Miracle-dz/UniFAR-FTUs huggingface dataset:
Histopathologic Findings in Ascending Aortas From Individuals With Loeys-Dietz Syndrome (LDS)

Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder resulting from genetic mutations in the transforming growth factor β receptors 1 and 2 (TGFBR1 and TGFBR2). The syndrome is characterized phenotypically by hypertelorism, bifid uvula, and/or cleft palate, and arterial tortuosity with aneurysms and dissections. LDS has a much more rapid clinical course than Marfan syndrome (MFS) and thus those diagnosed with LDS are currently being recommended for prophylactic aortic root replacement at younger ages and with smaller aortic dimensions. Aortic root tissue obtained at surgery was compared between 15 patients carrying a diagnosis of LDS, 11 patients with MFS and 11 control aortas to evaluate the range of histopathologic changes in LDS. Standard hematoxylin and eosin and Movat pentachrome stains were performed. LDS samples had increased medial collagen and a subtle but diffuse form of elastic fiber fragmentation and extracellular matrix deposition, referred to as diffuse medial degeneration. LDS samples had significantly more diffuse medial degeneration compared with MFS and control samples (P<0.05), significantly less medial degeneration of the “cystic” variety compared with MFS (P<0.01) and significantly more collagen deposition than control samples (P<0.01). Additionally, an immunohistochemical stain for pSmad2, a marker of TGFβ activity, was significantly increased in LDS patients compared with controls (P<0.001). Overall, the histologic findings of LDS are best appreciated with special stains to evaluate fibrosis and elastic fiber fragmentation. The changes described, although not entirely specific for LDS, help differentiate this entity from other vascular diseases in the appropriate clinicopathologic setting.
Modelling relationships between match events and match outcome in elite football

Abstract Identifying match events that are related to match outcome is an important task in football match analysis. Here we have used generalised mixed linear modelling to determine relationships of 16 football match events and 1 contextual variable (game location: home/away) with the match outcome. Statistics of 320 close matches (goal difference ≤ 2) of season 2012–2013 in the Spanish First Division Professional Football League were analysed. Relationships were evaluated with magnitude-based inferences and were expressed as extra matches won or lost per 10 close matches for an increase of two within-team or between-team standard deviations (SD) of the match event (representing effects of changes in team values from match to match and of differences between average team values, respectively). There was a moderate positive within-team effect from shots on target (3.4 extra wins per 10 matches; 99% confidence limits ±1.0), and a small positive within-team effect from total shots (1.7 extra wins; ±1.0). Effects of most other match events were related to ball possession, which had a small negative within-team effect (1.2 extra losses; ±1.0) but a small positive between-team effect (1.7 extra wins; ±1.4). Game location showed a small positive within-team effect (1.9 extra wins; ±0.9). In analyses of nine combinations of team and opposition end-of-season rank (classified as high, medium, low), almost all between-team effects were unclear, while within-team effects varied depending on the strength of team and opposition. Some of these findings will be useful to coaches and performance analysts when planning training sessions and match tactics.
SM2PH‐db: an interactive system for the integrated analysis of phenotypic consequences of missense mutations in proteins involved in human genetic diseases

Understanding how genetic alterations affect gene products at the molecular level represents a first step in the elucidation of the complex relationships between genotypic and phenotypic variations, and is thus a major challenge in the postgenomic era. Here, we present SM2PH‐db (http://decrypthon.igbmc.fr/sm2ph), a new database designed to investigate structural and functional impacts of missense mutations and their phenotypic effects in the context of human genetic diseases. A wealth of up‐to‐date interconnected information is provided for each of the 2,249 disease‐related entry proteins (August 2009), including data retrieved from biological databases and data generated from a Sequence–Structure–Evolution Inference in Systems‐based approach, such as multiple alignments, three‐dimensional structural models, and multidimensional (physicochemical, functional, structural, and evolutionary) characterizations of mutations. SM2PH‐db provides a robust infrastructure associated with interactive analysis tools supporting in‐depth study and interpretation of the molecular consequences of mutations, with the more long‐term goal of elucidating the chain of events leading from a molecular defect to its pathology. The entire content of SM2PH‐db is regularly and automatically updated thanks to a computational grid data federation facilities provided in the context of the Decrypthon program. Hum Mutat 31:127–135, 2010. © 2009 Wiley‐Liss, Inc.
Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome

Atypical hemolytic uremic syndrome (aHUS) is characterized by acute renal failure, thrombocytopenia and microangiopathic hemolytic anemia, and occurs with an estimated incidence in the USA of 2 per 1,000,000. Disease pathogenesis is related to dysregulation of the alternative pathway (AP) of the complement cascade at the level of the cell membrane secondary to mutations in a number of complement genes including complement factor H (CFH), complement factor H‐related 5 (CFHR5), complement factor I (CFI), CD46 (MCP), complement factor B (CFB), complement component 3 (C3) and thrombomodulin (THBD). Since aHUS is rare, mutation rate data in large patient cohorts are scarce. Here we present the first cohort of American patients in whom mutation screening was completed on all genes currently implicated in aHUS. In addition to identifying a number of novel variants, we provide information on the relative frequency of mutations in these genes in an American aHUS population. Twelve percent (12%) of patients carrying disease‐associated genetic variants segregated mutations in more than one gene mandating comprehensive genetic testing in the diagnosis and management of these patients. ©2010 Wiley‐Liss, Inc.
The influence of shoe drop on the kinematics and kinetics of children tennis players

Abstract This study investigated the immediate effects of reducing the shoe drop (i.e. the difference between the heel and the forefoot height) on the kinematics and kinetics of the lower extremities of children tennis players performing a tennis-specific movement. Thirteen children tennis players performed a series of simulated open stance forehands wearing 3 pairs of shoes differing only in the drop: 0 (D0), 6 (D6) and the control condition of 12 mm (D12). Two embedded forceplates and a motion capture system were used to analyse the ground reaction forces and ankle and knee joint angles and moments of the leading lower limb. In D6 compared with D12, the peak impact force was reduced by 24% (p = .004) and the ankle was less dorsiflexed at foot strike (p = .037). In D0 compared with D12, the peak impact force was reduced by 17% (p = .049), the ankle was less dorsiflexed at foot strike (p = .045) and the knee was more flexed at foot strike (p = .007). In addition, 4 out of 13 participants (31%) presented a forefoot strike pattern for some of the trials in D0. No difference was observed across shoe conditions for the peak knee extensor moment (p = .658) or the peak ankle plantarflexor moment (p = .071). The results provide preliminary data supporting the hypothesis that for children tennis players, using a 6-mm lower shoe drop might reduce heel impact forces and thus limit potentially impact-related injuries.
Effects of strength and endurance exercise order on endocrine responses to concurrent training

Abstract The present study examined the effect of strength and endurance training order on the endocrine milieu associated with strength development and performance during concurrent training. A randomised, between-groups design was employed with 30 recreationally resistance-trained males completing one of four acute experimental training protocols; strength training (ST), strength followed by endurance training (ST-END), endurance followed by strength training (END-ST) or no training (CON). Blood samples were taken before each respective exercise protocol, immediately upon cessation of exercise, and 1 h post cessation of exercise. Blood samples were subsequently analysed for total testosterone, cortisol and lactate concentrations. Ability to maintain 80% 1RM during strength training was better in ST and ST-END than END-ST (both p < .05). Immediately following the respective exercise protocols all training interventions elicited significant increases in testosterone (p < .05). ST and END-ST resulted in greater increases in cortisol than ST-END (both p < .05). The testosterone:cortisol ratio was similar following the respective exercise protocols. Blood lactate concentrations post-training were greater following END-ST and ST than ST-END (both p < .05). Conducting endurance exercise prior to strength training resulted in impaired strength training performance. Blood cortisol and lactate concentrations were greater when endurance training was conducted prior to strength training than vice versa. As such, it may be suggested that conducting endurance prior to strength training may result in acute unfavourable responses to strength training when strength training is conducted with high loads.
The role of estrogens in neuropsychiatric disorders

This review is a résumé of the most important findings in the research area of estrogenic effects in neuropsychiatric disorders published throughout the year 2001. The influence of estrogen in disorders like schizophrenia, Alzheimer's disease, and affective disorders are discussed. Moreover, animal and in-vitro studies with the objective to delineate the mechanisms for estrogenic involvement in anxiety, mood, cognition, and neuroprotection are also reviewed.
Evaluation of body composition with bioimpedence. A comparison between athletic and non-athletic children

Abstract Purpose: Conventional Bioelectrical Impedance Analysis (BIA) or Bioelectrical Impedance Vector Analysis (BIVA) can provide direct evaluations of body composition. The purpose of this study was to evaluate lean and fat mass (FM), and hydration of children involved in daily competitive sports. Methods: 190 non-athletic [8.2–10.5 years] and 29 competitive children [8.0–10.5 years] were enrolled. They were evaluated: at baseline (t0), 6 months (t1) and one year (t2). Anthropometric, BIA and BIVA, lean and FM, and hydration evaluations were performed. Results: Resistance (R/h) and reactance (Xc/h) were lower at t0 in competitive individuals when compared to controls. Xc/h (+3.28) significantly increases in competitive when compared to non-competitive individuals (+0.66, p for difference: 0.011), while phase angle (PA) was lower at t0 (5.72 vs. 6.17, p < .001) and after 6 months (p = .001). Total body water adjusted for height (TBW/h) significantly increased only in non-athletes (+0.50 ± 0.13, p < .001) between t0 and t1. At t1, extracellular water (ECW) significantly decreased (p = .026) in the two groups: −0.45 ± 0.19% in non-competitive, −1.63 ± 0.49% in competitive subjects, while intracellular water (ICW) increased. At one-year follow-up (t2), there were no statistically significant differences in R/h, Xc/h and PA in competitive individuals when compared to baseline and t1. Furthermore, we observed at t2 that hours/week of training, age, male gender and body mass index can influence FFM/h and FM/h in both competitive and non-competitive subjects. In particular, a direct correlation was for hours/week and FFM/h, inverse for hours/week and FM/h. Conclusions: Body mass index does not allow evaluating differences in lean body mass and FM between athletes and non-athletes. BIA and BIVA can give more reliable details about body composition differences in competitive adolescents and non-competitive, outlining a progressive decline in ECW and increase in ICW without affecting TBW composition of athletes.
Differences in forearm strength, endurance, and hemodynamic kinetics between male boulderers and lead rock climbers

This study examined differences in the oxygenation kinetics and strength and endurance characteristics of boulderers and lead sport climbers. Using near infrared spectroscopy, 13-boulderers, 10-lead climbers, and 10-controls completed assessments of oxidative capacity index and muscle oxygen consumption (m⩒O2) in the flexor digitorum profundus (FDP), and extensor digitorum communis (EDC). Additionally, forearm strength (maximal volitional contraction MVC), endurance (force–time integral FTI at 40% MVC), and forearm volume (FAV and ΔFAV) was assessed. MVC was significantly greater in boulderers compared to lead climbers (mean difference = 9.6, 95% CI 5.2–14 kg). FDP and EDC oxidative capacity indexes were significantly greater (p = .041 and .013, respectively) in lead climbers and boulderers compared to controls (mean difference = −1.166, 95% CI (−3.264 to 0.931 s) and mean difference = −1.120, 95% CI (−3.316 to 1.075 s), respectively) with no differences between climbing disciplines. Climbers had a significantly greater FTI compared to controls (mean difference = 2205, 95% CI= 1114–3296 and mean difference = 1716, 95% CI = 553–2880, respectively) but not between disciplines. There were no significant group differences in ΔFAV or m⩒O2. The greater MVC in boulderers may be due to neural adaptation and not hypertrophy. A greater oxidative capacity index in both climbing groups suggests that irrespective of climbing discipline, trainers, coaches, and practitioners should consider forearm specific aerobic training to aid performance.
Sport expertise in perception–action coupling revealed in a visuomotor tracking task

Abstract We compared the visuomotor coordination of tennis players with different levels of expertise (Super-Experts, Experts and Non-Experts) in a visuomotor tracking (VMT) task. Participants were asked to track a moving target which could rebound on the sides of a 2D screen. Results indicated that the VMT task allowed the discrimination of expertise. Multiple regression analysis revealed that performance could be explained by the temporal adaptation of participants to rebounds and the number of movement adaptations. Compared to Non-Experts, the Experts had a shorter perturbation time with higher adaptation and regulation. This corresponds to a better perception–action coupling and the predominant use of a prospective control process. Results also indicate that perception–action coupling capacities are transferable to virtual tasks, and allow us to reveal processes of visuomotor coordination that differentiate experts and novices.
Cellular oxygen sensing, signalling and how to survive translational arrest in hypoxia

Hypoxia is a consequence of inadequate oxygen availability. At the cellular level, lowered oxygen concentration activates signal cascades including numerous receptors, ion channels, second messengers, as well as several protein kinases and phosphatases. This, in turn, activates trans‐factors like transcription factors, RNA‐binding proteins and miRNAs, mediating an alteration in gene expression control. Each cell type has its unique constellation of oxygen sensors, couplers and effectors that determine the activation and predominance of several independent hypoxia‐sensitive pathways. Hence, altered gene expression patterns in hypoxia result from a complex regulatory network with multiple divergences and convergences. Although hundreds of genes are activated by transcriptional control in hypoxia, metabolic rate depression, as a consequence of reduced ATP level, causes inhibition of mRNA translation. In a multi‐phase response to hypoxia, global protein synthesis is suppressed, mainly by phosphorylation of eIF2‐alpha by PERK and inhibition of mTOR, causing suppression of 5′‐cap‐dependent mRNA translation. Growing evidence suggests that mRNAs undergo sorting at stress granules, which determines the fate of mRNA as to whether being translated, stored, or degraded. Data indicate that translation is suppressed only at ‘free’ polysomes, but is active at subsets of membrane‐bound ribosomes. The recruitment of specific mRNAs into subcellular compartments seems to be crucial for local mRNA translation in prolonged hypoxia. Furthermore, ribosomes themselves may play a significant role in targeting mRNAs for translation. This review summarizes the multiple facets of the cellular adaptation to hypoxia observed in mammals.
FAS mRNA editing in human systemic lupus erythematosus

FAS/FASL system plays a central role in maintaining peripheral immune tolerance. Human Systematic Lupus Erythematosus (SLE) is a prototypic systemic autoimmune disease characterized by expansion of autoreactive lymphocytes. It remains unclear whether a defective FAS/FASL system is involved in the pathogenesis of SLE. In this study, we have discovered a novel nucleotide insertion in FAS mRNA. We demonstrate that this novel FAS mutation occurs at mRNA levels, likely through a site‐specific mRNA editing process. The mRNA editing mutation is unique for human FAS because the similar mRNA editing event is absent in other human TNF receptor (TNFR) family genes with death domains (DR5, DR6, and TNFR1) and in murine FAS. The adenine insertion mutation in the coding region message causes the alteration of human FAS mRNA reading frame. Functionally, cells expressing the edited FAS (edFAS) were refractory to FAS‐mediated apoptosis. Surprisingly, cells from SLE patients produced significantly more edFAS products compared to cells from normal healthy controls. Additionally, we demonstrated that persistent engagement of T‐cell receptor increases human FAS mRNA editing in human T cells. Our data suggest that the site‐specific FAS mRNA editing mutation may play a critical role in human immune responses and in the pathogenesis of human chronic inflammatory diseases. Hum Mutat 32:1268–1277, 2011. ©2011 Wiley Periodicals, Inc.
The efficacy of workplace ergonomic interventions to control musculoskeletal disorders: A critical analysis of the peer-reviewed literature

The purpose of this paper is to examine the efficacy of workplace ergonomic interventions to control musculoskeletal disorders. The peer-reviewed literature prior to 1 January 1999 was examined and 101 studies were found that met the selection criteria. Eight studies involved back belt use (8.2%), 21 involved ergonomic and/or lifting training as the only or primary intervention (21.4%), 10 examined tools or technologies as the only interventions (9.8%), 15 were exercise interventions (11.2%), one involved job redesign (1%), and 47 studies involved multiple intervention components (48%) Eighty-four per cent of all of the studies found some positive results, although the majority had mixed results. Only 32% of the studies used experimental or quasi-experimental designs. The methodological, practical, and policy-related implications are discussed.
Vastus lateralis surface and single motor unit electromyography during shortening, lengthening and isometric contractions corrected for mode‐dependent differences in force‐generating capacity

Aim: Knee extensor neuromuscular activity, rectified surface electromyography (rsEMG) and single motor unit EMG was investigated during isometric (60° knee angle), shortening and lengthening contractions (50–70°, 10° s−1) corrected for force–velocity‐related differences in force‐generating capacity. However, during dynamic contractions additional factors such as shortening‐induced force losses and lengthening‐induced force gains may also affect force capacity and thereby neuromuscular activity. Therefore, even after correction for force–velocity‐related differences in force capacity we expected neuromuscular activity to be higher and lower during shortening and lengthening, respectively, compared to isometric contractions.
Motor Resonance and Linguistic Focus

Previous studies have demonstrated that verbal descriptions of actions activate compatible motor responses (Glenberg & Kaschak, 2002; Zwaan & Taylor, 2006). The present study replicates previous findings showing that, within a sentence, such activation is localized on the verb that denotes the action. Moreover, motor resonance is found to yield to linguistic focus. If a postverbal adverb maintains focus on a matching action (“slowly” or “quickly”), motor resonance occurs, but if the adverb shifts the focus to the agent (e.g., “obediently” or “eagerly”), a cessation of motor resonance ensues. These findings are discussed within the context of theories of motor resonance, action understanding, mental simulation, and linguistic focus.
Short article: Irrelevant speech effects and statistical learning

Immediate serial recall of visually presented verbal stimuli is impaired by the presence of irrelevant auditory background speech, the so-called irrelevant speech effect. Two of the three main accounts of this effect place restrictions on when it will be observed, limiting its occurrence either to items processed by the phonological loop (the phonological loop hypothesis) or to items that are not too dissimilar from the irrelevant speech (the feature model). A third, the object-oriented episodic record (O-OER) model, requires only that the memory task involves seriation. The present studies test these three accounts by examining whether irrelevant auditory speech will interfere with a task that does not involve the phonological loop, does not use stimuli that are compatible with those to be remembered, but does require seriation. Two experiments found that irrelevant speech led to lower levels of performance in a visual statistical learning task, offering more support for the O-OER model and posing a challenge for the other two accounts.
A Multifactorial Likelihood Model for MMR Gene Variant Classification Incorporating Probabilities Based on Sequence Bioinformatics and Tumor Characteristics: A Report from the Colon Cancer Family Registry

Mismatch repair (MMR) gene sequence variants of uncertain clinical significance are often identified in suspected Lynch syndrome families, and this constitutes a challenge for both researchers and clinicians. Multifactorial likelihood model approaches provide a quantitative measure of MMR variant pathogenicity, but first require input of likelihood ratios (LRs) for different MMR variation‐associated characteristics from appropriate, well‐characterized reference datasets. Microsatellite instability (MSI) and somatic BRAF tumor data for unselected colorectal cancer probands of known pathogenic variant status were used to derive LRs for tumor characteristics using the Colon Cancer Family Registry (CFR) resource. These tumor LRs were combined with variant segregation within families, and estimates of prior probability of pathogenicity based on sequence conservation and position, to analyze 44 unclassified variants identified initially in Australasian Colon CFR families. In addition, in vitro splicing analyses were conducted on the subset of variants based on bioinformatic splicing predictions. The LR in favor of pathogenicity was estimated to be ∼12‐fold for a colorectal tumor with a BRAF mutation‐negative MSI‐H phenotype. For 31 of the 44 variants, the posterior probabilities of pathogenicity were such that altered clinical management would be indicated. Our findings provide a working multifactorial likelihood model for classification that carefully considers mode of ascertainment for gene testing.