Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural and Biochemical Analysis of a Single Amino-Acid Mutant of WzzBSF That Alters Lipopolysaccharide O-Antigen Chain Length in Shigella flexneri

Lipopolysaccharide (LPS), a surface polymer of Gram-negative bacteria, helps bacteria survive in different environments and acts as a virulence determinant of host infection. The O-antigen (Oag) component of LPS exhibits a modal chain-length distribution that is controlled by polysaccharide co-polymerases (PCPs). The molecular basis of the regulation of Oag chain-lengths remains unclear, despite extensive mutagenesis and structural studies of PCPs from Escherichia coli and Shigella. Here, we identified a single mutation (A107P) of the Shigella flexneri WzzBSF, by a random mutagenesis approach, that causes a shortened Oag chain-length distribution in bacteria. We determined the crystal structures of the periplasmic domains of wild-type WzzBSF and the A107P mutant. Both structures form a highly similar open trimeric assembly in the crystals, and show a similar tendency to self-associate in solution. Binding studies by bio-layer interferometry reveal cooperative binding of very short (VS)-core-plus-O-antigen polysaccharide (COPS) to the periplasmic domains of both proteins, but with decreased affinity for the A107P mutant. Our studies reveal that subtle and localized structural differences in PCPs can have dramatic effects on LPS chain-length distribution in bacteria, for example by altering the affinity for the substrate, which supports the role of the structure of the growing Oag polymer in this process.
Deep structural brain lesions associated with consciousness impairment early after haemorrhagic stroke

Background The significance of deep structural lesions on level of consciousness early after intracerebral haemorrhage (ICH) is largely unknown. Methods We studied a consecutive series of patients with spontaneous ICH that underwent MRI within 7 days of the bleed. We assessed consciousness by testing for command following from time of MRI to hospital discharge, and determined 3-months functional outcomes using the Glasgow Outcome Scale-Extended (GOS-E). ICH and oedema volumes, intraventricular haemorrhage (IVH), and midline shift (MLS) were quantified. Presence of blood and oedema in deep brain regions previously implicated in consciousness were assessed. A machine learning approach using logistic regression with elastic net regularization was applied to identify parameters that best predicted consciousness at discharge controlling for confounders. Results From 158 ICH patients that underwent MRI, 66% (N=105) were conscious and 34% (N=53) unconscious at the time of MRI. Almost half of unconscious patients (49%, N= 26) recovered consciousness by ICU discharge. Focal lesions within subcortical structures predicted persistent impairment of consciousness at discharge together with MLS, IVH, and ICH and oedema volumes (AUC 0.74; 95%-CI 0.73-0.75). Caudate nucleus, midbrain peduncle, and pontine tegmentum were implicated as critical structures. Unconscious patients predicted to recover consciousness had better 3-month functional outcomes than those predicted to remain unconscious (35% vs 0% GOS-E ≥4; p-value=0.02). Conclusion MRI lesions within key subcortical structures together with measures reflecting the mass effect of the haemorrhage (lesion volumes, IVH, MLS) obtained within one week of ICH can help predict early recovery of consciousness and 3-month functional outcome.
ORIGINAL RESEARCH The Food Additive Maltodextrin Promotes Endoplasmic Reticulum Stress – Driven Q2 Mucus Depletion and Exacerbates Intestinal In ﬂ ammation

This study reports that the polysaccharide maltodextrin, which is a common additive used in Western diet for food processing, triggers endoplasmic reticulum stress in goblet cells. Our data support the hypothesis that a Western diet rich in maltodextrin can contribute to gut disease susceptibility and can help Q8 design preventive programs for subjects at high risk to develop in ﬂ ammatory bowel diseases. BACKGROUND stabilizers,
Consumption experience , choice experience and the endowment effect

This paper reports an experiment investigating how different kinds of experience influence the endowment effect. Previous studies have investigated how the endowment effect is influenced by experience gained through repetition of decision problems and trading in natural and experimental markets. In this study we explore how it is influenced by experience of consuming elements of a potential endowment and by experience of choosing prior to acquiring an endowment. We find evidence of an endowment effect and that measured loss aversion predicts the reluctance to trade. We find no effect of consumption experience. Choice experience increases trading. Finally, we find evidence of a new species of 'splitting effect', whereby acquiring an endowment in two instalments significantly reduces trading. JEL classification: C91, D12
Mapping of linear B-cell epitopes of the S2 subunit of pertussis toxin

The linear immunogenic and antigenic structure of the S2 subunit of pertussis toxin was investigated with synthetic peptides corresponding to regions of the protein sequence predicted to contain surface-exposed hydrophilic beta turns. Five peptides as peptide-bovine serum albumin conjugates were recognized by anti-pertussis toxin antiserum and were thus designated "immunogenic epitopes. " Two prominent immunogenic epitopes were specified by peptides corresponding to sequences spanning R107-120 and R186-199, whereas peptides corresponding to residues R35-50 and R91-106 were only bound in low titer. Three peptides as thyroglobulin conjugates elicited antisera in rabbits that bound intact pertussis toxin by enzyme-linked immunosorbent assay and immunoblot. These peptides were designated "antigenic epitopes. " The most prominent antigenic determinant was localized to the N-terminal end of the S2 sequence encompassing residue R1-7. Peptides R35-50 and R91-106 represented two minor antigenic epitopes. Antisera to two additional peptides corresponding to residues R134-149 and R186-199 recognized the S2 subunit only by Western blotting (immunoblotting). Only antiserum raised against peptide R91-106 also recognized the S3 subunit by Western blotting, indicating a marked antigenic and probably also structural difference between the two highly homologous subunits.
mir-19 promotes the proliferation of clear cell renal cell carcinoma by targeting the FrK–PTen axis

Background: The non-receptor tyrosine kinase Fyn-related kinase (FRK) has been reported to affect cell proliferation in several cancer types. However, its effect on the proliferation of clear cell renal cell carcinoma (ccRCC) remains largely unknown. Purpose: The objective of this study was to investigate the expression pattern and function of FRK in ccRCC. We further determined how FRK interacted with other molecules to regulate ccRCC proliferation. Patients and methods: The expression of FRK in ccRCC samples and paired normal renal tissues from 30 patients were analyzed by immunoblotting, immunohistochemistry and quantitative PCR. Then the role of FRK in ccRCC proliferation was analyzed by Cell Counting Kit-8, colony formation assay and EdU incorporation assay. In addition, the miRNA targeting FRK was predicted through a bioinformatic approach and validated by quantitative PCR, immunoblotting and luciferase reporter assay. Finally, the underlying mechanism of FRK regulation of ccRCC proliferation was also determined. Results: Low expression of FRK was detected in ccRCC samples and predicted poor survival for ccRCC patients. FRK inhibited the proliferation of ccRCC cells via phosphorylating downstream PTEN. miR-19 was identified as a novel suppressor of FRK in renal cancer cells and it promoted the proliferation of ccRCC by inhibiting the FRK–PTEN axis. Conclusion: Our results unravel a new regulatory mechanism involved in ccRCC proliferation and may be useful in the identification of therapeutic targets for ccRCC.
Knowledge, attitudes, and practices of Cameroonian physicians with regards to pain management at the emergency department: a multicenter cross-sectional study

Introduction: Pain is the most frequent presenting complaint in patients consulting or admitted to the emergency department (ED). Thus, its acute management is often done by physicians working in the ED. These practitioners are often general practitioners and not emergency medicine physicians in resource-poor settings. Hence, a mastery of pain management by these physicians may be important in relieving acute pain. We aimed to assess the knowledge, to determine the attitudes and practices of physicians in the management of pain in EDs of Cameroon. Methods: We carried out a prospective analytic cross-sectional study over four months in the year 2018. We enrolled all consenting physicians who were neither emergency medicine doctors nor anesthesiologists working at the EDs of �ve tertiary hospitals of Cameroon. Using a 30-item structured questionnaire, data on the knowledge, attitudes, and practices of pain management at the ED by these clinicians were studied. We used an externally validated score to assess the knowledge as either poor, insu�cient, moderate or good. Results: A total of 58 physicians were included; 18 interns and 39 general practitioners. Their mean age was 28.6 ± 3 years and their average number of years of practice was 2.9 years. The level of knowledge was rated “poor” in 77.6% of physicians. Being a general practitioner was signi�cantly associated with a poor level of knowledge (p=0.02; OR=5.1). We found a negative and signi�cant correlation between knowledge and years of practice (p=0.04; r2= 0.06). More than three-quarter (82.8%) of participants used a pain scale to evaluate the severity of pain. The most used scale being the Visual Analog scale (56.9%). The most frequently used analgesic was paracetamol (98.3%), although only 3.5% of physicians correctly knew its half-life, delay of onset of action and duration of action. Conclusion: These �ndings suggest that physicians in EDs of Cameroon have poor knowledge and suboptimal practices in pain management. General practice and a greater number of professional experience seemed to favour these attitudes. Overall, there is an urgent need for refresher courses in acute pain management for physicians working in these resource-limited EDs. This is one of the largest and �rst series to assess the knowledge, to determine the attitudes and practices of physicians in the management of pain in EDs of Cameroon and perhaps sub-Saharan Africa at large. This study shows the low level of physicians' knowledge about pain management, as well as suboptimal practices, particularly in terms of acute pain management. General practice and a greater number of professional experience seemed to favour these attitudes. Overall, this study emphasizes an urgent need to organize regular refresher courses on pain management for clinicians working in EDs in resource-limited settings.
Expanding the diversity of Accumulibacter with a novel type and deciphering the transcriptional and morphological features among co-occurring strains

Accumulibacter is the major polyphosphate-accumulating organism (PAO) in global wastewater treatment systems. Its phylogenetic and functional diversity has been continuously updated in recent years. In addition to its widely recognized two sublineages, Types I and II, here we discovered a novel type enriched in laboratory bioreactors. Core gene- and machine learning-based gene feature profiling supported that Type III Accumulibacter was potential PAO with the unique function of using dimethyl sulfoxide as electron acceptor. On the basis of the correlation between the similarity of ppk1 and genome, the number of ppk1-represented Accumulibacter species was estimated to be over one hundred, suggesting that the currently recognized species are only the tip of the iceberg. Meanwhile, multiple Accumulibacter strains co-occurring in a bioreactor were investigated for their inter-strain transcriptional and morphological features. Metatranscriptomics of seven co-occurring strains indicated that the expression level and interphasic dynamics of PAO phenotype-related genes had minimal correlation with their phylogeny. In particular, expression of denitrifying and poly-P metabolism genes had higher inter-strain and interphasic divergence compared with glycogen and polyhydroxyalkanoates metabolic genes. A strategy of cloning rRNA genes from different strains based on similar genomic synteny was successfully applied to differentiate their morphology via fluorescence in situ hybridization. Our study further expanded the phylogenetic and functional diversity of Accumulibacter. We also proposed that deciphering the function and capability of certain Accumulibacter should be environment- and population-specific. Importance Accumulibacter, as the core functional but uncultured taxa for enhanced biological phosphorus removal, has attracted much attentions on its phylogenetic and functional diversity and intra-genus niche differentiation in the last two decades. It was well-known that this genus had two sub-lineages (Type I and II) since 2002. In this study, a novel type (Type III) with proposed novel functional feature was discovered by the metagenomic approach. By linking average nucleotide identity of Accumulibacter genomes and the similarity of the ppk1 sequences, a phylogenetic biomarker that has been largely deposited in database, we estimated that its global species-level diversity was higher than 100. Moreover, as we found the co-occurrence of multiple Accumulibacter strains in one bioreactor, the simultaneous transcriptional divergence of the co-occurring strains was interesting for understanding their niche differentiation in a single community. The results suggested the decoupling feature between transcriptional pattern with phylogeny for co-occurring strains.
Unweaving tangled mortality and antibiotic consumption data to detect disease outbreaks – Peaks, growths, and foresight in swine production

As our capacity to collect and store health data is increasing, a new challenge of transforming data into meaningful information for disease monitoring and surveillance has arisen. The aim of this study was to explore the potential of using livestock mortality and antibiotic consumption data as a proxy for detecting disease outbreaks at herd level. Changes in the monthly records of mortality and antibiotic consumption were monitored in Danish swine herds that became positive for porcine reproductive and respiratory syndrome (PRRS) and porcine pleuropneumonia. Laboratory serological results were used to identify herds that changed from a negative to a positive status for the diseases. A dynamic linear model with a linear growth component was used to model the data. Alarms about state changes were raised based on forecast errors, changes in the growth component, and the values of the retrospectively smoothed values of the growth component. In all cases, the alarms were defined based on credible intervals and assessed prior and after herds got a positive disease status. The number of herds with alarms based on mortality increased by 3% in the 3 months prior to laboratory confirmation of PRRS-positive herds (Se = 0.47). A 22% rise in the number of weaner herds with alarms based on the consumption of antibiotics for respiratory diseases was found 1 month prior to these herds becoming PRRS-positive (Se = 0.22). For porcine pleuropneumonia-positive herds, a 10% increase in antibiotic consumption for respiratory diseases in sow herds was seen 1 month prior to a positive result (Se = 0.5). Monitoring changes in mortality data and antibiotic consumption showed changes at herd level prior to and in the same month as confirmation from diagnostic tests. These results also show a potential value for using these data streams as part of surveillance strategies.
Cost-effectiveness of adding ezetimibe and/or PCSK9 inhibitors to high-dose statins for secondary prevention of cardiovascular disease in Chinese adults

Abstract Objectives The latest international guideline recommended the add-on therapy of ezetimibe and PCSK9 inhibitors in selected people for the secondary prevention of cardiovascular diseases (CVDs). However, it remains unclear whether these regimens fit the Chinese healthcare system economically. Methods Based on the Chinese context, this simulation study evaluated four therapeutic strategies including the high-dose statin-only group, ezetimibe plus statin group, PCSK9 inhibitors plus statin group, and PCSK9 inhibitors plus ezetimibe plus statin group. The team developed a Markov model to estimate the incremental cost-effectiveness ratio (ICER). With each 1-yr cycle, the simulation subjects could have nonfatal cardiovascular events (stroke and/or myocardial infarction) or death (vascular or nonvascular death event) with a follow-up duration of 20 yr. Cardiovascular risk reduction was gathered from a network meta-analysis, and cost and utility data were gathered from hospital databases and published research. Results For Chinese adults receiving high-dose statins for secondary prevention of CVDs, the ICER was US$68,910 per quality-adjusted life year (QALY) for adding PCSK9 inhibitors, US$20,242 per QALY for adding ezetimibe, US$51,552 per QALY for adding both drugs. Given a threshold of US$37,655 (three times of Chinese GDP), the probability of cost-effectiveness is 2.9 percent for adding PCSK9 inhibitors, 53.1 percent for adding ezetimibe, and 16.8 percent for adding both drugs. To meet the cost-effectiveness, an acquisition price reduction of PCSK9 inhibitors of 33.6 percent is necessary. Conclusion In Chinese adults receiving high-dose statins for the secondary prevention of CVDs, adding ezetimibe is cost-effective compared to adding PCSK9 inhibitors and adding both drugs.
Sex, Age, and Growth of Black Rockfish Sebastes melanops from a newly exploited population in the Gulf of Alaska, 1993-1999

A newly exploited population of black rockfish Sebastes melanops were sampled from commercial landings in the Gulf of Alaska from 1993–1999 to identify issues in future management of this resource. Fish were measured, sexed, and sagittal otoliths were removed and aged. Males dominated the catches, comprising 71% of the samples. The majority of the catch was between 38 and 53 cm fork length, with a distinct mode at 39 cm fork length in 1997 in both the Kodiak and Alaska Peninsula Areas. Length-at-age for each year revealed differences in growth between sexes, with females larger than males. Growth differences between areas were observed but were significant for only males. The oldest fish aged was 48 years old, with the majority of the catch between 8 and 20 years old. Variations in year class strength were large and apparent in all areas. Strong recruitment events in 1979 and 1990 were tracked throughout the entire range of collection years and throughout the Gulf of Alaska. Research priorities for black rockfish in the Gulf of Alaska should focus on determining the relationship between sex-specific depth distributions, changes in sex compositions with respect to reproductive timing, age of maturity, and the affects of local and large scale environmental conditions on recruitment. Maintenance of a time series of biological data such as age and growth and monitoring specific fishing practices may offer indicators of long-term fishing effects on successful recruitment. Authors: CARRIE L. WORTON works for the Alaska Department of Fish and Game, Division of Commercial Fisheries, 211 Mission Road, Kodiak, Alaska 99615. E-mail: carrie_worton@fishgame.state. ak.us. GREGG E. ROSENKRANZ works for the Alaska Department of Fish and Game, Division of Commercial Fisheries, 211 Mission Road, Kodiak, Alaska 99615. Acknowlegments: Joan Brodie for aging otoliths, and Bonnie Jones for data entry. Special thanks to all dockside samplers who collected the data: Rachel Alinsunurin, Tonya Brockman, Tom Dinnocenzo, Mary Forner, Donna Higginbotham, Boris Lesniak, Cort Neff, Kim Phillips, Mike Ruccio, Ty Swanson, and Ani Thomas. We also thank three anonymous reviewers for their useful comments. INTRODUCTION Black rockfish Sebastes melanops range from Alaska to California (Hart 1973) and are one of 30 rockfish (genus Sebastes) species that are commercially and recreationally harvested in the Gulf of Alaska (GOA). Commercial fishing for black rockfish in the GOA and the Aleutian Islands began in the early 1990s and is managed by the Alaska Department of Fish and Game (ADFG Wallace and Tagart 1994). Rockfish population dynamics are characterized by high variability in year-class strength; large year classes, which occasionally arise, are believed to be important to long-term maintenance of populations (Leaman and Beamish 1984). Past studies suggest that major oceanographic changes, such as El Nino, may influence
Churches as Social Insurance: Oil Risk and Religion in the U.S. South

Religious communities are important providers of social insurance. We show that risk associated with oil dependence facilitated the proliferation of religious communities throughout the U.S. South during the twentieth century. Known oil abundance predicts higher rates of church membership, which are not driven by selective migration or local economic development. Consistent with a social insurance channel, greater oil price volatility increases effects, while greater access to credit, state-level social insurance, and private insurance crowd out effects. Religious communities limit spillovers of oil price shocks across sectors, reducing increases in unemployment following a negative shock by about 30 percent.
CADet: Fully Self-Supervised Out-Of-Distribution Detection With Contrastive Learning

Handling out-of-distribution (OOD) samples has become a major stake in the real-world deployment of machine learning systems. This work explores the application of self-supervised contrastive learning to the simultaneous detection of two types of OOD samples: unseen classes and adversarial perturbations. Since in practice the distribution of such samples is not known in advance, we do not assume access to OOD examples. We ﬁrst show that similarity functions trained with contrastive learning can be leveraged with the maximum mean discrepancy (MMD) two-sample test to verify whether two independent sets of samples are drawn from the same distribution. Inspired by this approach, we introduce CADet (Contrastive Anomaly Detection), a method based on contrastive transformations to perform anomaly detection on single samples. CADet compares favorably to adversarial detection methods to detect adversarially perturbed samples on ImageNet. Simultaneously, it achieves comparable performance to unseen label detection methods on two challenging benchmarks: ImageNet-O and iNaturalist. CADet is fully self-supervised and requires neither labels for in-distribution samples nor access to OOD examples.
Dynamic-FACT: A Dynamic Framework for Adaptive Context-Aware Translation

“Document-level neural machine translation (NMT) has garnered considerable attention sincethe emergence of various context-aware NMT models. However, these static NMT models aretrained on fixed parallel datasets, thus lacking awareness of the target document during infer-ence. In order to alleviate this limitation, we propose a dynamic adapter-translator frameworkfor context-aware NMT, which adapts the trained NMT model to the input document prior totranslation. Specifically, the document adapter reconstructs the scrambled portion of the originaldocument from a deliberately corrupted version, thereby reducing the performance disparity be-tween training and inference. To achieve this, we employ an adaptation process in both the train-ing and inference stages. Our experimental results on document-level translation benchmarksdemonstrate significant enhancements in translation performance, underscoring the necessity ofdynamic adaptation for context-aware translation and the efficacy of our methodologies.Introduction”