Miracle-dz/UniFAR-FTUs huggingface dataset:
Physical Activity, Genetic Susceptibility, and the Risk of Latent Autoimmune Diabetes in Adults and Type 2 Diabetes

Abstract Purpose Physical activity (PA) has been linked to a reduced risk of type 2 diabetes by reducing weight and improving insulin sensitivity. We investigated whether PA is associated with a lower incidence of latent autoimmune diabetes in adults (LADA) and whether the association is modified by genotypes of human leukocyte antigen (HLA), transcription factor 7-like 2 (TCF7L2)-rs7903146, or the fat mass and obesity-associated gene, FTO-rs9939609. Methods We combined data from a Swedish case-control study and a Norwegian prospective study including 621 incident cases of LADA and 3596 cases of type 2 diabetes. We estimated adjusted pooled relative risks (RRs) and 95% CI of diabetes in relation to high (≥ 30 minutes of moderate activity 3 times/week) self-reported leisure time PA, compared to sedentariness. Results High PA was associated with a reduced risk of LADA (RR 0.61; CI, 0.43-0.86), which was attenuated after adjustment for body mass index (BMI) (RR 0.90; CI, 0.63-1.29). The reduced risk applied only to noncarriers of HLA-DQB1 and -DRB1 (RR 0.49; CI, 0.33-0.72), TCF7L2 (RR 0.62; CI, 0.45-0.87), and FTO (RR 0.51; CI, 0.32-0.79) risk genotypes. Adjustment for BMI attenuated but did not eliminate these associations. For type 2 diabetes, there was an inverse association with PA (RR 0.49; CI, 0.42-0.56), irrespective of genotype. Main Conclusions Our findings indicate that high PA is associated with a reduced risk of LADA in individuals without genetic susceptibility.
A noncanonical role of NOD-like receptor NLRP14 in PGCLC differentiation and spermatogenesis

Significance NOD-like receptors (NLRs) are traditionally recognized as key surveillance pattern recognition receptors (PRRs) during innate immune regulation. Several NLRs exhibit highly restricted expression in mammalian germline, where their physiological functions are largely unknown. Here we report that Nlrp14, an NLR specifically expressed in testis and ovary, plays a critical role in regulating germ cell differentiation and reproduction. Nlrp14 deficiency led to decreased primordial germ cell-like cell (PGCLC) differentiation in vitro and reproduction failure in both male and female mice in vivo. In the male mice, Nlrp14 knockout strongly compromised differentiation of spermatogonial stem cells and meiosis. Mechanistically, NLRP14 protected HSPA2 from proteasome-mediated degradation by recruiting BAG2, loss of which was further confirmed in a human mutation associated with male sterility. NOD-like receptors (NLRs) are traditionally recognized as major inflammasome components. The role of NLRs in germ cell differentiation and reproduction is not known. Here, we identified the gonad-specific Nlrp14 as a pivotal regulator in primordial germ cell-like cell (PGCLC) differentiation in vitro. Physiologically, knock out of Nlrp14 resulted in reproductive failure in both female and male mice. In adult male mice, Nlrp14 knockout (KO) inhibited differentiation of spermatogonial stem cells (SSCs) and meiosis, resulting in trapped SSCs in early stages, severe oligozoospermia, and sperm abnormality. Mechanistically, NLRP14 promoted spermatogenesis by recruiting a chaperone cofactor, BAG2, to bind with HSPA2 and form the NLRP14−HSPA2−BAG2 complex, which strongly inhibited ChIP-mediated HSPA2 polyubiquitination and promoted its nuclear translocation. Finally, loss of HSPA2 protection and BAG2 recruitment by NLRP14 was confirmed in a human nonsense germline variant associated with male sterility. Together, our data highlight a unique proteasome-mediated, noncanonical function of NLRP14 in PGCLC differentiation and spermatogenesis, providing mechanistic insights of gonad-specific NLRs in mammalian germline development.
An improved optimistic three-stage model for the spread of HIV amongst injecting intravenous drug users

We start off this paper with a brief introduction to modeling Human Immunodeficiency Virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS) amongst sharing, injecting drug users (IDUs). Then we describe the mathematical model which we shall use which extends an existing model of the spread of HIV and AIDS amongst IDUs by incorporating loss of HIV infectivity over time. This is followed by the derivation of a key epidemiological parameter, the basic reproduction number $sf(R)_0$. Next we give some analytical equilibrium, local and global stability results. We show that if $sf(R)_0 \le 1$ then the disease will always die out. For $sf(R)_0 > 1$ there is the disease-free equilibrium (DFE) and a unique endemic equilibrium. The DFE is unstable. An approximation argument shows that we expect the endemic equilibrium to be locally stable. We next discuss a more realistic version of the model, relaxing the assumption that the number of addicts remains constant and obtain some results for this model. The subsequent section gives simulations for both models confirming that if $sf(R)_0 \le 1$ then the disease will die out and if $sf(R)_0 > 1$ then if it is initially present the disease will tend to the unique endemic equilibrium. The simulation results are compared with the original model with no loss of HIV infectivity. Next the implications of these results for control strategies are considered. A brief summary concludes the paper.
Intramyocardial Transplantation of Umbilical Cord Mesenchymal Stromal Cells in Chronic Ischemic Cardiomyopathy: A Controlled, Randomized Clinical Trial (HUC-HEART Trial)

Background and Objectives The HUC-HEART Trial (ClinicalTrials.gov Identifier: NCT02323477) was a controlled, prospective, phase I/II, multicenter, single-blind, three-arm randomized study of intramyocardial delivery of human umbilical cord-derived mesenchymal stromal cells (HUC-MSCs) combined with coronary artery bypass-grafting (CABG) in patients with chronic ischemic cardiomyopathy (CIC). The trial aimed to assess (i) the safety and the efficacy of cell transplantation during one-year follow-up, (ii) to compare the efficacy of HUC-MSCs with autologous bone-marrow-derived mononuclear cells (BM-MNCs) in the same clinical settings. Methods and Results Fifty-four patients who were randomized to receive HUC-MSCs (23×106) (n=26) or BM-MNCs (70×107) (n=12) in combination with CABG surgery. The control patients (n=16) received no cells/vehicles but CABG intervention. All patients were screened at baseline and 1, 3, 6, 12 months after transplantation. Forty-six (85%) patients completed 12 months follow-up. No short/mid-term adverse events were encountered. Decline in NT-proBNP (baseline∼6 months) in both cell-treated groups; an increase in left ventricular ejection fraction (LVEF) (5.4%) and stroke volume (19.7%) were noted (baseline∼6 or 12 months) only in the HUC-MSC group. Decreases were also detected in necrotic myocardium as 2.3% in the control, 4.5% in BM-MNC, and 7.7% in the HUC-MSC groups. The 6-min walking test revealed an increase in the control (14.4%) and HUC-MSC (23.1%) groups. Conclusions Significant findings directly related to the intramyocardial delivery of HUC-MSCs justified their efficacy in CIC. Stricter patient selection criteria with precisely aligned cell dose and delivery intervals, rigorous follow-up by detailed diagnostic approaches would further help to clarify the responsiveness to the therapy.
ChartSeer: Interactive Steering Exploratory Visual Analysis With Machine Intelligence

During exploratory visual analysis (EVA), analysts need to continually determine which subsequent activities to perform, such as which data variables to explore or how to present data variables visually. Due to the vast combinations of data variables and visual encodings that are possible, it is often challenging to make such decisions. Further, while performing local explorations, analysts often fail to attend to the holistic picture that is emerging from their analysis, leading them to improperly steer their EVA. These issues become even more impactful in the real world analysis scenarios where EVA occurs in multiple asynchronous sessions that could be completed by one or more analysts. To address these challenges, this work proposes ChartSeer, a system that uses machine intelligence to enable analysts to visually monitor the current state of an EVA and effectively identify future activities to perform. ChartSeer utilizes deep learning techniques to characterize analyst-created data charts to generate visual summaries and recommend appropriate charts for further exploration based on user interactions. A case study was first conducted to demonstrate the usage of ChartSeer in practice, followed by a controlled study to compare ChartSeer’s performance with a baseline during EVA tasks. The results demonstrated that ChartSeer enables analysts to adequately understand current EVA status and advance their analysis by creating charts with increased coverage and visual encoding diversity.
Control of ovarian and fat body expression of the Drosophila yolk protein 3 gene

In Drosophila the three yolk protein (yp) genes are expressed in the adult female fat body and ovary. The yolk proteins (YP5) are stored in the oocyte for utilisation during embryogenesis. Within the intergenic region of ypi and yp2, a fat body enhancer (FBE) and two ovarian enhancers have been found to direct YP1 and YP2 tissueand sex-specific expression. The male and female forms of Doublesex protein (DSXM and DSXF respectively) have been found to bind to the FBE and are thought to confer the sex-specificity of yp expression to the fat body of females only. Other possible trans-acting factors have also been shown to bind to the FBE in vivo, these include AEF-1 and C/EBP proteins. The dsx gene is at the end of the sex determination pathway, other genes that operate from this branch of the pathway include hermaphrodite (her) and into-sex (ix), and it is possible that HER and IX proteins could also regulateyp gene expression. Upstream of yp3 are sequences that direct female-, fat body-specific yp3 expression (FBE3) and ovarian-specific yp3 expression (0E3). This project involved analysis of FBE3 and 0E3 to gain thrther understanding of the regulation of yp3 expression. The role of DSX in the regulation of yp3 has been investigated; the FBE3 was divided into smaller subfragments and it was determined that one of these fragments can bind DSX in vitro. These subfragments were cloned into reporter gene constructs to test their capabilities in directing correct lacZ expression pattern in vivo, using P-element mediated transformation. This revealed that the fragment capable of binding DSX in vitro, could direct lacZ expression in fat body cells, but this expression was not sexspecific, both male and female fat bodies showed reporter gene expression. C/EBP was reported to bind to the FBE in vitro and considered to be a potential activator of yp gene expression. From C/EBP mutant analysis, there was no observed difference from wild type in the level of YP expression in vivo; thus it is unlikely that C/EBP has a regulatory role in yp gene expression in the fat body.
Prognostic Value Of Blood Cultures as an Illness Severity Marker In Emergency Medical Admissions.

BACKGROUND Positive blood cultures predict mortality. The prognostic value of blood culture performance itself has not been fully defined. METHODS We evaluated medical admissions from 2002-2017. We defined blood culture category as 1) no culture 2) negative culture 3) positive culture. We employed a multivariable logistic regression model to evaluate outcomes. RESULTS We evaluated 78,568 blood cultures in 106,586 admissions. 30-day in-hospital mortality for no culture was 2.8% (95%CI 2.7, 2.9), culture negative 8.9% (95%CI 8.5, 9.3) and culture positive 16.7% (95%CI 15.5, 17.9). There was significant interaction between blood culture category and illness severity, OR 1.06 (95%CI 1.05, 1.08), and comorbidity, OR 1.09 (95%CI 1.09, 1.10). CONCLUSION Performance and results of blood cultures are independently associated with increased mortality.
PhosphoShield: Improving Trypsin Digestion of Phosphoproteins by Shielding the Negatively Charged Phosphate Moiety.

Protein phosphorylation is a post-translational modification that is essential to cellular signaling, cellular function, and associated disease progression. Bottom-up proteomics based on enzymatic digestion is the most widely used approach for identifying and quantifying phosphoproteins in complex biological samples. Researchers have largely optimized the experimental conditions for trypsin digestion, and it is now a routine procedure. However, trypsin digestion is impaired by the presence of phosphorylated residues in the protein sequence. This impairment arises from the fact that there are commonly salt bridges between a negatively charged phosphate group and the side chain of protonated arginine or lysine. On average, 55% of all phosphopeptides have their phosphosites located less than three amino acid residues from a cleavage site. Salt bridges reduce the cleavage accessibility for trypsin by masking the basic site chain groups of arginine and lysine. Thus, there are frequent miss-cleavages in the vicinity of phosphorylation sites, thereby lessening both the depth of proteome coverage and the quantification accuracy of phosphoproteomics. In this work, we propose a method termed PhosphoShield, to mitigate salt bridge formation by adding a digallium complex that exhibits a high binding affinity to the phosphate group. We tested our method using quantitative mass spectrometry analyses of the phosphoproteome of human liver cancer cells (HepG2). PhosphoShield enhances the cleavage frequency of at least 17% of tryptic phosphopeptides having cleavage sites close to the phosphate group.
Evolution in the Genus Egernia (Lacertilia: Scincidae)

glacial periods. It is suggested that expansion along the eastern and western sides of the Great Dividing Range resulted in the formation of several species pairs. Continuation of this expansion westward to Western Australia resulted in further species formation. Other possible major sources of speciation are isolation of populations in north-western Australia, Tasmania and the mountain ranges of central Australia. It is suggested that the expansion of populations from the rainforest "pool" has resulted in the formation of the species groups, while expansion to other areas has resulted in the differentiation of species within these groups.
Maternal personality, social support, and changes in depressive, anxiety, and stress symptoms during pregnancy and after delivery: A prospective-longitudinal study

Background The role of maternal personality and perceived social support for peripartum changes in psychopathological symptoms remains unresolved. Methods In a regional-epidemiological sample of 306 women, depressive, anxiety, and stress symptoms were assessed three times during pregnancy and three times after delivery with the 21-item version of the Depression Anxiety Stress Scale. In pregnancy, the Big Five personality traits and perceived social support were assessed with the short version of the Big Five Inventory and the Social Support Questionnaire. Results Multilevel analyses revealed that depressive (b = -0.055) and stress (b = -0.047) symptoms decreased from early to late pregnancy. After delivery, anxiety symptoms were lower (two months postpartum: b = -0.193; four/ 16 months postpartum: b = -0.274), but stress symptoms were higher (two months postpartum: b = 0.468; four/ 16 months postpartum: b = 0.320) than during pregnancy. Across the peripartum period, more conscientious and more extraverted women experienced lower depressive and stress symptoms (b = -0.147 to -0.177), and more emotionally stable women experienced lower depressive, anxiety, and stress symptoms (b = -0.294 to -0.415). More emotionally stable women more strongly increased in anxiety during pregnancy (b = 0.019), and more extraverted women less strongly increased in depression after delivery (b = -0.010). Moreover, peripartum depressive, anxiety, and stress symptoms were lower in women with higher perceived social support (b = -0.225 to -0.308). Conclusions Less emotionally stable, less conscientious, and less extraverted women and women with lower perceived social support seem to be at increased risk for peripartum psychopathological symptoms and might thus particularly profit from targeted prevention.
Reduced Dose of Beta-Alanine Is Sufficient to Maintain Performance in Repeated Sprints

Abstract Zandona, BA, Ramos, RA, de Oliveira, CdS, McAnulty, SR, Ferreira, LHB, Smolarek, AC, Enes, AAN, Urbinati, KMdSS, Aragon, AA, Schoenfeld, BJ, and de Souza Junior, TP. Reduced Dose of Beta-Alanine Is Sufficient to Maintain Performance in Repeated Sprints. J Strength Cond Res 36(6): 1636–1642, 2022—Beta-alanine (BA) supplementation has been shown to be effective in improving physical performance by increasing carnosine concentration. However, it is still necessary to know the effect of a maintenance dose on performance. Thus, this study aimed to investigate the effects of a maintenance dose of BA supplementation on performance. Forty-four anaerobically trained men with 23.9 ± 3.8 years of age, 176.0 ± 0.05 cm height, 81.2 ± 7.5 kg body mass, and 15.5 ± 2.9% of body fat performed a cycle ergometer test consisting of 4 sprints of 30 s with 4 minutes of active recovery. The study comprised 3 phases: (a) presupplementation, (b) supplementation with 6.4 g·d−1 BA or placebo, and (c) postsupplementation with a maintenance dose of 1.2 g·d−1 of BA or interruption of supplementation. Data were analyzed using generalized estimated equations with a priori 0.05 level of significance. The placebo group and interruption group presented a lower power (7.28 ± 0.66 and 7.71 ± 0.42 W·kg−1 vs. 8.04 ± 0.84 and 9.25 ± 1.18 W·kg−1, respectively; p < 0.05) during the third sprint in postsupplementation, whereas the maintenance group maintained the required power (7.47 ± 1.03 vs. 8.74 ± 1.07 W·kg−1; p > 0.05). The placebo group also presented higher percentage of fatigue (44.5% ± 12.3 and 44.8% ± 7.7 vs. 37.6 ± 7.2%; p = 0.021) and higher subjective perception of exertion (8.92 ± 0.90 vs. 8.00 ± 1.60; p = 0.028). Therefore, the maintenance dose of 1.2 g·d−1 BA was effective in maintaining performance, whereas a reduction in performance was observed after supplementation interruption.
Effect of an integrated neonatal care kit on cause-specific neonatal mortality in rural Pakistan

ABSTRACT Background In 2018, Pakistan had the world’s highest neonatal mortality rate. Within Pakistan, most neonatal deaths occur in rural areas where access to health facilities is limited, and robust vital registration systems are lacking. To improve newborn survival, there is a need to better understand the causes of neonatal death in high burden settings and engage caregivers in the promotion of newborn health. Objective To describe the causes of neonatal death in a rural area in Pakistan and to estimate the effect of an integrated neonatal care kit (iNCK) on cause-specific neonatal mortality. Methods We analyzed data from a community-based, cluster-randomized controlled trial of 5286 neonates in Rahim Yar Khan (RYK), Punjab, Pakistan between April 2014 and August 2015. In intervention clusters, Lady Health Workers (LHW) delivered the iNCK and education on its use to pregnant women while control clusters received the local standard of care. The iNCK included interventions to prevent and identify signs of infection, identify low birthweight (LBW), and identify and manage hypothermia. Verbal autopsies were attempted for all deaths. The primary outcome was cause-specific neonatal mortality. Results Verbal autopsies were conducted for 84 (57%) of the 147 reported neonatal deaths. The leading causes of death were infection (44%), intrapartum-related complications (26%) and prematurity/LBW (20%). There were no significant differences in neonatal mortality due to prematurity/LBW (RR 0.43; 95% CI 0.15–1.24), infection (RR 1.10; 95% CI 0.58–2.10) or intrapartum-related complications (RR 1.04; 95% CI 0.0.45–2.41) among neonates who died in the intervention arm compared to those who died in the control arm. Conclusion The major causes of neonatal deaths in RYK, Pakistan mirror the global landscape of neonatal deaths. The iNCK did not significantly reduce any cause-specific neonatal mortality.
Flexural properties of salvaged dead yellow-cedar from Southeast Alaska

A decline and mortality problem is affecting yellow-cedar trees on more than a half-million acres in southeast Alaska. Because of the high decay resistance of yellow-cedar, dead snags may remain standing for 100 years or more. Currently, this wood is primarily used for firewood. The results of the study reported here indicate that the flexural properties of wood from dead yellow-cedar snags is little affected by how long the trees have been dead. Living yellow-cedar trees are sometimes infected with black stain, which remains in the trees after they die. Black stain does not reduce the flexural properties of wood from either live or dead trees. Thus, utilization options for wood from dead cedar snags can be broadened to higher value uses consistent with those for wood from live cedar trees.
Feeding, Development and Reproduction of the Predatory Mite, Hypoaspis Vacua on Various Kinds of Food Substances (Acari: Laelapidae)

The predacious mite, Hypoaspis Vacua (Michael) successfully developed from larva to adult stage when fed on eggs of housefly, Musca domestica (L.) and nymphs of acarid mite, Rhizoglyphus echinopus (Fum. & Rob.) in the laboratory. The duration of the immature stages and of the adult stage were determined. Food type greatly affected female fecundity and feeding capacity. Immature stages of H. vacua consumed in total an average of 13.6 eggs of M. domestica and 33.0 nymphs of R. echinopus, whereas each day throughout her life, the adult female consumed an average of 4.1 eggs of M. domestica and 13.23 nymphs of R. echinopus. Eggs of housefly were the most suitable diet, as it prolonged adult longevity (76.8 days) and increased female fecundity (13 eggs/female/day). RésuméL’acarien prédateur, Hypoaspis Vacua (Michael) s’est développé avec succès depuis la larve jusqu’au stade adulte quand il s’alimentait sur des oeufs de la mouche domestique Musca domestica (L.) et des larves de l’acarien Rhizoglyphus echinopus (Fum. et Rob.) au laboratoire. Les durées des stades non murs et adulte ont été déterminées. Le type de nourriture affectait grandement la fécondité des femelles et la capacité de prise alimentaire. Les stades pré-adultes consomment au total enmoyenne 13,6 M. domestica et 33,0 R. echinopusp par jour pendant toute leur existence, la famella adulte une moyenne de 4,1 M. domestica et 13,23 R. echinopus. Les oeufs de la mouche domestique offraient le régime alimentaire convenant le mieux puisqu’ils prolongeaient la longévité des adultes (76,8 jours) et augentaient la fécondié des femelles (1,3 oeufs/femele/jour).
The elimination of radiocaesium from fish

1. A general model for fish to predict the elimination rate of radiocaesium from a regression of water temperature, weight and a categorical variable for exposure (steady state, non-steady state), was developed from published data. 2. The generality of the new model for the elimination of radiocaesium from fish provides aquatic ecologists with the means to simplify greatly and improve existing methods for estimating ration for fish through the use of 137 Cs based bioenergetics models. 3. Comparisons of the general model with other less complete data suggests that the model is applicable to many of the common taxa of north temperate fish. 4. Fish whose tissue pools are equilibrated to ambient concentrations (steady state) appear to eliminate radiocaesium at a rate much slower than those in non-steady state. Application of previous laboratory models to steady state field situations would overestimate the elimination rate of radiocaesium by 1.4-fold.