know almost nothing about the organization of their genotype spaces, and how readily novel adaptive phenotypes can originate in such spaces. Such knowledge may help us compare and contrast natural and artificial evolving systems, including the extent to which natural systems are more evolvable. Any such comparison should take into account that the genotype-phenotype map of artifical systems has not evolved, but in contrast to that of natural systems, is designed. Here we address these issues with the Avida platform for digital evolution[30]. Digital evolution is a form of evolutionary computation in which self-replicating computer programs—digital organisms—evolve within a user-defined computational environment[31–33]. Avida is the most widely used software platform for research in digital evolution[33]. It satisfies the three essential requirements for evolution to occur: replication, heritable variation, and differential fitness. The latter arises through competition for the limited resources of memory space and central processing unit( CPU) time. A digital organism in Avida consists of a sequence of instructions—its genome or genotype—and a virtual CPU, which executes these instructions. Some of these instructions are involved in copying an organism’s genome, which is the only way the organism can pass on its genetic material to future generations. To reproduce, a digital organism must copy its genome instruction by instruction into a new region of memory through a process that may lead to errors( i. e., mutations). A mutation occurs when an instruction is copied incorrectly, and is instead replaced in the offspring genome by an instruction chosen at random( with a uniform distribution) from a set of possible instructions. Some instructions are required for replication( i. e., viability), whereas others are required to complete computational operations( such as addition, multiplications, and bit-shifts), and are executed on binary numbers taken from the environment through input-output instructions. When the output of processing these numbers equals the result of a specific Boolean logic operation, the digital organism is said to have a functional trait represented by that logic operation( Fig 1). An organism can be rewarded for having a functional trait with virtual CPU-cycles, which speeds up its execution of instructions. These rewards create an additional selective pressure( besides streamlining replication) which favours those organisms with mutations that have produced sequences of instructions in their genomes that encode functional traits. Organisms that are more successful—those that replicate faster—are more likely to spread through a population. We use the Avida framework to characterize the genotype-phenotype map of its digital organisms, where this mapping is defined by a direct relationship between complex interactions among computer instructions and the ability for digital organisms to perform Boolean operations. On the one hand, we find that some properties of these maps resemble those found in natural systems, such as robustness, epistasis, and genotype networks. On the other hand, we also characterize a property that has not been found in natural systems. That is, a relationship between phenotypic complexity and the ability to bring forth novel phenotypes[42]. This property may be present but hidden in natural systems, whose overwhelming complexity hinders the analysis of their genotype-phenotype maps. Digital organisms have thus helped us identify a novel hypothesis about the evolvability of natural systems, potentially leading to new fundamental biological principles.\nDiscussion:\nOur analysis of the genotype-phenotype map in the artificial life system Avida( see Fig 5) revealed that the number of genotypes forming a phenotype differs greatly among phenotypes. The more complex the logic operations are that a phenotype performs, the fewer genotypes form this phenotype. Genotypes with any one phenotype tend to form one or more networks whose members are likely connected to one another by series of small genotypic changes that leave the phenotype unchanged, and thus help explore different regions of genotype space. The larger any one such network is, the greater is the number of novel phenotypes that can be reached through single point mutations from its members. We also find that the accessibility of novel phenotypes is highly asymmetric: it is much harder to evolve more complex phenotypes than simpler ones through single point mutations. One of the obvious parallels between biological systems and Avida is that our digital organisms are to some extent robust to genotypic changes, i. e., to “point mutations” in their instruction sequence. It is this robustness that might give rise to large phenotype-preserving genotype networks[54, 55]. In natural systems, most robustness to mutations is a consequence of the fact that organisms must persist in multiple different environments[55]. In an artificial system like Avida, robustness can be achieved in simple ways, by providing a genome with more instructions than needed, as we did. The resulting excessive genomic size allows more flexibility in tinkering with instructions while preserving a phenotype, which facilitates the origin of novel phenotypes near these genotypes. Observations like this provide guiding principles to design evolvable artificial systems. The genotype networks we examined are not all connected, and may consist of multiple different components. However, this fragmentation is most pronounced when we require the strict preservation of phenotypes in the random walks that aim to connect different organisms with the same phenotype. During some steps of these random walks, genotypes fortuitously acquire novel computational abilities that they do not require, and if we do not allow such “innovative” steps, some genotype networks are disconnected. If, however, we admit such steps, the chances for all phenotypes we examined to be connected in a single genotype network increases. We view such non-adaptive novel traits, which also exist in metabolic systems[56], as analogous to potential exaptations[44]. They are not adaptive, but could become adaptive in the right environment. Moreover, they can help bridge gaps between disconnected genotype networks, and thus make more genotypes accessible by populations subject to phenotype-preserving point mutation. This additional connectivity, in turn, makes more novel phenotypes accessible that reside near these genotypes. The asymmetric phenotypic transitions we observe, where the likelihood of reaching phenotype i from phenotype j through a single point mutation is not equal to the converse probability, also have parallels in natural systems. For example, such asymmetries have been observed in phenotypic transitions between different RNA secondary structures[46, 47, 57]. They also occur in anisotropic morphospaces of paleobiology[58], where a clade’s propensity to vary depends on the direction of phenotypic change. In our study system, asymmetric phenotypic transitions result from the vastly different number of genotypes that encode each phenotype. Some phenotypes, regardless of their adaptive value, are more likely to be “discovered” by evolving populations than others. Because such differences in phenotypic rarity are pervasive in other systems[8, 42, 53, 54, 59, 60], asymmetric transitions are likely to be a universal characteristic of phenotypic evolution. Regardless of their causes, they have practical consequences. For example, they can lead to spurious incidences of convergent evolution, and they can mislead reconstructions of ancestral phenotypes[61]. To our knowledge, the relationship we found between phenotypic complexity and evolvability has not been reported for any natural system. These relationships exist on two levels of organization. The first is that of individual genotypes with a specific phenotype. Mutations are more likely to create novel phenotypes in digital organisms with complex phenotypes. It is not difficult to see why, and we fully expect similar causes to be at work in natural systems. Phenotypes emerge from the coordinated execution of “genetic building blocks”, which are analogous to developmental processes guided by regulatory programs in biology. These building blocks can be modified to perform different logic operations. Evolving genomes can “discover” complex phenotypes only by combining the genetic building blocks of preexisting, simpler phenotypes[62]. The genome of organisms with complex phenotypes is expected to harbor more such building blocks, which can be altered and combined in more ways than in organisms with simpler phenotypes. The second level of organization is that of the entire genotype space. Here, we observe that complex phenotypes are more rare, that is, they are encoded by fewer genotypes.( The larger minimal genomes required for such phenotypes are consistent with this observation, because they constrain genotypic evolution to a smaller region of genotype space). The main consequence of the rarity of complex phenotypes is that the total number of novel phenotypes from any of these genotypes—phenotypic evolvability—is lower. Both levels of organization can help explain the relationship of asymmetric transitions to phenotypic complexity, i. e., single mutations from any one phenotype are more likely to yield a simple phenotype than a complex one, and the most complex phenotypes can be reached only through multiple steps. From the individual, mechanistic perspective, mutations are more likely to lead to a loss than a gain of a function in a genetic building block required for a phenotype. They are thus more likely to create a simpler phenotype( or an inviable organism), than a complex phenotype. This asymmetry is also at the core of why the most complex phenotypes must be built in multiple small steps. From the collective, genotype space perspective, mutations are simply less likely to “hit” the smaller target of a complex phenotype with a small genotype network. We expect that natural systems, which display dramatic differences in the number of genotypes that form specific phenotypes[8, 42, 53, 54, 59, 60] would show a similar relationship between complexity and evolvability. If so, two predictions follow. First, mutations in an evolving population whose members have a complex phenotype are more likely to create novel phenotypes. Second, on long evolutionary time scales, these phenotypes may be less diverse than for organisms with a simpler phenotype. Our results also have implications for the development of genetic languages in artificial life[63]. Not only can Avida organisms display robustness to mutations, Avida’s genetic language is itself robust to several modifications of the instruction set[64]. Only few modifications, such as the separation of the input and output instruction can alter an organism’s ability to perform logic operations. Future studies may systematically compare different genotype-phenotype maps, and identify those that are most evolvable. Their insights may also guide synthetic biologists in designing genetically engineered devices primed for evolutionary innovation[65].", "role": "user" }, { "content": "The phenotype of an organism comprises the set of morphological and functional traits encoded by its genome . In natural evolving systems , phenotypes are organized into mutationally connected networks of genotypes , which increase the likelihood for an evolving population to encounter novel adaptive phenotypes ( i . e . , its evolvability ) . We do not know whether artificial systems , such as self-replicating and evolving computer programs—digital organisms—are more or less evolvable than natural systems . By studying how genotypes map onto phenotypes in digital organisms , we characterize many commonalities between natural and artificial evolving systems . In addition , we show that phenotypic complexity can both facilitate and constrain evolution , which harbors lessons not only for designing evolvable artificial systems , but also for synthetic biology .", "role": "assistant" } ]

[ { "content": "Which dataset would be most relevant for this research query?\n\nQuery: We propose a fast algorithm: detection and annotation for vehicles (DAVE), which\n\nKeyphrases: vehicle detection annotation video\n\nDataset descriptions:\nCompCars: The Comprehensive Cars (CompCars) dataset contains data from two scenarios, including images from web-nature and surveillance-nature. The web-nature data contains 163 car makes with 1,716 car models.\nGVGAI: The General Video Game AI (GVGAI) framework is widely used in research which features a corpus of over 100 single-player games and 60 two-player games. These are fairly small games, each focusing on specific mechanics or skills the players should be able to demonstrate, including clones of classic arcade games such as Space Invaders, puzzle games like Sokoban, adventure games like Zelda or game-theory problems such as the Iterative Prisoners Dilemma.\nDAWN: DAWN emphasizes a diverse traffic environment (urban, highway and freeway) as well as a rich variety of traffic flow. The DAWN dataset comprises a collection of 1000 images from real-traffic environments, which are divided into four sets of weather conditions: fog, snow, rain and sandstorms.\nPathTrack: PathTrack is a dataset for person tracking which contains more than 15,000 person trajectories in 720 sequences.\n\nOptions: A: CompCars B: GVGAI C: DAWN D: PathTrack", "role": "user" }, { "content": "CompCars", "role": "assistant" } ]

[ { "content": "Identify relationships between chemical compounds and genes in this abstract. Use only these relation types: ['DOWNREGULATOR', 'SUBSTRATE', 'INDIRECT-REGULATOR', 'PART-OF', 'MODULATOR-ACTIVATOR', 'REGULATOR', 'INHIBITOR', 'COFACTOR', 'UPREGULATOR', 'ACTIVATOR', 'ANTAGONIST', 'NOT', 'INDIRECT-DOWNREGULATOR', 'SUBSTRATE_PRODUCT-OF', 'INDIRECT-UPREGULATOR', 'AGONIST', 'PRODUCT-OF', 'MODULATOR', 'DIRECT-REGULATOR', 'UNDEFINED', 'AGONIST-INHIBITOR', 'AGONIST-ACTIVATOR', 'MODULATOR-INHIBITOR'].\n\nFormat your output as a JSON array with entries like [\"<Entity_A>\", \"<RELATION_A_B>\", \"<Entity_B>\"].\n\nAbstract:\nCurrent understanding of TRPM7 pharmacology and drug development for stroke. The initial excitement and countless efforts to find a pharmacological agent that disrupts the excitotoxic pathway of ischemic neuronal death have only led to disappointing clinical trials. Currently, a thrombolytic agent called recombinant tissue plasminogen activator (rt-PA) is the only pharmacological treatment available for patients with acute ischemic stroke in most countries. Even though its efficacy has been confirmed repeatedly, rt-PA is considerably underused due to reasons including a short therapeutic window and repeated complications associated with its use. A search for alternative mechanisms that may operate dependently or independently with the well-established excitotoxic mechanism has led researchers to the discovery of newly described non-glutamate mechanisms. Among the latter, transient receptor potential melastatin 7 (TRPM7) is one of the important nonglutamate mechanisms in stroke, which has been evaluated in both in-vitro and in-vivo. In this review, we will discuss the current state of pharmacological treatments of ischemic stroke and provide evidence that TRPM7 is a promising therapeutic target of stroke.", "role": "user" }, { "content": "[]", "role": "assistant" } ]

[ { "content": "Extract drug combinations from this sentence and classify each combination into one of these categories:\n- POS: Positive interaction between drugs\n- NEG: Negative interaction between drugs\n- COMB: Drugs used together with unknown interaction type\n\nOutput only a JSON array where each entry is [drug_1, drug_2, ..., drug_n, category].\n\nparagraph: Scedosporium apiospermum pneumonia after autologous bone marrow transplantation. Although opportunistic infections after bone marrow transplantation (BMT) are very common, only five cases of Pseudallescheria boydii infection have been reported in the literature, two of which were autopsy findings. A case of Scedosporium apiospermum infection after BMT , treated initially with amphotericin B ( total dose of 2.5 g ) and then with itraconazole ( for 25 days ) , is reported here . When the patient failed to improve, Scedosporium apiospermum pneumonia was diagnosed and therapy was changed. The patient was treated successfully with miconazole (600 mg/8h for 32 days) and ketoconazole (200 mg/8h for 7 days) plus surgery.\n\nsentence: A case of Scedosporium apiospermum infection after BMT , treated initially with amphotericin B ( total dose of 2.5 g ) and then with itraconazole ( for 25 days ) , is reported here .", "role": "user" }, { "content": "[[\"amphotericin\", \"itraconazole\", \"NEG\"]]", "role": "assistant" } ]

[ { "content": "Extract all chemical entities (ChEBI) from this biomedical text. Output as JSON array.\n\nText: OurexperimentsshowthatageneticdeficiencyofCAIIinmicehomozygousforamutationintheCar2genedoesnotalterIOP.", "role": "user" }, { "content": "[]", "role": "assistant" } ]

[ { "content": "Classify the intent of this citation sentence by choosing from: [\"Method\", \"Background\", \"Result\"].\n\nMethod: Cites for methodology\nBackground: Cites for background information\nResult: Cites for findings\n\nCitation: TPC, TFC, FRAP, DPPH, and ORAC values were slightly different from, but comparable to, values in other reports (Cardador-Martinez et al., 2002; Heimler et al., 2005; Xu et al., 2007).", "role": "user" }, { "content": "Result", "role": "assistant" } ]

[ { "content": "Find all [\"Chemical\"] entities in this text. Output a JSON object.\n\nText:\nPurification and structural characterisation of phospholipase A1 (Vespapase, Ves a 1) from Thai banded tiger wasp (Vespa affinis) venom. The Thai banded tiger wasp (Vespa affinis) is one of the most dangerous vespid species in Southeast Asia, and stinging accidents involving this species still cause fatalities. In the present study, four forms of V. affinis phospholipase A(1) were identified through a proteomics approach. Two of these enzymes were purified by reverse-phase chromatography, and their biochemical properties were characterised. These enzymes, designated Ves a 1s, are not glycoproteins and exist as 33441.5 and 33474.4 Da proteins, which corresponded with the 34-kDa band observed via SDS-PAGE. The thermal stabilities of these enzymes were stronger than snake venom. Using an in vivo assay, no difference was found in the toxicities of the different isoforms. Furthermore, the toxicity of these enzymes does not appear to be correlated with their PLA(1) activity. The cDNAs of the full-length version of Ves a 1s revealed that the Ves a 1 gene consists of a 1005-bp ORF, which encodes 334 amino acid residues, and 67- and 227-bp 5' and 3' UTRs, respectively. The two isoforms are different by three nucleotide substitutions, resulting in the replacement of two amino acids. Through sequence alignment, these enzymes were classified as members of the pancreatic lipase family. The structural modelling of Ves a 1 used the rat pancreatic lipase-related protein 2 (1bu8A) as a template because it has PLA(1) activity, which demonstrated that this enzyme belongs to the α/β hydrolase fold family. The Ves a 1 structure, which is composed of seven α-helixes and eleven β-strands, contains the β-strand/ɛSer/α-helix structural motif, which contains the Gly-X-Ser-X-Gly consensus sequence. The typical surface structures that play important roles in substrate selectivity (the lid domain and the β9 loop) were shortened in the Ves a 1 structure, which suggests that this enzyme may only exhibit phospholipase activity. Moreover, the observed insertion of proline into the lid domain of the Ves a 1 structure is rare. We therefore propose that this proline residue might be involved in the stability and activity of Ves a 1s.", "role": "user" }, { "content": "{\"Chemical\": [\"amino acid\", \"proline\", \"nucleotide\", \"Ser\", \"amino acids\", \"Gly\"]}", "role": "assistant" } ]

[ { "content": "Based on the dataset descriptions below, which datasets would be suitable for the following research question? Your response should be a JSON array.\n\nQuestion: I am going to train a model for person re-identification.\n\nKeywords: person re-identification image paragraph-level\n\nDataset descriptions:\nCUHK03: The CUHK03 consists of 14,097 images of 1,467 different identities, where 6 campus cameras were deployed for image collection and each identity is captured by 2 campus cameras. This dataset provides two types of annotations, one by manually labelled bounding boxes and the other by bounding boxes produced by an automatic detector.\nPartial-iLIDS: Partial iLIDS is a dataset for occluded person person re-identification. It contains a total of 476 images of 119 people captured by 4 non-overlapping cameras.\nConvAI2: The ConvAI2 NeurIPS competition aimed at finding approaches to creating high-quality dialogue agents capable of meaningful open domain conversation. The ConvAI2 dataset for training models is based on the PERSONA-CHAT dataset.\nCUHK02: CUHK02 is a dataset for person re-identification. It contains 1,816 identities from two disjoint camera views.\nMarket-1501: Market-1501 is a large-scale public benchmark dataset for person re-identification. It contains 1501 identities which are captured by six different cameras, and 32,668 pedestrian image bounding-boxes obtained using the Deformable Part Models pedestrian detector.\n\nOptions: A: CUHK03 B: Partial-iLIDS C: ConvAI2 D: CUHK02 E: Market-1501", "role": "user" }, { "content": "[\"CUHK03\", \"Market-1501\"]", "role": "assistant" } ]

[ { "content": "Find all entities of these types in the text: [\"Gene\"].\n\nOutput a JSON object.\n\nText:\nEGCG inhibits growth of human pancreatic tumors orthotopically implanted in Balb C nude mice through modulation of FKHRL1/FOXO3a and neuropilin. Human pancreatic cancer is currently one of the fourth leading causes of cancer-related mortality with a 5-year survival rate of less than 5 %. Since pancreatic carcinoma is largely refractory to conventional therapies, there is a strong medical need for the development of novel and innovative cancer preventive strategies. The forkhead transcription factors of the O class (FOXO) play a major role in cell proliferation, angiogenesis, metastasis, and tumorigenesis. The objectives of this study were to examine whether FKHRL1/FOXO3a modulates antitumor activity of (-)-epigallocatechin-3-gallate (EGCG), an active ingredient in green tea, in pancreatic cancer model in vivo. PANC-1 cells were orthotopically implanted into Balb c nude mice and gavaged with EGCG after tumor formation. Cell proliferation and apoptosis were measured by Ki67 and TUNEL staining, respectively. The expression of PI3K, AKT, ERK, and FOXO3a/FKHRL1 and its target genes were measured by the western blot analysis and/or q-RT-PCR. FOXO-DNA binding was measured by gel shift assay. EGCG-treated mice showed significant inhibition in tumor growth which was associated with reduced phosphorylation of ERK, PI3K, AKT, and FKHRL1/FOXO3a, and modulation of FOXO target genes. EGCG induced apoptosis by upregulating Bim and activating caspase-3. EGCG modulated markers of cell cycle (p27/KIP1), angiogenesis (CD31, VEGF, IL-6, IL-8, SEMA3F, and HIF1α), and metastasis (MMP2 and MMP7). The inhibition of VEGF by EGCG was associated with suppression of neuropilin. EGCG inhibited epithelial-mesenchymal transition by upregulating the expression of E-cadherin and inhibiting the expression of N-cadherin and Zeb1. These data suggest that EGCG inhibits pancreatic cancer orthotopic tumor growth, angiogenesis, and metastasis which are associated with inhibition of PI3K/AKT and ERK pathways and activation of FKHRL1/FOXO3a. As a conclusion, EGCG can be used for the prevention and/or treatment of pancreatic cancer.", "role": "user" }, { "content": "{\"Gene\": [\"PI3K\", \"Ki67\", \"FOXO\", \"caspase-3\", \"AKT\", \"HIF1\\u03b1\", \"CD31\", \"Bim\", \"IL-6\", \"neuropilin\", \"forkhead transcription factors of the O class\", \"FKHRL1\", \"p27\", \"SEMA3F\", \"VEGF\", \"N-cadherin\", \"FOXO3a\", \"KIP1\", \"MMP2\", \"E-cadherin\", \"ERK\", \"IL-8\", \"Zeb1\", \"MMP7\"]}", "role": "assistant" } ]

[ { "content": "Write a Related Work section based on these abstracts. Use numerical citations like [1], [2], etc.\n\nMain Abstract:\nWe propose an online object-level SLAM system which builds a persistent and accurate 3D graph map of arbitrary reconstructed objects. As an RGB-D camera browses a cluttered indoor scene, Mask-RCNN instance segmentations are used to initialise compact per-object Truncated Signed Distance Function (TSDF) reconstructions with object size-dependent resolutions and a novel 3D foreground mask. Reconstructed objects are stored in an optimisable 6DoF pose graph which is our only persistent map representation. Objects are incrementally refined via depth fusion, and are used for tracking, relocalisation and loop closure detection. Loop closures cause adjustments in the relative pose estimates of object instances, but no intra-object warping. Each object also carries semantic information which is refined over time and an existence probability to account for spurious instance predictions. We demonstrate our approach on a hand-held RGB-D sequence from a cluttered office scene with a large number and variety of object instances, highlighting how the system closes loops and makes good use of existing objects on repeated loops. We quantitatively evaluate the trajectory error of our system against a baseline approach on the RGB-D SLAM benchmark, and qualitatively compare reconstruction quality of discovered objects on the YCB video dataset. Performance evaluation shows our approach is highly memory efficient and runs online at 4-8Hz (excluding relocalisation) despite not being optimised at the software level.\n\nCited Abstract(s):\n[1]: In this paper, we present a system for automatically learning segmentations of objects given changes in dense RGB-D maps over the lifetime of a robot. Using recent advances in RGB-D mapping to construct multiple dense maps, we detect changes between mapped regions from multiple traverses by performing a 3-D difference of the scenes. Our method takes advantage of the free space seen in each map to account for variability in how the maps were created. The resulting changes from the 3-D difference are our discovered objects, which are then used to train multiple segmentation algorithms in the original map. The final objects can then be matched in other maps given their corresponding features and learned segmentation method. If the same object is discovered multiple times in different contexts, the features and segmentation method are refined, incorporating all instances to better learn objects over time. We verify our approach with multiple objects in numerous and varying maps.\n\n[2]: Robots that are operating for extended periods of time need to be able to deal with changes in their environment and represent them adequately in their maps. In this paper, we present a novel 3D reconstruction algorithm based on an extended Truncated Signed Distance Function (TSDF) that enables to continuously refine the static map while simultaneously obtaining 3D reconstructions of dynamic objects in the scene. This is a challenging problem because map updates happen incrementally and are often incomplete. Previous work typically performs change detection on point clouds, surfels or maps, which are not able to distinguish between unexplored and empty space. In contrast, our TSDF-based representation naturally contains this information and thus allows us to more robustly solve the scene differencing problem. We demonstrate the algorithms performance as part of a system for unsupervised object discovery and class recognition. We evaluated our algorithm on challenging datasets that we recorded over several days with RGB-D enabled tablets. To stimulate further research in this area, all of our datasets are publicly available3.\n\n[3]: In this paper, we present an unsupervised framework for discovering, detecting, tracking, and reconstructing dense objects from a video sequence. The system simultaneously localizes a moving camera, and discovers a set of shape and appearance models for multiple objects, including the scene background. Each object model is represented by both a 2D and 3D level-set. This representation is used to improve detection, 2D-tracking, 3D-registration and importantly subsequent updates to the level-set itself. This single framework performs dense simultaneous localization and mapping as well as unsupervised object discovery. At each iteration portions of the scene that fail to track, such as bulk outliers on moving rigid bodies, are used to either seed models for new objects or to update models of known objects. For the latter, once an object is successfully tracked in 2D with aid from a 2D level-set segmentation, the level-set is updated and then used to aid registration and evolution of a 3D level-set that captures shape information. For a known object either learned by our system or introduced from a third-party library, our framework can detect similar appearances and geometries in the scene. The system is tested using single and multiple object data sets. Results demonstrate an improved method for discovering and reconstructing 2D and 3D object models, which aid tracking even under significant occlusion or rapid motion.", "role": "user" }, { "content": "Another approach to object discovery is through dense change detection between successive mappings of the same scene [1] [3] [2] . Unlike these systems, our system is designed for online use and does not require changes to occur in a scene before objects are detected. These approaches are complementary to our proposed approach, providing supervisory signals for CNN fine-tuning, and enabling additional object database filtering mechanisms.", "role": "assistant" } ]

[ { "content": "Summarize the article in an uncomplicated manner.\n\nTitle: A Signature of Genomic Instability Resulting from Deficient Replication Licensing\nArticle:\nAbstract:\nInsufficient licensing of DNA replication origins has been shown to result in genome instability, stem cell deficiency, and cancers. However, it is unclear whether the DNA damage resulting from deficient replication licensing occurs generally or if specific sites are preferentially affected. To map locations of ongoing DNA damage in vivo, the DNAs present in red blood cell micronuclei were sequenced. Many micronuclei are the product of DNA breaks that leave acentromeric remnants that failed to segregate during mitosis and should reflect the locations of breaks. To validate the approach we show that micronuclear sequences identify known common fragile sites under conditions that induce breaks at these locations( hydroxyurea). In MCM2 deficient mice a different set of preferred breakage sites is identified that includes the tumor suppressor gene Tcf3, which is known to contribute to T-lymphocytic leukemias that arise in these mice, and the 45S rRNA gene repeats.\nIntroduction:\nLicensing of DNA replication origins begins early during the G1-phase of the cell cycle when ORC and CDC6 recruit CDT1-MCM2-7 to the chromatin[reviewed in 1]. MCM2-7 is a heterotypic hexameric complex that is the replicative helicase and, once loaded, its association with the DNA is stable until it becomes active during S-phase. Licensing is restricted to the G1-phase of the cell cycle to prevent endo-reduplication of the DNA by relicensing already duplicated DNA during S-phase. Many more sites are licensed with MCM2-7 complexes than are typically used in S-phase and these dormant origins are thought to serve as a backup system for recovering replication in the event of replication fork stalling or collapse[2–3]. The importance of this system of backup origins for maintaining genome stability is demonstrated by the observation that mice in which MCM2-7 proteins are deficient or compromised develop normally but exhibit increased genome instability, high rates of cancer and stem cell deficiencies[4–6]. The cancers that arise in MCM deficient mice can be highly specific to a particular genetic background. For example, >80% of hypomorphic MCM4( Mcm4Chaos3/Chaos3) females succumb to mammary adenocarcinomas when carried on the C3H genetic background on which it was isolated[4]. In contrast when bred into a C57Bl/6J background females are highly prone to histiocytic sarcoma[7]. Similarly, MCM2 deficient( Mcm2IRES-CreERT2/ IRES-CreERT2) mice exhibit near to 100% penetrance of T-lymphocytic leukemia( TLL) within 5 months on the 129Sv background on which they were constructed[5] but a broader spectrum of tumor types with more variable latencies in a mixed 129Sv/BALB/c genetic background[8]. The genetic lesions that occur in tumors arising in MCM deficient or hypomorphic mice are largely copy number alterations( CNAs) with a preponderance of deletions averaging 400–500 kbp in size[9–10]. Several recurrent deletion sites are found in TLLs from MCM2 deficient mice where, on the 129Sv genetic background, the Tcf3 gene on Chr10 is affected in all tumors examined[9]. Tcf3 is a transcriptional regulator that plays a central role in T-cell differentiation and prior studies have shown that loss of Tcf3 is sufficient to drive TLL in mice[11]. Importantly, the Tcf3 gene lies within a region of Chr10 that shows preferential loss of origin function in MEFs from MCM2 deficient mice[12]. Replication licensing may become limiting due to genetic deletion of Mcm2-7, which occurs in many tumors[12], oncogenic stress[1] and during stem cell aging[13]. It is not known if under these conditions genome instability is elevated generally across the genome or whether specific locations are at increased risk; although loss of MCM expression in aging hematopoietic stem cells( HSCs) has been correlated with nucleolar associated DNA damage foci[13]. In the present study we use micronuclear DNA sequences to show that the region of Chr10 carrying the Tcf3 gene is also the site of elevated ongoing genome instability even prior to tumor initiation in MCM2 deficient mice on the 129Sv genetic background. The increased instability at this site predicts the high rate of genetic lesions affecting the Tcf3 gene and consequent high rate of TLL in these mice. In addition to loss of Tcf3, MCM2 deficient mice exhibit genetic lesions within the 45S ribosomal RNA gene repeats clusters on Chrs 12, 16, 18 and 19 consistent with the observed nucleolar associated DNA damage foci in aging HSCs. The present study demonstrates that the consequences of reduced MCM expression on local genome instability is reflected in micronuclear DNA sequences allowing prediction of specific genetic lesions in the etiology of cancer and during aging.\nDiscussion:\nChromosomal fragile sites are genomic locations that are hotspots for genome instability leading to translocations, amplifications and deletions. Such locations were first defined cytogenetically following treatment of cells in culture with agents that impede DNA polymerase( including aphidicolin, hydroxyurea, 5-azacytidine and bromodeoxyuridine) and mapping breaks in banded metaphase chromosomes. Numerous studies have characterized sites that are frequently affected in human and mouse cells and led to identification of a set of locations termed common fragile sites that are affected under conditions of chemically induced replication stress in a high proportion of individuals. These sites have been extensively characterized and are significantly associated with the presence of large, transcriptionally active, and late replicating genes over 300 kbp in size[16]. The frequency of chromosome breaks at these locations is dependent on cell type and the specific agent used to induce replication stress. Here we have used the representation of different genomic regions in micronuclear DNA sequences to infer the frequency of chromosome breaks in erythroid cells in vivo. Many micronuclear sequences result from the presence of double strand DNA breaks that lead to failure of acentromeric portions of chromosomes to segregate to the nucleus during mitosis. Further we take advantage of the fact that micronuclei are retained in maturing RBCs following enucleation in mammals. In contrast to defining fragile sites cytogenetically, harvesting micronuclei from RBCs allows recovery of tens of millions chromosomal remnants each of which defines a breakpoint that can be queried at nucleotide level resolution by high throughput sequencing. Although there is a concern that erythroblasts( just before enucleation) may not reflect the DNA repair and checkpoint responses typical of other cells, application of the Mic-Seq method to define fragile sites in mice treated with hydryoxyurea shows that the method identifies 5 of the 8 molecularly characterized fragile sites previously defined in mouse lymphocytes[22] including those occurring at the Wwox and Immp2 genes. Further sites detected in this study support that the majority of the most sensitive HU induced fragile sites occur within subdomains of the transcribed regions of large( >300 kbp), transcriptionally active, genes similar to prior studies and consistent with the possibility of interference between the transcription and replication machinery under conditions of DNA polymerase inhibition[15–16, 20]. Similar to HU treatment, reduced replication licensing results in genome instability, increased DSBs, and chromosomal deletions and rearrangements[2–5, 9]. The mechanism resulting in this damage is likely to differ from that mediating HU induced damage; however, it has not been previously determined whether similar or different locations across the genome are preferentially affected. In this study we demonstrate that MCM2 deficient mice exhibit a distinct sequence tag distribution profile in Mic-Seq relative to HU treated mice. HU induced fragile sites are not preferentially sensitive to MCM2 deficiency( e. g. Fig 4, panels a and b) and there is little overlap with early replicating fragile sites induced by higher concentrations of HU[23]. Unlike HU treated mice, the locations at which MCM2 deficient mice exhibit localized damage by Mic-Seq analysis are largely locations that are already sensitive in wt cells but become more prone to breakage in MCM2 deficient mice. Differences in the genome instability profiles are likely to reflect differences in the mechanisms by which HU and MCM2 deficiency affect genome stability. Prior studies have shown that, unlike HU or aphidicolin, reducing MCM levels does not affect the rate of DNA polymerization since similar tract lengths of CldU or IdU incorporation are found between wt and MCM deficient cells by DNA fiber analysis[2–3, 8]. However, DNA fiber analysis also shows that MCM deficient cells are unable to initiate DNA synthesis from dormant origins under conditions( HU treatment) that lead to replication fork stalling[2–3, 8] consistent with a reduction in the frequency of licensed origins. Short nascent strand analysis has shown that origin usage does not decline uniformly across the genome, but rather specific locations lose function preferentially, in MCM2 deficient MEFs[12]. These locations tend to occur in gene rich, early replicating, regions of the genome although they are not exclusive to transcribed regions of active genes and include origins within inactive genes and intergenic regions[12]. In contrast, Mic-Seq localizes sites that are preferentially prone to breakage to subsets of both early and late replicating regions. This result suggests that factors in addition to the degree of reduction in replication licensing affect the rate of chromosome breaks under conditions of MCM2-7 deficiency. However, even in late replicating regions of the genome these factors are not the same as those determining fragile site locations following HU treatment since the locations that become sensitized to breakage by MCM2 deficiency are not known common fragile sites, or large genes generally, and many contain few or no transcribed regions. Even within early replicating regions of the genome chromosomal breaks detected by Mic-Seq show only a modest correlation with locations where SNS analysis demonstrates that origin usage is most affected. Nonetheless, it is important that many of the locations showing recurrent deletions in the TLLs that arise in MCM2 deficient mice[9] are sites at which there is both a preferential loss of origin function[12] and an increase in DSBs detected by Mic-Seq. In particular, loss of Tcf3 is sufficient to drive TLL formation[11] and the region carrying this gene shows a strong differential signal between wt and MCM2 deficient mice in both SNS and Mic-Seq analyses. These differences are apparent in samples taken well before tumorigenesis is observed, likely before tumors are initiated, and support that an increased DSB rate detected by Mic-Seq can in some instances predict a high probability of tumor occurrence. The strongest signals observed by Mic-Seq in MCM2 deficient mice are associated with chromosomes carrying nucleoli and implicate a high rate of DSBs within rDNA clusters as the location of much of the DNA damage, and the source of a large proportion of the additional micronuclei, found in MCM2 deficient mice. This observation confirms and extends prior studies showing that, as mice age, MCM levels are suppressed in HSCs and, coincident with the loss of MCM expression, nucleolar associated γ-H2AX foci accumulate[13]. The presence of unidirectional replication fork barriers[reviewed in 24] may sensitize rRNA gene repeats to loss of licensed replication origins. These results demonstrate that experimental reduction of MCM proteins in young asymptomatic mice is sufficient to cause a profile of genome instability that predicts at least a subset of chromosomal locations where genetic damage is found in both cancers and during aging. The observation that, unlike HU, many locations where MCM2 deficiency causes instability can already be detected in young wt mice suggests that even under normal conditions the distribution of licensed DNA replication origins contributes to base line levels of chromosomal instability. Although replication stress is widely recognized as a potent cause of genomic instability[1, 25], the present study emphasizes that different mechanisms leading to replication stress have very different consequences for instability at various locations across the genome and can result in very different phenotypic outcomes.", "role": "user" }, { "content": "Many RBC micronuclei result from double strand DNA breaks that give rise to acentromeric chromosomal fragments that fail to incorporate into nuclei during mitosis and consequently remain in the cell following enucleation . Here , RBC micronuclear DNA is sequenced ( Mic-Seq ) to define the locations of breaks genome-wide and this assay is used to study ongoing genome instability resulting from insufficient DNA replication origin licensing . Using a mouse model , we show that there is increased instability at discrete sites across the genome , which include genes that are recurrently deleted in the T-lymphocytic leukemias that eventually arise in these mice . Mic-Seq may provide an effective means of predicting locations that are susceptible to genetic damage and these predictions may have prognostic value .", "role": "assistant" } ]

[ { "content": "Write an abstract for the research paper below.\n\nPaper text:\none of the most important causes of hypertension in pregnancy is pheochromocytoma but its occurrence is rare .\nit has high morbidity and mortality for mother and fetus . due to the similarity to other forms of hypertension , diagnosis of pheochromocytoma\ndiagnosis of pheochromocytoma is based on catecholamine 's concentration ( epinephrine , norepinephrine , dopamine , and vanillylmandelic acid [ vma ] ) in 24 h urine collection .\nsensitivity of the test would be increased if 24 h urine collection begins at onset of a paroxysm .\nsensitivity of abdominal computed tomography ( ct ) for diagnoses of adrenal pheochromocytoma is 93100% and extra - adrenal pheochromocytoma is 90% .\nother diagnostic techniques included metaiodobenzylguanidine imaging , positron emission tomography imaging , and somatostatin receptor scintigraphy . management of pheochromocytoma includes medical therapy ( phenoxybenzamine , propranolol ) and surgery .\na 27-year - old woman para 1 live 1 admitted with chief complaint of sudden onset of headache , confusion , nausea and vomiting , shortness of breath , tachypnea , and hypertension 2 days after cesarean section .\nher cesarean section was performed at term pregnancy due to fetal distress under spinal anesthesia .\nher pulse rate was 125/min ; systolic blood pressure was labile ( 70230 mmhg ) and failed to respond to conventional treatment .\nantinuclear a antibodies and antineutrophil cytoplasmic antibody were normal ( nl ) , but epinephrine = 65.2 ( nl : 1.722.4 g/24 h ) , norepinephrine = 364 ( nl : 12.585.5 g/24 h ) , metanephrine = 2071 ( nl : 30180 mcg/24 h ) , normetanephrine = 1337 ( nl : 103390 mcg/24 h ) , and vma = 17.18 ( nl : 1.46.5 mg/24 h ) were increased in 24 h urine collection .\nthe patient was given medical treatment with phenoxybenzamine and propranolol , but treatment was not effective ; hence , she underwent adrenalectomy .\npheochromocytoma is a neuroendocrine tumor derived from adrenal chromaffin cells , and extra - adrenal paraganglioma could cause secondary hypertension .\nhigh amount of catecholamine 's release ( norepinephrine , epinephrine , and dopamine ) causes the typical manifestations of pheochromocytoma .\nvasoconstriction is one of the -receptors stimulation symptoms , whereas vasodilation is due to 2-receptors stimulation .\nincreases in intra - abdominal pressure , fetal movement , uterine contraction , delivery process , abdominal surgical intervention , and even general anesthesia can make pheochromocytoma clinically overt in pregnancy .\nsigns and symptoms in pheochromocytoma are similar to other forms of hypertension , including the new - onset hypertensive syndromes in pregnancy , gestational hypertension , and preeclampsia .\nhypertension can be insidious , and the pregnant women may even symptomatic till delivery . signs and symptoms of pheochromocytoma are nausea and vomiting , abdominal pain , severe constipation ( megacolon ) , chest pain , congestive heart failure , cardiac dysrhythmia , and conduction defects .\npreeclampsia is usually manifested by proteinuria , sudden weight gain , edema , rise in liver enzymes , and coagulation disorders .\npregnant woman with pheochromocytoma rarely has proteinuria , liver or coagulation abnormalities , sudden weight gain , and edema .\nit should be started as soon as the -methyl - parathyrosine ( a tyrosine hydroxylase inhibitor ) diagnosis is established and should be given for 1014 days . the best treatment in pregnancy is phenoxybenzamine ( pregnancy class c ) .\nthe -blockers should not prescribe before -blocker drugs because -blockers alone can rise blood pressure dramatically due to unopposed -adrenergic effects in patients with epinephrine - secreting tumors especially . in patients with intolerance to combine - and -blockers , we can use -methyl - parathyrosine but its safety during pregnancy is questionable .\nthe surgery time is controversial depending on factors such as gestational age of pregnancy , clinical response to treatment , the accessibility of the tumor for surgery , and fetal condition .\nsome physicians recommended surgical tumor removal after adequate medical treatment in early gestational age by laparoscopic adrenalectomy if tumor size is < 7 cm .\nafter 24 weeks of gestation , an elective cesarean section done then surgical procedure is recommended .\nvaginal delivery is accompanied with higher mortality rate ( 31% ) as compared with cesarean section ( 19% ) . in pregnant women , early diagnosis and treatment of pheochromocytoma\nif appropriate management was done for pheochromocytoma , pregnancy loss is seen only in 11% of patients .\ncatecholamines do not cross the placenta , but placental abruption due to paroxysmal hypertension and then rebound hypotension can cause severe hypoxia and fetal wastage .\nearly diagnose and management has been attributed to improvement in maternal outcomes . with earlier diagnosis and presurgical preparation ,\nmaternal mortality has decreased to 2% from 48% in older literature . in patients with a suspicious family history of pheochromocytoma , paraganglioma , or evidence of genetic cause , genetic testing should be considered .\none of the rare but important causes of hypertension in pregnancy is pheochromocytoma with high morbidity and mortality of mother and fetus .\nphenoxybenzamine is safe in pregnancy , but -adrenergic blockers must be initiated only if necessary because their association with intrauterine growth retardation . during the second trimester , resection of tumor\ncan often be safe or tumor resection simultaneous with cesarean section in mature fetus . individualized approach for each patient is recommended .\npheochromocytoma presentations are different in pregnancy , but in the second half of pregnancy , new - onset or superimposed preeclampsia may be mistaken with it . high clinical suspicion ,\nearly diagnosis and treatment , and collaboration among specialists are required for better management of patients and improved outcome .", "role": "user" }, { "content": "pheochromocytoma is a catecholamine - producing tumor . \n there are a very few reported cases of clinical pheochromocytoma . here , we report a 27-year - old woman para 1 live 1 with chief complaint of headache , confusion , nausea , and vomiting 2 days after cesarean section . \n she was anxious and had palpitation . on physical examination , \n fever , tachycardia , tachypnea , high blood pressure , and right thyroid nodule were found . \n she was managed as pregnancy - induced hypertension at first . in laboratory data , epinephrine , \n norepinephrine , metanephrine , normetanephrine , and vanillylmandelic acid were increased in 24 h urine collection . \n an adrenal mass was detected in abdominal computed tomography . \n regarding clinical and paraclinical findings , pheochromocytoma was diagnosed . \n the patient received medical treatment , but it was not effective ; hence , she underwent adrenalectomy .", "role": "assistant" } ]

[ { "content": "Extract entities of these types from the text: [\"Drug\", \"Brand\", \"DrugGroup\", \"UnapprovedDrug\"].\n\nOutput a JSON object with entity types as keys and lists of found entities as values.\n\nText:\nAntiacid, clarithromycin, Didanosine, Fluconazole, Fluoxetine, Indanavir, Ketoconazole, Phenytoin, Phenobarbitol, carbamazepine, Rifabutin, Rifampin, Ritanovir, Saquinavir.", "role": "user" }, { "content": "{\"Brand\": [], \"Drug\": [\"Rifampin\", \"Fluconazole\", \"Didanosine\", \"clarithromycin\", \"carbamazepine\", \"Phenytoin\", \"Rifabutin\", \"Fluoxetine\", \"Ketoconazole\", \"Saquinavir\"], \"DrugGroup\": [], \"UnapprovedDrug\": []}", "role": "assistant" } ]

[ { "content": "Extract drug combinations from this sentence and classify each combination into one of these categories:\n- POS: Positive interaction between drugs\n- NEG: Negative interaction between drugs\n- COMB: Drugs used together with unknown interaction type\n\nOutput only a JSON array where each entry is [drug_1, drug_2, ..., drug_n, category].\n\nparagraph: Carboplatin and etoposide for recurrent malignant glioma following surgical and radiotherapy failure : A clinical study conducted at the Northern Israel Oncology Center . We conducted a phase II study using carboplatin and etoposide on patients with recurrent malignant glioma to investigate tumor response. ### methods From January 1995 to March 1997, 21 patients with recurrent malignant glioma were treated with a carboplatin (300 mg/m(2), day 1)/etoposide (100 mg/m(2), days 1-3) regimen every 3-4 weeks. The following radiologic parameters were evaluated: tumor size, central lucency, degree of contrast enhancement, and mass effect. No patient had received chemotherapy previously. Dose escalation corresponded to hematologic tolerance and to general and neurologic performance status. Most patients were treated postoperatively with involved field radiotherapy followed by a boost to the tumor area, as defined on the presurgery computed tomography scan or on magnetic resonance imaging. Mean interval to introduction of chemotherapy was 8.8 months (range, 7-36 months). Patients received a mean of four cycles [range, 2-8 cycles]. ### results Only 2 patients showed moderate radiological response, while 12 patients died of progressive disease. Mean time to progression following discontinuation of chemotherapy was 5.8 months (range, 1-11 months). The other patients survived with persistent disease and are being treated palliatively. Toxicity was manageable (1, neutropenic sepsis; 1, thrombocytopenia (45,000/mm(3)); 2, temporarily elevated transaminase level; 2, steroid-induced erosive gastritis). ### conclusions This phase II regimen proved to be ineffective in recurrent malignant glioma. Further studies incorporating innovative drug regimens and schedules are warranted. J. Surg. Oncol., 1999;71:167-170.\n\nsentence: Carboplatin and etoposide for recurrent malignant glioma following surgical and radiotherapy failure : A clinical study conducted at the Northern Israel Oncology Center .", "role": "user" }, { "content": "[[\"Carboplatin\", \"etoposide\", \"NEG\"]]", "role": "assistant" } ]

[ { "content": "Extract all unique entities of these types from the following clinical trial criteria: [\"Negation\", \"Observation\", \"ReferencePoint\", \"Procedure\", \"Drug\", \"Measurement\", \"Value\", \"Person\", \"Multiplier\", \"Device\", \"Qualifier\", \"Mood\", \"Temporal\", \"Condition\", \"Visit\", \"Scope\"].\n\nOutput a JSON object with entity types as keys and lists of extracted entities as values. If no entities are found for a type, use [].\n\nText:\n\nPatients who had history of systemic antibiotic usage over the previous 4 months \nPatients who were pregnant \nPatients who had received non-surgical periodontal treatment within the past 6 months \nPatients who had received surgical periodontal treatment within the past 12 months \nPatients who were smokers \nPatients with a history of stroke or an acute cardiovascular event over the previous 12 months.", "role": "user" }, { "content": "{\"Condition\": [\"pregnant\", \"stroke\", \"smokers\"], \"Device\": [], \"Drug\": [\"systemic antibiotic\"], \"Measurement\": [], \"Mood\": [], \"Multiplier\": [], \"Negation\": [], \"Observation\": [\"history\"], \"Person\": [], \"Procedure\": [\"acute cardiovascular event\", \"surgical periodontal treatment\", \"non-surgical periodontal treatment\"], \"Qualifier\": [], \"ReferencePoint\": [], \"Scope\": [], \"Temporal\": [\"within the past 12 months\", \"over the previous 12 months\", \"over the previous 4 months\", \"within the past 6 months\"], \"Value\": [], \"Visit\": []}", "role": "assistant" } ]

[ { "content": "Output a JSON object with \"verdict\" and \"evidence\" fields based on the claim and abstract below.\n\nClaim: Coronavirus: what is remdesivir and how effective is it against Covid-19? Remdesivir is an experimental antiviral made by pharmaceutical firm Gilead Sciences that was first developed to treat Ebola\n\nAbstract:\nRemdesivir is one of the most promising drugs to treat COVID-19 based on the following facts: remdesivir has a broad-spectrum antiviral mechanism of action; it demonstrated in vitro activity against SARS-CoV-2 and in vivo efficacy in animal models against the similar coronavirus MERS-CoV; its safety profile has been tested in Ebola patients and in compassionate use in COVID-19 patients.\nCurrently, remdesivir is being investigated in ten randomized controlled trials against COVID-19.\nThe dose regimen of remdesivir is an IV loading dose of 200 mg on day 1 followed by daily IV maintenance doses of 100 mg for 5-9 days.\nBased on our data analysis, however, remdesivir with IV administration alone is unlikely to achieve excellent clinical efficacy.\nThis analysis is based on the following observations: plasma exposures of remdesivir and its active metabolite are unlikely to be correlated with its clinical efficacy; remdesivir and its active metabolites are unlikely to be adequate in the lung to kill the SARS-CoV-2 virus.\nEven if remdesivir demonstrates benefits in the current randomized controlled trials, its efficacy may be limited.\nWe suggest that a combination of an IV and pulmonary delivery dose regimen should be studied immediately to realize a potentially more effective antiviral therapy against COVID-19.\nGraphical abstract.", "role": "user" }, { "content": "{\"verdict\": \"NEI\", \"evidence\": []}", "role": "assistant" } ]

[ { "content": "Extract all unique entities from this biomedical abstract. Only choose entities from these types: [\"Virus\", \"MedicalDevice\", \"BodySubstance\", \"SpatialConcept\", \"BiologicFunction\", \"ResearchActivity\", \"AnatomicalStructure\", \"ProfessionalOrOccupationalGroup\", \"HealthCareActivity\", \"BiomedicalOccupationOrDiscipline\", \"Bacterium\", \"Chemical\", \"InjuryOrPoisoning\", \"IntellectualProduct\", \"Finding\", \"ClinicalAttribute\", \"Organization\", \"Eukaryote\", \"Food\", \"BodySystem\", \"PopulationGroup\"].\n\nOutput a JSON object where keys are entity types and values are lists of extracted entities. If no entities found for a type, use empty list [].\n\nAbstract: Mutation profiles of synchronous colorectal cancers from a patient with Lynch syndrome suggest distinct oncogenic pathways Patients with Lynch syndrome often present with multiple synchronous or metachronous colorectal cancers (CRCs). The presence of multiple CRCs with distinct genetic profiles and driver mutations could complicate treatment as each cancer may respond differently to therapy. Studies of sporadic CRCs suggested that synchronous tumors have distinct etiologies, but could not rule out differences in genetic background. The presence of multiple cancers in a patient with a predisposing mutation provides an opportunity to profile synchronous cancers in the same genetic background. Here, we describe the case of a patient with Lynch syndrome that presented with six synchronous CRCs. Microsatellite instability (MSI) and genomic profiling indicated that each lesion had a unique pattern of instability and a distinct profile of affected genes. These findings support the idea that in Lynch syndrome, synchronous CRCs can develop in parallel with distinct mutation profiles and that these differences may inform treatment decisions.", "role": "user" }, { "content": "{\"AnatomicalStructure\": [\"affected genes\"], \"Bacterium\": [], \"BiologicFunction\": [\"mutations\", \"mutation\", \"synchronous cancers\", \"MSI\", \"multiple cancers\", \"Lynch syndrome\", \"synchronous\", \"CRCs\", \"cancer\", \"multiple synchronous\", \"synchronous CRCs\", \"colorectal cancers\", \"synchronous tumors\", \"metachronous\", \"Microsatellite instability\", \"oncogenic\", \"Mutation\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [], \"ClinicalAttribute\": [], \"Eukaryote\": [], \"Finding\": [\"instability\", \"sporadic\", \"lesion\"], \"Food\": [], \"HealthCareActivity\": [\"therapy\", \"genetic profiles\", \"genomic profiling\"], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [], \"MedicalDevice\": [], \"Organization\": [], \"PopulationGroup\": [], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [], \"SpatialConcept\": [\"pattern\"], \"Virus\": []}", "role": "assistant" } ]

[ { "content": "Write an abstract for this chemistry paper.\n\nTitle:\nGlobal Aromaticity at the Nanoscale\n\nPaper sections:\n\n<p>linear chain of C-C bonds with bond order 1.5 and negligible bond length alternation (like the C-C bonds in benzene) resulting in charge delocalisation, but if the chain exceeds a critical length, the symmetry collapses, localising the charge 8,9 . It is not clear whether similar effects limit the size of an aromatic ring, or whether molecular ring currents can extend into the domain of mesoscopic phenomena such as Aharonov-Bohm oscillations 6 . Many new globally aromatic macrocycles have been reported during the last few years [10][11][12][13][14][15][16][17][18][19][20] , but none with more than 80 π-electrons. Here we explore circuits of up to 162 π-electrons in a large family of nanorings in a wide range of oxidation states. In these nanorings, each porphyrin contributes 10 electrons to the Hückel π-electron count, and each linking alkyne contributes 2 electrons, so a nanoring cation c-PN[b x e y ] Q+ has an electron count of 10N + 4x + 2y -Q (where N is the number of porphyrin units; x and y are the number of butadiyne and ethyne links respectively). Further evidence is provided by the trihexylsilyl (THS) 1 H and 13 C signals. In each spectrum, we observe one group of THS signals that is essentially unshifted, at 0-2 ppm as in the neutral compounds (THS out , coloured orange in Figure 1, near the zero-shielding cone of the nanoring), and one group of THS signals that is shielded or deshielded, depending on the direction of the ring current (THS in , coloured green in Figure 1). Interconversion of THS in and THS out is slow on the NMR timescale and the assignment of THS in signals is confirmed by the observation of NOEs to protons of the template (T6 or Fluorinated templates allow the aromaticity of nanorings to be evaluated using 19 F NMR, as exemplified by the extended six-legged template T6ef (Figure 3). Two molecules of this template stack to form a stable 2:1 complex with the nanoring, c-P12[b 12 ]•(T6ef) 2</p><p>(circuit electron count: 168 πe when neutral 23 ), in which the CF 3 groups are positioned to probe the global ring current. The CF 3 19 F resonance is shielded in the aromatic 6+ and 10+ oxidation states, but deshielded in the antiaromatic 8+ oxidation state (Figure 3a).</p><p>These shifts of the CF 3 19 F resonance are fully consistent with shifts of the THS in 1 H signals (shaded green, Figure 3a) and they agree with the predictions of NICS calculations S79), but it is remarkable that these open-shell species give spectra that are sharp enough to be observed.</p><p>We used the 12-porphyrin nanoring c-P12[b 12 ] to explore the relationship between 3D conformation and aromaticity. The magnitude of the ring current induced in a macroscopic ring of metal wire depends on the total magnetic flux passing through the ring. If the ring has a figure-of-eight shape, with two equal lobes such that the magnetic flux passing through each loop induces equal and opposite currents, then there will be no net ring current. We sought to test whether this principle applies on the molecular scale, so we synthesised a small six-legged template, T6f, which forms a figure-of-eight shaped 23 1:2 complex c-P12[b 12 ]•(T6f) 2 (note that this system is doubly twisted, not Möbius 24,25 , Figure 3b) and investigated the ring currents in this system by 1 NICS calculations (Supplementary Figure S90). The suppression of ring currents in figureof-eight shaped annulenes has been predicted theoretically 24,26 , but it has not been observed experimentally in other figure-of-eight shaped aromatic systems 10,11,18,24,25,27 , probably because they were not the right shape to achieve cancellation of the ring current.</p><p>The topology of a closed ribbon can be described by the linking number L k , the writhe W r and the twist T w (ref. in Figure 4). The formation of a mixed valence state appears to be essential for efficient nanoscale charge delocalisation, just as the presence of a partially filled band is essential for conductance in an extended lattice 30 .</p><p>Hückel's rule was originally formulated to explain the unusual properties of benzene, and other molecules with 6 π-electrons 4 . It is remarkable that this simple rule correctly predicts the magnetic response of large oxidised nanorings with circuits of up to 162 πelectrons. This work shows that electronic delocalisation can extend coherently around molecular rings with circumferences of 16 nm. These supramolecular rings allow the magnitude of the ring current to be controlled by topology and by the oxidation state in a way that has not yet been demonstrated for small molecules.</p>\n\nMethods\n<p>All 1 H NMR oxidation titrations were carried out by adding thianthrenium hexafluoroantimonate to a solution of the porphyrin nanoring in CD 2 Cl 2 at -60 °C to -20 °C (see SI for details). At the end of the titration, decamethylferrocene (FeCp 2 *) was added to reduce the porphyrin nanoring back to its neutral form; this process is highly reversible.</p>", "role": "user" }, { "content": "Aromaticity is an important concept for predicting electronic delocalisation in molecules, particularly for designing organic semiconductors and single-molecule electronic devices 1 . It is most simply defined by the ability of a cyclic molecule to sustain a ring current when placed in a magnetic field 2,3 . Hückel's rule 4 states that if a ring has [4n+2] π-electrons, it will be aromatic with an induced magnetisation that opposes the external field inside the ring, whereas if it has 4n π-electrons, it will be antiaromatic with the opposite magnetisation. This rule reliably predicts the behaviour of small molecules, typically with circuits of less than about 22 π-electrons (n = 5) 5 . It is not clear whether aromaticity has a size limit and whether Hückel's rule is valid in much larger macrocycles. Here, we present evidence for global aromaticity in a wide variety of porphyrin nanorings, with circuits of up to 162 π-electrons (n = 40; diameter 5 nm). We show that aromaticity can be controlled by changing the molecular structure, oxidation state and three-dimensional conformation. Whenever a global ring current is observed, its direction is correctly predicted by Hückel's rule. The magnitude of the current is maximised when the average oxidation state of the porphyrin units is around 0.5-0.7, when the system starts to resemble a conductor with a partially filled valence band. Our results show that aromaticity can arise in large macrocycles, bridging the size gap between ring currents in molecular and mesoscopic rings 6 .The extent of electronic delocalisation in linear molecules is limited by the onset of symmetry-breaking transitions, which can be viewed as Peierls-type electron-vibration interactions or as shifts in mixed-valence behaviour 7 . For example, cyanine dyes feature a", "role": "assistant" } ]

[ { "content": "Extract all unique entities of these types from the following clinical trial criteria: [\"Negation\", \"Observation\", \"ReferencePoint\", \"Procedure\", \"Drug\", \"Measurement\", \"Value\", \"Person\", \"Multiplier\", \"Device\", \"Qualifier\", \"Mood\", \"Temporal\", \"Condition\", \"Visit\", \"Scope\"].\n\nOutput a JSON object with entity types as keys and lists of extracted entities as values. If no entities are found for a type, use [].\n\nText:\n\nHealthy\nMale\n>7 Metabolic Equivalents\nWritten informed consent\nChronic pain syndrome\nDrug abuse\nAlcohol abuse\nSuspicion of neurologic dysfunction at tested sites\nOngoing treatment with antidepressants\nOngoing treatment with analgesics\nPretreatment with any CYP3A inducers or inhibitors\nKnown allergy to tested drugs\nElevated eye pressure\nObstructive uropathy\nHeart disease\nPulmonary disease\nNeurological disease\nPsychiatric illness", "role": "user" }, { "content": "{\"Condition\": [\"Heart disease\", \"Neurological disease\", \"Pulmonary disease\", \"Drug abuse\", \"Chronic pain syndrome\", \"Psychiatric illness\", \"Alcohol abuse\", \"Elevated eye pressure\", \"allergy\", \"Obstructive uropathy\", \"neurologic dysfunction\"], \"Device\": [], \"Drug\": [\"CYP3A inducers\", \"antidepressants\", \"cers \\nKnown al\", \"tested drugs\", \"analgesics\"], \"Measurement\": [\"Metabolic Equivalents\"], \"Mood\": [\"Suspicion\"], \"Multiplier\": [], \"Negation\": [], \"Observation\": [], \"Person\": [\"Male\"], \"Procedure\": [\"treatment\", \"Pretreatment\"], \"Qualifier\": [\"tested sites\"], \"ReferencePoint\": [], \"Scope\": [\"CYP3A inducers or inhibitors\"], \"Temporal\": [\"Ongoing\"], \"Value\": [\"Healthy\", \"\\u003e7\"], \"Visit\": []}", "role": "assistant" } ]

[ { "content": "Classify the topics of this COVID-19 literature paragraph by selecting from these categories:\n\n- Epidemic Forecasting: Predictions about COVID-19 spread\n- Treatment: Therapeutic methods or medication\n- Prevention: Measures to prevent spread\n- Mechanism: Biological mechanisms of the virus\n- Case Report: Report of a COVID-19 case\n- Transmission: How COVID-19 is transmitted\n- Diagnosis: Diagnosing COVID-19 in individuals\n\nYour output should be a valid JSON array with topics in double quotes and separated by commas. No additional text should be included.\n\nArticle:\n\nBACKGROUND: Coronavirus disease 2019 (COVID-19) and heat related-illness are systemic febrile diseases. In the summer during the COVID-19 pandemic, a differential diagnosis between the two conditions is important. However, no studies have compared and distinguished heat-related illness from COVID-19. We aimed to compare the data between patients with early-stage heat-related illness and those with COVID-19. METHODS: This retrospective observational study included 90 patients with early-stage heat-related illness selected from Heatstroke STUDY 2017-2019 (nationwide registries of heat-related illness in Japan) and 86 patients with laboratory-confirmed COVID-19 with complaints of fever or fatigue and were admitted to one of two hospitals in Tokyo, Japan. RESULTS: Amongvital signs, systolic blood pressure (119 vs. 125 mmHg, p = 0.02), oxygen saturation (98% vs. 97%, p < 0.001), and body temperature (36.6 vs. 37.6 degrees C, p<0.001) showed significant between-group differences for the heatstroke and COVID-19 groups, respectively. Numerous intergroup differences in laboratory findings were present, including white blood cell counts (10.8 vs. 5.2 x 10(3)/muL, p<0.001), creatinine (2.2 vs. 0.85 mg/dL, p<0.001), and C-reactive protein (0.2 vs. 2.8 mg/dL, p<0.001), although a logistic regression model achieved an area under the curve (AUC) of 0.966 using these three factors. A Random Forest machine learning model achieved accuracy, precision, recall, and AUC of 0.908, 0.976, 0.842, and 0.978, respectively. Creatinine was the most important feature of this model. CONCLUSIONS: Acute kidney injury was associated with heat-related illness, which could be key in distinguishing or evaluating patients with fever in the summer during the COVID-19 pandemic.", "role": "user" }, { "content": "[\"Treatment\", \"Diagnosis\"]", "role": "assistant" } ]

[ { "content": "Which dataset would be most relevant for this research query?\n\nQuery: A system for generating natural language descriptions of images.\n\nKeyphrases: image description images\n\nDataset descriptions:\nChart2Text: Chart2Text is a dataset that was crawled from 23,382 freely accessible pages from statista.com in early March of 2020, yielding a total of 8,305 charts, and associated summaries. For each chart, the chart image, the underlying data table, the title, the axis labels, and a human-written summary describing the statistic was downloaded.\nDjango: The Django dataset is a dataset for code generation comprising of 16000 training, 1000 development and 1805 test annotations. Each data point consists of a line of Python code together with a manually created natural language description.\nVisual Madlibs: Visual Madlibs is a dataset consisting of 360,001 focused natural language descriptions for 10,738 images. This dataset is collected using automatically produced fill-in-the-blank templates designed to gather targeted descriptions about: people and objects, their appearances, activities, and interactions, as well as inferences about the general scene or its broader context.\nCOCO: The MS COCO (Microsoft Common Objects in Context) dataset is a large-scale object detection, segmentation, key-point detection, and captioning dataset. The dataset consists of 328K images.\n\nOptions: A: Chart2Text B: Django C: Visual Madlibs D: COCO", "role": "user" }, { "content": "COCO", "role": "assistant" } ]

[ { "content": "Output a JSON object with \"verdict\" and \"evidence\" fields based on the claim and abstract below.\n\nClaim: Wearing a mask may offer protection against catching severe covid-19\n\nAbstract:\nIn the context of Coronavirus Disease (2019) (COVID-19) cases globally, there is a lack of consensus across cultures on whether wearing face masks is an effective physical intervention against disease transmission.\nThis study 1) illustrates transmission routes of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2); 2) addresses controversies surrounding the mask from perspectives of attitude, effectiveness, and necessity of wearing the mask with evidence that the use of mask would effectively interrupt the transmission of infectious diseases in both hospital settings and community settings; and 3) provides suggestion that the public should wear the mask during COVID-19 pandemic according to local context.\nTo achieve this goal, government should establish a risk adjusted strategy of mask use to scientifically publicize the use of masks, guarantee sufficient supply of masks, and cooperate for reducing health resources inequities.", "role": "user" }, { "content": "{\"verdict\": \"SUPPORT\", \"evidence\": [\"This study 1) illustrates transmission routes of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2); 2) addresses controversies surrounding the mask from perspectives of attitude, effectiveness, and necessity of wearing the mask with evidence that the use of mask would effectively interrupt the transmission of infectious diseases in both hospital settings and community settings; and 3) provides suggestion that the public should wear the mask during COVID-19 pandemic according to local context.\"]}", "role": "assistant" } ]

[ { "content": "Output a JSON object with \"verdict\" and \"evidence\" fields based on the claim and abstract below.\n\nClaim: If you continue to smoke, you also have a greater risk for respiratory infections like colds, flu and also covid-19.\n\nAbstract:\nIntroduction Epidemiological and laboratory research seems to suggest that smoking and perhaps nicotine alone could reduce the severity of COVID-19.\nLikewise, there is some evidence that inhaled corticosteroids could also reduce its severity, opening the possibility that nicotine and inhaled steroids could be used as treatments.\nMethods In this prospective cohort study, we will link English general practice records from the QResearch database to Public Health England's database of SARS-CoV-2 positive tests, Hospital Episode Statistics, admission to intensive care units, and death from COVID-19 to identify our outcomes: hospitalisation, ICU admission, and death due to COVID.\nUsing Cox regression, we will perform sequential adjustment for potential confounders identified by separate directed acyclic graphs to: 1.\nAssess the association between smoking and COVID-19 disease severity, and how that changes on adjustment for smoking-related comorbidity.\n2. More closely characterise the association between smoking and severe COVID-19 disease by assessing whether the association is modified by age (as a proxy of length of smoking), gender, ethnic group, and whether people have asthma or COPD.\n3. Assess for evidence of a dose-response relation between smoking intensity and disease severity, which would help create a case for causality.\n4.\nExamine the association between former smokers who are using NRT or are vaping and disease severity.\n5. Examine whether pre-existing respiratory disease is associated with severe COVID-19 infection.\n6. Assess whether the association between chronic obstructive pulmonary disease (COPD) and asthma and COVID-19 disease severity is modified by age, gender, ethnicity, and smoking status.\n7. Assess whether the use of inhaled corticosteroids is associated with severity of COVID-19 disease.\n8. To assess whether the association between use of inhaled corticosteroids and severity of COVID-19 disease is modified by the number of other airways medications used (as a proxy for severity of condition) and whether people have asthma or COPD.\nConclusions This representative population sample will, to our knowledge, present the first comprehensive examination of the association between smoking, nicotine use without smoking, respiratory disease, and severity of COVID-19.\nWe will undertake several sensitivity analyses to examine the potential for bias in these associations.", "role": "user" }, { "content": "{\"verdict\": \"NEI\", \"evidence\": []}", "role": "assistant" } ]

[ { "content": "Extract all chemical entities (ChEBI) from this biomedical text. Output as JSON array.\n\nText: Inaddition,levelsofBATtriglycerideweresimilarbetweenthetwogenotypes(unpublisheddata).", "role": "user" }, { "content": "[\"triglyceride\"]", "role": "assistant" } ]

[ { "content": "Classify the intent of this citation from an NLP research paper. \n\nYour answer must be one word from: [\"Background\", \"Extends\", \"Uses\", \"Motivation\", \"CompareOrContrast\", \"FutureWork\"]. No other text allowed.\n\nSection Title:\nconclusion\n\nContext before:\nOn the WSJ corpus our system performed slightly better than the combination of the Alembic and SATZ systems described in Palmer and Hearst (1997) (0.44% vs. 0.5% error rate). The error rate on sentence boundaries in the Brown corpus was not significantly worse than the lowest quoted before (Riley 1989: 0.28% vs. 0.20% error rate). Despite its simplicity, the performance of our approach was on the level with the previously highest reported results on the same test collections.\n\nCitation:\nOn the WSJ corpus our system performed slightly better than the combination of the Alembic and SATZ systems described in Palmer and Hearst ( 1997 ) ( 0.44 % vs. 0.5 % error rate ) .\n\nContext after:\nAlthough these error rates seem to be very small, they are quite significant. Unlike general POS tagging, in which it is unfair to expect an error rate of less than 2% because even human annotators have a disagreement rate of about 3%, sentence boundaries are much less ambiguous (with a disagreement of about 1 in 5,000). This shows that an error rate of 1 in 200 (0.5%) is still far from reaching the disagreement level. On the other hand, one error in 200 periods means that there is one error in every two documents in the Brown corpus and one error in every four documents in the WSJ corpus.", "role": "user" }, { "content": "CompareOrContrast", "role": "assistant" } ]

[ { "content": "Write an abstract for the research paper below.\n\nPaper text:\nnarrow band imaging ( nbi ) is an optical digital method of image - enhanced endoscopy .\nsince then , in most countries where gastrointestinal endoscopies are performed , nbi is one of the most frequently used optical digital methods of performing image - enhanced endoscopy . in this review paper , the technology basis of nbi and its research and development ( r&d ) history\n, an nbi filter is placed between a xenon lamp and a red - green - blue rotary filter .\nthe light moves in and out onto the optical axis , and the spectrum of the illumination can be transformed from broad - band blue , green , and red to narrow band blue and green as shown in the upper and lower graph of fig .\nthe left and right images were taken under conventional white light and nbi , respectively . on the nbi image ,\nthe thin capillary network on the mucosal surface has a brownish appearance and thick blood vessels have a cyan appearance .\nowing to nbi s unique color allocation rules , an nbi s final color image has a different color reproduction from the conventional one . as shown in fig .\n3 , the narrow band blue image , which is taken at 415 nm in the center wavelength illumination , has the blue and green channel of an observation display . the narrow band green image , which is taken at 540 nm in the center wavelength , is allocated to the red channel of the display .\nthis color allocation rule is the only one that has an enhancement effect on the capillary network .\nlight as a wave has a wavelength , which means the distance between peaks in each wave .\nblue light with a narrow bandwidth looks more vivid compared with a broad bandwidth because when light contains more wavelengths , saturation decreases .\nlight having a broad bandwidth within the range between 400 and 700 nm looks white .\ninterestingly , different wavelengths have different behaviors in biological tissue . in optical turbid medium ,\nwhen light strikes small particles such as complex proteins , organelles , and cell structures , its light energy diffuses three - dimensionally .\nwhen there is a multitude of particles , multiple scattering occurs as scattered light scatters again by striking another particle .\nlight propagates diffusively because of this light scattering even with a flux of light . a schematic diagram of the interaction between light and living tissue is shown in fig .\n4 . when light enters biological tissue , some reflects off the surface and some diffuses within the body .\nmultiple scattering occurs among light and small particles such as cell nuclei , cell organelles , and nuclei in the tissue . as a result , light propagates diffusively through the tissue .\nthe propagation of light is determined by its wavelength . while red light diffuses widely and deeply because of its long wavelength , blue light , having a short wavelength , diffuses with a smaller range .\na part of the scattered light is absorbed by the blood . to be accurate ,\ntherefore , the color of the gastrointestinal mucosa is mainly determined by hemoglobin . as mentioned above\nthese center wavelengths match with the two absorption peaks of the hemoglobin . owing to strong scattering and absorption ,\nin may 1999 , the idea of nbi was first conceived . to confirm the feasibility of nbi\n, a study was conducted using a multi - spectrum camera capable of producing spectroscopic images and high - powered light source ; i had volunteered as a test subject .\nthe study revealed that the use of 415 nm narrowband light can improve the contrast of capillary images that have been difficult to observe with conventional white light . the first image of living tissue ever produced using nbi is shown in fig .\n5 . then , the development of a nbi endoscopy system started in co - operation with dr .\nsano of national cancer center hospital east . on december 14 , 1999 , based on a study using the nbi prototype , we confirmed that it was a promising technology for endoscopic examination of hollow viscous mucosa , including the colon , stomach , and esophagus .\nwe started to develop products in cooperation with not only japanese endoscopists but also from around the world by improving the capacity of the prototype .\nexera ii ( olympus clv-180 evis exera ii xenon light source , olympus cv-180 evis exera ii video system center ) and evis lucera spectrum ( olympus clv-260sl evis lucera spectrum xenon light source , olympus cv-260sl evis lucera spectrum video system center ; olympus , tokyo , japan ) were introduced in 2005 and 2006 , respectively , as the next generation system equipped with high - definition television and nbi .\nsince the first - generation nbi was introduced in the market , olympus r&d has been committed to improving the performance of nbi .\nthe first - generation nbi had a limitation in brightness : on gastric observation , the distal end of the endoscope needed to be carefully advanced to the mucosa to obtain sufficient brightness in the nbi mode .\nthis insufficient brightness adversely affected the operability of the endoscope . to overcome this limitation , we made various modifications to increase the brightness of nbi .\nwe developed a high - intensity discharge lamp , intensified the brightness of the lens in the light source , improved the sensitivity of the image sensor , and worked on image processing in the processor to reduce noise .\nas a result of these modifications at various parts of the system from the tip of the endoscope to the light source and signal processor , the second - generation nbi is able to deliver brightness more than one - and - a - half times as high as the first - generation nbi and to get twice the viewable distance in the lumen .\nthe difference in the brightness of test models between the first - generation ( fig .\nwe , olympus r&d , are now improving its quality for improved ease of use . understanding optical tissue characteristics and physician demands", "role": "user" }, { "content": "the first launch of narrow band imaging ( nbi ) was in 2005 . \n since then , in most countries where gastrointestinal endoscopies are performed , nbi is the most commonly used optical digital method of performing image - enhanced endoscopy . \n thanks to the outstanding efforts of many endoscopists , many clinical studies have been performed and clinical evidence has been gathered . in japan , since 2010 , nbi has been reimbursed under the japanese national health insurance system . \n this is owing to the establishment of clinical evidence by physicians . \n however , even though endoscope systems with nbi function have been widely used outside of japan , dissemination of knowledge on how to use nbi is insufficient . in this review paper , the technology basis of nbi and its research and development history \n are described . \n i hope this information will be helpful for updating physicians knowledge of nbi .", "role": "assistant" } ]

[ { "content": "Output a JSON object with \"verdict\" and \"evidence\" fields based on the claim and abstract below.\n\nClaim: It's unclear why taking an ACE inhibitor or an ARB might curb Covid-19\n\nAbstract:\nAngiotensin-converting enzyme (ACE) inhibitors (ACEIs) and angiotensin II type­1 receptor blockers (ARBs) are among the most widely prescribed drugs for the treatment of arterial hypertension, heart failure and chronic kidney disease.\nA number of studies, mainly in animals and not involving the lungs, have indicated that these drugs can increase expression of angiotensin-converting enzyme 2 (ACE2).\nACE2 is the cell entry receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) that is currently battering the globe.\nThis has led to the hypothesis that use of ACEIs and ARBs may increase the risk of developing severe COVID-19.\nIn this point of view paper, possible scenarios regarding the impact of ACEI/ARB pharmacotherapy on COVID-19 are discussed in relation to the currently available evidence.\nAlthough further research on the influence of blood-pressure-lowering drugs, including those not targeting the renin-angiotensin system, is warranted, there are presently no compelling clinical data showing that ACEIs and ARBs increase the likelihood of contracting COVID-19 or worsen the outcome of SARS-CoV­2 infections.\nThus, unless contraindicated, use of ACEIs/ARBs in COVID-19 patients should be continued in line with the recent recommendations of medical societies.", "role": "user" }, { "content": "{\"verdict\": \"CONTRADICT\", \"evidence\": [\"This has led to the hypothesis that use of ACEIs and ARBs may increase the risk of developing severe COVID-19.\"]}", "role": "assistant" } ]

[ { "content": "Write a literature review chapter based on these paper abstracts.\nLiterature Review Title: Deep Learning for Person Re-identification: A Survey and Outlook \nChapter Title: End-to-End Re-ID \n1. Abstract of Cited Paper (BIB001): Existing person re-identification benchmarks and methods mainly focus on matching cropped pedestrian images between queries and candidates. However, it is different from real-world scenarios where the annotations of pedestrian bounding boxes are unavailable and the target person needs to be searched from a gallery of whole scene images. To close the gap, we propose a new deep learning framework for person search. Instead of breaking it down into two separate tasks---pedestrian detection and person re-identification, we jointly handle both aspects in a single convolutional neural network. An Online Instance Matching (OIM) loss function is proposed to train the network effectively, which is scalable to datasets with numerous identities. To validate our approach, we collect and annotate a large-scale benchmark dataset for person search. It contains 18,184 images, 8,432 identities, and 96,143 pedestrian bounding boxes. Experiments show that our framework outperforms other separate approaches, and the proposed OIM loss function converges much faster and better than the conventional Softmax loss. \n2. Abstract of Cited Paper (BIB002): We investigate the problem of person search in the wild in this work. Instead of comparing the query against all candidate regions generated in a query-blind manner, we propose to recursively shrink the search area from the whole image till achieving precise localization of the target person, by fully exploiting information from the query and contextual cues in every recursive search step. We develop the Neural Person Search Machines (NPSM) to implement such recursive localization for person search. Benefiting from its neural search mechanism, NPSM is able to selectively shrink its focus from a loose region to a tighter one containing the target automatically. In this process, NPSM employs an internal primitive memory component to memorize the query representation which modulates the attention and augments its robustness to other distracting regions. Evaluations on two benchmark datasets, CUHK-SYSU Person Search dataset and PRW dataset, have demonstrated that our method can outperform current state-of-the-arts in both mAP and top-1 evaluation protocols. \n3. Abstract of Cited Paper (BIB003): Tracking multiple persons in a monocular video of a crowded scene is a challenging task. Humans can master it even if they loose track of a person locally by re-identifying the same person based on their appearance. Care must be taken across long distances, as similar-looking persons need not be identical. In this work, we propose a novel graph-based formulation that links and clusters person hypotheses over time by solving an instance of a minimum cost lifted multicut problem. Our model generalizes previous works by introducing a mechanism for adding long-range attractive connections between nodes in the graph without modifying the original set of feasible solutions. This allows us to reward tracks that assign detections of similar appearance to the same person in a way that does not introduce implausible solutions. To effectively match hypotheses over longer temporal gaps we develop new deep architectures for re-identification of people. They combine holistic representations extracted with deep networks and body pose layout obtained with a state-of-the-art pose estimation model. We demonstrate the effectiveness of our formulation by reporting a new state-of-the-art for the MOT16 benchmark. The code and pre-trained models are publicly available. \n4. Abstract of Cited Paper (BIB004): Multi-Target Multi-Camera Tracking (MTMCT) tracks many people through video taken from several cameras. Person Re-Identification (Re-ID) retrieves from a gallery images of people similar to a person query image. We learn good features for both MTMCT and Re-ID with a convolutional neural network. Our contributions include an adaptive weighted triplet loss for training and a new technique for hard-identity mining. Our method outperforms the state of the art both on the DukeMTMC benchmarks for tracking, and on the Market-1501 and DukeMTMC-ReID benchmarks for Re-ID. We examine the correlation between good Re-ID and good MTMCT scores, and perform ablation studies to elucidate the contributions of the main components of our system. Code is available1. \n5. Abstract of Cited Paper (BIB005): Person re-identification has achieved great progress with deep convolutional neural networks. However, most previous methods focus on learning individual appearance feature embedding, and it is hard for the models to handle difficult situations with different illumination, large pose variance and occlusion. In this work, we take a step further and consider employing context information for person search. For a probe-gallery pair, we first propose a contextual instance expansion module, which employs a relative attention module to search and filter useful context information in the scene. We also build a graph learning framework to effectively employ context pairs to update target similarity. These two modules are built on top of a joint detection and instance feature learning framework, which improves the discriminativeness of the learned features. The proposed framework achieves state-of-the-art performance on two widely used person search datasets. \n6. Abstract of Cited Paper (BIB006): Person search has recently gained attention as the novel task of finding a person, provided as a cropped sample, from a gallery of non-cropped images, whereby several other people are also visible. We believe that i. person detection and re-identification should be pursued in a joint optimization framework and that ii. the person search should leverage the query image extensively (e.g. emphasizing unique query patterns). However, so far, no prior art realizes this. We introduce a novel query-guided end-to-end person search network (QEEPS) to address both aspects. We leverage a most recent joint detector and re-identification work, OIM [37]. We extend this with i. a query-guided Siamese squeeze-and-excitation network (QSSE-Net) that uses global context from both the query and gallery images, ii. a query-guided region proposal network (QRPN) to produce query-relevant proposals, and iii. a query-guided similarity subnetwork (QSimNet), to learn a query-guided reidentification score. QEEPS is the first end-to-end query-guided detection and re-id network. On both the most recent CUHK-SYSU [37] and PRW [46] datasets, we outperform the previous state-of-the-art by a large margin. \n7. Abstract of Cited Paper (BIB007): Person search aims at localizing and identifying a query person from a gallery of uncropped scene images. Different from person re-identification (re-ID), its performance also depends on the localization accuracy of a pedestrian detector. The state-of-the-art methods train the detector individually, and the detected bounding boxes may be sub-optimal for the following re-ID task. To alleviate this issue, we propose a re-ID driven localization refinement framework for providing the refined detection boxes for person search. Specifically, we develop a differentiable ROI transform layer to effectively transform the bounding boxes from the original images. Thus, the box coordinates can be supervised by the re-ID training other than the original detection task. With this supervision, the detector can generate more reliable bounding boxes, and the downstream re-ID model can produce more discriminative embeddings based on the refined person localizations. Extensive experimental results on the widely used benchmarks demonstrate that our proposed method performs favorably against the state-of-the-art person search methods. \n8. Abstract of Cited Paper (BIB008): Multi-target multi-camera tracking (MTMCT) systems track targets across cameras. Due to the continuity of target trajectories, tracking systems usually restrict their data association within a local neighborhood. In single camera tracking, local neighborhood refers to consecutive frames; in multi-camera tracking, it refers to neighboring cameras that the target may appear successively. For similarity estimation, tracking systems often adopt appearance features learned from the re-identification (re-ID) perspective. Different from tracking, re-ID usually does not have access to the trajectory cues that can limit the search space to a local neighborhood. Due to its global matching property, the re-ID perspective requires to learn global appearance features. We argue that the mismatch between the local matching procedure in tracking and the global nature of re-ID appearance features may compromise MTMCT performance. ::: To fit the local matching procedure in MTMCT, in this work, we introduce locality aware appearance metric (LAAM). Specifically, we design an intra-camera metric for single camera tracking, and an inter-camera metric for multi-camera tracking. Both metrics are trained with data pairs sampled from their corresponding local neighborhoods, as opposed to global sampling in the re-ID perspective. We show that the locally learned metrics can be successfully applied on top of several globally learned re-ID features. With the proposed method, we report new state-of-the-art performance on the DukeMTMC dataset, and a substantial improvement on the CityFlow dataset.\n\nLiterature Review:", "role": "user" }, { "content": "End-to-end Re-ID alleviates the reliance on additional step for bounding boxes generation. It involves the person Re-ID from raw images or videos, and multi-camera tracking. Re-ID in Raw Images/Videos This task requires that the model jointly performs the person detection and reidentification in a single framework BIB001 , BIB002 . It is challenging due to the different focuses of two major components. Zheng et al. BIB001 present a two-stage framework, and systematically evaluate the benefits and limitations of person detection for the later stage person Re-ID. Xiao et al. BIB002 design an end-to-end person search system using a single convolutional neural network for joint person detection and re-identification. A Neural Person Search Machine (NPSM) BIB003 is developed to recursively refine the searching area and locate the target person by fully exploiting the contextual information between the query and the detected candidate region. Similarly, a contextual instance expansion module BIB006 is learned in a graph learning framework to improve the end-to-end person search. A query-guided end-to-end person search system BIB007 is developed using the Siamese squeeze-and-excitation network to capture the global context information with query-guided region proposal generation. A localization refinement scheme with discriminative Re-ID feature learning is introduced in BIB008 to generate more reliable bounding boxes. Yamaguchi et al. investigate a more challenging problem, i.e., searching for the person from raw videos with text description. A multi-stage method with spatio-temporal person detection and multi-modal retrieval is proposed. Further exploration along this direction is expected. Multi-camera Tracking End-to-end person Re-ID is also closely related to multi-person, multi-camera tracking BIB005 . A graph-based formulation to link person hypotheses is proposed for multi-person tracking BIB004 , where the holistic features of the full human body and body pose layout are combined as the representation for each person. Ristani et al. BIB005 learn the correlation between the multi-target multicamera tracking and person Re-ID by hard-identity mining and adaptive weighted triplet learning. Recently, a locality aware appearance metric (LAAM) BIB009 with both intra-and inter-camera relation modeling is proposed.", "role": "assistant" } ]

[ { "content": "Classify the intent of this citation sentence by choosing from: [\"Method\", \"Background\", \"Result\"].\n\nMethod: Cites for methodology\nBackground: Cites for background information\nResult: Cites for findings\n\nCitation: …August 14, 2015 10 / 21\nproxies may have difficulty evaluating the impact of conditions on dimensions of health such as pain and emotion; Tilford et al. (2005) [79] called for more research to be conducted on calculation methods for young child when discussing the issues surrounding the…", "role": "user" }, { "content": "Method", "role": "assistant" } ]

[ { "content": "Classify the topics of this COVID-19 literature paragraph by selecting from these categories:\n\n- Epidemic Forecasting: Predictions about COVID-19 spread\n- Treatment: Therapeutic methods or medication\n- Prevention: Measures to prevent spread\n- Mechanism: Biological mechanisms of the virus\n- Case Report: Report of a COVID-19 case\n- Transmission: How COVID-19 is transmitted\n- Diagnosis: Diagnosing COVID-19 in individuals\n\nYour output should be a valid JSON array with topics in double quotes and separated by commas. No additional text should be included.\n\nArticle:\n\nINTRODUCTION AND AIMS: The Australian Treatment Outcomes Profile (ATOP) is a brief clinical tool measuring recent substance use, health and wellbeing among clients attending alcohol and other drug (AOD) treatment services. It has previously been assessed for concurrent validity and inter-rater reliability. In this study we examine whether it is suitable for administration over the telephone. DESIGN AND METHODS: We recruited a sample of 107 AOD clients across public sector specialist AOD treatment services in New South Wales, Australia between 2016 and 2018. Participants had a mean age of 47 years and 46% were female. Participants completed a face-to-face ATOP and a phone ATOP with a researcher within 5 days. Comparisons between the two administration modes were undertaken using Spearman's rank correlation coefficient for continuous or ordinal variables, and Cohen's Kappa for nominal variables. RESULTS: Among 107 participants, 59% were attending for alcohol treatment and 41% for opioid treatment. Most ATOP items (76%) reached above 0.7 (good) or 0.9 (excellent) agreement between face-to-face and telephone use. DISCUSSION AND CONCLUSIONS: Our findings suggest that the ATOP is a suitable instrument for telephone monitoring of recent substance use, health and social functioning among AOD clients. Its validation for remote use over the telephone will support staff to monitor clients' risks and outcomes-of particular relevance in response to the COVID-19 pandemic in which services are increasingly relying on telework approaches to client monitoring.", "role": "user" }, { "content": "[\"Prevention\"]", "role": "assistant" } ]

[ { "content": "Classify the intent of this citation sentence by choosing from: [\"Method\", \"Background\", \"Result\"].\n\nMethod: Cites for methodology\nBackground: Cites for background information\nResult: Cites for findings\n\nCitation: …back-propagation learning, Mixture-ofExperts (ME) model (Jacobs et al., 1991; Jordan & Jacobs, 1994; Jordan & Xu, 1995) and its alternative model (Xu, 1998a; Xu et al., 1995), as well as normalized RBF nets (Moody & Darken, 1989; Nowlan, 1990; Xu et al., 1994) and its extensions (Xu, 1998a), but…", "role": "user" }, { "content": "Background", "role": "assistant" } ]