Miracle-dz/UniFAR-FTUs huggingface dataset:
Cellular Microenvironment Dictates Androgen Production by Murine Fetal Leydig Cells in Primary Culture1

ABSTRACT Despite the fact that fetal Leydig cells are recognized as the primary source of androgens in male embryos, the mechanisms by which steroidogenesis occurs within the developing testis remain unclear. A genetic approach was used to visualize and isolate fetal Leydig cells from remaining cells within developing mouse testes. Cyp11a1-Cre mice were bred to mT/mG dual reporter mice to target membrane-tagged enhanced green fluorescent protein (GFP) within steroidogenic cells, whereas other cells expressed membrane-tagged tandem-dimer tomato red. Fetal Leydig cell identity was validated using double-labeled immunohistochemistry against GFP and the steroidogenic enzyme 3beta-HSD, and cells were successfully isolated as indicated by qPCR results from sorted cell populations. Because fetal Leydig cells must collaborate with neighboring cells to synthesize testosterone, we hypothesized that the fetal Leydig cell microenvironment defined their capacity for androgen production. Microfluidic culture devices were used to measure androstenedione and testosterone production of fetal Leydig cells that were cultured in cell-cell contact within a mixed population, were isolated but remained in medium contact via compartmentalized co-culture with other testicular cells, or were isolated and cultured alone. Results showed that fetal Leydig cells maintained their identity and steroidogenic activity for 3–5 days in primary culture. Microenvironment dictated proficiency of testosterone production. As expected, fetal Leydig cells produced androstenedione but not testosterone when cultured in isolation. More testosterone accumulated in medium from mixed cultures than from compartmentalized co-cultures initially; however, co-cultures maintained testosterone synthesis for a longer time. These data suggest that a combination of cell-cell contact and soluble factors constitute the ideal microenvironment for fetal Leydig cell activity in primary culture.
Quantifying co-creative writing experiences

ABSTRACT Collaboration with artificial intelligence (AI) is a growing trend even in the field of creativity. This paper examines which quantitative metrics can be used to comparatively analyse human-computer co-creativity with children. To study this question, 24 schoolchildren of age 10–11 wrote a poem with three co-creative poetry writing processes: a human-computer, a human-human, and a human-human-computer process. The computational participant in the processes was an AI-based application called the Poetry Machine. The children were asked to evaluate their user experience with a 5-point Likert-type questionnaire after each writing process and a comparative questionnaire after finishing all processes. The metrics used in the evaluation were immediate fun, long-term enjoyment, creativity, self-expression, outcome satisfaction, ease of starting and finishing writing, quality of ideas and support from others, and ownership. Significant differences were found in fun, long-term enjoyment, quality of ideas, support, and ownership. The high number of statistically relevant results was enabled by exposing all participants to all writing processes, and the comparative questionnaire. The human-human-computer process was evaluated the best in long-term enjoyment and the human-computer process the weakest in support and idea quality. Creativity and ease of finishing writing turned out to be outlining metrics for the co-creative processes.
Systematic Review of Pharyngeal and Esophageal Manometry in Healthy or Dysphagic Older Persons (>60 years)

We undertook a systematic review of swallowing biomechanics, as assessed using pharyngeal and esophageal manometry in healthy or dysphagic older individuals aged over 60 years of age, comparing findings to studies of younger participants. PRISMA-P methodology was used to identify, select, and evaluate eligible studies. Across studies, older participants had lower upper esophageal sphincter (UES) resting pressures and evidence of decreased UES relaxation when compared to younger groups. Intrabolus pressures (IBP) above the UES were increased, demonstrating flow resistance at the UES. Pharyngeal contractility was increased and prolonged in some studies, which may be considered as an attempt to compensate for UES flow resistance. Esophageal studies show evidence of reduced contractile amplitudes in the distal esophagus, and an increased frequency of failed peristaltic events, in concert with reduced lower esophageal sphincter relaxation, in the oldest subjects. Major motility disorders occurred in similar proportions in older and young patients in most clinical studies, but some studies show increases in achalasia or spastic motility in older dysphagia and noncardiac chest pain patients. Overall, study qualities were moderate with a low likelihood of bias. There were few clinical studies specifically focused on swallowing outcomes in older patient groups and more such studies are needed.
Heart Failure and Problems with Frailty Syndrome: Why it is Time to Care About Frailty Syndrome in Heart Failure

Frailty syndrome (FS) is an independent predictor of mortality in cardiovascular disease and is found in 15–74% of patients with heart failure (HF). The syndrome has a complex, multidimensional aetiology and contributes to adverse outcomes. Proper FS diagnosis and treatment determine prognosis and support the evaluation of treatment outcomes. Routine FS assessment for HF patients should be included in daily clinical practice as an important prognostic factor within a holistic process of diagnosis and treatment. Multidisciplinary team members, particularly nurses, play an important role in FS assessment in hospital and primary care settings, and in the home care environment. Raising awareness of concurrent FS in patients with HF patients and promoting targeted interventions may contribute to a decreased risk of adverse events, and a better prognosis and quality of life.
DNA barcoding of Corydalis, the most taxonomically complicated genus of Papaveraceae

Abstract The genus Corydalis is recognized as one of the most taxonomically challenging plant taxa. It is mainly distributed in the Himalaya–Hengduan Mountains, a global biodiversity hotspot. To date, no effective solution for species discrimination and taxonomic assignment in Corydalis has been developed. In this study, five nuclear and chloroplast DNA regions, ITS, ITS2, matK, rbcL, and psbA‐trnH, were preliminarily assessed based on their ability to discriminate Corydalis to eliminate inefficient regions, and the three regions showing good performance (ITS, ITS2 and matK) were then evaluated in 131 samples representing 28 species of 11 sections of four subgenera in Corydalis using three analytical methods (NJ, ML, MP tree; K2P‐distance and BLAST). The results showed that the various approaches exhibit different species identification power and that BLAST shows the best performance among the tested approaches. A comparison of different barcodes indicated that among the single barcodes, ITS (65.2%) exhibited the highest identification success rate and that the combination of ITS + matK (69.6%) provided the highest species resolution among all single barcodes and their combinations. Three Pharmacopoeia‐recorded medicinal plants and their materia medica were identified successfully based on the ITS and ITS2 regions. In the phylogenetic analysis, the sections Thalictrifoliae, Sophorocapnos, Racemosae, Aulacostigma, and Corydalis formed well‐supported separate lineages. We thus hypothesize that the five sections should be classified as an independent subgenus and that the genus should be divided into three subgenera. In this study, DNA barcoding provided relatively high species discrimination power, indicating that it can be used for species discrimination in this taxonomically complicated genus and as a potential tool for the authentication of materia medica belonging to Corydalis.
Comparing RADseq and microsatellites for estimating genetic diversity and relatedness — Implications for brown trout conservation

Abstract The conservation and management of endangered species requires information on their genetic diversity, relatedness and population structure. The main genetic markers applied for these questions are microsatellites and single nucleotide polymorphisms (SNPs), the latter of which remain the more resource demanding approach in most cases. Here, we compare the performance of two approaches, SNPs obtained by restriction‐site‐associated DNA sequencing (RADseq) and 16 DNA microsatellite loci, for estimating genetic diversity, relatedness and genetic differentiation of three, small, geographically close wild brown trout (Salmo trutta) populations and a regionally used hatchery strain. The genetic differentiation, quantified as F ST, was similar when measured using 16 microsatellites and 4,876 SNPs. Based on both marker types, each brown trout population represented a distinct gene pool with a low level of interbreeding. Analysis of SNPs identified half‐ and full‐siblings with a higher probability than the analysis based on microsatellites, and SNPs outperformed microsatellites in estimating individual‐level multilocus heterozygosity. Overall, the results indicated that moderately polymorphic microsatellites and SNPs from RADseq agreed on estimates of population genetic structure in moderately diverged, small populations, but RADseq outperformed microsatellites for applications that required individual‐level genotype information, such as quantifying relatedness and individual‐level heterozygosity. The results can be applied to other small populations with low or moderate levels of genetic diversity.
Environmental DNA metabarcoding of wild flowers reveals diverse communities of terrestrial arthropods

Abstract Terrestrial arthropods comprise the most species‐rich communities on Earth, and grassland flowers provide resources for hundreds of thousands of arthropod species. Diverse grassland ecosystems worldwide are threatened by various types of environmental change, which has led to decline in arthropod diversity. At the same time, monitoring grassland arthropod diversity is time‐consuming and strictly dependent on declining taxonomic expertise. Environmental DNA (eDNA) metabarcoding of complex samples has demonstrated that information on species compositions can be efficiently and non‐invasively obtained. Here, we test the potential of wild flowers as a novel source of arthropod eDNA. We performed eDNA metabarcoding of flowers from several different plant species using two sets of generic primers, targeting the mitochondrial genes 16S rRNA and COI. Our results show that terrestrial arthropod species leave traces of DNA on the flowers that they interact with. We obtained eDNA from at least 135 arthropod species in 67 families and 14 orders, together representing diverse ecological groups including pollinators, parasitoids, gall inducers, predators, and phytophagous species. Arthropod communities clustered together according to plant species. Our data also indicate that this experiment was not exhaustive, and that an even higher arthropod richness could be obtained using this eDNA approach. Overall, our results demonstrate that it is possible to obtain information on diverse communities of insects and other terrestrial arthropods from eDNA metabarcoding of wild flowers. This novel source of eDNA represents a vast potential for addressing fundamental research questions in ecology, obtaining data on cryptic and unknown species of plant‐associated arthropods, as well as applied research on pest management or conservation of endangered species such as wild pollinators.
Absence of human papillomavirus in oral cavity squamous cell carcinomas among Saudi patients

This study aimed to examine the possible association of human papillomavirus (HPV) with oral cavity squamous cell carcinomas (OCSCCs) in Saudi Arabia. Forty‐five paraffin‐embedded tumor blocks that represent different subsets of OCSCCs between 2010 and 2014 were retrieved and histologically evaluated. The presence of high‐risk HPV (16, 18, 31, and 33) was assessed by p16‐immunohistochemistry followed by DNA detection using in situ hybridization technique. Twenty‐four patients were male with the mean age of 59.3 years, and 21 patients were female with the mean age of 61.2 years. Forty‐one cases were positive for p16 immunostaining, and the remaining four cases were negative. However, none of the 45 cases showed DNA‐expression for any HPV subtypes (16, 18, 31, and 33). High‐risk HPV appears not to be involved in the etiology of OCSCCs in older Saudi patients, but further studies with cross section of a younger age group are still required.
Obesity, Physical Fitness and Inflammation in the Elderly

Among the elderly, obesity is paradoxically associated with a lower mortality risk. Thus, this study describes fitness levels by Body Mass Index (BMI) category and the associations of high-sensitivity C-reactive protein (hs-CRP) and Vitamin D levels with muscle strength, in community-dwelling older adults. A cross-sectional study, with 1338 subjects having mean age of 78.3 years, were assessed in anthropometrics, muscle strength, and cardiorespiratory fitness. In a sub-sample, blood samples were collected and objective markers of inflammation were provided: high-sensitivity C-reactive protein (hs-CRP) and Vitamin D (25(OH) D). Obese women (BMI ≥ 30.0 kg/m2) showed significantly better results for grip strength than normal weight group (BMI between 18.5–24.9 kg/m2): 22.3 (7.0) vs. 20.0 (6.8); p = 0.002. After adjustment, higher levels of hs-CRP were an independent predictor of lower levels of grip strength (β = −0.213, 95% CI: −0.424; −0.002) and Vitamin D levels were positively associated with higher levels of muscle strength (β = 0.098, 95% CI: 0.008–0.189). The multivariate analysis found a significant and positive association between 25(OH) D and grip strength: (β = 0.098, 95% CI: 0.008–0.189). A positive pattern of higher levels of absolute strength among obese older subjects could have an important impact on morbidity and mortality risk, through the inverse association with acute inflammation and an increase in Vitamin D profile.
Biomarkers in Routine Heart Failure Clinical Care

Heart failure is a clinical condition with complex pathophysiology that involves many different processes. Diagnosis is often difficult in patients presenting for the first time with breathlessness. Many biomarkers have been identified that are elevated in heart failure and their role in assessing prognosis has also been investigated. However, at present the natriuretic peptides appear to be the gold standard biomarker against which the other biomarkers are compared. In this review we will examine the evidence behind the other biomarkers for use in heart failure patients and the current guidelines for their use.
Zika Virus Infection, Basic and Clinical Aspects: A Review Article

Background: Zika virus infection has recently attracted the attention of medical community. While clinical manifestations of the infection in adult cases are not severe and disease is not associated with high mortality rates, Zika virus infection can have an impact on fetal development and lead to severe neurodevelopmental abnormalities. Methods: To gain insight into different aspects of Zika virus infection, a comprehensive literature review was performed. With regard to epidemiology and geographical distribution of Zika virus infection, relevant information was extracted from CDC and WHO websites. Results: In this review, we discuss different basic and clinical aspects of Zika virus infection including virology, epidemiology and pathogenesis of disease. Laboratory methods required for the diagnosis of disease together with ethical issues associated with Zika virus infection will also be discussed in detail. Conclusion: Herein, we have tried to provide a multi-faceted view of Zika virus infection, with greater emphasis on disease status in Eastern Mediterranean Region.
Cellular Uptake and Delivery of Myeloperoxidase to Lysosomes Promote Lipofuscin Degradation and Lysosomal Stress in Retinal Cells*

Neutrophil myeloperoxidase (MPO) catalyzes the H2O2-dependent oxidation of chloride anion to generate hypochlorous acid, a potent antimicrobial agent. Besides its well defined role in innate immunity, aberrant degranulation of neutrophils in several inflammatory diseases leads to redistribution of MPO to the extracellular space, where it can mediate tissue damage by promoting the oxidation of several additional substrates. Here, we demonstrate that mannose 6-phosphate receptor-mediated cellular uptake and delivery of MPO to lysosomes of retinal pigmented epithelial (RPE) cells acts to clear this harmful enzyme from the extracellular space, with lysosomal-delivered MPO exhibiting a half-life of 10 h. Lysosomal-targeted MPO exerts both cell-protective and cytotoxic functions. From a therapeutic standpoint, MPO catalyzes the in vitro degradation of N-retinylidene-N-retinylethanolamine, a toxic form of retinal lipofuscin that accumulates in RPE lysosomes and drives the pathogenesis of Stargardt macular degeneration. Furthermore, chronic cellular uptake and accumulation of MPO in lysosomes coincides with N-retinylidene-N-retinylethanolamine elimination in a cell-based model of macular degeneration. However, lysosomal-delivered MPO also disrupts lysosomal acidification in RPE cells, which coincides with nuclear translocation of the lysosomal stress-sensing transcription factor EB and, eventually, cell death. Based on these findings we predict that under periods of acute exposure, cellular uptake and lysosomal degradation of MPO mediates elimination of this harmful enzyme, whereas chronic exposure results in progressive accumulation of MPO in lysosomes. Lysosomal-accumulated MPO can be both cell-protective, by promoting the degradation of toxic retinal lipofuscin deposits, and cytotoxic, by triggering lysosomal stress and cell death.
Obstetric Triage Scales; a Narrative Review

Introduction: The growing demand for high-quality obstetric care and treatment has led to the advent and development of a field known as obstetric triage. The present review study aimed to examine the development of tools and criteria for obstetric triage services. Methods: In this narrative review, two authors searched for related articles using the keywords of “obstetric triage, gynecology triage, perinatal Triage, maternity triage, midwifery triage” AND “tool, index, scale, questionnaire, system”. With Persian and English language limitation, searches were performed in Scopus, Google Scholar, Scientific Information Database, ProQuest, Medline, Embase and Web of Science databases for articles published from 2000 to 2018. Results: Out of the 289 articles reviewed in this study, 8 articles met the eligibility criteria. Out of these 8 articles, 6 were dedicated to introducing a tool designed and only 2 introduced an obstetric triage system. The obstetric triage tools and systems covered included Emergency Severity Index (ESI), Obstetric Triage Acuity Scale (OTAS), Birmingham symptom specific obstetric triage system (BSOTS), Maternal Fetal Triage Index (MFTI), Florida Hospital Obstetric Triage Acuity Tool, self-assessment questionnaire for gynecologic emergencies (SAQ-GE) and Perinatal Emergency Team Response Assessment (PETRA). Overall, the validity and reliability of the studied method were investigated and found to be acceptable in only 5 of the reviewed studies. Conclusion: The review showed the lack of consensus on how to devise a single standardized tool or system for obstetric triage. The comparison of different obstetric triage tools and systems demonstrated the need for a standardized and widely-approved system with high validity and reliability and standard definitions for obstetric triage to determine the right priority and waiting times of obstetric care services.
Host sex, size, and hemoparasite infection influence the effects of ectoparasitic burdens on free‐ranging iguanas

Abstract Investigations focusing on host–ectoparasite interactions in animals have revealed asymptomatic to severe health and fitness consequences suggesting that species mobilize different interspecific response mechanisms. Fewer studies, however, have examined intraspecific responses to ectoparasitic burdens. In this study, we analyzed host health and fitness responses to increasing ectoparasite burdens along with the presence/absence of hemoparasites of free‐ranging insular rock iguanas (Cyclura cychlura) in The Bahamas. Using hematology, plasma biochemistry, as well as body condition and growth rate comparisons, we failed to find significant associations of tick burdens with annual growth rate, corticosterone, packed cell volume, total white blood cell, and heterophil, monocyte, eosinophil or hemoglobin measures. We did, however, find mixed and significant associations of tick burdens with lymphocyte and basophil counts, heterophil‐to‐lymphocyte ratios, and body condition indices. These associations varied by sex, size, and hemoparasite infection status suggesting that different life stages of iguanas may invest differently in immune responses, and impacts may be modulated based on size and sex of hosts, and coinfection status.
Dopamine compartmentalization, selective dopaminergic vulnerabilities in Parkinson's disease and therapeutic opportunities

Progressive depletion of selected dopamine neurons is central to much Parkinson's disease (PD) disability. Although symptomatic treatments can ameliorate the disabilities that this neuronal depletion causes, no current strategy is documented to slow these losses. There is substantial evidence that dopamine in intracytoplasmic/extravesicular neuronal compartments can be toxic. Here, I review evidence that supports roles for dopamine compartmentalization, mediated largely by serial actions of plasma membrane SLC6A3/DAT and vesicular SLC18A2/VMAT2 transporters, in the selective patterns of dopamine neuronal loss found in PD brains. This compartmentalization hypothesis for the dopamine cell type specificity of PD lesions nominates available drugs for amelioration of damage arising from miscompartmentalized dopamine and raises cautions in using other drugs.
A Comparison between the Ability of Revised Trauma Score and Kampala Trauma Score in Predicting Mortality; a Meta-Analysis

Introduction: Describing injury severity in trauma patients is vital. In some recent articles the Revised Trauma Score (RTS) and Kampala Trauma Score (KTS) have been suggested as easily performed and feasible triage tools which can be used in resource-limited settings. The present meta-analysis was performed to evaluate and compare the accuracy of the RTS and KTS in predicting mortality in low-and middle income countries (LMICs). Methods: Two investigators searched the Web of Science, Embase, and Medline databases and the articles which their exact number of true-positive, true-negative, false-positive, and false-negative results could be extracted were selected. Sensitivity and subgroup analysis were performed using Stata software version 14 to determine the factor(s) affecting the accuracy of the RTS and KTS in predicting mortality and source(s) of heterogeneity. Results: The heterogeneity was high (I2 > 80%) among 11 relevant studies (total n = 20,631). While the sensitivity of the KTS (0.88) was slightly higher than RTS (0.82), the specificity, diagnostic odds ratio, negative likelihood ratio, and positive likelihood ratio of the KTS (0.73, 20, 0.16, 3.30, respectively) were lower than those of the RTS (0.91, 45, 0.20, 8.90, respectively). The area under the summary-receiver operator characteristic curve for KTS and RTS was 0.88 and 0.93, respectively. Conclusion: However, regarding accuracy and performance, RTS was better than KTS for distinguishing between mortality and survival; both of them are beneficial trauma scoring tools which can be used in LMICs. Further studies are required to specify the appropriate choice of the RTS or KTS regarding the type of injury and different conditions of the patient.