Drugst.One - a plug-and-play solution for online systems medicine and network-based drug repurposing.

In recent decades, the development of new drugs has become increasingly expensive and inefficient, and the molecular mechanisms of most pharmaceuticals remain poorly understood. In response, computational systems and network medicine tools have emerged to identify potential drug repurposing candidates. However, these tools often require complex installation and lack intuitive visual network mining capabilities.

Heterozygous THBS2 pathogenic variant causes Ehlers-Danlos syndrome with prominent vascular features in humans and mice.

Ehlers-Danlos syndromes (EDS) are a group of connective tissue disorders caused by mutations in collagen and collagen-interacting genes. We delineate a novel form of EDS with vascular features through clinical and histopathological phenotyping and genetic studies of a three-generation pedigree, displaying an apparently autosomal dominant phenotype of joint hypermobility and frequent joint dislocations, atrophic scarring, prolonged bleeding time and age-related aortic dilatation and rupture. Coagulation tests as well as platelet counts and function were normal.

The predictive capacity of polygenic risk scores for disease risk is only moderately influenced by imputation panels tailored to the target population.

Motivation: Polygenic risk scores (PRSs) predict individuals' genetic risk of developing complex diseases. They summarize the effect of many variants discovered in genome-wide association studies (GWASs). However, to date, large GWASs exist primarily for the European population and the quality of PRS prediction declines when applied to other ethnicities.

Human-like scene interpretation by a guided counterstream processing.

In modeling vision, there has been a remarkable progress in recognizing a range of scene components, but the problem of analyzing full scenes, an ultimate goal of visual perception, is still largely open. To deal with complete scenes, recent work focused on the training of models for extracting the full graph-like structure of a scene. In contrast with scene graphs, humans' scene perception focuses on selected structures in the scene, starting with a limited interpretation and evolving sequentially in a goal-directed manner [G.

ZNF750 Regulates Skin Barrier Function by Driving Cornified Envelope and Lipid Processing Pathways.

The epidermis is a constantly renewing stratified epithelial tissue that provides essential protective barrier functions. The major barrier is located at the outermost layers of the epidermis, formed by terminally differentiated keratinocytes reinforced by proteins of their cornified envelope and sequestered intercellular lipids. Disruptions to epidermal differentiation characterize various skin disorders.

Insights into abusive workplace behavior.

Objectives: This paper explores definitions, incidences, and outcomes of workplace abuse - a widespread, worldwide social phenomenon impinging on the well-being of workers in a developing labor market - and possible directions for delineating and standardizing classifications of the phenomenon that facilitate workers' protection. Furthermore, we employ Tepper's Abusive Supervision Survey Questionnaire [ASSQ] to identify managerial abuse in organizations regarding the type of organization (public/private), gender of the perpetrator, gender of the target, and the managerial role, of each of the abuse items. Finally, we suggest directions for further research and practical measures designed to facilitate the diminution of behavioral abuse in the workplace in the foreseeable future.

Ataxia Telangiectasia Mutated Signaling Delays Skin Pigmentation upon UV Exposure by Mediating MITF Function toward DNA Repair Mode.

Skin pigmentation is paused after sun exposure; however, the mechanism behind this pausing is unknown. In this study, we found that the UVB-induced DNA repair system, led by the ataxia telangiectasia mutated (ATM) protein kinase, represses MITF transcriptional activity of pigmentation genes while placing MITF in DNA repair mode, thus directly inhibiting pigment production. Phosphoproteomics analysis revealed ATM to be the most significantly enriched pathway among all UVB-induced DNA repair systems.

Clinical outcome of planned oocyte cryopreservation at advanced age.

Purpose: To report outcome of planned oocyte cryopreservation (POC) in the first 8 years of this treatment in our center.

Methods: A retrospective study in a university-affiliated medical center.

Results: A total of 446 women underwent POC during 2011-2018.

Assessment of Predictors for SARS-CoV-2 Antibodies Decline Rate in Health Care Workers after BNT162b2 Vaccination-Results from a Serological Survey.

Background: SARS-CoV-2 is a novel human pathogen causing Coronavirus Disease 2019 that has caused widespread global mortality and morbidity. Since health workers in Israel were among the first to be vaccinated, we had a unique opportunity to investigate the post-vaccination level of IgG anti-S levels antibodies (Abs) and their dynamics by demographic and professional factors. Methods: Prospective Serological Survey during December 2020−August 2021 at Barzilai Medical Center among 458 health care workers (HCW) followed for 6 months after the second BNT162b2 vaccine dose.

Whole-Genome Duplication Shapes the Aneuploidy Landscape of Human Cancers.

Unlabelled: Aneuploidy is a hallmark of cancer with tissue-specific prevalence patterns that suggest it plays a driving role in cancer initiation and progression. However, the contribution of aneuploidy to tumorigenesis depends on both cellular and genomic contexts. Whole-genome duplication (WGD) is a common macroevolutionary event that occurs in more than 30% of human tumors early in tumorigenesis.

The DOMINO web-server for active module identification analysis.

Motivation: Active module identification (AMI) is an essential step in many omics analyses. Such algorithms receive a gene network and a gene activity profile as input and report subnetworks that show significant over-representation of accrued activity signal ('active modules'). Such modules can point out key molecular processes in the analyzed biological conditions.

Proinflammatory Pathways Are Activated in the Human Q344X Rhodopsin Knock-In Mouse Model of Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is a hereditary disease of the retina that results in complete blindness. Currently, there are very few treatments for the disease and those that exist work only for the recessively inherited forms. To better understand the pathogenesis of RP, multiple mouse models have been generated bearing mutations found in human patients including the human Q344X rhodopsin knock-in mouse.

Direction selectivity in retinal bipolar cell axon terminals.

The ability to encode the direction of image motion is fundamental to our sense of vision. Direction selectivity along the four cardinal directions is thought to originate in direction-selective ganglion cells (DSGCs) because of directionally tuned GABAergic suppression by starburst cells. Here, by utilizing two-photon glutamate imaging to measure synaptic release, we reveal that direction selectivity along all four directions arises earlier than expected at bipolar cell outputs.

DOMINO: a network-based active module identification algorithm with reduced rate of false calls.

Algorithms for active module identification (AMI) are central to analysis of omics data. Such algorithms receive a gene network and nodes' activity scores as input and report subnetworks that show significant over-representation of accrued activity signal ("active modules"), thus representing biological processes that presumably play key roles in the analyzed conditions. Here, we systematically evaluated six popular AMI methods on gene expression and GWAS data.

Structure-function studies of the magnetite-biomineralizing magnetosome-associated protein MamC.

Magnetotactic bacteria are Gram-negative bacteria that navigate along geomagnetic fields using the magnetosome, an organelle that consists of a membrane-enveloped magnetic nanoparticle. Magnetite formation and its properties are controlled by a specific set of proteins. MamC is a small magnetosome-membrane protein that is known to be active in iron biomineralization but its mechanism has yet to be clarified.

Efficacy of temporal processing training to improve phonological awareness among dyslexic and normal reading students.

One of the leading theories for dyslexia suggests that it is the result of a difficulty in auditory temporal processing (ATP). This theory, as well as others, is supported by studies showing group differences and correlation between phonological awareness and ATP. However, these studies do not provide causal relationship.