Long-Term Treatment With Ocrelizumab in Patients With Early-Stage Relapsing MS: Nine-Year Data From the OPERA Studies Open-Label Extension.

Background And Objectives: Patients with multiple sclerosis (MS) may demonstrate better disease control when treatment is initiated on high-efficacy disease-modifying therapies (DMTs) from onset. This subgroup analysis assessed the long-term efficacy and safety profile of the high-efficacy DMT ocrelizumab (OCR) as first-line therapy for early-stage relapsing MS (RMS).

Methods: Post hoc exploratory analyses of efficacy and safety were performed in a subgroup of treatment-naive patients with RMS who received ≥1 dose of OCR in the multicenter OPERA I/II (NCT01247324/NCT01412333) studies.

The Sikkim flood of October 2023: Drivers, causes and impacts of a multihazard cascade.

On 3 October 2023, a multihazard cascade in the Sikkim Himalaya, India, was triggered by 14.7 million m of frozen lateral moraine collapsing into South Lhonak Lake, generating an ~20 m tsunami-like impact wave, breaching the moraine, and draining ~50 million m of water. The ensuing Glacial Lake Outburst Flood (GLOF) eroded ~270 million m of sediment, which overwhelmed infrastructure, including hydropower installations along the Teesta River.

A framework for managing infectious diseases in rural areas in low- and middle-income countries in the face of climate change-East Africa as a case study.

Climate change is having unprecedented impacts on human health, including increasing infectious disease risk. Despite this, health systems across the world are currently not prepared for novel disease scenarios anticipated with climate change. While the need for health systems to develop climate change adaptation strategies has been stressed in the past, there is no clear consensus on how this can be achieved, especially in rural areas in low- and middle-income countries that experience high disease burdens and climate change impacts simultaneously.

Ancient genomics and the origin, dispersal, and development of domestic sheep.

The origins and prehistory of domestic sheep () are incompletely understood; to address this, we generated data from 118 ancient genomes spanning 12,000 years sampled from across Eurasia. Genomes from Central Türkiye ~8000 BCE are genetically proximal to the domestic origins of sheep but do not fully explain the ancestry of later populations, suggesting a mosaic of wild ancestries. Genomic signatures indicate selection by ancient herders for pigmentation patterns, hornedness, and growth rate.

Conformational dynamics of a multienzyme complex in anaerobic carbon fixation.

In the ancient microbial Wood-Ljungdahl pathway, carbon dioxide (CO) is fixed in a multistep process that ends with acetyl-coenzyme A (acetyl-CoA) synthesis at the bifunctional carbon monoxide dehydrogenase/acetyl-CoA synthase complex (CODH/ACS). In this work, we present structural snapshots of the CODH/ACS from the gas-converting acetogen , characterizing the molecular choreography of the overall reaction, including electron transfer to the CODH for CO reduction, methyl transfer from the corrinoid iron-sulfur protein (CoFeSP) partner to the ACS active site, and acetyl-CoA production. Unlike CODH, the multidomain ACS undergoes large conformational changes to form an internal connection to the CODH active site, accommodate the CoFeSP for methyl transfer, and protect the reaction intermediates.

Synchronization in spiking neural networks with short and long connections and time delays.

Synchronization is fundamental for information processing in oscillatory brain networks and is strongly affected by time delays via signal propagation along long fibers. Their effect, however, is less evident in spiking neural networks given the discrete nature of spikes. To bridge the gap between these different modeling approaches, we study the synchronization conditions, dynamics underlying synchronization, and the role of the delay of a two-dimensional network model composed of adaptive exponential integrate-and-fire neurons.

Congenital pulmonic and aortic stenosis in Newfoundland dogs: Results of a 14-year French cardiovascular screening program (921 dogs).

Introduction: Aortic stenosis (AS) and pulmonic stenosis (PS) are two of the most common canine congenital heart diseases (CHD), with a high relative risk for Newfoundland dogs to develop inherited subvalvular AS. For this reason, a cardiovascular screening program has been set up by the French Newfoundland kennel club in order to manage mattings and reduce AS prevalence.

Materials And Methods: The records of untreated and non-anesthetized adult Newfoundland dogs screened between 2010 and 2023 were retrospectively reviewed.

Habitat suitability mapping and landscape connectivity analysis to predict African swine fever spread in wild boar populations: A focus on Northern Italy.

African swine fever (ASF) is a highly contagious disease affecting wild and domestic pigs, characterised by severe haemorrhagic symptoms and high mortality rates. Originally confined to Sub-Saharan Africa, ASF virus genotype II has spread to Europe since 2014, mainly affecting Eastern Europe, and progressing through wild boar migrations and human action. In January 2022, the first case of ASF, due to genotype II, was reported in North-western Italy, in a wild boar carcass.

Net buffer load during regional citrate anticoagulated continuous renal replacement therapy.

Background: Regionally anticoagulated continuous renal replacement therapy with citrate is the first choice for critically ill patients with acute kidney injury. If citrate that reaches the patient exceeds the metabolic capacity, metabolic alkalosis will follow. Bicarbonate from the treatment fluids will also reach the patient and add to the bicarbonate load.

Fast and accurate imputation of genotypes from noisy low-coverage sequencing data in bi-parental populations.

Motivation: Genotyping of bi-parental populations can be performed with low-coverage next-generation sequencing (LC-NGS). This allows the creation of highly saturated genetic maps at reasonable cost, precisely localized recombination breakpoints (i.e.

Prevalence of advanced hepatic fibrosis and individualization of associated risk factors by Bayesian analysis in MASLD patients in French cardio-metabolic health networks.

The aim of this study was to determine the prevalence of advanced hepatic fibrosis and to individualize using Bayesian analysis its associated risk factors in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) being cared for in three Alsatian cardio-metabolic health networks in the North East of France. Overall, 712 patients aged ≥18 years with a female predominance were included into a prospective, cross-sectional, and observational study. Advanced fibrosis and severe steatosis were evaluated using transient elastography (FibroScan®).

Hypointense Findings on Hepatobiliary Phase MR Images.

Hepatobiliary (HB) contrast agents are increasingly valuable diagnostic tools in MRI, offering a wider range of applications as their clinical use expands. Normal hepatocytes take up HB contrast agents, which are subsequently excreted in bile. This property creates a distinct HB phase providing valuable insights into liver function and biliary anatomy.

The Mixed Transition-Metal Cyanamide MnCr(NCN).

The ternary transition-metal cyanamide MnCr(NCN) was synthesized by a solid-state metathesis reaction between MnCl, CrCl, and ZnNCN. Powder X-ray diffraction reveals that MnCr(NCN) adopts an orthorhombic [NiAs]-derived structure with symmetry, featuring a hexagonally close-packed array of NCN with metal cations in 3/4 of the octahedral interstitial holes. The question of cation order was addressed via the combinatorial use of X-ray powder diffraction, neutron powder diffraction, electron diffraction, and HAADF-STEM measurements.

Systematic bias in malaria parasite relatedness estimation.

Genetic studies of Plasmodium parasites increasingly feature relatedness estimates. However, various aspects of malaria parasite relatedness estimation are not fully understood. For example, relatedness estimates based on whole-genome-sequence (WGS) data often exceed those based on sparser data types.

Reporting of concomitant and rescue topical therapies in atopic dermatitis randomised controlled trials evaluating a systemic treatment: a scoping review.

Background: Randomised controlled trials (RCTs) evaluating new systemic treatments for atopic dermatitis (AD) have increased dramatically over the last decade. These trials often incorporate topical therapies either as permitted concomitant or rescue treatments. Differential use of these topicals post-randomisation introduces potential bias as they may nullify or exaggerate treatment responses.

Physiological effects of nasal high flow therapy during exercise in patients with chronic obstructive pulmonary disease: A crossover randomised controlled trial.

Background: Nasal high flow (NHF) has been proposed to sustain high intensity exercise in people with COPD, but we have a poor understanding of its physiological effects in this clinical setting.

Research Question: What is the effect of NHF during exercise on dynamic respiratory muscle function and activation, cardiorespiratory parameters, endurance capacity, dyspnoea and leg fatigue as compared to control intervention.

Study Design And Methods: Randomized single-blind crossover trial including COPD patients.

Knee kinematics during gait in patients with discoid lateral meniscus: a systematic review.

Introduction: The aim of this study was to evaluate the difference between symptomatic discoid lateral meniscus (DLM) and healthy knees in terms of gait analysis.

Evidence Acquisition: A systematic review was conducted from the electronic databases PubMed/MEDLINE, EMBASE and Scopus. The review was performed on studies that reported data on kinematics, gait analysis, biomechanics in discoid lateral meniscus, before and after surgery.

Origin and In-Office Treatment of Retrograde Cricopharyngeus Dysfunction.

Importance: Retrograde cricopharyngeus dysfunction (R-CPD) is an emerging disorder associated with disabling symptoms. The origin of R-CPD remains unknown.

Objective: To investigate the development of symptoms, diagnosis approach, and therapeutic outcomes of R-CPD in patients treated with in-office botulinum toxin injection (BTI) into the cricopharyngeus.

Adjuvant Atezolizumab for Early Triple-Negative Breast Cancer: The ALEXANDRA/IMpassion030 Randomized Clinical Trial.

Importance: Triple-negative breast cancer is an aggressive subtype with a high incidence in young patients, a high incidence in non-Hispanic Black women, and a high risk of progression to metastatic cancer, a devastating sequela with a 12- to 18-month life expectancy. Until recently, one strategy for treating early-stage triple-negative breast cancer was chemotherapy after surgery. However, it was not known whether the addition of immune therapy to postsurgery chemotherapy would be beneficial.

Advancing High-Throughput Cellular Atomic Force Microscopy with Automation and Artificial Intelligence.

Atomic force microscopy (AFM) has reached a significant level of maturity in biology, demonstrated by the diversity of modes for obtaining not only topographical images but also insightful mechanical and adhesion data by performing force measurements on delicate samples with a controlled environment (e.g., liquid, temperature, pH).