Miracle-dz/UniFAR-FTUs huggingface dataset:
Influence of the playing surface on changes of direction and plantar pressures during an agility test in youth futsal players

Abstract The ability to effect a change of direction (COD) when performing high-speed actions is essential in team sports like futsal. Nevertheless, the interaction effect of sports surfaces on this ability remains unknown. This research aimed to analyse the plantar pressures and time performance of 15 youth futsal players when performing CODs on two playing surfaces with different mechanical properties. The shock absorption and vertical deformation of one synthetic flooring surface and one wooden flooring surface were assessed. CODs were evaluated using a modified version of the Agility T-Test, while total time of the test, time of CODs, and plantar pressure in CODs were all recorded. The wooden flooring surface displayed higher values of shock absorption (35.70% ± 2.87%) and vertical deformation (2.77 ± 0.38 mm) compared with the synthetic flooring (p < 0.01). Faster CODs were performed on the wooden flooring than on the synthetic flooring (−0.05 s, 95% confidence interval [CI]: −0.10 to −0.007, effect size [ES]: 0.07, p < 0.05), but no differences in total test time were found (p > 0.05). Finally, no differences in plantar pressures by playing surface were found. In sum, the differences in the mechanical properties of the two futsal surfaces affected the performance of futsal players in the modified agility test. However, these differences were not great enough to generate different plantar pressures on players, probably due to playerś own adaptations.
MgrA Negatively Impacts Staphylococcus aureus Invasion by Regulating Capsule and FnbA

Virulence genes are regulated by a complex regulatory network in Staphylococcus aureus. Some of the regulators are global in nature and affect many downstream genes. MgrA is a multiple-gene regulator that has been shown to activate genes involved in capsule biosynthesis and repress surface protein genes. The goal of this study was to demonstrate the biological significance of MgrA regulation of capsule and surface proteins. ABSTRACT Virulence genes are regulated by a complex regulatory network in Staphylococcus aureus. Some of the regulators are global in nature and affect many downstream genes. MgrA is a multiple-gene regulator that has been shown to activate genes involved in capsule biosynthesis and repress surface protein genes. The goal of this study was to demonstrate the biological significance of MgrA regulation of capsule and surface proteins. We found that strain Becker possessed one fibronectin-binding protein, FnbA, and that FnbA was the predominant protein involved in invasion of nonphagocytic HeLa cells. By genetic analysis of strains with different amounts of capsule, we demonstrated that capsule impeded invasion of HeLa cells by masking the bacterial cell wall-anchored protein FnbA. Using variants with different levels of mgrA transcription, we further demonstrated that MgrA negatively impacted invasion by activating the cap genes involved in capsule biosynthesis and repressing the fnbA gene. Thus, we conclude that MgrA negatively impacts cell invasion of S. aureus Becker by promoting capsule and repressing FnbA.
Biallelic Mutations in TSC2 Lead to Abnormalities Associated with Cortical Tubers in Human iPSC-Derived Neurons

Tuberous sclerosis complex (TSC) is a genetic disorder caused by mutations in TSC1 or TSC2. Patients frequently have epilepsy, autism spectrum disorder, and/or intellectual disability, as well as other systemic manifestations. In this study, we differentiated human induced pluripotent stem cells (iPSCs) from a female patient with TSC with one or two mutations in TSC2 into neurons using induced expression of NGN2 to examine neuronal dysregulation associated with the neurological symptoms in TSC. Using this method, neuronal differentiation was comparable between the three genotypes of iPSCs. We observed that TSC2+/− neurons show mTOR complex 1 (mTORC1) hyperactivation and associated increased cell body size and process outgrowth, as well as exacerbation of the abnormalities by loss of the second allele of TSC2 in TSC2−/− neurons. Interestingly, iPSC-derived neurons with either a single or biallelic mutation in TSC2 demonstrated hypersynchrony and downregulation of FMRP targets. However, only neurons with biallelic mutations of TSC2 demonstrated hyperactivity and transcriptional dysregulation observed in cortical tubers. These data demonstrate that loss of one allele of TSC2 is sufficient to cause some morphological and physiological changes in human neurons but that biallelic mutations in TSC2 are necessary to induce gene expression dysregulation present in cortical tubers. Finally, we found that treatment of iPSC-derived neurons with rapamycin reduced neuronal activity and partially reversed gene expression abnormalities, demonstrating that mTOR dysregulation contributes to both phenotypes. Therefore, biallelic mutations in TSC2 and associated molecular dysfunction, including mTOR hyperactivation, may play a role in the development of cortical tubers. SIGNIFICANCE STATEMENT In this study, we examined neurons derived from induced pluripotent stem cells with two, one, or no functional TSC2 (tuberous sclerosis complex 2) alleles and found that loss of one or both alleles of TSC2 results in mTORC1 hyperactivation and specific neuronal abnormalities. However, only biallelic mutations in TSC2 resulted in elevated neuronal activity and upregulation of cell adhesion genes that is also observed in cortical tubers. These data suggest that loss of heterozygosity of TSC1 or TSC2 may play an important role in the development of cortical tubers, and potentially epilepsy, in patients with TSC.
GDGT cyclization proteins identify the dominant archaeal sources of tetraether lipids in the ocean

Significance Archaea synthesize distinctive membrane-spanning lipids (GDGTs) that are readily preserved in ancient sediments and utilized as paleotemperature proxies to reconstruct sea surface temperatures deep in Earth’s past. However, properly interpreting GDGT-based biomarker proxies requires an accurate assessment of the archaea that contribute to GDGT pools in modern environments and of the proteins necessary for synthesizing GDGTs. In this study, we identify 2 radical SAM proteins in Sulfolobus acidocaldarius that are required to produce these molecules. Bioinformatics analyses of these GDGT ring synthesis proteins reveal that Thaumarchaeota are the dominant source of cyclized GDGTs in the open ocean, allowing us to constrain one factor of uncertainty in the application of GDGT-based paleotemperature proxies. Glycerol dibiphytanyl glycerol tetraethers (GDGTs) are distinctive archaeal membrane-spanning lipids with up to eight cyclopentane rings and/or one cyclohexane ring. The number of rings added to the GDGT core structure can vary as a function of environmental conditions, such as changes in growth temperature. This physiological response enables cyclic GDGTs preserved in sediments to be employed as proxies for reconstructing past global and regional temperatures and to provide fundamental insights into ancient climate variability. Yet, confidence in GDGT-based paleotemperature proxies is hindered by uncertainty concerning the archaeal communities contributing to GDGT pools in modern environments and ambiguity in the environmental and physiological factors that affect GDGT cyclization in extant archaea. To properly constrain these uncertainties, a comprehensive understanding of GDGT biosynthesis is required. Here, we identify 2 GDGT ring synthases, GrsA and GrsB, essential for GDGT ring formation in Sulfolobus acidocaldarius. Both proteins are radical S-adenosylmethionine proteins, indicating that GDGT cyclization occurs through a free radical mechanism. In addition, we demonstrate that GrsA introduces rings specifically at the C-7 position of the core GDGT lipid, while GrsB cyclizes at the C-3 position, suggesting that cyclization patterns are differentially controlled by 2 separate enzymes and potentially influenced by distinct environmental factors. Finally, phylogenetic analyses of the Grs proteins reveal that marine Thaumarchaeota, and not Euryarchaeota, are the dominant source of cyclized GDGTs in open ocean settings, addressing a major source of uncertainty in GDGT-based paleotemperature proxy applications.
Absolute Quantification of Apolipoproteins Following Treatment with Omega-3 Carboxylic Acids and Fenofibrate Using a High Precision Stable Isotope-labeled Recombinant Protein Fragments Based SRM Assay

Applications of LC-SRM in clinical research are still limited. SIS PrEST are a novel class of standards added prior to trypsinization. We have developed a semi-automated sample preparation workflow and a SIS PrEST LC-SRM/MS Tier 2 assay for absolute quantification of 13 apolipoproteins in human plasma and applied it on clinical samples from the EFFECT I study. We demonstrate, for the first time, that SIS PrEST can be applied for exploratory biomarker research in clinical settings and capture drug effects. Graphical Abstract Highlights The first application of stable isotope-labeled recombinant protein fragments internal standards (SIS PrEST) on clinical samples. Development of a high-precision quantitative SIS PrEST based LC-SRM Tier 2 assay for 13 apolipoproteins. Semi-automated workflow enables precise and robust high-throughput sample processing. The assay quantifies the effects of fenofibrate and omega-3 carboxylic acids on apolipoproteins in human plasma. Stable isotope-labeled standard (SIS) peptides are used as internal standards in targeted proteomics to provide robust protein quantification, which is required in clinical settings. However, SIS peptides are typically added post trypsin digestion and, as the digestion efficiency can vary significantly between peptides within a protein, the accuracy and precision of the assay may be compromised. These drawbacks can be remedied by a new class of internal standards introduced by the Human Protein Atlas project, which are based on SIS recombinant protein fragments called SIS PrESTs. SIS PrESTs are added initially to the sample and SIS peptides are released on trypsin digestion. The SIS PrEST technology is promising for absolute quantification of protein biomarkers but has not previously been evaluated in a clinical setting. An automated and scalable solid phase extraction workflow for desalting and enrichment of plasma digests was established enabling simultaneous preparation of up to 96 samples. Robust high-precision quantification of 13 apolipoproteins was achieved using a novel multiplex SIS PrEST-based LC-SRM/MS Tier 2 assay in non-depleted human plasma. The assay exhibited inter-day coefficients of variation between 1.5% and 14.5% (median = 3.5%) and was subsequently used to investigate the effects of omega-3 carboxylic acids (OM3-CA) and fenofibrate on these 13 apolipoproteins in human plasma samples from a randomized placebo-controlled trial, EFFECT I (NCT02354976). No significant changes were observed in the OM3-CA arm, whereas treatment with fenofibrate significantly increased apoAII and reduced apoB, apoCI, apoE and apoCIV levels. The reduction in apoCIV following fenofibrate treatment is a novel finding. The study demonstrates that SIS PrESTs can facilitate the generation of robust multiplexed biomarker Tier 2 assays for absolute quantification of proteins in clinical studies.
The Neglected Insulin: IGF-II, a Metabolic Regulator with Implications for Diabetes, Obesity, and Cancer

When originally discovered, one of the initial observations was that, when all of the insulin peptide was depleted from serum, the vast majority of the insulin activity remained and this was due to a single additional peptide, IGF-II. The IGF-II gene is adjacent to the insulin gene, which is a result of gene duplication, but has evolved to be considerably more complicated. It was one of the first genes recognised to be imprinted and expressed in a parent-of-origin specific manner. The gene codes for IGF-II mRNA, but, in addition, also codes for antisense RNA, long non-coding RNA, and several micro RNA. Recent evidence suggests that each of these have important independent roles in metabolic regulation. It has also become clear that an alternatively spliced form of the insulin receptor may be the principle IGF-II receptor. These recent discoveries have important implications for metabolic disorders and also for cancer, for which there is renewed acknowledgement of the importance of metabolic reprogramming.
Evolving Public Views On The Likelihood Of Violence From People With Mental Illness: Stigma And Its Consequences.

Highly publicized acts of violence routinely spark reactions that place blame on the perpetrator's presumed mental illness. Despite solid evidence that people with mental illness are unlikely to be dangerous, such prejudice can lead to support for inappropriately using legal means to force people into treatment. We examined trends in public perceptions of violence and support for coerced treatment across a twenty-two-year period using data from three National Stigma Studies. The studies gave respondents one of three vignettes describing people who met clinical criteria for mental disorders or one describing a person with nonclinical "daily troubles. " Perceptions regarding potential violence and support for coercion generally rose over time-significantly so for schizophrenia. By 2018 over 60 percent of respondents saw people who met criteria for schizophrenia as dangerous to others, and 44-59 percent supported coercive treatment. Sixty-eight percent saw people with alcohol dependence as dangerous to others, and 26-38 percent supported coercion. Lower but substantial percentages were reported for people with depression and, remarkably, for those with nonclinical "daily troubles," who were viewed as dangerous. These findings reflect political discourse, not scientific data, and could lead to policies that would be ineffective and misdirect the search for the underlying roots of violence while unnecessarily increasing stigma toward people with mental illness.
Extensive Metabolic Profiles of Leaves and Stems from the Medicinal Plant Dendrobium officinale Kimura et Migo

Dendrobium officinale Kimura et Migo is a commercially and pharmacologically highly prized species widely used in Western Asian countries. In contrast to the extensive genomic and transcriptomic resources generated in this medicinal species, detailed metabolomic data are still missing. Herein, using the widely targeted metabolomics approach, we detect 649 diverse metabolites in leaf and stem samples of D. officinale. The majority of these metabolites were organic acids, amino acids and their derivatives, nucleotides and their derivatives, and flavones. Though both organs contain similar metabolites, the metabolite profiles were quantitatively different. Stems, the organs preferentially exploited for herbal medicine, contained larger concentrations of many more metabolites than leaves. However, leaves contained higher levels of polyphenols and lipids. Overall, this study reports extensive metabolic data from leaves and stems of D. officinale, providing useful information that supports ongoing genomic research and discovery of bioactive compounds.
Patient Concerns in the Immediate Postoperative Period After Mohs Micrographic Surgery.

BACKGROUND Postoperative concerns after Mohs micrographic surgery (MMS) are not well characterized. OBJECTIVE To better define patient concerns and contributing characteristics in the immediate postoperative period after MMS. MATERIALS AND METHODS A standardized telephone encounter template was implemented to better assess patient concerns in the 24-hour postoperative period. A review was then performed of patients undergoing MMS from October 2016 to July 2017 to assess for the most common patient concerns and association with clinical characteristics. RESULTS We included 307 patients. Overall, 60.6% of patients reported a concern. Fifty-four percent of patients reported pain. Most pain was characterized as "a little" (67.7%). On univariate analysis, flap repairs, location on the upper extremities, and swelling were associated with higher mean postoperative pain. Tumor type was not associated with increased pain. On multivariate analyses, patients with larger defects and associated edema were statistically significantly associated with higher degrees of pain. CONCLUSION Over half of patients experience postoperative concerns after MMS, most commonly pain. The immediate postoperative period may be an optimal time to identify patient concerns allowing for reassurance or early intervention when necessary.
Novel Real-Time Prediction of Liver Graft Function During Hypothermic Oxygenated Machine Perfusion Before Liver Transplantation.

OBJECTIVE The aim of this study was to determine the predictive value of machine perfusate analysis on graft outcome. BACKGROUND Ex situ machine perfusion (MP) is gaining increasing interest to potentially repair injured organs and to assess organ function. In the field of liver transplantation, however, no studies exist on reliable prediction of graft function during MP. METHODS We have used hypothermic oxygenated perfusion (HOPE) for donation after circulatory death (DCD) or extended criteria donation after brain death (DBD) human liver grafts during the last 7 years. Our series includes 100 HOPE-treated liver-transplanted patients with an overall tumor-censored 5-year graft survival of 89%. We monitored 54 livers during HOPE in terms of fluorometric analysis of released mitochondrial flavin (flavin mononucleotide, FMN) in the machine perfusate. RESULTS Real-time optical measurement of mitochondrial FMN release in machine perfusates of livers disclosed a strong correlation with lactate clearance and coagulation factors at day 1 and 2 after transplantation. Receiver-operating characteristic curve analysis revealed an area under the curve (AUROC) of 0.79 [95% confidence interval (CI), 0.62-0.97] for severe allograft dysfunction and for early graft loss (AUROC 0.93, 95% CI, 0.84-1.0). CONCLUSIONS Assessment of flavin, a marker of mitochondrial complex I injury, in the perfusate provides a fast prediction of liver graft function and loss during ex situ MP before implantation. This finding may have high clinical relevance, as liver grafts from extended DBD or DCD donors carry considerable risks for recipients. On-line estimation of outcome before implantation would therefore substantially increase safe utilization of liver grafts.
The Gut Microbiota in Celiac Disease and Probiotics

Celiac disease (CeD) is an immune-mediated enteropathy, and unique in that the specific trigger is known: gluten. The current mainstay of therapy is a gluten-free diet (GFD). As novel therapies are being developed, complementary strategies are also being studied, such as modulation of the gut microbiome. The gut microbiota is involved in the initiation and perpetuation of intestinal inflammation in several chronic diseases. Intestinal dysbiosis has been reported in CeD patients, untreated or treated with GFD, compared to healthy subjects. Several studies have identified differential bacterial populations associated with CeD patients and healthy subjects. However, it is still not clear if intestinal dysbiosis is the cause or effect of CeD. Probiotics have also been considered as a strategy to modulate the gut microbiome to an anti-inflammatory state. However, there is a paucity of data to support their use in treating CeD. Further studies are needed with therapeutic microbial formulations combined with human trials on the use of probiotics to treat CeD by restoring the gut microbiome to an anti-inflammatory state.
Clinical Variables and Genetic Risk Factors Associated with the Acute Outcome of Ischemic Stroke: A Systematic Review

Stroke is a complex disease and one of the main causes of morbidity and mortality among the adult population. A huge variety of factors is known to influence patient outcome, including demographic variables, comorbidities or genetics. In this review, we expound what is known about the influence of clinical variables and related genetic risk factors on ischemic stroke outcome, focusing on acute and subacute outcome (within 24 to 48 hours after stroke and until day 10, respectively), as they are the first indicators of stroke damage. We searched the PubMed data base for articles that investigated the interaction between clinical variables or genetic factors and acute or subacute stroke outcome. A total of 61 studies were finally included in this review. Regarding the data collected, the variables consistently associated with acute stroke outcome are: glucose levels, blood pressure, presence of atrial fibrillation, prior statin treatment, stroke severity, type of acute treatment performed, severe neurological complications, leukocyte levels, and genetic risk factors. Further research and international efforts are required in this field, which should include genome-wide association studies.
Nonoperative Treatment of Elbow Ulnar Collateral Ligament Injuries With and Without Platelet-Rich Plasma in Professional Baseball Players: A Comparative and Matched Cohort Analysis

Background: Recent studies evaluating nonoperative treatment of elbow ulnar collateral ligament (UCL) injuries augmented with platelet-rich plasma (PRP) have shown promising results. To date, no comparative studies have been performed on professional baseball players who have undergone nonoperative treatment with or without PRP injections for UCL injuries. Hypothesis: Players who received PRP injections would have better outcomes than those who did not receive PRP. Study Design: Cohort study; Level of evidence, 3. Methods: The Major League Baseball (MLB) Health and Injury Tracking System identified 544 professional baseball players who were treated nonoperatively for elbow UCL injuries between 2011 and 2015. Of these, 133 received PRP injections (PRP group) before starting their nonoperative treatment program, and 411 did not (no-PRP group). Player outcomes and a Kaplan-Meier survival analysis were compared between groups. In addition, to reduce selection bias, a 1:1 matched comparison of the PRP group versus the no-PRP group was performed. Players were matched by age, position, throwing side, and league status: major (MLB) and minor (Minor League Baseball [MiLB]). A single radiologist with extensive experience in magnetic resonance imaging (MRI) interpretation of elbow injuries in elite athletes analyzed 243 MRI scans for which images were accessible for tear location and grade interpretation. Results: Nonoperative treatment of UCL injuries resulted in an overall 54% rate of return to play (RTP). Players who received PRP had a significantly longer delay in return to throwing (P < .001) and RTP (P = .012). The matched cohort analysis showed that MLB and MiLB pitchers in the no-PRP group had a significantly faster return to throwing (P < .05) and the MiLB pitchers in the no-PRP group had a significantly faster RTP (P = .045). The survival analysis did not reveal significant differences between groups over time. The use of PRP, MRI grade, and tear location were not statistically significant predictors for RTP or progression to surgery. Conclusion: In this retrospective matched comparison of MLB and MiLB pitchers and position players treated nonoperatively for a UCL tear, PRP did not improve RTP outcomes or ligament survivorship, although there was variability with respect to PRP preparations, injection protocols, time from injury to injection, and rehabilitation programs. MRI grade and tear location also did not significantly affect RTP outcomes or progression to surgery.