Efficient assay for evaluating drug efficacy and synergy against emerging SARS-CoV-2 strains.

Novel and repurposed antiviral drugs are available for the treatment of coronavirus disease 2019 (COVID-19). However, antiviral combinations may be more potent and lead to faster viral clearance, but the methods for screening antiviral combinations against respiratory viruses are not well established and labor-intensive. Here, we describe a time-efficient (72-96 h) and simple drug-sensitivity assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using standard 96-well plates.

Stakeholder perspectives on non-invasive brain stimulation.

Non-invasive brain stimulation (NIBS) techniques such as transcranial direct current stimulation (tDCS) or transcranial magnetic stimulation (TMS) have made great progress in recent years and offer boundless potential for the neuroscientific research and treatment of disorders. However, the possible use of NIBS devices for neuro-doping and neuroenhancement in healthy individuals and the military are poorly regulated. The great potentials and diverse applications can have an impact on the future development of the technology and society.

Upregulation of keratin 15 is required for varicella-zoster virus replication in keratinocytes and is attenuated in the live attenuated vOka vaccine strain.

Varicella-zoster virus (VZV) is the etiological agent of chickenpox and shingles, diseases characterised by epidermal virus replication in skin and mucosa and the formation of blisters. We have previously shown that VZV infection has a profound effect on keratinocyte differentiation, altering the normal pattern of epidermal gene expression. In particular, VZV infection reduces expression of suprabasal keratins 1 and 10 and desmosomal proteins, disrupting epidermal structure to promote expression of a blistering phenotype.

Castanet: a pipeline for rapid analysis of targeted multi-pathogen genomic data.

Motivation: Target enrichment strategies generate genomic data from multiple pathogens in a single process, greatly improving sensitivity over metagenomic sequencing and enabling cost-effective, high-throughput surveillance and clinical applications. However, uptake by research and clinical laboratories is constrained by an absence of computational tools that are specifically designed for the analysis of multi-pathogen enrichment sequence data. Here we present an analysis pipeline, Castanet, for use with multi-pathogen enrichment sequencing data.

Increased circulation of GII.17 noroviruses, six European countries and the United States, 2023 to 2024.

We report an increase in GII.17 norovirus outbreaks and sporadic infections of acute gastroenteritis in Austria, Germany, France, Ireland, the Netherlands, England and the United States during the 2023/24 season. A decrease in GII.

Positronium lifetime validation measurements using a long-axial field-of-view positron emission tomography scanner.

Background: Positron emission tomography (PET) traditionally uses coincident annihilation photons emitted from a positron interacting with an electron to localize cancer within the body. The formation of positronium (Ps), a bonded electron-positron pair, has not been utilized in clinical applications of PET due to the need to detect either the emission of a prompt gamma ray or the decay of higher-order coincident events. Assessment of the lifetime of the formed Ps, however, can potentially yield additional diagnostic information of the surrounding tissue because Ps properties vary due to void size and molecular composition.

HerpesDRG: a comprehensive resource for human herpesvirus antiviral drug resistance genotyping.

The prevention and treatment of many herpesvirus associated diseases is based on the utilization of antiviral therapies, however therapeutic success is limited by the development of drug resistance. Currently no single database cataloguing resistance mutations exists, which hampers the use of sequence data for patient management. We therefore developed HerpesDRG, a drug resistance mutation database that incorporates all the known resistance genes and current treatment options, built from a systematic review of available genotype to phenotype literature.

Investigations into the Concentrations and Metabolite Profiles of Doping Agents and Antidepressants in Human Seminal Fluid Using Liquid Chromatography-Mass Spectrometry.

Exogenous substances, including drugs and chemicals, can transfer into human seminal fluid and influence male fertility and reproduction. In addition, substances relevant in the context of sports drug testing programs, can be transferred into the urine of a female athlete (after unprotected sexual intercourse) and trigger a so-called adverse analytical finding. Here, the question arises as to whether it is possible to distinguish analytically between intentional doping offenses and unintentional contamination of urine by seminal fluid.

Case series: Congenital enterovirus infection-associated haemophagocytic lymphohistiocytosis and subsequent neutropaenia.

Congenital enterovirus infection can be associated with a pro-inflammatory state triggering haemophagocytic lymphohistiocytosis (HLH). Enteroviruses are also known to cause transient neutropenia in healthy children. Two infants presented with temperature instability, lethargy, thrombocytopaenia, hepatosplenomegaly and evidence of hyperinflammation in the setting of perinatal maternal rash and household contacts with gastrointestinal symptoms.

Holistic evaluation of a machine learning-based timing calibration for PET detectors under varying data sparsity.

Modern PET scanners offer precise TOF information, improving the SNR of the reconstructed images. Timing calibrations are performed to reduce the worsening effects of the system components and provide valuable TOF information. Traditional calibration procedures often provide static or linear corrections, with the drawback that higher-order skews or event-to-event corrections are not addressed.

Reconstruction of the historic time course of blood-borne virus contamination of clotting factor concentrates, 1974-1992.

Factor VIII and IX clotting factor concentrates manufactured from pooled plasma have been identified as potent sources of virus infection in persons with hemophilia (PWHs) in the 1970s and 1980s. To investigate the range and diversity of viruses over this period, we analysed 24 clotting factor concentrates for several blood-borne viruses. Nucleic acid was extracted from 14 commercially produced clotting factors and 10 from nonremunerated donors, preserved in lyophilized form (expiry dates: 1974-1992).

Triple Blockade of Oncogenic RAS Signaling Using KRAS and MEK Inhibitors in Combination with Irradiation in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest of human malignancies and carries an exceptionally poor prognosis. It is mostly driven by multiple oncogenic alterations, with the highest mutation frequency being observed in the KRAS gene, which is a key oncogenic driver of tumorogenesis and malignant progression in PDAC. However, KRAS remained undruggable for decades until the emergence of G12C mutation specific KRAS inhibitors.

FAS(APO), DAMP, and AKT Phosphoproteins Expression Predict the Development of Nosocomial Infection After Pediatric Burn Injury.

Pediatric burn injuries are a leading cause of morbidity with infections being the most common acute complication. Thermal injuries elicit a heightened cytokine response while suppressing immune function; however, the mechanisms leading to this dysfunction are still unknown. Our aim was to identify extracellular proteins and circulating phosphoprotein expression in the plasma after burn injury to predict the development of nosocomial infection (NI).

A useful formula for periodic Jacobi matrices on trees.

We introduce a function of the density of states for periodic Jacobi matrices on trees and prove a useful formula for it in terms of entries of the resolvent of the matrix and its "half-tree" restrictions. This formula is closely related to the one-dimensional Thouless formula and associates a natural phase with points in the bands. This allows streamlined proofs of the gap labeling and Aomoto index theorems.

Acute cardiovascular and muscular response to rowing ergometer exercise in artificial gravity - a pilot trial.

Prolonged immobilization and spaceflight cause cardiovascular and musculoskeletal deconditioning. Combining artificial gravity through short-arm centrifugation with rowing exercise may serve as a countermeasure. We aimed to compare the tolerability, muscle force production, cardiovascular response, and power output of rowing on a short-arm centrifuge and under terrestrial gravity.

Complementary information concerning the suspected interindividual transmission of GW1516, a substance prohibited in sport, through intimate contact: a case report.

Purpose: Inadvertent and/or unknowing exposure to drugs and drug residues has been frequently debated in situations of so-called adverse analytical finding (AAF) in the context of sports drug testing programs. Transfer of drug residues via unprotected intercourse is a conceivable scenario but scientific data and authentic case reports are scarce. Herein, investigations into two AAFs with the peroxisome proliferator-activated receptor delta (PPARδ) agonist GW1516 are reported and discussed.

Safety, tolerability, viral kinetics, and immune correlates of protection in healthy, seropositive UK adults inoculated with SARS-CoV-2: a single-centre, open-label, phase 1 controlled human infection study.

Background: A SARS-CoV-2 controlled human infection model (CHIM) has been successfully established in seronegative individuals using a dose of 1×10 50% tissue culture infectious dose (TCID) pre-alpha SARS-CoV-2 virus. Given the increasing prevalence of seropositivity to SARS-CoV-2, a CHIM that could be used for vaccine development will need to induce infection in those with pre-existing immunity. Our aim was to find a dose of pre-alpha SARS-CoV-2 virus that induced infection in previously infected individuals.