Miracle-dz/UniFAR-FTUs huggingface dataset:
Spectrum of Pathogenic Variants in SRD5A2 in Indian Children with 46,XY Disorders of Sex Development and Clinically Suspected Steroid 5α-Reductase 2 Deficiency

The aim of this study was to assess the prevalence of pathogenic variants in the SRD5A2 gene in children with 46,XY disorders of sex development (DSD) with normal to high serum testosterone levels and absence of Müllerian structures on imaging and to evaluate the genotype-phenotype correlation. Seventy-five patients with 46,XY DSD and probable clinical diagnosis of 5α-reductase 2 deficiency or androgen insensitivity syndrome were enrolled. Genetic analysis was done for pathogenic variants in SRD5A2, and the genotype-phenotype correlation was studied. As a result, 10 pathogenic or likely pathogenic biallelic variants in SRD5A2, either homozygous or compound heterozygous, were identified in 25 of 75 (33.3%) patients. The hCG stimulated testosterone: dihydrotestosterone (T:DHT) ratio was elevated in all patients with pathogenic variants in SRD5A2 and in nearly 90% of those without pathogenic variants in SRD5A2 in whom this was assessed. The missense pathogenic variant p.R246Q was a hotspot. One novel pathogenic variant p.Y178*, and a variant p.F194I, not previously reported in patients with 5α-reductase 2 deficiency, were identified. The missense variant p.F194I was predicted as deleterious and damaging by in silico analysis and as likely to reduce the enzyme activity by protein modeling. In conclusion, pathogenic variants in SRD5A2 can be detected in a wide spectrum of Indian patients with 46,XY DSD. Molecular genetic analysis should be considered as a first-line test as the T:DHT ratio lacks specificity and a hotspot variant is present in a vast majority.
Higher Stability in Leaf Water Status in Heat-Tolerant Cultivars of Greengram (Vigna radiata (L.) Wilczek)

Greengram is adapted to relatively warm, dry climatic conditions and temperatures during reproductive period of >40°C during the day result in yield reduction. Greengram cultivars SAMRAT and IPM 02-3, which were developed from Indian Institute of Pulses Research shows higher heat tolerance than other cultivars. For an effective breeding program understanding of the mechanism controlling the heat tolerance in heat tolerant cultivar is necessary. High temperature often coincides with intensive solar radiation, which causes excessive transpiration and temporal water deficit in plants in the mid-day and there was a cultivar difference in mid-day depression of leaf water status. In heat-tolerant cultivars, mid-day depression in leaf water status was smaller and stomatal conductance was higher than those in heat-sensitive cultivars, well reflecting stomatal conductance and growth. Chlorophyll stability index showed less reduction in heat tolerant cultivars than susceptible ones under heat stress environment. The results are discussed in terms of heat tolerance strategies in relation to changes in leaf water status and gas exchange in plants. We conclude that daily stability in leaf water status could be a reliable characteristic to estimate heat tolerance in greengram.
HIV‐1 capsids mimic a microtubule regulator to coordinate early stages of infection

While the microtubule end‐binding protein, EB1 facilitates early stages of HIV‐1 infection, how it does so remains unclear. Here, we show that beyond its effects on microtubule acetylation, EB1 also indirectly contributes to infection by delivering the plus‐end tracking protein (+TIP), cytoplasmic linker protein 170 (CLIP170) to the cell periphery. CLIP170 bound to intact HIV‐1 cores or in vitro assembled capsid–nucleocapsid complexes, while EB1 did not. Moreover, unlike EB1 and several other +TIPs, CLIP170 enhanced infection independently of effects on microtubule acetylation. Capsid mutants and imaging revealed that CLIP170 bound HIV‐1 cores in a manner distinct from currently known capsid cofactors, influenced by pentamer composition or curvature. Structural analyses revealed an EB‐like +TIP‐binding motif within the capsid major homology region (MHR) that binds SxIP motifs found in several +TIPs, and variability across this MHR sequence correlated with the extent to which different retroviruses engage CLIP170 to facilitate infection. Our findings provide mechanistic insights into the complex roles of +TIPs in mediating early stages of retroviral infection, and reveal divergent capsid‐based EB1 mimicry across retroviral species.
Multi-View Separable Pyramid Network for AD Prediction at MCI Stage by 18F-FDG Brain PET Imaging

Alzheimer’s Disease (AD), one of the main causes of death in elderly people, is characterized by Mild Cognitive Impairment (MCI) at prodromal stage. Nevertheless, only part of MCI subjects could progress to AD. The main objective of this paper is thus to identify those who will develop a dementia of AD type among MCI patients. 18F-FluoroDeoxyGlucose Positron Emission Tomography (18F-FDG PET) serves as a neuroimaging modality for early diagnosis as it can reflect neural activity via measuring glucose uptake at resting-state. In this paper, we design a deep network on 18F-FDG PET modality to address the problem of AD identification at early MCI stage. To this end, a Multi-view Separable Pyramid Network (MiSePyNet) is proposed, in which representations are learned from axial, coronal and sagittal views of PET scans so as to offer complementary information and then combined to make a decision jointly. Different from the widely and naturally used 3D convolution operations for 3D images, the proposed architecture is deployed with separable convolution from slice-wise to spatial-wise successively, which can retain the spatial information and reduce training parameters compared to 2D and 3D networks, respectively. Experiments on ADNI dataset show that the proposed method can yield better performance than both traditional and deep learning-based algorithms for predicting the progression of Mild Cognitive Impairment, with a classification accuracy of 83.05%.
Stabilization of Perturbed Continuous-Time Systems Using Event-Triggered Model Predictive Control

In this article, event-triggered model predictive control (EMPC) of continuous-time nonlinear systems with bounded disturbances is studied. Two novel event-triggered control schemes are proposed. In the first strategy, an event-triggering condition, designed based on the state error between the actual system state and the optimal one, with an absolute threshold is considered. In the second strategy, an event-triggering condition with a mixed threshold is designed to further save the computational resources. The minimal interevent times of both event-triggered control schemes are obtained to avoid the Zeno behavior. Sufficient conditions of recursive feasibility for these two triggering strategies, which refer to the prediction horizon, the triggering level, and the disturbance bound, are obtained, respectively. Input-to-state practical stability (ISpS) of both event-triggered control systems is established without requiring the system state entering the terminal set in finite time, respectively. Finally, the numerical simulation shows the effectiveness of the proposed methods.
Quantitative Proteomic Profiling of Murine Ocular Tissue and the Extracellular Environment

Mass spectrometry‐based proteomics provides a robust and reliable method for detecting and quantifying changes in protein abundance among samples, including cells, tissues, organs, and supernatants. Physical damage or inflammation can compromise the ocular surface permitting colonization by bacterial pathogens, commonly Pseudomonas aeruginosa, and the formation of biofilms. The interplay between P. aeruginosa and the immune system at the site of infection defines the host's ability to defend against bacterial invasion and promote clearance of infection. Profiling of the ocular tissue following infection describes the nature of the host innate immune response and specifically the presence and abundance of neutrophil‐associated proteins to neutralize the bacterial biofilm. Moreover, detection of unique proteins produced by P. aeruginosa enable identification of the bacterial species and may serve as a diagnostic approach in a clinical setting. Given the emergence and prevalence of antimicrobial resistant bacterial strains, the ability to rapidly diagnose a bacterial infection promoting quick and accurate treatment will reduce selective pressure towards resistance. Furthermore, the ability to define differences in the host immune response towards bacterial invasion enhances our understanding of innate immune system regulation at the ocular surface. Here, we describe murine ocular infection and sample collection, as well as outline protocols for protein extraction and mass spectrometry profiling from corneal tissue and extracellular environment (eye wash) samples. © 2020 Wiley Periodicals LLC.
What exercise prescription is optimal to improve body composition and cardiorespiratory fitness in adults living with obesity? A network meta‐analysis

Current international guidelines recommend people living with obesity should be prescribed a minimum of 300 min of moderately intense activity per week for weight loss. However, the most efficacious exercise prescription to improve anthropometry, cardiorespiratory fitness (CRF) and metabolic health in this population remains unknown. Thus, this network meta‐analysis was conducted to assess and rank comparative efficacy of different exercise interventions on anthropometry, CRF and other metabolic risk factors. Five electronic databases were searched for randomized controlled trials (RCTs) that compared different exercise modalities to improve anthropometry, CRF and/or metabolic health in adults living with obesity. RCTs were evaluated using the Cochrane risk of bias tool. A random effects network meta‐analysis was performed within a frequentist framework. Of the 6663 articles retrieved, 45 studies with a total 3566 participants were included. Results reveal that while any type of exercise intervention is more effective than control, weight loss induced is modest. Interventions that combine high‐intensity aerobic and high‐load resistance training exert beneficial effects that are superior to any other exercise modality at decreasing abdominal adiposity, improving lean body mass and increasing CRF. Clinicians should consider this evidence when prescribing exercise for adults living with obesity, to ensure optimal effectiveness.
Validation of Progression-Free Survival Rate at 6 Months and Objective Response for Estimating Overall Survival in Immune Checkpoint Inhibitor Trials

Key Points Question Can surrogate end points, such as progression-free survival, be used to estimate overall survival in immunotherapy trials? Findings This systematic review and meta-analysis using data from 60 published immunotherapy randomized clinical trials in advanced solid cancers found that 6-month progression-free survival in the immunotherapy arm estimated 12-month overall survival well using a statistical model that accounts for tumor type. Meaning These findings suggest that this model could assist with selecting immunotherapy agents for further testing in large randomized clinical trials and with regulatory approvals in rare cancers for which randomized trials are not feasible.
An Ensemble of Hyperdimensional Classifiers: Hardware-Friendly Short-Latency Seizure Detection With Automatic iEEG Electrode Selection

We propose a new algorithm for detecting epileptic seizures. Our algorithm first extracts three features, namely mean amplitude, line length, and local binary patterns that are fed to an ensemble of classifiers using hyperdimensional (HD) computing. These features are embedded into prototype vectors representing ictal (during seizures) and interictal (between seizures) brain states are constructed. These vectors can be computed at different spatial scales ranging from a single electrode up to many electrodes. This flexibility allows our algorithm to identify the electrodes that discriminate best between ictal and interictal brain states. We assess our algorithm on the SWEC-ETHZ iEEG dataset that includes 99 short-time iEEG seizures recorded with 36 to 100 electrodes from 16 drug-resistant epilepsy patients. Using $k$-fold cross-validation and all electrodes, our algorithm surpasses state-of-the-art algorithms yielding significantly shorter latency (8.81 s vs. 11.57 s) in seizure onset detection, and higher specificity (97.31% vs. 94.84%) and accuracy (96.85% vs. 95.42%). We can further reduce the latency of our algorithm to 3.74 s by allowing a slightly higher percentage of false alarms (2% specificity loss). Using only the top 10% of the electrodes ranked by our algorithm, we still maintain superior latency, sensitivity, and specificity compared to the other algorithms with all the electrodes. We finally demonstrate the suitability of our algorithm to deployment on low-cost embedded hardware platforms, thanks to its robustness to noise/artifacts affecting the signal, its low computational complexity, and the small memory-footprint on a RISC-V microcontroller.
Shiga toxin-producing bacteria as emerging enteric pathogens associated with outbreaks of foodborne illness in the Islamic Republic of Iran.

Background Detection of the cause of diarrhoeal diseases is important for the management of the outbreaks. Aims This study investigated the prevalence of Shiga toxin-producing bacteria in stool samples of patients with diarrhoea associated with outbreaks of foodborne illness in the Islamic Republic of Iran. Methods A total of 532 stool and rectal swab samples from 70 sporadic outbreaks during May 2014 to August 2015 were examined for infection with Shiga toxin-producing bacteria. The isolates were examined for carriage of the virulence genes stx1 and stx2 in all isolates and eae/ehxA in Escherichia coli. Results E. coli, Shigella spp. , Citrobacter spp. , Enterobacter spp. , Klebsiella spp. and other enteric bacteria were detected in 77.7% (376/484), 5.0% (24/484), 3.9% (19/484), 0.4% (2/484), 3.7% (18/484) and 9.3% (45/484) of the samples respectively. Of the 196 sorbitol-negative E. coli strains, 3 (1.5%) carried the stx1 gene as did 2 of the 19 (10.5%) Citrobacter strains. Conclusion Shiga toxin-producing Citrobacter spp. strains should be considered as a newly emerging foodborne pathogen in outbreaks.
Role of amoebae for survival and recovery of ‘non-culturable’ Helicobacter pylori cells in aquatic environments

ABSTRACT Helicobacter pylori is a fastidious Gram-negative bacterium that infects over half of the world's population, causing chronic gastritis and is a risk factor for stomach cancer. In developing and rural regions where prevalence rate exceeds 60%, persistence and waterborne transmission are often linked to poor sanitation conditions. Here we demonstrate that H. pylori not only survives but also replicates within acidified free-living amoebal phagosomes. Bacterial counts of the clinical isolate H. pylori G27 increased over 50-fold after three days in co-culture with amoebae. In contrast, a H. pylori mutant deficient in a cagPAI gene (cagE) showed little growth within amoebae, demonstrating the likely importance of a type IV secretion system in H. pylori for amoebal infection. We also demonstrate that H. pylori can be packaged by amoebae and released in extracellular vesicles. Furthermore, and for the first time, we successfully demonstrate the ability of two free-living amoebae to revert and recover viable but non-cultivable coccoid (VBNC)-H. pylori to a culturable state. Our studies provide evidence to support the hypothesis that amoebae and perhaps other free-living protozoa contribute to the replication and persistence of human-pathogenic H. pylori by providing a protected intracellular microenvironment for this pathogen to persist in natural aquatic environments and engineered water systems, thereby H. pylori potentially uses amoeba as a carrier and a vector of transmission.
Anti‐HBc and hepatitis B virus DNA among HBsAg‐negative blood donors from the main central blood bank units in Eastern Libya

Post‐transfusion hepatitis B virus (PTHB) infection is still a public health problem in the world. In many developed countries, nucleic acid testing (NAT) for detection of Hepatitis B Virus (HBV)‐DNA has been implemented to enhance blood donation safety. In Libya, however, the testing for HBV infection is limited to the detection of HBV surface antigen (HBsAg) only.
Proximate Analysis, Physicochemical Properties and Chemical Constituents Characterization of Moringa Oleifera (Moringaceae) Seed Oil Using GC-MS Analysis

The fixed oil from M. Oleifera seed oil was analyzed by a combination of GC and GCMS. Twenty four (24) constituents amounting to 96.81% of the total oil were identified. The major constituents were Oleic acid (22.51%), Palmitic acid (10.64%), 9-octadecenol (12.76%) and phenylbut-3-yne (5.79%). The fixed oil of M. Oleifera seed is rich in fatty acids (44.93%) followed by hydrocarbons (32.95%), others are aldehyde (12.76%) esters (3.55%) and oxygenated hydrocarbon (2.62%). The oil was found to contain moderate level of unsaturated fatty acids, mainly Oleic acid (22.51%) and Erucic acid (1.98%). The dominant saturated acids were Palmitic (10.64%), Stearic acid (6.07%), Arachidic acid (2.21%) and Docosanoic (Behenic acid) (1.03%). The physio-chemical analyses and proximate composition of the n-hexane extract of M. Oleifera seed oil were also determined using standard analytical methods. Results showed that the specific gravity and refractive index were 0.9050 & 1.456. The recorded acid value, iodine value, Saponification number, free fatty acids and peroxide values were in the order 6.73mgKOHg-1, 68.65g100g-1, 180.92mgKOHg-1, 4.21mgKOHg-1, 2.60 meqKg-1. The percentage yield of the oil was 38.0% and the color of the oil was cream yellow. The following fatty acids were identified from the GCMS analysis. Myristic acid, Oleic acid, Palmitic acid, Stearic acid, Erucic acid, Arachidic acid and Docosanoic acid (Behenic acid). The result of the proximate composition showed that the seed contain 10.50% moisture, 39.57% crude protein, 5.00% ash, 5.00% crude fiber, 32.50% fat and 7.44% carbohydrate. The seed oil of M. Oleifera showed good physio-chemical properties and could be utilized successfully as a source of edible oil for human consumption and for industrial applications.
Effects of the adiponectin mimetic compound ALY688 on glucose and fat metabolism in visceral and subcutaneous rat adipocytes

ABSTRACT Adiponectin regulates white adipose tissue (WAT) metabolism and promotes insulin-sensitizing and anti-atherosclerotic effects in vivo. In this context, small molecule adiponectin receptor agonists have become of great therapeutic value for the treatment of metabolic diseases. Here, we investigated the effects of the adiponectin mimetic compound ALY688 on WAT metabolism. To accomplish this, rat epididymal (Epid) and subcutaneous inguinal (Sc Ing) adipocytes were isolated and incubated with ALY688. Subsequently, several parameters of glucose and fat metabolism were assessed. ALY688 promoted AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation, enhanced glucose oxidation, and suppressed fat oxidation in adipocytes from both fat depots. ALY688 did not affect basal and insulin-stimulated rates of glucose uptake, glucose incorporation into lipids, and AKTSer473 and p38 mitogen-activated protein kinase (MAPK) phosphorylations in either Epid or Sc Ing adipocytes. ALY688 did not alter basal lipolysis in Epid and Sc Ing adipocytes, but it enhanced isoproterenol-induced lipolysis in Epid adipocytes. Adiponectin receptor 2 (AdipoR2) mRNA was the prevalent isoform expressed in all adipocytes, and Epid adipocytes displayed significantly higher AdipoR2 mRNA expression than Sc Ing adipocytes. In conclusion, ALY688 can regulate adiposity and affect glycaemic control by altering substrate portioning in the WAT in a fat depot-specific manner.
Transdiagnostic perspective on psychological inflexibility and emotional dysregulation

Abstract Background: Psychological inflexibility and emotional dysregulation are a hallmark of psychopathology, being intrinsically embedded in emotional and personality disorders. However, the transdiagnostic mechanisms of psychological inflexibility and emotional dysregulation domains are still a matter of discussion. Aims: The present study aims to explore the relationships between cognitive fusion (as a measure of psychological inflexibility), emotion regulation strategies, such as cognitive reappraisal and emotional suppression and emotional dysregulation domains in two different samples. Method: In a cross-sectional design, 297 individuals were assessed with self-report measures and divided into non-clinical (n = 231) and clinical samples (n = 66), according to diagnosis. Results: Results showed that the degree of cognitive fusion was higher in the clinical sample. However, significant correlations between cognitive fusion, emotional regulation strategies and emotional dysregulation domains were found in the two samples. Cognitive reappraisal and emotional dysregulation domains predicted cognitive fusion and mediated the relationship between cognitive fusion and symptomatology in the two samples. Conclusions: Relationships between cognitive fusion and emotional dysregulation domains were found independent of diagnosis. The implementation of emotion regulation strategies may be related to individual differences. However, cognitive fusion, reappraisal and lack of strategies may be core transdiagnostic features in psychological inflexibility and emotion dysregulation.
Immunothrombosis and thromboinflammation in host defense and disease

Abstract Platelets are increasingly being recognized for playing roles beyond thrombosis and hemostasis. Today we know that they mediate inflammation by direct interactions with innate immune cells or secretion of cytokines/chemokines. Here we review their interactions with neutrophils and monocytes/macrophages in infection and sepsis, stroke, myocardial infarction and venous thromboembolism. We discuss new roles for platelet surface receptors like GPVI or GPIb and also look at platelet contributions to the formation of neutrophil extracellular traps (NETs) as well as to deep vein thrombosis during infection, e.g. in COVID-19 patients.
The importance of individual-to-society feedbacks in animal ecology and evolution.

The social decisions that individuals make-who to interact with and how frequently-gives rise to social structure. The resulting social structure then determines how individuals interact with their surroundings-resources and risks, pathogens and predators, competitors and cooperators. However, despite intensive research on (i) how individuals make social decisions and (ii) how social structure shapes social processes (e.g. cooperation, competition and conflict), there are still few studies linking these two perspectives. These perspectives represent two halves of a feedback loop: individual behaviour scales up to define the social environment, and this environment, in turn, feeds back by shaping the selective agents that drive individual behaviour. We first review well-established research areas that have captured both elements of this feedback loop-host-pathogen dynamics and cultural transmission. We then highlight areas where social structure is well studied but the two perspectives remain largely disconnected. Finally, we synthesise existing research on 14 distinct research topics to identify new prospects where the interplay between social structure and social processes are likely to be important but remain largely unexplored. Our review shows that the inherent links between individuals' traits, their social decisions, social structure, and social evolution, warrant more consideration. By mapping the existing and missing connections among many research areas, our review highlights where explicitly considering social structure and the individual-to-society feedbacks can reveal new dimensions to old questions in ecology and evolution.