Miracle-dz/UniFAR-FTUs huggingface dataset:
The H-NS protein is involved in the biogenesis of flagella in Escherichia coli

The function of the flagellum-chemotaxis regulon requires the expression of many genes and is positively regulated by the cyclic AMP-catabolite activator protein (cAMP-CAP) complex. In this paper, we show that motile behavior was affected in Escherichia coli hns mutants. The loss of motility resulted from a complete lack of flagella. A decrease in the level of transcription of the flhD and fliA genes, which are both required for the synthesis of flagella, was observed in the presence of an hns mutation. Furthermore, the Fla- phenotype was not reversed to the wild type in the presence of a cfs mutation which renders the flagellum synthesis independent of the cAMP-CAP complex. These results suggest that the H-NS protein acts as a positive regulator of genes involved in the biogenesis of flagella by a mechanism independent of the cAMP-CAP pathway.
Alpha-actinin localization in the cleavage furrow during cytokinesis

We used antibodies against alpha-actinin and myosin labeled directly with contrasting fluorochromes to localize these contractile proteins simultaneously in dividing chick embryo cells. During mitosis anti- alpha-actinin stains diffusely the entire cytoplasm including the mitotic spindle, while in the same cells intense antimyosin staining delineates the spindle. During cytokinesis both antibodies stain the cleavage furrow intensely, and until the midbody forms the two staining patterns in the same cell are identical at the resolution of the light microscope. Thereafter the anti-alpha-actinin staining of the furrow remains strong, but the antimyosin staining diminishes. These observations suggest that alpha-actinin participates along with actin and myosin in the membrane movements associated with cytokinesis.
Human Trafficking in the United States: Citizen Empathy & Awareness

Trafficking in human beings, or modern slavery, provides billions of dollars in revenue for transnational criminal groups and results in suffering for millions of victims. This is an issue that has recently garnered national media attention, but there are only limited data on its scope and nature within the United States, and no known data are available on layperson knowledge of or attitudes towards trafficked people. The objective of this study was two-fold: to gauge the American public’s knowledge of human trafficking as a human rights violation and public health crisis and to gather insight into empathy and attributions towards foreign women forced into prostitution. The study used responses to vignettes to assess attitudes towards women involved in various forms of commercial sexual activity. The vignette portrayed a fictitious woman in prostitution (“Ana”) and had two independent variables: citizenship and consent. Ana was either foreign (Ukrainian) or domestic (American), and her engagement was either voluntary (sex work) or involuntary (sex trafficking). Participants were 223 volunteers recruited from OSU undergraduate psychology courses. Participants completed various self-report measures: the Interpersonal Reactivity Index (assessing trait empathy), the Belief in a Just World Questionnaire, the Attitudes toward Prostitution Scale, the Attitudes toward Rape Victims Scale, and the Illinois Rape Myth Acceptance Scale. Participants also completed a pilot survey designed to measure knowledge of human trafficking in the United States. As predicted, empathy was highest for trafficked women, regardless of citizenship status. Trafficked foreign women received the highest empathy overall, and American prostitutes received the least. Empathy for Ana was strongly associated with a personal desire to help her, a belief in the government’s responsibility to help her, and interpersonal empathy. People with less
Effective modified conservative tissue preserving protocol to treat stage I axillary hidradenitis suppurativa: a prospective cohort study of 627 patients with five years follow-up

Abstract Background: Hidradenitis suppurativa is a chronic inflammatory cutaneous disorder that involves the infundibular terminal follicles in areas rich in apocrine glands and associated with the formation of abscesses and fistulating sinus. The clinical course is variable, and definitive evidence-based guidelines for the management are not well-established. Conservative treatment is controversial, and surgical excision is the recommended method. Herein, we aim to analyze the results of a modified conservative tissue preserving management protocol for stage I axillary hidradenitis suppurativa. Methods: A prospective cohort study of the results of 627 patients who were diagnosed and treated for stage I axillary hidradenitis suppurativa between January 2001 and December 2010 was done. Three hundred and forty nine (55.7%) were females, and 278 (44.3%) were males. The modified conservative treatment protocol consisted of three times per day washing the affected area with antibacterial soap, application of warm compresses for 10 min, followed by application of topical sodium fusidate 2% ointment (fusidic acid), with abstinence of armpits shaving during the treatment period. Results: Four hundred and sixty one (73.5%) patients had complete healing within two weeks, 127 (20.3%) within three weeks, 39 (6.2%) within four weeks. The recurrence rate was 5.9% (37 patients) in which all patients were retreated conservatively and had complete healing, none required surgical intervention. Conclusions: We conclude that hidradenitis suppurativa continues to be a challenging disease for patients and physicians. Tissue preserving conservative method using the fusidic acid ointment for treating stage I axillary hidradenitis suppurativa showed a promising result. Further research should be conducted on the optimal treatment regimen.
Remodeling of chromatin structure within the promoter is important for bmp-2-induced fgfr3 expression

Fibroblast growth factor receptor 3 (FGFR3) plays an important role in cartilage development. Although upregulation of FGFR3 expression in response to bone morphogenetic protein-2 (BMP-2) has been reported, the molecular mechanisms remain unknown. In this study, we used in vivo approaches to characterize BMP-2-induced alterations in the chromatin organization of the FGFR3 core promoter. Chromatin immunoprecipitation analysis demonstrated that the binding of Brg1, a component of the SWI/SNF remodeling complex, may selectively remodel a chromatin region (encompassing nucleotide –90 to +35), uncovering the transcription start site and three Sp1-binding sites, as revealed by nuclease digestion hypersensitivity assays. We then showed an increase in the association of Sp1 with the proximal promoter, followed by the recruitment of p300, resulting in a change of the histone ‘code’, such as in phosphorylation and methylation. Collectively, our study results suggest a model for BMP-2-induced FGFR3 expression in which the core promoter architecture is specifically regulated.
Effects of Neutral and Fearful Mood on Duration Estimation of Neutral and Fearful Face Stimuli

Previous research showed that fearful faces produce longer temporal estimates than neutral faces. This study probed whether fearful mood enhances this effect. In two experiments, participants viewed neutral and threatening film excerpts and subsequently evaluated the duration of neutral and fearful faces in a bisection task. In Experiment 1, where neutral mood was induced before fearful mood, skin conductance levels (SCLs) and subjective emotion ratings indicated successful mood induction. Compared to neutral mood, fearful mood lengthened subjective duration estimates irrespective of stimulus quality. Additionally, stimuli of fearful faces were temporally overestimated relative to neutral faces; but only in neutral, not in fearful mood. In Experiment 2, where fearful mood was induced before neutral mood, subjective emotion ratings, but not SCLs, indicated successful mood induction. Moreover, neither mood nor facial expressions influenced duration estimation. Taken together, the results show that fearful mood may accelerate an internal pacemaker but does not enhance temporal perception differences between fearful and neutral faces. Additionally, this study highlights the importance of dissociating stimulus, state, and trait emotionality for our understanding of emotional influences on temporal perception.
Survival After Endovascular vs Open Aortic Aneurysm Repairs.

IMPORTANCE To our knowledge, long-term outcomes of open and endovascular (EVAR) repairs of abdominal aortic aneurysms (AAAs) have not been studied on a population level outside a controlled trial setting. OBJECTIVE To determine long-term outcomes of EVAR vs open repair on a population level. DESIGN, SETTING, AND PARTICIPANTS Analysis of the longitudinally linked California Office of Statewide Health Planning and Development inpatient database from 2001 to 2009. Median follow-up was 3.3 years. EXPOSURES Endovascular vs open repairs. MAIN OUTCOMES AND MEASURES Mortality and complications at 30 days, as well as long-term mortality and complications up to 9 years. RESULTS In this observational study, a total of 23 670 patients were studied, with 52% receiving EVAR. Endovascular repair was associated with improved 30-day outcomes (all-cause mortality, readmission, surgical site infection, pneumonia, and sepsis), as well as significantly improved survival until 3 years postoperatively. After 3 years, mortality was higher for patients who underwent an EVAR repair. No significant difference in long-term mortality was observed for the entire cohort on adjusted analysis (hazard ratio, 0.99; 95% CI, 0.94-1.04; P = .64). Endovascular repair was found to be associated with a significantly higher rate of reinterventions and AAA late ruptures. CONCLUSIONS AND RELEVANCE The survival advantage for EVAR repair in a statewide population is maintained for 3 years. After 3 years, EVAR repair was associated with higher mortality; however, these mortality differences did not reach statistical significance over the entire study period. Reintervention and late AAA rupture rates are higher after EVAR repair.
Postpartum blood loss: visual estimation versus objective quantification with a novel birthing drape.

INTRODUCTION Immediate postpartum haemorrhage (PPH) is the most common cause of maternal mortality worldwide. Most recommendations focus on its prevention and management. Visual estimation of blood loss is widely used for the early detection of PPH, but the most appropriate method remains unclear. This study aimed to compare the efficacy of visual estimation and objective measurement using a sterile under-buttock drape, to determine the volume of postpartum blood loss. METHODS This study evaluated patients aged ≥ 18 years with low-risk term pregnancies, who delivered vaginally. Immediately after delivery, a birth attendant inserted the drape under the patient's buttocks. Postpartum blood loss was measured by visual estimation and then compared with objective measurement using the drape. All participants received standard intra- and postpartum care. RESULTS In total, 286 patients with term pregnancies were enrolled. There was a significant difference in postpartum blood loss between visual estimation and objective measurement using the under-buttock drape (178.6 ± 133.1 mL vs. 259.0 ± 174.9 mL; p < 0.0001). Regarding accuracy at 100 mL discrete categories of postpartum blood loss, visual estimation was found to be inaccurate, resulting in underestimation, with low correspondence (27.6%) and poor agreement (Cohen's kappa coefficient 0.07; p < 0.05), compared with objective measurement using the drape. Two-thirds of cases of immediate PPH (65.4%) were misdiagnosed using visual estimation. CONCLUSION Visual estimation is not optimal for measurement of postpartum blood loss in PPH. This method should be withdrawn from standard obstetric practice and replaced with objective measurement using the sterile under-buttock drape.
Atomic resolution probe for allostery in the regulatory thin filament

Significance The cardiac thin filament (CTF) is a complex and highly dynamic multiprotein complex that regulates heart function at the molecular level. Mutations in proteins that comprise the thin filament cause cardiomyopathic remodeling that is due, in part, to dysregulation of Ca2+ binding. Many of the known mutations in multiple thin filament proteins occur at a significant physical distance from the Ca2+ binding domain; thus, the elucidation of molecular mechanisms has been challenging. We have developed and now apply an atomistic model of the CTF to this question and have obtained molecular insight that both provides disease mechanisms and facilitates future rational drug design. Finding the molecular cause of disease is the first step in designing molecular interventions. Calcium binding and dissociation within the cardiac thin filament (CTF) is a fundamental regulator of normal contraction and relaxation. Although the disruption of this complex, allosterically mediated process has long been implicated in human disease, the precise atomic-level mechanisms remain opaque, greatly hampering the development of novel targeted therapies. To address this question, we used a fully atomistic CTF model to test both Ca2+ binding strength and the energy required to remove Ca2+ from the N-lobe binding site in WT and mutant troponin complexes that have been linked to genetic cardiomyopathies. This computational approach is combined with measurements of in vitro Ca2+ dissociation rates in fully reconstituted WT and cardiac troponin T R92L and R92W thin filaments. These human disease mutations represent known substitutions at the same residue, reside at a significant distance from the calcium binding site in cardiac troponin C, and do not affect either the binding pocket affinity or EF-hand structure of the binding domain. Both have been shown to have significantly different effects on cardiac function in vivo. We now show that these mutations independently alter the interaction between the Ca2+ ion and cardiac troponin I subunit. This interaction is a previously unidentified mechanism, in which mutations in one protein of a complex indirectly affect a third via structural and dynamic changes in a second to yield a pathogenic change in thin filament function that results in mutation-specific disease states. We can now provide atom-level insight that is potentially highly actionable in drug design.
Effects of Sacubitril/Valsartan in the PARADIGM-HF Trial (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) According to Background Therapy

Background—In the PARADIGM-HF trial (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure), the angiotensin receptor neprilysin inhibitor sacubitril/valsartan was more effective than the angiotensin-converting enzyme inhibitor enalapril in patients with heart failure and reduced ejection fraction. We examined whether this benefit was consistent irrespective of background therapy. Methods and Results—We examined the effect of study treatment in the following subgroups: diuretics (yes/no), digitalis glycoside (yes/no), mineralocorticoid receptor antagonist (yes/no), and defibrillating device (implanted defibrillating device, yes/no). We also examined the effect of study drug according to &bgr;-blocker dose (≥50% and <50% of target dose) and according to whether patients had undergone previous coronary revascularization. We analyzed the primary composite end point of cardiovascular death or heart failure hospitalization, as well as cardiovascular death. Most randomized patients (n=8399) were treated with a diuretic (80%) and &bgr;-blocker (93%); 47% of those taking a &bgr;-blocker were treated with ≥50% of the recommended dose. In addition, 4671 (56%) were treated with a mineralocorticoid receptor antagonist, 2539 (30%) with digoxin, and 1243 (15%) had a defibrillating device; 2640 (31%) had undergone coronary revascularization. Overall, the sacubitril/valsartan versus enalapril hazard ratio for the primary composite end point was 0.80 (95% confidence interval, 0.73–0.87; P<0.001) and for cardiovascular death was 0.80 (0.71–0.89; P<0.001). The effect of sacubitril/valsartan was consistent across all subgroups examined. The hazard ratio for primary end point ranged from 0.74 to 0.85 and for cardiovascular death ranged from 0.75 to 0.89, with no treatment-by-subgroup interaction. Conclusions—The benefit of sacubitril/valsartan, over an angiotensin-converting enzyme inhibitor, was consistent regardless of background therapy and irrespective of previous coronary revascularization or &bgr;-blocker dose. Clinical Trial Registration—URL: http://www.clinicaltrials. gov. Unique identifier: NCT01035255.
Inter-observer agreement of standard joint counts in early rheumatoid arthritis: a comparison with grey scale ultrasonography--a preliminary study.

OBJECTIVES The aims of the present study were to assess the inter-observer agreement of standard joint count and to compare clinical examination with grey scale ultrasonography (US) findings in patients with early rheumatoid arthritis (RA). METHODS The study was conducted on 44 RA patients with a disease duration of <2 yrs. Clinical evaluation was performed independently by two rheumatologists for detection of tenderness in 44 joints and swelling in 42 joints. All patients underwent US assessment by a rheumatologist experienced in this method and blinded to the clinical findings. Joint inflammation was detected by US when synovial fluid and/or synovial hypertrophy was identified using OMERACT preliminary definitions. The inter-observer reliability was calculated by overall agreement (percentage of observed exact agreement) and kappa (kappa)-statistics. The reliability of US was calculated in 12 RA patients. RESULTS There was fair to moderate inter-observer agreement on individual joint counts for either tenderness or joint swelling apart from the glenohumeral joint. US detected a higher number of inflamed joints than did clinical examination. The mean (+/-S.D.) US joint count for joint inflammation was 19.1 (+/-4.1), while the mean (+/-S.D.) number of swollen joints was 12.6 (+/-3.6), with a significant difference of P = 0.01. CONCLUSIONS Our results provide evidence in favour of the hypothesis that clinical examination is far from optimal for assessing joint inflammation in patients with early RA. Furthermore, this study suggests that US can considerably improve the detection of signs of joint inflammation both in terms of sensitivity and reliability.
Identification of a Human Respiratory Syncytial Virus Cell Entry Inhibitor by Using a Novel Lentiviral Pseudotype System

ABSTRACT Lentiviral budding is governed by group-specific antigens (Gag proteins) and proceeds in the absence of cognate viral envelope proteins, which has been exploited to create pseudotypes incorporating envelope proteins from nonlentiviral families. Here, we report the generation of infectious lentiviral pseudoparticles incorporating human respiratory syncytial virus (hRSV) F protein alone (hRSV-Fpp) or carrying SH, G, and F proteins (hRSV-SH/G/Fpp). These particles recapitulate key infection steps of authentic hRSV particles, including utilization of glycosaminoglycans and low-pH-independent cell entry. Moreover, hRSV pseudoparticles (hRSVpp) can faithfully reproduce phenotypic resistance to a small-molecule fusion inhibitor in clinical development (BMS-433771) and a licensed therapeutic F protein-targeting antibody (palivizumab). Inoculation of several human cell lines from lung and liver revealed more than 30-fold differences in susceptibility to hRSVpp infection, suggesting differential expression of hRSV entry cofactors and/or restriction factors between these cell types. Moreover, we observed cell-type-dependent functional differences between hRSVpp carrying solely F protein or SH, G, and F proteins with regard to utilization of glycosaminoglycans. Using hRSVpp, we identified penta-O-galloyl-β-d-glucose (PGG) as a novel hRSV cell entry inhibitor. Moreover, we show that PGG also inhibits cell entry of hRSVpp carrying F proteins resistant to BMS-433771 or palivizumab. This work sheds new light on the mechanisms of hRSV cell entry, including possible strategies for antiviral intervention. Moreover, hRSVpp should prove valuable to dissect hRSV envelope protein functions, including the interaction with cell entry factors. IMPORTANCE Lentiviral pseudotypes are highly useful to specifically dissect the functions of viral and host factors in cell entry, which have been exploited for numerous viruses. Here, we successfully created hRSVpp and show that they faithfully recapitulate key characteristics of parental hRSV cell entry. Importantly, hRSVpp accurately mirror hRSV resistance to small-molecule fusion inhibitors and clinically approved therapeutic antibodies. Moreover, we observed highly different susceptibilities of cell lines to hRSVpp infection and also differences between hRSVpp types (with F protein alone or with SH, G, and F proteins) in regard to cell entry. This indicates differential expression of host factors determining hRSV cell entry between these cell lines and highlights the fact that the hRSVpp system is useful to explore the functional properties of hRSV envelope protein combinations. Therefore, this system will be highly useful to study hRSV cell entry and host factor usage and to explore antiviral strategies targeting hRSV cell entry.
Factors Accounting for Mathematics Achievement of Singaporean Eighth-Graders

This article explores the pattern of variation in mathematics achievement by Singaporean students. The data were obtained from 4,599 secondary school students who participated in the 2007 Trends in International Mathematics and Science Study (TIMSS). A three-level multilevel linear model was used, for which the results indicate that out of the total variance in mathematics achievement, 23.40%, 53.25%,and 23.34% accounted for student-, classroom-, and school-level differences, respectively. At the student level, mathematics self-concept, home educational resources, and attitude towards mathematics were the strongest predictors of achievement. Meanwhile, at the classroom level, teaching limitations, school climate as perceived by the teachers and teachers’ age were the most influential factors. At the same time, school climate as perceived by school principals and good attendance at school were the most influential factors at the school level.
Role of epicardial adipose tissue in atrial fibrillation.

besity is a major risk factor for cardiovascular disease, including atrial fibrillation (AF). However, the mechanisms for this association have not been well clarified. Recent studies suggest that obesity-related diseases may be mediated, at least in part, by regional adipose deposits.1 For example, expansion and inflammation of perivascular adipose tissue have been implicated not only in the development of endothelial dysfunction and atherosclerosis, but also in the pathogenesis of insulin resistance. Furthermore, several studies have shown that epicardial adipose tissue (EAT) is not only an anatomic depot of fat, but also may serve as a local source of proinflammatory cytokines related to coronary artery disease (CAD). 2 Although there are several studies reporting an association between EAT and CAD, the evidence concerning the association between EAT and arrhythmia is relatively limited.3,4