Miracle-dz/UniFAR-FTUs huggingface dataset:
Age-specific reference values improve the diagnostic performance of AMH in polycystic ovary syndrome

Abstract Background The increased secretion of anti-Müllerian hormone (AMH) by the growing follicles has been supposed as a determinative feature of polycystic ovary syndrome (PCOS). The diagnostic performance of AMH in PCOS is superior compared to the free androgen index (FAI) and luteinizing hormone (LH)/follicle-stimulating hormone (FSH) quotient. We established age-dependent reference ranges to further improve the diagnostic performance of AMH. Methods In a cross-sectional study, in samples of 4712 reproductive age patients, ranging from 14 to 50 years, BMI, AMH and other reproductive hormones were determined by immunoassay or tandem mass spectrometry (LC-MS/MS) to calculate age-specific reference ranges and the diagnostic performance. Results Age-specific diagnostic performances for Elecsys® AMH, FAI and LH/FSH ratio were established in the reference group. No significant difference in BMI was found between the groups. AMH values were significantly negatively correlated with age (r = −0.628, p < 0.001) in patients with normal ovarian function, but there was no correlation between age and AMH levels in PCOS patients (r = − 0.041, p < 0.174). In all the study groups, AMH showed a weak correlation between FAI and LH/FSH ratio (r = 0.302, p < 0.001 and r = 0.434, p < 0.001, respectively). The sensitivity/specificity for AMH, FAI and LH/FSH ratio were 89/96%, 71/69% and 75/72%, respectively, according to the Youden index. Conclusions We determined the age-dependent reference ranges for serum AMH levels in a large population-based study and calculated the age-specific diagnostic performance of FAI and LH/FSH ratio, which allows physicians to evaluate patients with PCOS who have normal AMH levels. AMH is suggested as the strongest diagnostic marker in patients with PCOS compared to FAI and LH/FSH ratio.
Cold Case Experiment Demonstrates the Potential Utility of Aquatic Microbial Community Assembly in Estimating a Postmortem Submersion Interval

Microbial community assembly (MCA) of both human and nonhuman animal carcasses provides indicators useful for estimating the postmortem interval (PMI) in terrestrial settings. However, there are fewer studies estimating postmortem submersion intervals (PMSIs) in aquatic habitats. No aquatic studies to date assessed MCA in the context of a death investigation, with all previous studies focusing on important basic ecological questions. Within the context of a cold case investigation, we performed an experiment using replicate adult swine carcasses to describe postmortem MCA variability within a nonflowing aquatic habitat. Using high‐throughput sequencing of carcass postmortem microbiomes, we described MCA variability and identified key taxa associated with decomposition in an aquatic habitat similar to the cold case body recovery site. We also modeled key taxa for estimating PMSIs, modeling within ±3 days (mean square error) postmortem using random forest regression. Our findings show significant changes in microbial communities as decomposition progressed, and several taxa were identified as important indicator taxa which may be useful for future estimates of PMSI. While descriptive, this study provides initial findings quantifying MCA variability within a nonflowing aquatic habitat. Within the context of the cold case investigation, we discuss how postmortem microbial samples collected at the time of body recovery could have been an important piece of evidence for understanding the PMSI of recovered remains. Additional experimental studies are needed to explicitly test and identify mechanisms associated with postmortem MCA variability in other habitats and under different temperature (e.g., seasons) conditions.
Morphological Phylogenetics Evaluated Using Novel Evolutionary Simulations

Abstract Evolutionary inferences require reliable phylogenies. Morphological data have traditionally been analyzed using maximum parsimony, but recent simulation studies have suggested that Bayesian analyses yield more accurate trees. This debate is ongoing, in part, because of ambiguity over modes of morphological evolution and a lack of appropriate models. Here, we investigate phylogenetic methods using two novel simulation models—one in which morphological characters evolve stochastically along lineages and another in which individuals undergo selection. Both models generate character data and lineage splitting simultaneously: the resulting trees are an emergent property, rather than a fixed parameter. Standard consensus methods for Bayesian searches (Mki) yield fewer incorrect nodes and quartets than the standard consensus trees recovered using equal weighting and implied weighting parsimony searches. Distances between the pool of derived trees (most parsimonious or posterior distribution) and the true trees—measured using Robinson-Foulds (RF), subtree prune and regraft (SPR), and tree bisection reconnection (TBR) metrics—demonstrate that this is related to the search strategy and consensus method of each technique. The amount and structure of homoplasy in character data differ between models. Morphological coherence, which has previously not been considered in this context, proves to be a more important factor for phylogenetic accuracy than homoplasy. Selection-based models exhibit relatively lower homoplasy, lower morphological coherence, and higher inaccuracy in inferred trees. Selection is a dominant driver of morphological evolution, but we demonstrate that it has a confounding effect on numerous character properties which are fundamental to phylogenetic inference. We suggest that the current debate should move beyond considerations of parsimony versus Bayesian, toward identifying modes of morphological evolution and using these to build models for probabilistic search methods. [Bayesian; evolution; morphology; parsimony; phylogenetics; selection; simulation. ]
The Influence of Pain Self-Management Education on the Prevalence of Opioid Prescription among Patients with Chronic Non-Cancer Pain: An Agent-Based Modeling Simulation

Chronic pain has no cure. It is a lifelong condition presenting a growing concern due to its high occurrence and effects on every facet of life. It cost about $635 billion each year in medical treatment and lost productivity (IOM, 2011). The management of chronic pain using prescription painkiller opioids has increased drastically in the last two decades, leading to a consequential increase in deaths from chronic opioid use. This Plan-Do-Study-Act quality improvement project investigates the problem of the prevalence of opioid prescription using agent-based computational modeling method. The simulation models the interaction of 50 patient-agents with pain self-management messages in an episode of 50 patient iterations (visits) for 10 simulated years. This interaction generates health benefit and risk outcomes represented by wellness data obtained when messages are processed. As the simulation runs, data are dynamically captured and visualized using wellness charts, time series plots, and benefit and risk regression plots. The result of the project provides evidence for research and practice on the process of achieving more impact of programs based on administering pain self-management education to patients with chronic non-cancer pain who are currently on opioid therapy and on the process of customizing interventions that might take advantage of the conditions of behavior change driven by pain self-management messages. The tools and the evidences in this project are highly recommended to nurse practitioners primary care providers involve with providing care to the vulnerable groups of patient with chronic non-cancer pain. These evidences might inform the formation of self-management interventions that might lead to a decline in opioid use and prescription and accelerate the acceptance of self-management practices.
Applying Educational Theory and Best Practices to Solve Common Challenges of Simulation‐based Procedural Training in Emergency Medicine

Procedural competency is an essential prerequisite for the independent practice of emergency medicine. Multiple studies demonstrate that simulation‐based procedural training (SBPT) is an effective method for acquiring and maintaining procedural competency and preferred over traditional paradigms (“see one, do one, teach one”). Although newer paradigms informing SBPT have emerged, educators often face circumstances that challenge and undermine their implementation. The goal of this paper is to identify and report on best practices and theory‐supported solutions to some of these challenges as derived using a process of expert consensus building and reviews of the existing literature on SBPT.
Colicin N Mediates Apoptosis and Suppresses Integrin-Modulated Survival in Human Lung Cancer Cells

The inherent limitations, including serious side-effects and drug resistance, of current chemotherapies necessitate the search for alternative treatments especially for lung cancer. Herein, the anticancer activity of colicin N, bacteria-produced antibiotic peptide, was investigated in various human lung cancer cells. After 24 h of treatment, colicin N at 5–15 µM selectively caused cytotoxicity detected by MTT assay in human lung cancer H460, H292 and H23 cells with no noticeable cell death in human dermal papilla DPCs cells. Flow cytometry analysis of annexin V-FITC/propidium iodide indicated that colicin N primarily induced apoptosis in human lung cancer cells. The activation of extrinsic apoptosis evidenced with the reduction of c-FLIP and caspase-8, as well as the modulation of intrinsic apoptosis signaling proteins including Bax and Mcl-1 were observed via Western blot analysis in lung cancer cells cultured with colicin N (10–15 µM) for 12 h. Moreover, 5–15 µM of colicin N down-regulated the expression of activated Akt (p-Akt) and its upstream survival molecules, integrin β1 and αV in human lung cancer cells. Taken together, colicin N exhibits selective anticancer activity associated with suppression of integrin-modulated survival which potentiate the development of a novel therapy with high safety profile for treatment of human lung cancer.
Cohort profile: the Maternal and Child Health and Nutrition in Acre, Brazil, birth cohort study (MINA-Brazil)

Purpose Maternal and Child Health and Nutrition in Acre, Brazil (MINA-Brazil) is a longitudinal, prospective population-based birth cohort, set-up to understand the effects of early environmental exposures and maternal lifestyle choices on growth and development of the Amazonian children. Participants Mother–baby pairs (n=1246) were enrolled at delivery from July 2015 to June 2016 in Cruzeiro do Sul, Acre, Brazil. Mothers of 43.7% of the cohort were recruited in the study during pregnancy from February 2015 to January 2016. Study visits took place during pregnancy, delivery, at 1 month, 6 months, 1 year and 2 years after delivery. In addition to clinical and epidemiological data, samples collected by the MINA-Brazil study include plasma, serum and extracted DNA from blood and faeces, which are stored in a biobank. Findings to date Key baseline reports found a high prevalence of gestational night blindness (11.5%; 95% CI 9.97% to 13.25%) and maternal anaemia (39.4%; 95% CI 36.84% to 41.95%) at delivery. Antenatal malaria episodes (74.6% of Plasmodium vivax) were diagnosed in 8.0% of the women and were associated with an average reduction in birth weight z-scores of 0.35 (95% CI 0.14 to 0.57) and in birth length z-scores of 0.31 (95% CI 0.08 to 0.54), compared with malaria-free pregnancies. At 2-year follow-up, data collection strategies combined telephone calls, WhatsApp, social media community and home visits to minimise losses of follow-up (retention rate of 79.5%). Future plans A 5-year follow-up visit is planned in 2021 with similar interviews and biospecimens collection. The findings from this prospective cohort will provide novel insights into the roles of prenatal and postnatal factors in determining early childhood development in an Amazonian population.
SWI/SNF chromatin remodeling complex and glucose metabolism are deregulated in advanced bladder cancer

Bladder cancer (BC) is a frequently diagnosed malignancy affecting predominantly adult and elderly populations. It is expected that due to the longer life time, BC will become even more frequent in the future; thus in consequence, it will represent serious health problem of older society part. The treatment of advanced BC is mostly ineffective due to its very aggressive behavior. So far, no effective targeted therapy is used for BC treatment. Here, we found that BC is characterized by lower protein levels of BRM, INI1, and BAF155 main subunits of SWI/SNF chromatin remodeling complex (CRC) which is involved in global control of gene expression and influences various important cellular processes like: cell cycle control, apoptosis, DNA repair, etc. Moreover, the expression of SMARCA2, a BRM encoding gene, strongly correlated with BC metastasis and expression of such metabolic genes as PKM2 and PRKAA1. Furthermore, the analysis of T24 and 5637 commonly used BC cell lines revealed different expression levels of metabolic genes including FBP1 gene encoding Frutose‐1,6‐Bisphosphatase, an enzyme controlling glycolysis flux and gluconeogenesis. The tested BC cell lines exhibited various molecular and metabolic alterations as well as differential glucose uptake, growth rate, and migration potential. We have shown that BRM subunit is involved in the transcriptional control of genes encoding metabolic enzymes. Moreover, we found that the FBP1 expression level and the SWI/SNF CRCs may serve as markers of molecular subtypes of BC. Collectively, this study may provide a new knowledge about the molecular and metabolic BC subtypes which likely will be of high importance for the clinic in the future.
Microbial and volatile profiling of soils suppressive to Fusarium culmorum of wheat

In disease-suppressive soils, microbiota protect plants from root infections. Bacterial members of this microbiota have been shown to produce specific molecules that mediate this phenotype. To date, however, studies have focused on individual suppressive soils and the degree of natural variability of soil suppressiveness remains unclear. Here, we screened a large collection of field soils for suppressiveness to Fusarium culmorum using wheat (Triticum aestivum) as a model host plant. A high variation of disease suppressiveness was observed, with 14% showing a clear suppressive phenotype. The microbiological basis of suppressiveness to F. culmorum was confirmed by gamma sterilization and soil transplantation. Amplicon sequencing revealed diverse bacterial taxonomic compositions and no specific taxa were found exclusively enriched in all suppressive soils. Nonetheless, co-occurrence network analysis revealed that two suppressive soils shared an overrepresented bacterial guild dominated by various Acidobacteria. In addition, our study revealed that volatile emission may contribute to suppression, but not for all suppressive soils. Our study raises new questions regarding the possible mechanistic variability of disease-suppressive phenotypes across physico-chemically different soils. Accordingly, we anticipate that larger-scale soil profiling, along with functional studies, will enable a deeper understanding of disease-suppressive microbiomes.
Liver transplant waitlist outcomes in alcoholic hepatitis compared with other liver diseases: An analysis of UNOS registry

There is growing interest in performing liver transplantation (LT) in patients with alcoholic hepatitis (AH) without a mandated abstinence period. The aim of this study is to investigate waitlist outcomes in AH patients compared to those with other liver diseases. Using data from the UNOS registry, adult patients listed for LT between 2009 and 2018 were evaluated. Waitlist outcomes were compared among liver diseases. A total of 64 646 patients were eligible, including 286 with AH, 16 871 with alcoholic cirrhosis (AC), 13 730 with hepatitis C (HCV), 10 315 with non‐alcoholic steatohepatitis (NASH), and 5841 with cholestatic liver disease (CLD). In comparison with AH patients, patients with HCV, NASH, and CLD had a significantly higher risk of waitlist mortality and a lower likelihood of recovery on the waitlist. These trends were more prominent in the waiting‐time period of 91‐365 days than in shorter periods. In intention‐to‐treat analysis, positive prognostic effect of LT was significant in AH patients with MELD score ≥35 (HR 0.04, P < .001). AH patients showed lower mortality risk and a higher chance of recovery while on waitlist than other liver diseases, especially when waiting time exceeded 90 days. These results indicate the importance of continuous evaluation of disease progression in AH patients awaiting LT.
Associations Among Emotional State, Sleep Quality, and Resting-State EEG Spectra: A Longitudinal Study in Graduate Students

University students are routinely influenced by a variety of natural stressors and experience irregular sleep-wake cycles caused by the necessity to trade sleep for studying while dealing with academic assignments. Often these factors result in long-term issues with daytime sleepiness, emotional instability, and mental exhaustion, which may lead to difficulties in the educational process. This study introduces the Daily Sampling System (DSS) implemented as a smartphone application, which combines a set of self-assessment scales for evaluating variations in the emotional state and sleep quality throughout a full academic term. In addition to submitting the daily sampling scores, the participants regularly filled in the Depression, Anxiety, and Stress Scales (DASS) reports and took part in resting-state EEG data recording immediately after report completion. In total, this study collected 1835 daily samples and 94 combined DASS with EEG datasets from 18 university students (aged 23–27 years), with 79.3± 15.3% response ratio in submitting the daily reports during an academic semester. The results of pairwise testing and multiple regression analysis demonstrate that the daily level of self-perceived fatigue correlates positively with stress, daytime sleepiness, and negatively with alertness on awakening, self-evaluated sleep quality, and sleep duration. The spectral analysis of the EEG data reveals a significant increase in the resting-state spectral power density across the theta and low-alpha frequency bands associated with increased levels of anxiety and stress. Additionally, the state of depression was accompanied by an intensification of high-frequency EEG activity over the temporal regions. No significant differences in prefrontal alpha power asymmetry were observed under the described experimental conditions while comparing the states of calmness and emotional arousal of the participants for the three conditions of depression, anxiety, and stress.
Dental health among 15 year old children from Strumica city in South-Eastern part of Republic of Macedonia

Aim: The aim of this study was to assess dental caries in 15-year-old children attending regular public secondary school in Strumica. Methods: The study was conducted during 2013 year for adolescents aged15. Inthis cross-sectional study, secondary school children from first grades [n=545] were selected from two Secondary Schools in Strumica. Participants dental status was evaluated using the 1997 World Health Organization caries diagnostic criteria for Decayed, Missing or Filled Teeth [DMFT] by 2 calibrated examiners. P value ≤0.05 was considered statistically significant. Results: The total number of children in the sample was 545, comprising 206 [37.80%] females and 339 [62.20%] males. The mean DMFT was 3.36, with standard deviation [SD] of 2.99 and 95% confidence interval [CI] of 3.11-3.61. Significant caries [SiC] index was 6.69. The prevalence of caries-free children was 19.08 %. The percentage of untreated caries or the ration of DT/DMFT was 0.4386 [43.86%]. Conclusions: Dental caries experience was seen to be moderate among secondary school children from Strumica city and its surrounding.
Alternatives to Biological Skin in Permeation Studies: Current Trends and Possibilities

The transdermal route of drugs has received increased attention in recent years due to numerous advantages over the oral and injectable routes, such as avoidance of the hepatic metabolism, protection of drugs from the gastrointestinal tract, sustained drug delivery, and good patient compliance. The assessment of ex vivo permeation during the pharmaceutical development process helps in understanding the product quality and performance of a transdermal delivery system. Generally, excised human skin relevant to the application site or animal skin is recommended for ex vivo permeation studies. However, the limited availability of the human skin and ethical issues surrounding the use of animal skin rendered these models less attractive in the permeation study. In the last three decades, enormous efforts have been put into developing artificial membranes and 3D cultured human skin models as surrogates to the human skin. This manuscript provides an insight on the European Medicines Agency (EMA) guidelines for permeation studies and the parameters affected when using Franz diffusion cells in the permeation study. The need and possibilities for skin alternatives, such as artificially cultured human skin models, parallel artificial membrane permeability assays (PAMPA), and artificial membranes for penetration and permeation studies, are comprehensively discussed.
A Refined 3-in-1 Fused Protein Similarity Measure: Application in Threshold-Free Hub Detection

An exhaustive literature survey shows that finding protein/gene similarity is an important step towards solving widespread bioinformatics problems, such as predicting protein-protein interactions, analyzing Protein-Protein Interaction Networks (PPINs), gene prioritization, and disease gene/protein detection. In this article, we have proposed an improved 3-in-1 fused protein similarity measure called FuSim-II. It is built upon combining the weighted average of biological knowledge extracted from three potential genomic/ proteomic resources such as Gene Ontology (GO), PPIN, and protein sequence. Furthermore, we have shown the application of the proposed measure in detecting potential hub-proteins from a given PPIN. Aiming that, we have proposed a multi-objective clustering-based protein hub detection framework with FuSim-II working as the underlying proximity measure. The PPINs of H. Sapiens and M. Musculus organisms are chosen for experimental purposes. Unlike most of the existing hub-detection methods, the proposed technique does not require to follow any protein degree cut-off or threshold to define hubs. A thorough assessment of efficiency between proposed and existing eight protein similarity measures along with eight single/multi-objective clustering methods has been carried out. Internal cluster validity indices like Silhouette and Davies Bouldin (DB) are deployed to accomplish analytical study. Also, a comparative performance analysis between proposed and five existing hub-proteins detection algorithms is conducted through the enrichment of essentiality study. The reported results show the improved performance of FuSim-II over existing protein similarity measures in terms of identifying functionally related proteins as well as relevant hub-proteins. Supplementary material is available at http://csse.szu. edu.cn/staff/cuilz/eng/index.html.