AlphaMissense prediction for the evaluation of missense variants in the diagnostic setting of neuromuscular disorders.

Next-generation sequencing has improved diagnostic outcomes for neuromuscular disorders, but interpreting rare missense variants remains challenging. We evaluated AlphaMissense, a recently developed machine learning tool, for predicting missense variant pathogenicity, using 45 (likely) pathogenic variants and 21 variants of uncertain significance from 58 deeply phenotyped patients. AlphaMissense predicted 69% of pathogenic variants correctly, but also classified 62% of variants of uncertain significance as pathogenic.

[Impact of a national policy change on rapid diagnostic testing for HIV, hepatitis C and syphilis by lay providers in community-based organisations and local public health centres: a cross-sectional study].

Background: To improve the diagnosis of undetected infections with the Human Immunodeficiency Virus (HIV), the Hepatitis C Virus (HCV) and syphilis infections among key populations, Section 24 of the Infection Protection Act was amended. Since 1 March 2020, non-medical staff have also been permitted to perform rapid tests. This study aims to examine the impact of the legal change in low-threshold AIDS and drug services as well as in public health offices.

The rs10191329 Risk Allele Is Associated With Pronounced Retinal Layer Atrophy in Multiple Sclerosis.

Objective: To investigate whether the rs10191329 risk allele in the DYSF-ZNF638 locus, which is implicated in central nervous system resilience rather than immune-mediated pathology, is associated with retinal layer thinning, a biomarker of neuroaxonal damage in relapsing multiple sclerosis (RMS).

Methods: From a prospective observational study, we included RMS patients with ≥ 2 optical coherence tomography (OCT) scans, excluding eyes with optic neuritis during the observation period. DNA samples were genotyped using the Illumina Infinium Global Screening Array-24 and variants imputed using the Haplotype Reference Consortium panel and Minimac4.

Machine Learning Identifies Sexual Behavior Subgroups Among Men Who Have Sex with Men in Switzerland.

Sexual behavior is heterogeneous and dynamic. Characterization of such complexity constitutes evidence for public health authorities and caregivers concerned with the framing of sexual health messages aimed at specific subgroups. We developed a machine-learning-based methodology for inference and characterization of such subgroups from longitudinal data on men who have sex with men (MSM) attending individual sexual health counseling sessions.

Genome-wide association study of long COVID.

Infections can lead to persistent symptoms and diseases such as shingles after varicella zoster or rheumatic fever after streptococcal infections. Similarly, severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection can result in long coronavirus disease (COVID), typically manifesting as fatigue, pulmonary symptoms and cognitive dysfunction. The biological mechanisms behind long COVID remain unclear.

How New Technologies Will Transform Total Knee Arthroplasty from a Singular Surgical Procedure to a Holistic Standardized Process.

Many new technologies focused mainly on improving surgical accuracy were first developed in total knee arthroplasty and have not yet shown significant value. These non-significant clinical improvements could potentially be explained by an inadequate target. In this current concept paper, the authors will describe how artificial intelligence (AI), robotic-assisted surgery, and custom implants allow the definition of new targets and the standardization of the TKA process.

Impact of increased diagnosis of early HIV infection and immediate antiretroviral treatment initiation on HIV transmission among men who have sex with men in the Netherlands.

The number of new HIV infections among men who have sex with men (MSM) in the Netherlands has been decreasing, but additional efforts are required to bring it further down. This study aims to assess the impact of increased diagnosis of early HIV infection combined with immediate antiretroviral treatment (ART) initiation on reducing HIV transmission among MSM. We developed an agent-based model calibrated to HIV surveillance and sexual behavior data for MSM in the Netherlands in 2017-2022.

Platform Process for an Autonomous Production of Virus-like Particles.

Virus-like particles (VLPs) are a promising platform as carriers for vaccination and general treatments against many pathogens. While there are long development timelines and challenges in the production of clinical-grade VLPs, this study introduces a platform process for the production and purification of those particles, aided by process analytical technology (PAT). Fed-batch cultivation and consecutive purification, including novel membrane technology and anion-exchange chromatography, showed robust process performance with design and control spaces defined in previous studies.

German evidence- and consensus-based guideline on the management of penile urethritis.

Urethritis is a common condition predominantly caused by sexually transmitted pathogens such as Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma genitalium. It is not possible to differentiate with certainty between pathogens on the basis of clinical characteristics alone. However, empirical antibiotic therapy is often initiated in clinical practice.

Interactions between leaf phenological type and functional traits drive variation in isoprene emissions in central Amazon forest trees.

The Amazon forest is the largest source of isoprene emissions, and the seasonal pattern of leaf-out phenology in this forest has been indicated as an important driver of seasonal variation in emissions. Still, it is unclear how emissions vary between different leaf phenological types in this forest. To evaluate the influence of leaf phenological type over isoprene emissions, we measured leaf-level isoprene emission capacity and leaf functional traits for 175 trees from 124 species of angiosperms distributed among brevideciduous and evergreen trees in a central Amazon forest.

Systematic assessment of COVID-19 host genetics using whole genome sequencing data.

Courses of SARS-CoV-2 infections are highly variable, ranging from asymptomatic to lethal COVID-19. Though research has shown that host genetic factors contribute to this variability, cohort-based joint analyses of variants from the entire allelic spectrum in individuals with confirmed SARS-CoV-2 infections are still lacking. Here, we present the results of whole genome sequencing in 1,220 mainly vaccine-naïve individuals with confirmed SARS-CoV-2 infection, including 827 hospitalized COVID-19 cases.

Radiative corrections: from medium to high energy experiments.

Radiative corrections are crucial for modern high-precision physics experiments, and are an area of active research in the experimental and theoretical community. Here we provide an overview of the state of the field of radiative corrections with a focus on several topics: lepton-proton scattering, QED corrections in deep-inelastic scattering, and in radiative light-hadron decays. Particular emphasis is placed on the two-photon exchange, believed to be responsible for the proton form-factor discrepancy, and associated Monte-Carlo codes.

Further delineation of the SCAF4-associated neurodevelopmental disorder.

While mostly de novo truncating variants in SCAF4 were recently identified in 18 individuals with variable neurodevelopmental phenotypes, knowledge on the molecular and clinical spectrum is still limited. We assembled data on 50 novel individuals with SCAF4 variants ascertained via GeneMatcher and personal communication. With detailed evaluation of clinical data, in silico predictions and structural modeling, we further characterized the molecular and clinical spectrum of the autosomal dominant SCAF4-associated neurodevelopmental disorder.

Self-reported hepatitis A and B vaccination coverage among men who have sex with men (MSM), associated factors and vaccination recommendations in 43 countries of the WHO European Region: results from the European MSM Internet Survey, EMIS-2017.

BackgroundHepatitis A and B vaccinations are recommended for men who have sex with men (MSM), given their increased risk of infection. However, data on vaccination programmes are scarce.AimTo use information on vaccination recommendations and vaccine uptake among MSM in the WHO European Region to guide prevention.

A conserved peptide-binding pocket in HyNaC/ASIC ion channels.

The only known peptide-gated ion channels-FaNaCs/WaNaCs and HyNaCs-belong to different clades of the DEG/ENaC family. FaNaCs are activated by the short neuropeptide FMRFamide, and HyNaCs by Hydra RFamides, which are not evolutionarily related to FMRFamide. The FMRFamide-binding site in FaNaCs was recently identified in a cleft atop the large extracellular domain.

NCBench: providing an open, reproducible, transparent, adaptable, and continuous benchmark approach for DNA-sequencing-based variant calling.

We present the results of the human genomic small variant calling benchmarking initiative of the German Research Foundation (DFG) funded Next Generation Sequencing Competence Network (NGS-CN) and the German Human Genome-Phenome Archive (GHGA). In this effort, we developed NCBench, a continuous benchmarking platform for the evaluation of small genomic variant callsets in terms of recall, precision, and false positive/negative error patterns. NCBench is implemented as a continuously re-evaluated open-source repository.

Bacteriophage therapy as an innovative strategy for the treatment of Periprosthetic Joint Infection: a systematic review.

Background: Periprosthetic Joint Infection (PJI) following hip and knee arthroplasty is a catastrophic complication in orthopaedic surgery. It has long been a key focus for orthopaedic surgeons in terms of prevention and management. With the increasing incidence of antibiotic resistance in recent years, finding more targeted treatment methods has become an increasingly urgent issue.

HIV Testing and Treatment among HIV-Positive Men who have Sex with Men (MSM) Living in Russia: Data from Two Waves of the European MSM Internet Survey.

We examined changes in HIV testing and medical care among men who have sex with men (MSM) in Russia. Data come from the 2010 and 2017 waves of the European MSM Internet Survey. From 2010 to 2017 there was an increase in the proportion who had ever received an HIV test (+ 11.

Digital Twin for Continuous Production of Virus-like Particles toward Autonomous Operation.

Lentiviral vector and virus-like particle (VLP) manufacturing have been published in fed-batch upstream and batch downstream modes before. Batch downstream and continuous upstream in perfusion mode were reported as well. This study exemplifies development and validation steps for a digital twin combining a physical-chemical-based mechanistic model for all unit operations with a process analytical technology strategy in order to show the efforts and benefits of autonomous operation approaches for manufacturing scale.

Ten-year minimal follow-up of lateral opening wedge distal femoral osteotomy for lateral femorotibial osteoarthritis: Good survivorship and high patient satisfaction.

Purpose: This study aimed (1) to determine complications and survival rates of lateral opening wedge distal femoral osteotomy (LOW-DFO) in the long term, (2) to assess their clinical outcomes in the long term and (3) to identify risk factors of failure.

Methods: Between 1991 and 2011, 62 LOW-DFOs were performed in the same department. Inclusion criteria were all isolated LOW-DFO performed for isolated lateral tibiofemoral osteoarthritis and valgus malalignment, with a minimum 10-year follow-up.

Pressurized Hot Water Extraction as Green Technology for Natural Products as Key Technology with Regard to Hydrodistillation and Solid-Liquid Extraction.

Hydrodistillation and solid-liquid extraction with organic solvents or supercritical CO are standard technologies for natural product manufacturing. Within this technology, portfolio pressurized hot water technology is ranked as a green, sustainable, resilient, kosher and halal manufacturing process. Essential for sustainability is energy integration for heating and cooling the auxiliary water as well as product concentration without evaporation but with the aid of low energy consuming ultra- and nanofiltration membrane technology.