Miracle-dz/UniFAR-FTUs huggingface dataset:
Fiber type-specific hypertrophy and increased capillarization in skeletal muscle following testosterone administration of young women.

It is well established that testosterone administration induces muscle fiber hypertrophy and myonuclear addition in men, however, it remains to be determined whether similar morphological adaptations can be achieved in women. The aim of the present study was therefore to investigate whether exogenously administered testosterone alters muscle fiber morphology in skeletal muscle of young healthy, physically active women. Thirty-five young (20-35 years), recreationally trained women were randomly assigned to either 10-week testosterone administration (10 mg daily) or placebo. Before and after the intervention, hormone concentrations and body composition were assessed, and muscle biopsies were obtained from the vastus lateralis. Fiber type composition, fiber size, satellite cell- and myonuclei content, as well as muscle capillarization were assessed in a fiber type-specific manner using immunohistochemistry. Following the intervention, testosterone administration elevated serum testosterone concentration (5.1-fold increase, P=0.001), and induced significant accretion of total lean mass (+1.9%, P=0.002) and leg lean mass (+2.4%, P=0.001). On the muscle fiber level, testosterone increased mixed fiber cross-sectional area (+8.2%, P=0.001), an effect primarily driven by increases in type II fiber size (9.2%, P=0.006). Whereas myonuclei content remained unchanged, a numerical increase (+30.8%) was found for satellite cells associated with type II fibers in the Testosterone group. In parallel with fiber hypertrophy, testosterone significantly increased capillary contacts (+7.5%, P=0.015) and capillary-to-fiber ratio (+9.2%, P=0.001) in type II muscle fibers. The current study provides novel insight into fiber type-specific adaptations present already after 10 weeks of only moderately elevated testosterone levels in women.
Addiction Severity Index (ASI) Findings: Implications for Counseling South Texas Homeless Persons

The Addiction Severity Index (ASI) was administered to 214 homeless persons who received counseling and counseling-related services from a large community counseling agency located in a major metropolitan area of approximately 1.4 million persons. Data analysis methods included descriptive statistics and multidimensional chi-square tests. Findings and counseling implications specific to medical status, employment status, drug and alcohol problems, legal status, family and social relationships, and child abuse experiences are reported.
Knowledge, attitude and prevalence of hepatitis B virus among healthcare workers: a cross-sectional, hospital-based study in Bamenda Health District, NWR, Cameroon

Introduction Hepatitis B virus (HBV) is a bloodborne virus which can be transmitted via percutaneous and mucocutaneous exposure to infected body fluid. Healthcare workers (HCWs) who are continuously exposed to different body fluids are at an increased risk of contracting and transmitting this virus. It is thus important to evaluate the knowledge and attitude of HCWs towards HBV and the prevalence of HBV infection among them. Methods This cross-sectional study was carried out between April and September 2017. Overall, 398 HCWs were recruited for this study. Knowledge on the route of HBV transmission and attitude towards HBV were evaluated using a well-structured questionnaire. Hepatitis B surface antigen (HBsAg) positivity was obtained using the Monolisa HBsAg ULTRA kit (Bio-Rad). Data were analysed using SPSS V.20. Results Among the HCWs who participated in this study, 338 (84.9%) had heard of HBV, and 269 (67.6%) of them had adequate knowledge on the route of HBV transmission. Medical doctors were the most knowledgeable among biomedical workers and students (76.5%). The rate of stigma was highest among nurses (87, 38.8%). The prevalence of HBsAg positivity was high (42, 10.6%) given that there is an efficient and available vaccine. Overall, over 70% of HCWs invited to participate in this study responded. Conclusion Knowledge on the route of HBV transmission was fair, and the level of stigmatisation of HBV-infected patients and the prevalence of HBV infection were high in this study. A sensitisation campaign should be carried out to educate HCWs on HBV, thus reducing the level of stigma associated with HBV as well as the probability of contracting HBV as a nosocomial infection.
Antibiotic Treatment Failure and Associated Outcomes Among Adult Patients With Community-Acquired Pneumonia in the Outpatient Setting: A Real-world US Insurance Claims Database Study

Abstract Background Antibiotic treatment failure is common among patients with community-acquired pneumonia (CAP) who are managed in the outpatient setting and is associated with higher mortality and increased health care costs. This study’s objectives were to quantify the occurrence of antibiotic treatment failure (ATF) and to evaluate clinical and economic outcomes between CAP patients who experienced ATF relative to those who did not. Methods Retrospective analysis of the MarketScan Commercial & Medicare Supplemental Databases was performed, identifying patients ≥18 years old, with a pneumonia diagnosis in the outpatient setting, and who received a fluoroquinolone, macrolides, beta-lactam, or tetracycline. ATF was defined as any of the following events within 30 days of initial antibiotic: antibiotic refill, antibiotic switch, emergency room visit, or hospitalization. Outcomes included 30-day all-cause mortality and CAP-related health care costs. Results During the study period, 251 947 unique patients met inclusion criteria. The mean age was 52.2 years, and 47.7% were male. The majority of patients received a fluoroquinolone (44.4%) or macrolide (43.6%). Overall, 22.1% were classified as ATFs. Among 18–64-year-old patients, 21.2% experienced treatment failure, compared with 25.7% in those >65 years old. All-cause mortality was greater in the antibiotic failure group relative to the non–antibiotic failure group (18.1% vs 4.6%, respectively), and the differences in 30-day mortality between antibiotic failure groups increased as a function of age. Mean 30-day CAP-related health care costs were also higher in the patients who experienced treatment failure relative to those who did not ($2140 vs $54, respectively). Conclusions Treatment failure and poor outcomes from outpatient CAP are common with current guideline-concordant CAP therapies. Improvements in clinical management programs and therapeutic options are needed.
Compound Kushen injection combined with platinum-based chemotherapy for stage III/IV non-small cell lung cancer: A meta-analysis of 37 RCTs following the PRISMA guidelines

Objective: Compound Kushen injection (CKI), one of the commonly used antitumor Chinese patent medicines, has been widely prescribed as adjunctive treatment to platinum-based chemotherapy (PBC) in patients with advanced non-small cell lung cancer (NSCLC). However, the efficacy and safety of this combination therapy for advanced NSCLC remain controversial. The objective of this study is to evaluate the effects of CKI combined with PBC on patients with stage III/IV non-small cell lung cancer. Methods: A systematic review and meta-analysis were performed following the PRISMA (Preferred Reported Items for Systematic Review and Meta-analysis) guidelines. All randomized controlled trials (RCTs) comparing CKI in combination with PBC versus PBC alone were retrieved and assessed for inclusion. Analyses were performed using Review Manager 5.3 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014), Comprehensive Meta-Analysis 3.0 (Biostat, Englewood, NJ, United States; 2016) and Trial Sequential Analysis software (TSA) (Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen, Denmark; 2011). The disease control rate (DCR) was regarded as the primary outcome, and the objective response rate (ORR), quality of life (QOL), survival rate, and toxicities were the secondary outcomes. Results: Thirty-seven trials, recruiting 3,272 patients with stage III/IV NSCLC, were included. The results showed that, CKI combined with PBC resulted in significant improvements in DCR (RR = 1.11, 95% CI 1.07 to 1.15, P < 0.00001), ORR (RR = 1.30, 95% CI 1.20 to 1.40, P < 0.00001), QOL (RR = 1.73, 95% CI 1.55 to 1.92, P < 0.00001), 1-year survival rate (RR = 1.51, 95% CI 1.18 to 1.94, P = 0.001), and a 58% decline in the incidence of severe toxicities (RR = 0.42, 95% CI 0.37 to 0.49, P < 0.00001). Conclusions: From the available evidence, our data indicate that CKI plus platinum-based chemotherapy is more effective in improving clinical efficacy and alleviating the toxicity of chemotherapy than platinum-based chemotherapy alone in the treatment of stage III/IV NSCLC. However, considering the intrinsic limitations of the included trials, high-quality RCTs with survival outcomes are still needed to further confirm our findings.
Overexpression of Semaphorin 3A is a Marker Associated with Poor Prognosis in Patients with Nasopharyngeal Carcinoma

Semaphorins were discovered as guidance signals that mediate neural development. Recent studies suggest that semaphorin 3A (Sema3A), a member of the semaphorin family, is involved in the development of several cancers. This study aimed to analyze the association of Sema3A with the clinical features of nasopharyngeal carcinoma (NPC), an Epstein–Barr virus-associated carcinoma, and the Epstein–Barr virus primary oncogene latent membrane protein 1 (LMP1). The expression of Sema3A and LMP1 was immunohistochemically examined in the 35 NPC specimens. The mean expression scores for Sema3A and LMP1 were 20.8% ± 14.5% and 13.9% ± 14.8%, respectively. The expression of Sema3A significantly correlated with that of LMP1 (r = 0.41, p = 0.014). In addition, the Sema3A high cohort showed significantly poorer prognosis than the Sema3A low cohort. Sema3A expression was higher in the LMP1-positive KH-1 and KR-4 cell lines compared to the LMP1-negative HeLa cells. Overexpression of LMP1 in the LMP1-negative AdAH cell line upregulated Sema3A expression, both at the transcriptional and translational level. Finally, Sema3A expression was associated with poor prognosis in patients with NPC. Our data suggest that LMP1 induces the expression of Sema3A, which may promote tumor progression in NPC.
Transient glacial incision in the Patagonian Andes from ~6 Ma to present

Early glaciations in the Patagonian Andes show that fast initial glacial erosion is transient and is not a steady condition. We report a mountain-scale record of erosion rates in the central Patagonian Andes from >10 million years (Ma) ago to present, which covers the transition from a fluvial to alpine glaciated landscape. Apatite (U-Th)/He ages of 72 granitic cobbles from alpine glacial deposits show slow erosion before ~6 Ma ago, followed by a two- to threefold increase in the spatially averaged erosion rate of the source region after the onset of alpine glaciations and a 15-fold increase in the top 25% of the distribution. This transition is followed by a pronounced decrease in erosion rates over the past ~3 Ma. We ascribe the pulse of fast erosion to local deepening and widening of valleys, which are characteristic features of alpine glaciated landscapes. The subsequent decline in local erosion rates may represent a return toward a balance between rock uplift and erosion.
Healthy Water-Based Tourism Experiences: Their Contribution to Quality of Life, Satisfaction and Loyalty

The scientific literature on tourism identifies two driving trends: the quest for experientiality and the growing connection between holidays and quality of life. The present research focuses on water-based activities practiced with a healthy purpose, capable of driving positive economic, social and environmental effects on the territory where this type of tourism is developed. Considering the growing demand of experiential tourism, it is important to assess the experiential value of these practices and their impact on the quality of life, satisfaction and loyalty. A sample of 184 customers of thermal spas and similar establishments was used to test the structural model proposed, employing the partial least squares technique. The results show the experiential value of healthy water-based activities and confirm their positive impact on the individuals’ quality of life, satisfaction and loyalty towards both the experience and the destination.
O-GlcNAcylation regulates the methionine cycle to promote pluripotency of stem cells

Significance The ability of embryonic stem cells to proliferate and differentiate is influenced by a number of factors. Among them, the metabolism of methionine, an essential amino acid, is considered highly important. However, the detailed regulatory mechanism of methionine metabolism and how the metabolism influences the stem cell fate still remain poorly understood. In this study, we identified AHCY, an important enzyme involved in the methionine metabolism, as a key player in the maintenance of stem cell identity. AHCY is dynamically modified by a single sugar N-acetylglucosamine, which responds to environmental cues to regulate its activity, and further influences stem cell proliferation and differentiation. Our finding expands our current understanding of the role of glycosylation in controlling cell fate decisions. Methionine metabolism is critical for the maintenance of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) pluripotency. However, little is known about the regulation of the methionine cycle to sustain ESC pluripotency. Here, we show that adenosylhomocysteinase (AHCY), an important enzyme in the methionine cycle, is critical for the maintenance and differentiation of mouse embryonic stem cells (mESCs). We show that mESCs exhibit high levels of methionine metabolism, whereas decreasing methionine metabolism via depletion of AHCY promotes mESCs to differentiate into the three germ layers. AHCY is posttranslationally modified with an O-linked β-N-acetylglucosamine sugar (O-GlcNAcylation), which is rapidly removed upon differentiation. O-GlcNAcylation of threonine 136 on AHCY increases its activity and is important for the maintenance of trimethylation of histone H3 lysine 4 (H3K4me3) to sustain mESC pluripotency. Blocking glycosylation of AHCY decreases the ratio of S-adenosylmethionine versus S-adenosylhomocysteine (SAM/SAH), reduces the level of H3K4me3, and poises mESC for differentiation. In addition, blocking glycosylation of AHCY reduces somatic cell reprogramming. Thus, our findings reveal a critical role of AHCY and a mechanistic understanding of O-glycosylation in regulating ESC pluripotency and differentiation.
Nurse Practitioners’ Knowledge of Prevention Guidelines and Counseling Practices Related to Primary Prevention of Skin Cancer Among Adolescents in Arizona

ABSTRACT Skin cancer is the most common cancer worldwide and one of the most preventable. Skin cancer incidence continues to rise among adolescents. The inconsistent practice guidelines for skin cancer prevention create challenges for counseling. The purposes of this study were to investigate skin cancer knowledge, attitudes, and primary prevention counseling practices by Arizona nurse practitioners caring for adolescents on an outpatient basis and to determine congruency of counseling with evidence-based guidelines. Participants completed a quantitative, descriptive, cross-sectional study using an online survey. The main variables were knowledge of skin cancer, skin cancer prevention, attitudes regarding counseling, current practice guideline use, and recommendations. Of the 67 participants who responded to the survey, 51 were eligible, and 44 completed the survey. Participant knowledge regarding skin cancer was moderate to low, and less was known about skin cancer in adolescents. Despite positive attitudes toward skin cancer prevention, participants reported low rates of counseling in practice, similar to previous interdisciplinary research. Reported recommendations used in practice were not reflective of any one particular guideline. Future research should explore barriers to incorporating primary prevention counseling practices and aim to educate nurse practitioners on skin cancer prevention.
Evaluation of elevated heart rate as a sympathetic nervous system biomarker in essential hypertension.

BACKGROUND There is a need for an easily accessible biomarker of sympathetic nervous activation in essential hypertension, but none exists. Heart rate (HR) has been suggested, but requires validation, now doubly important as an elevated HR in hypertension has emerged as an independent cardiovascular risk factor. METHODS Isotope dilution methodology was used to measure total and regional noradrenaline spillover and adrenaline secretion rates in 30 patients with unmedicated essential hypertension and in a comparator group of 48 healthy participants with normal blood pressure. The particular interest was in the relationship of measured HR to cardiac noradrenaline spillover, the measure of cardiac sympathetic activity. RESULTS Sympathetic activation was present in the patients with essential hypertension, evident in significantly increased mean cardiac, renal and total noradrenaline spillover rates. Adrenaline secretion was normal. HR in hypertension correlated directly with cardiac noradrenaline spillover (r = 0.82, P = 9.3 × 10), but not with renal noradrenaline spillover or adrenaline secretion. 67% of the variance in HR was attributable to differences in cardiac sympathetic activity. Among hypertensive patients there was no internal correlation between cardiac noradrenaline spillover, renal noradrenaline spillover and adrenaline secretion; the sympathetic activation commonly was not 'global'. In healthy participants HR did not correlate with measures of sympathetic activity or adrenaline secretion. CONCLUSION When sympathetic activation exists in essential hypertension it is differentiated, not necessarily involving all sympathetic outflows. An elevated HR proved to be a biomarker of cardiac sympathetic activation but not activation of the renal sympathetic outflow. Identifying activation of the cardiac sympathetic outflow as the prime mechanism of hypertension tachycardia is relevant to therapies which should now be considered to minimize cardiovascular risk in this clinical setting. Is an elevated HR a valid biomarker of sympathetic activation in essential hypertension? Yes, but only for the cardiac sympathetic outflow. The unavoidable principle is that regional differentiation of sympathetic responses in essential hypertension means that no simple test can ever represent each and every sympathetic outflow.
Resting State BOLD Variability of the Posterior Medial Temporal Lobe Correlates with Cognitive Performance in Older Adults with and without Risk for Cognitive Decline

Abstract Local brain signal variability [SD of the BOLD signal (SDBOLD]] correlates with age and cognitive performance, and recently differentiated Alzheimer’s disease (AD) patients from healthy controls. However, it is unknown whether changes to SDBOLD precede diagnosis of AD or mild cognitive impairment. We compared ostensibly healthy older adult humans who scored below the recommended threshold on the Montreal cognitive assessment (MoCA) and who showed reduced medial temporal lobe (MTL) volume in a previous study (“at-risk” group, n = 20), with healthy older adults who scored within the normal range on the MoCA (“control” group, n = 20). Using multivariate partial least-squares analysis we assessed the correlations between SDBOLD and age, MoCA score, global fractional anisotropy, global mean diffusivity, and four cognitive factors. Greater SDBOLD in the MTL and occipital cortex positively correlated with performance on cognitive control/speed tasks but negatively correlated with memory scores in the control group. These relations were weaker in the at-risk group. A post hoc analysis assessed associations between MTL volumes and SDBOLD in both groups. This revealed a negative correlation, most robust in the at-risk group, between MTL SDBOLD and MTL subregion volumetry, particularly the entorhinal and parahippocampal regions. Together, these results suggest that the association between SDBOLD and cognition differs between the at-risk and control groups, which may be because of lower MTL volumes in the at-risk group. Our data indicate relations between MTL SDBOLD and cognition may be helpful in understanding brain differences in individuals who may be at risk for further cognitive decline.
Coronavirus disease 2019 (COVID-19) outbreak in Iran: Actions and problems

1. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020;395:507–513. 2. Zou L, Ruan F, Huang M, et al. SARS-CoV-2 viral load in upper respiratory specimens of infected patients. N Engl J Med 2020;382:1177–11793. 3. Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia inWuhan, China. JAMA 2020;323:1061–1069. 4. HolshueML, DeBolt C, Lindquist S, et al. First case of 2019 novel coronavirus in the United States. N Engl J Med 2020;382:929–936.
Comparative Study of Transcriptomics-Based Scoring Metrics for the Epithelial-Hybrid-Mesenchymal Spectrum

The Epithelial-mesenchymal transition (EMT) is a cellular process implicated in embryonic development, wound healing, and pathological conditions such as cancer metastasis and fibrosis. Cancer cells undergoing EMT exhibit enhanced aggressive behavior characterized by drug resistance, tumor-initiation potential, and the ability to evade immune system. Recent in silico, in vitro, and in vivo evidence indicates that EMT is not an all-or-none process; instead, cells stably acquire one or more hybrid epithelial/mesenchymal (E/M) phenotypes which often can be more aggressive than purely epithelial or mesenchymal cell populations. Thus, the EMT status of cancer cells can prove to be a critical estimate of patient prognosis. Recent attempts have employed different transcriptomics signatures to quantify EMT status in cell lines and patient tumors. However, a comprehensive comparison of these methods, including their accuracy in identifying cells in the hybrid E/M phenotype(s), is lacking. Here, we compare three distinct metrics that score EMT on a continuum, based on the transcriptomics signature of individual samples. Our results demonstrate that these methods exhibit good concordance among themselves in quantifying the extent of EMT in a given sample. Moreover, scoring EMT using any of the three methods discerned that cells undergo varying extents of EMT across tumor types. Separately, our analysis also identified tumor types with maximum variability in terms of EMT and associated an enrichment of hybrid E/M signatures in these samples. Moreover, we also found that the multinomial logistic regression (MLR) based metric was capable of distinguishing between ‘pure’ individual hybrid E/M vs. mixtures of epithelial (E) and mesenchymal (M) cells. Our results, thus, suggest that while any of the three methods can indicate a generic trend in the EMT status of a given cell, the MLR method has two additional advantages: a) it uses a small number of predictors to calculate the EMT score, and b) it can predict from the transcriptomic signature of a population whether it is comprised of ‘pure’ hybrid E/M cells at the single-cell level or is instead an ensemble of E and M cell subpopulations.