Safety and efficacy of nipocalimab in adults with generalised myasthenia gravis (Vivacity-MG3): a phase 3, randomised, double-blind, placebo-controlled study.

Background: Given burdensome side-effects and long latency for efficacy with conventional agents, there is a continued need for generalised myasthenia gravis treatments that are safe and provide consistently sustained, long-term disease control. Nipocalimab, a neonatal Fc receptor blocker, was associated with dose-dependent reductions in total IgG and anti-acetylcholine receptor (AChR) antibodies and clinically meaningful improvements in the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale in patients with generalised myasthenia gravis in a phase 2 study. We aimed to assess the safety and efficacy of nipocalimab in a phase 3 study.

Tuberculosis and people who use drugs: why focus on this overlooked population is important and why adapted interventions are necessary.

People who use drugs show a higher incidence and prevalence of tuberculosis than people who do not use drugs in areas where Mycobacterium tuberculosis is endemic. However, this population is largely neglected in national tuberculosis programmes. Strategies for active case finding, screening, and linkage to care designed for the general population are not adapted to the needs of people who use drugs, who are stigmatised and difficult to reach.

Crossing the blood-brain barrier: emerging therapeutic strategies for neurological disease.

The blood-brain barrier is a physiological barrier that can prevent both small and complex drugs from reaching the brain to exert a pharmacological effect. For treatment of neurological diseases, drug concentrations at the target site are a fundamental parameter for therapeutic effect; thus, the blood-brain barrier is a major obstacle to overcome. Novel strategies have been developed to circumvent the blood-brain barrier, including CSF delivery, intracranial delivery, ultrasound-based methods, membrane transporters, receptor-mediated transcytosis, and nanotherapeutics.

Hidradenitis suppurativa.

Hidradenitis suppurativa is a chronic inflammatory disease characterised by painful, deep-seated nodules, abscesses, and draining tunnels in the skin of axillary, inguinal, genitoanal, or inframammary areas. In recent years, the body of knowledge in hidradenitis suppurativa has advanced greatly. This disorder typically starts in the second or third decade of life.

Advancing long-read nanopore genome assembly and accurate variant calling for rare disease detection.

More than 50% of families with suspected rare monogenic diseases remain unsolved after whole-genome analysis by short-read sequencing (SRS). Long-read sequencing (LRS) could help bridge this diagnostic gap by capturing variants inaccessible to SRS, facilitating long-range mapping and phasing and providing haplotype-resolved methylation profiling. To evaluate LRS's additional diagnostic yield, we sequenced a rare-disease cohort of 98 samples from 41 families, using nanopore sequencing, achieving per sample ∼36× average coverage and 32-kb read N50 from a single flow cell.

Structures and mRNP remodeling mechanism of the TREX-2 complex.

mRNAs are packaged with proteins into messenger ribonucleoprotein complexes (mRNPs) in the nucleus. mRNP assembly and export are of fundamental importance for all eukaryotic gene expression. Before export to the cytoplasm, mRNPs undergo dynamic remodeling governed by the DEAD-box helicase DDX39B (yeast Sub2).

A forward genetic screen identifies potassium channel essentiality in SHH medulloblastoma maintenance.

Distinguishing tumor maintenance genes from initiation, progression, and passenger genes is critical for developing effective therapies. We employed a functional genomic approach using the Lazy Piggy transposon to identify tumor maintenance genes in vivo and applied this to sonic hedgehog (SHH) medulloblastoma (MB). Combining Lazy Piggy screening in mice and transcriptomic profiling of human MB, we identified the voltage-gated potassium channel KCNB2 as a candidate maintenance driver.

Ligand interaction landscape of transcription factors and essential enzymes in E. coli.

Knowledge of protein-metabolite interactions can enhance mechanistic understanding and chemical probing of biochemical processes, but the discovery of endogenous ligands remains challenging. Here, we combined rapid affinity purification with precision mass spectrometry and high-resolution molecular docking to precisely map the physical associations of 296 chemically diverse small-molecule metabolite ligands with 69 distinct essential enzymes and 45 transcription factors in the gram-negative bacterium Escherichia coli. We then conducted systematic metabolic pathway integration, pan-microbial evolutionary projections, and independent in-depth biophysical characterization experiments to define the functional significance of ligand interfaces.

Geographical variation in the long-arm of childhood.

Scholars have documented the lasting impact of childhood socioeconomic status (SES) on health, but few studies have considered how state contexts in childhood shape health trajectories based on childhood SES across the life course. The current project uses data from the Panel Study of Income Dynamics, 2009-2021 (N = 18,227 person-year observations of adults aged 18-41) to build on these studies by 1) examining state variation in the relationship between childhood SES and adult self-rated health, and 2) assessing the contributions of childhood state-level economic context in moderating this relationship. Logistic regression models first confirmed the expected relationship between childhood SES and adult self-rated health that parallels other literature (OR = 1.

Prolonged length of stay among individuals presenting to the emergency department with psychosis: Associations with sociodemographic and visit-level characteristics.

Introduction: Individuals experiencing psychosis commonly initiate and engage in treatment within an emergency department (ED) setting. Understanding factors contributing to adverse ED experiences is critical for improving psychosis-related treatment. Prolonged ED length of stay (LOS), which can be conversely associated with treatment quality, is not well explored among individuals experiencing psychosis.

Isolated subsegmental pulmonary embolism identification based on international classification of diseases (ICD)-10 codes and imaging reports.

Background: Isolated subsegmental pulmonary embolism (issPE) is a commonly encountered diagnosis. Although the International Classification of Diseases (ICD)-10 codes are used for research, their validity for identifying issPE is unknown. Moreover, issPE diagnosis is challenging, and the findings from radiology reports may conflict with those from expert radiologists.

Characterization of senescence-associated transcripts in the human placenta.

Introduction: Fusion of mononucleated cytotrophoblasts into syncytium leads to trophoblast senescence. Yet, premature senescence is associated with preeclampsia, fetal growth restriction (FGR), and related obstetrical syndromes. A set of 28 transcripts that comprise senescence-associated secretory phenotype (SASP) was recently described in placentas from women with preeclampsia.

Health effects of occupational exposure to jet fuels used in the military: A systematic review of the epidemiologic literature.

Background: Jet fuels are a common chemical exposure in occupational settings involving aircraft. Jet fuels are heterogeneous mixtures of aromatic and aliphatic hydrocarbons, as well as non-hydrocarbon performance additives. Several components of jet fuels have been linked to adverse health outcomes.

Three-dimensional kinematics in patients with anterior shoulder instability - A systematic review with meta-analysis.

Anterior Shoulder Instability (ASI) is a common orthopedic condition often resulting in altered shoulder kinematics. Understanding the biomechanics of the unstable shoulder is critical to determine the most appropriate treatment. This study aims to conduct the first systematic review and meta-analysis of three-dimensional (3D) shoulder kinematic studies in ASI patients.

Associations of Serum Urate and Cardiovascular Events in a Clinical Trial of Interleukin-1β Blockade.

Background: Serum urate (SU) associates with cardiovascular (CV) events, mortality, and gout.

Objectives: The purpose of this study was to assess whether SU predicts CV risk in a trial of interleukin (IL)-1β inhibition with canakinumab, and whether IL-1β blockade, kidney function, or gout alter these associations.

Methods: This study is a subanalysis of the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS), which randomized 10,061 patients with prior myocardial infarction and elevated high-sensitivity C-reactive protein to 3 doses of canakinumab or placebo.

Treatment of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) in stormwater using polishing columns with biochar and granular activated carbon.

Polycyclic Aromatic Hydrocarbons (PAHs) and Polychlorinated Biphenyls (PCBs) are recalcitrant organic pollutants often detected in stormwater. Various stormwater control measures (SCMs) can remove PAHs and PCBs by filtration, adsorption, and biodegradation. However, dissolved PAHs and PCBs remain present in the treated outflow of SCMs.

Understanding the interaction between selected microplastics and the toxic dye "Congo red" in water.

This study thoroughly investigated the adsorption of Congo Red (CR) dye onto various microplastics (MPs), including high-density polyethylene (HDPE), polyvinyl chloride (PVC), low-density polyethylene (LDPE), polypropylene (PP) and polyethylene terephthalate (PET). Initial adsorption capacities (q) revealed that HDPE had the highest value (21.90 mg/g), followed by PVC (4.

Management of renal cell carcinoma with ablation in comparison to nephrectomy: A 5-year analysis of inpatient procedural data to evaluate utilization disparities in the United States.

Purpose: To perform a nationwide analysis of ablation compared to partial and total nephrectomy for the management of renal cell carcinoma (RCC) to evaluate utilization trends and disparities in the USA.

Materials And Methods: The 2016-2020 National Inpatient Sample was analyzed. Using ICD-10, we identified the diagnosis of RCC then analyzed the utilization trends of ablation and nephrectomies (both partial and complete).

Okra seed polysaccharides mitigate neuroinflammation and cognitive impairment via modulation of Nrf2/HO-1, HMGB1/RAGE/TLR4/NF-κB, NLRP3/Caspase-1, JAK-2/STAT-3, AMPK/SIRT1/m-TOR, PI3K/AKT/CREB/BDNF/TrkB and PERK/CHOP/Bcl-2 axes.

Global healthcare systems are under tremendous strain due to the increasing prevalence of neurodegenerative disorders. Growing data suggested that overconsumption of high-fat/high-carbohydrates diet (HFHCD) is associated with enhanced incidence of metabolic alterations, neurodegeneration, and cognitive dysfunction. Functional foods have gained prominence in curbing metabolic and neurological deficits.

Racial and ethnic disparities in post-acute care service utilization after stroke.

Evidence examining disparities in post-acute care (PAC) utilization among various racial and ethnic groups after stroke and the influence of social determinants of health (SDOH) in these decisions is lacking. Thus, we searched the literature from January 2000 to November 2023 regarding PAC among individuals after stroke through: 1) Pubmed, 2) Scopus, 3) Web of Science, 4) Embase, and 5) CINAHL. We found 14 studies.

Influence of prosthetic foot selection on walking performance during various load carriage conditions.

Background: Ambulatory individuals with lower limb amputations often face challenges with body support, body propulsion, and balance control. Carrying an infant, toddler, backpack, or other load can exacerbate these challenges and highlights the importance of prescribing the most suitable prosthetic foot. The aim of this study was to examine the influence of five different prosthetic feet on walking performance during various load carriage conditions.

Advances in dietary polyphenols: Regulation of inflammatory bowel disease (IBD) via bile acid metabolism and the gut-brain axis.

Dietary polyphenols represent a diverse group of plant-derived compounds known for their extensive biological activities, offering significant promise in the prevention and treatment of various chronic illnesses. Despite their potential, advancements in their research have been curtailed by challenges in structural analysis and limitations in existing research models. This review marks a pioneering exploration into how bile acids, gut microbiota, and the gut-brain axis serve as conduits through which dietary polyphenols can exert therapeutic effects on Inflammatory Bowel Disease (IBD).

Rewiring cancer: 3D genome determinants of cancer hallmarks.

In modern cancer biology, Hanahan and Weinberg's classic depiction of the Hallmarks of Cancer serves as a heuristic for understanding malignant phenotypes [1]. Genetic determinants of these phenotypes promote cancer induction and progression, and these mutations drive current approaches to understanding and treating cancer. Meanwhile, for over a century, pathologists have noted that profound alterations of nuclear structure accompany transformation, integrating these changes into diagnostic classifications (Figure 1).

Breast ultrasound imaging systems performance evaluation using novel Contrast-Detail (C-D) and Anechoic-Target (A-T) phantoms.

Unlabelled: Ultrasound imaging plays an important role in the early detection and management of breast cancer. This study aimed to evaluate the imaging performance of a range of clinically-used breast ultrasound systems using a set of novel spherical lesion contrast-detail (C-D) and anechoic-target (A-T) phantoms.

Methods: C-D and A-T phantoms were imaged using a range of clinical breast ultrasound systems and imaging modes.

Inequality in COVID-19 vaccine acceptance and uptake: A repeated cross-sectional analysis of COVID vaccine acceptance and uptake in 13 countries.

Background COVID-19 vaccine hesitancy was a key barrier to ending the pandemic via mass immunisation. Objectives Assess magnitudes and differences in socioeconomic inequality in stated COVID-19 vaccine acceptance (hesitancy) and uptake. Methods Online surveys were conducted in 13 countries, collecting data from 15,337 and 18,189 respondents respectively.