Miracle-dz/UniFAR-FTUs huggingface dataset:
Hospital use in survivors of transient ischaemic attack compared with survivors of stroke in central China: a nested case–control study

Objectives There is a lack of knowledge regarding post-discharge hospitalisation utilisation after transient ischaemic attack (TIA) in China. The aim of this study is to quantify rehospitalisation use in survivors of TIA compared with their own previous hospital use and matched survivors of stroke. Design Nested case–control study of electronic medical records datasets. Setting 958 hospitals in Henan, China, from July 2012 to December 2015. Participants In total, 4823 survivors of stroke were matched to the TIA cohort (average age: 64.5 years; proportion of men: 48.4%) at a 1:1 ratio. All subjects with an onset of stroke/TIA were recorded with a 1-year look-back and follow-up. Outcome measures Adjusted difference-in-differences (DID) values in 1-year hospital lengths of stay (LOSs) and readmission within 7, 30 and 90 days. Results There was an increase in hospital admissions in survivors of TIA in the year after the index hospitalisation compared with the prior year. Of the 2449 rehospitalisation events that occurred during the first year after TIA, stroke (20.6%) was the most common reason for rehospitalisation. There was no difference in the stroke-specific readmission rates between the TIA and stroke cohorts (p=0.198). The TIA cohort had fewer readmissions within 30 days and 90 days after all-cause discharge compared with the controls. The corresponding covariate-adjusted DID values were −3.5 percentage points (95% CI −5.3 to −1.8) and −4.5 (95% CI −6.5 to −2.4), respectively. A similar trend was observed in the 1-year LOS. In the stratified analysis, the DID reductions were not significant in patients with more comorbidities or in rural patients. Conclusions Compared with survivors of stroke, survivors of TIA use fewer hospital resources up to 1 year post-discharge. Greater attention to TIAs among patients with more comorbidities and rural patients may provide an opportunity to reduce hospital use.
31° South: The physiology of adaptation to arid conditions in a passerine bird

Arid environments provide ideal ground for investigating the mechanisms of adaptive evolution. High temperatures and low water availability are relentless stressors for many endotherms, including birds; yet birds persist in deserts. While physiological adaptation probably involves metabolic phenotypes, the underlying mechanisms (plasticity, genetics) are largely uncharacterized. To explore this, we took an intraspecific approach that focused on a species that is resident over a mesic to arid gradient, the Karoo scrub‐robin (Cercotrichas coryphaeus). Specifically, we integrated environmental (climatic and primary productivity), physiological (metabolic rates: a measure of energy expenditure), genotypic (genetic variation underlying the machinery of energy production) and microbiome (involved in processing food from where energy is retrieved) data, to infer the mechanism of physiological adaptation. We that found the variation in energetic physiology phenotypes and gut microbiome composition are associated with environmental features as well as with variation in genes underlying energy metabolic pathways. Specifically, we identified a small list of candidate adaptive genes, some of them with known ties to relevant physiology phenotypes. Together our results suggest that selective pressures on energetic physiology mediated by genes related to energy homeostasis and possibly microbiota composition may facilitate adaptation to local conditions and provide an explanation to the high avian intraspecific divergence observed in harsh environments.
Psychometric properties and factor structure of an Ecuadorian version of the Alcohol Use Disorders Identification Test (AUDIT) in college students

Background The Alcohol Use Disorders Identification Test (AUDIT) is the gold standard in assessing harmful alcohol intake, which is responsible for substantial morbidity and mortality. Objective The goal of this study is to evaluate the psychometric properties and factor structure of an Ecuadorian adaptation of a Spanish translation of the AUDIT in a large sample of college students in Ecuador. Methods A total of 7905 students, including 46.26% males, and 53.75% females, from 11 universities in Ecuador, were surveyed. The questionnaire was tested for two- and three-factor structures, reliability, and correlations with other health related measures. Results The Kaiser-Meyer-Olkin test for sampling adequacy was satisfactory (.0885), and Bartlett´s test for sphericity was significant (p < .001). Although both models showed a good fit to the data, the two-factor model was preferred based on the high correlations between the factors 2 and 3 within the three-factor model (.86 for the total sample, .77 for females, and .91 for males). The reliability for the two-factor model was good, as indicated by Cronbach´s α = . 806 (factor I) and . 716 (factor II) for the total sample, . 808 (factor I) and . 667 (factor II) for females, and . 787 (factor I) and . 728 (factor II) for males. Additionally, the AUDIT scores positively correlated with several health-related measures: stress, psychological inflexibility, loneliness and depression/anxiety symptomatology. Conclusion The Ecuadorian adaptation of the Spanish version of the AUDIT has good reliability, and internal consistency and correlates with other health related measures, proving to be a reliable tool that can be used by researchers and clinicians to screen hazardous alcohol intake in college students.
Low seroprevalence rates of Zika virus in Kuala Lumpur, Malaysia.

BACKGROUND Zika virus (ZIKV) is believed to be endemic in Southeast Asia. However, there have been few Zika cases reported to date in Malaysia, which could be due to high pre-existing levels of population immunity. METHODS To determine Zika virus (ZIKV) seroprevalence in Kuala Lumpur, Malaysia, 1085 serum samples from 2012, 2014-2015 and 2017 were screened for anti-ZIKV antibodies using a ZIKV NS1 blockade-of-binding assay. Reactive samples were confirmed using neutralization assays against ZIKV and the four dengue virus (DENV) serotypes. A sample was possible ZIKV seropositive with a ZIKV 50% neutralization (NT50) titre ≥20. A sample was probable ZIKV seropositive if, in addition, all DENV NT50 titres were <20 or the ZIKV NT50 titre was >4-fold greater than the highest DENV NT50 titre. RESULTS We found low rates of possible ZIKV seropositivity (3.3% [95% confidence interval {CI} 2.4 to 4.6]) and probable ZIKV seropositivity (0.6% [95% CI 0.3 to 1.4]). Possible ZIKV seropositivity was independently associated with increasing age (odds ratio [OR] 1.04 [95% CI 1.02 to 1.06], p<0.0001) and male gender (OR 3.5 [95% CI 1.5 to 8.6], p=0.005). CONCLUSIONS The low ZIKV seroprevalence rate, a proxy for population immunity, does not explain the low incidence of Zika in dengue-hyperendemic Kuala Lumpur. Other factors, such as the possible protective effects of pre-existing flavivirus antibodies or reduced transmission by local mosquito vectors, should be explored. Kuala Lumpur is at high risk of a large-scale Zika epidemic.
Multiple Functional Domains of the Yeast l,3-β-Glucan Synthase Subunit Fks1p Revealed by Quantitative Phenotypic Analysis of Temperature-Sensitive Mutants

In the article byH.Okada,M.Abe,M.Asakawa-Minemura, A.Hirata,H.Qadota, K.Morishita, S.Ohnuki, S. Nogami, andY.Ohya (GENETICS 184: 1013–1024), entitled “Multiple Functional Domains of the Yeast l,3-b-Glucan Synthase Subunit Fks1p Revealed by Quantitative Phenotypic Analysis of Temperature-Sensitive Mutants,” on page 1017, in Table 3, four mutation points (V302N, T605I, M76IT, and I722V)were erroneously linked to strains fks1-1082, fks1-1093, and fks1-1163, respectively. These four mutation points were found to be incorrect after DNA resequencing performed by Anna Savchenko, Farzan Ghanegolmohammadi, and Yoshikazu Ohya. Table 3 has now been corrected, with the incorrect mutation point for fks1-1082, V302N, replaced with the correct mutation point, V302D. The two incorrect mutation points for fks1-1093, T605I andM76IT, have been replaced with the single mutation point, Y710H. The incorrect mutation point for fks1-1163, I722V, has been removed.
Application of confocal, SHG and atomic force microscopy for characterizing the structure of the most superficial layer of articular cartilage

The surface of articular cartilage plays a crucial role in attenuating and transmitting mechanical loads in synovial joints to facilitate painless locomotion. Disruption to the surface of articular cartilage causes changes to its frictional properties instigating the deterioration of the tissue. In this study, we physically peeled the most superficial layer, a transparent membrane of 20.0 ± 4.7 µm thick, from the central loading region of femoral condyles of sheep. The ultrastructure of this layer without interference from the underlying cartilage was independently investigated using confocal, second harmonic generation and atomic force microscopy. We found that the most superficial layer contains chondrocytes, densely packed collagen, coarse elastic fibres and a fine elastic network. The elastic fibres are most prevalent at the surface of the layer, where collagen and chondrocyte densities are lowest. At the interface of this most superficial layer with the underlying bulk cartilage, a dense fibrillar network exists, formed mainly by collagen fibrils and elastin microfibrils. By contrast, the interface of the underlying cartilage with the most superficial layer contains collagen fibrils, fine microfibrils and microfibrils distinctively laced on one side. The findings of this study will play an important role in understanding the mechanical function and wear resistance of articular cartilage, and in developing more promising tissue engineering techniques to treat cartilage defects and osteoarthritis.
A PARP1–BRG1–SIRT1 axis promotes HR repair by reducing nucleosome density at DNA damage sites

Abstract Creating access to DNA double-strand break (DSB) sites in the chromatin context is an essential step during the repair process, but much remains to be determined about its regulatory mechanisms. Here, using a novel reporter cassette for simultaneous detection of homologous recombination (HR) and nonhomologous end joining (NHEJ) at the same chromosomal site, we report that the efficiency of HR but not NHEJ negatively correlates with nucleosome density. We demonstrate that PARP1 is required for HR by modulating nucleosome density at damage sites. Mechanistic studies indicate that the ATPase domain of BRG1 and the ZnF domain of SIRT1 interact with poly-ADP ribose (PAR) in response to DNA damage, and are responsible for bringing the two factors to broken DNA ends. At DNA damage sites, BRG1 and SIRT1 physically interact, whereupon SIRT1 deacetylates BRG1 at lysine residues 1029 and 1033, stimulating its ATPase activity to remodel chromatin and promote HR.
Established PABPN1 intranuclear inclusions in OPMD muscle can be efficiently reversed by AAV-mediated knock-down and replacement of mutant expanded PABPN1.

Oculopharyngeal muscular dystrophy (OPMD) is a rare autosomal dominant late onset muscular dystrophy affecting approximately 1:100000 individuals in Europe. OPMD is mainly characterized by progressive eyelid drooping (ptosis) and dysphagia although muscles of the limbs can also be affected late in life. This muscle disease is due to a trinucleotide repeat expansion in the polyA binding protein nuclear-1 (PABPN1) gene. Patients express a protein with an 11-18 alanine tract that is misfolded and prone to form intranuclear inclusions (INIs) which are the hallmark of the disease. Other features of OPMD include muscle fibrosis and atrophy in affected muscles. Currently no pharmacological treatments are available and OPMD patients can only be referred to surgeons for cricopharyngeal myotomy or corrective surgery of extraocular muscles to ease ptosis. We recently tested a 2 AAV "silence" and "replace" vector-based gene therapy treatment in a mouse model of OPMD. We demonstrate here that this gene therapy approach can revert already established insoluble aggregates and partially rescues the muscle from atrophy, which are both crucially important since in most cases OPMD patients already have an established disease when diagnosed. This strategy also prevents the formation of muscle fibrosis and stabilizes the muscle strength to the level of healthy muscles. Furthermore, we show here that similar results can be obtained using a single AAV vector incorporating both the "silence" and "replace" cassettes. These results further support the application of a gene therapy approach as a novel treatment for OPMD in humans.
Identification of functionally important residues and structural features in a bacterial lignostilbene dioxygenase

Lignostilbene-α,β-dioxygenase A (LsdA) from the bacterium Sphingomonas paucimobilis TMY1009 is a nonheme iron oxygenase that catalyzes the cleavage of lignostilbene, a compound arising in lignin transformation, to two vanillin molecules. To examine LsdA's substrate specificity, we heterologously produced the dimeric enzyme with the help of chaperones. When tested on several substituted stilbenes, LsdA exhibited the greatest specificity for lignostilbene (kcatapp = 1.00 ± 0.04 × 106 m−1 s−1). These experiments further indicated that the substrate's 4-hydroxy moiety is required for catalysis and that this moiety cannot be replaced with a methoxy group. Phenylazophenol inhibited the LsdA-catalyzed cleavage of lignostilbene in a reversible, mixed fashion (Kic = 6 ± 1 μm, Kiu = 24 ± 4 μm). An X-ray crystal structure of LsdA at 2.3 Å resolution revealed a seven-bladed β-propeller fold with an iron cofactor coordinated by four histidines, in agreement with previous observations on related carotenoid cleavage oxygenases. We noted that residues at the dimer interface are also present in LsdB, another lignostilbene dioxygenase in S. paucimobilis TMY1009, rationalizing LsdA and LsdB homo- and heterodimerization in vivo. A structure of an LsdA·phenylazophenol complex identified Phe59, Tyr101, and Lys134 as contacting the 4-hydroxyphenyl moiety of the inhibitor. Phe59 and Tyr101 substitutions with His and Phe, respectively, reduced LsdA activity (kcatapp) ∼15- and 10-fold. The K134M variant did not detectably cleave lignostilbene, indicating that Lys134 plays a key catalytic role. This study expands our mechanistic understanding of LsdA and related stilbene-cleaving dioxygenases.
Unemployment among young people and mental health: A systematic review

Aim: The aim of this systematic review is to obtain a better understanding of the association between unemployment among young people and mental health. Methods: After screening the title and abstract of 794 articles drawn from four electronic databases, 52 articles remained for full-text reading. Of these, 20 studies met the inclusion criteria and were assessed on methodological quality. All steps were performed independently by two reviewers. Finally, a total of 17 articles were included in the systematic review. Results: Analysis of cross-sectional studies (N = 5) showed an association between unemployment among young people and mental health. An effect of unemployment on mental health was found when considering cohort studies (N = 12) that did not control for confounders (7/7). When controlling for confounders except mental health at baseline, this effect decreased in most studies leading to mixed results, although the majority (6/8) still found an effect. However, when taking mental health at baseline into account as one of the confounders, only a minority of studies (3/8) found a significant effect of unemployment on mental health. Conclusions: This systematic review showed an association between unemployment among young people and mental health. However, whether there is a causal relationship is less clear. More evidence from, for example, natural experiments and longitudinal studies that control for confounding variables, especially mental health at baseline, is required to better understand the association and potential causation between unemployment among young people and mental health.
Estrogen Regulates the Satellite Cell Compartment in Females

Skeletal muscle mass, strength, and regenerative capacity decline with age, with many measures showing greater deterioration in females about the time estrogen levels decrease at menopause. Here we show that maintenance of muscle stem cells, satellite cells, as well as self-renewal and differentiation into muscle fibers, are severely compromised by estrogen deficiency. Mechanistically, by hormone replacement, use of a selective estrogen-receptor modulator (bazedoxifene), and conditional estrogen receptor knockout, we implicate 17β-estradiol and satellite cell expression of estrogen receptor α (ERα) and show that estrogen signaling through this receptor is necessary to prevent apoptosis of satellite cells. Early data from a biopsy study of women who transitioned from peri-to post-menopause are consistent with the loss of satellite cells coincident with the decline in estradiol in humans. Together, these results demonstrate an important role for estrogen in satellite cell maintenance and muscle regeneration in females.
POU1F1 transcription factor promotes breast cancer metastasis via recruitment and polarization of macrophages

Cancer progression requires cells surrounding tumors be reeducated and activated to support tumor growth. Oncogenic signals from malignant cells directly influence stromal composition and activation, but the factors mediating this communication are still not well understood. We have previously shown that the transcription factor POU class 1 homeobox 1 (POU1F1), also known as Pit‐1, induces profound changes on neoplastic cell‐autonomous processes favoring metastasis in human breast cancer. Here we describe for the first time Pit‐1‐mediated paracrine actions on macrophages in the tumor microenvironment by using cell lines in vitro, zebrafish and mouse models in vivo, and samples from human breast cancer patients. Through the release of CXCL12, Pit‐1 in tumor cells was found to mediate the recruitment and polarization of macrophages into tumor‐associated macrophages (TAMs). In turn, TAMs collaborated with tumor cells to increase tumor growth, angiogenesis, extravasation and metastasis to lung. Our data reveal a new mechanism of cooperation between tumor cells and macrophages favoring metastasis and poor clinical outcome in human breast cancer, which suggests that Pit‐1 and CXCL12 should be further studied as potential prognostic and therapeutic indicators. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Effect of pulmonary rehabilitation with assistive use of short-acting β2 agonist in COPD patients using long-acting bronchodilators

ABSTRACT Background: Assistive use of short-acting β2 agonists (SABAs) reportedly improves exercise tolerance, activities of daily living, and health-related quality of life (HRQOL) in patients with chronic obstructive pulmonary disease (COPD). However, the effect of SABA on physical activity (PA) is unclear. Objective: This study aimed to determine whether assistive use of SABA increases PA and whether additional pulmonary rehabilitation (PR) can aid further improvement. Methods: Twelve outpatients with COPD and dyspnea during daily activities despite regular use of long-acting bronchodilators were enrolled. This study comprised a 2-week pre-intervention investigation, a 12-week investigation of SABA effects, and an 8-week investigation of the additional effects of PR. Assistive use of SABA was allowed up to 4 times per day after the pre-intervention period. PA was measured for 14 consecutive days using an accelerometer sensor. Dyspnea, exercise tolerance, and HRQOL were evaluated at entry, at 4 and 12 weeks after initiating SABA use, and after completing PR. Results: Assistive use of SABA improved breathlessness during daily activities and increased PA (p < .001). PA and HRQOL were also improved following PR (p < .001 and p = .013, respectively). Conclusions: Combined therapy of SABA and PR can increase PA and HRQOL in COPD patients.
Methyl and methylene vibrations response in amino acids of typical proteins in water solution under high-frequency electromagnetic field

ABSTRACT The aim of this paper was to study the response of methyl (CH3) and methylene (CH2) vibration bands in amino acids of some typical proteins diluted in bidistilled water solution after exposure to a high-frequency electromagnetic fields using Fourier Transform Infrared (FTIR) Spectroscopy. Hemoglobin in H2O solution and bovine serum albumin and myoglobin diluted in different D2O solutions were exposed for 4 h to a power density of 0.95 W/m2 at the frequency of 1750 MHz, emitted by operational mobile phones Nokia model 105 and Samsung model GT-E1270, in order to study the response of stretching vibrations of CH3 and CH2 that are in amino acids of those proteins. The main result was that CH3 stretching bands increased significantly in myoglobin in D2O solution because this protein is represented by a single protein chain so that the torque induced by the applied field is larger than that induced on the other two proteins. Otherwise, CH2 stretching vibrations decreased in intensity significantly for all exposed proteins. This result can be explained as well, assuming that, given a fixed volume, a decrease of population of CH2 occurred after exposure because of the alignment of proteins α-helices along the direction of the applied electromagnetic field.
Idiopathic Multicentric Castleman Disease with Autoimmune Hemolytic Anemia and Production of Anti-drug Antibody against Tocilizumab

Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder, and only a few cases have been reported to be complicated with autoimmune hemolytic anemia (AIHA). A 43-year-old man who presented with multiple swollen lymph nodes was diagnosed with iMCD. He was also diagnosed with AIHA based on laboratory findings, including the results of a bone marrow aspiration study. The patient was treated with tocilizumab; however, the effect was limited, probably due to anti-drug antibodies. Tocilizumab was therefore switched to rituximab, and his anemia was improved. Complication with AIHA should be carefully considered when iMCD patients present with severe anemia.
It feels real: physiological responses to a stressful virtual reality environment and its impact on working memory

Background: Virtual reality (VR) is increasingly used to study and treat psychiatric disorders. Its fidelity depends in part on the extent to which the VR environment provides a convincing simulation, for example whether a putatively stressful VR situation actually produces a stress response. Methods: We studied the stress response in 28 healthy men exposed either to a stressor VR elevator (which simulated travelling up the outside of a tall building and culminated in the participant being asked to step off the elevator platform), or to a control elevator. We measured psychological and physiological (salivary cortisol and alpha-amylase, blood pressure, pulse, skin conductance) stress indices. We also measured subsequent performance on the N-back task because acute stress has been reported to impact on working memory. Results: Compared to participants in the control elevator, those in the external elevator had increases in skin conductance, pulse and subjective stress and anxiety ratings, altered heart rate variability, and a delayed rise in cortisol. N-back performance was unaffected. Conclusions: A putatively stressful VR elevator produces a physiological as well as a psychological stress response, supporting its use in the investigation and treatment of stress-related disorders, and its potential value as an experimental laboratory stressor.