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.

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.

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.

The kinetics of aqueous thiolated arsenic oxidation.

Thiolated arsenic (As) compounds have been identified in various natural and engineered environments worldwide and are important for the biogeochemical cycling of As, yet quantitative data regarding their stability and transformation rates remains scarce. This study investigates the oxidation kinetics of mono-, di-, and tri-thioarsenate at varying pH, Fe, and (thio-)As concentrations in the aqueous phase. Experiments conducted over four weeks revealed that all thioarsenates were oxidized faster at lower pH, with rates of up to several μmoles/L/d at a pH of 3.

Migration of vanadium oxide nanoparticles in saturated porous media.

Vanadium oxides nanoparticles (VO-NPs) as emerging functional materials are widely applied in high-technology industries. However, their environmental behaviors remain largely known. In this study, the migration of three common VO-NPs (VO VO, and VO) in saturated porous media has been investigated.

Anticancer diiron aminocarbyne complexes with labile N-donor ligands.

The novel diiron amine complexes [FeCp(CO)(NHR')(μ-CO){μ-CN(Me)(Cy)}]CFSO [R' = H, 3; Cy, 4; CHCHNH, 5; CHCHNMe, 6; CHCH(4-CHOMe), 7; CHCH(4-CHOH), 8; Cp = η-CH, Cy = CH = cyclohexyl] were synthesized in 49-92 % yields from [FeCp(CO)(μ-CO){μ-CN(Me)(Cy)}]CFSO, 1a, using a straightforward two-step procedure. They were characterized by IR and multinuclear NMR spectroscopy, and the structure of 7 was confirmed through X-ray diffraction analysis. Complexes 3-8 and the acetonitrile adducts [FeCp(CO)(NCMe)(μ-CO){μ-CN(Me)(R)}]CFSO (R = Cy, 2a; Me, 2b; Xyl = 2,6-CHMe, 2c) were assessed for their water solubility, octanol-water partition coefficient and stability in physiological-like solutions.

Motor variability regulation analysis in trampolinists.

In trampolining, optimizing body orientation during landing reduces injury risk and enhances performance. As trampolinists are subject to motor variability, anticipatory inflight corrections are necessary to regulate their body orientation before landing. We investigated the evolution of a) body orientation and b) limb position (i.

Ingestion of polyethylene microplastics impacts cichlid behaviour despite having low retention time.

Microplastics, particles between 0.001 and 5 mm in diameter, are ubiquitous in the environment and their consumption by aquatic organisms is known to lead to a variety of adverse effects. However, studies on the effects of microplastics on prey fish have not shown consistent trends, with results varying across species and plastic type used.

Motor and visuospatial processing profile in a cross-conditions study: A comparison between developmental coordination disorder and nonverbal learning disability.

Background: Neurodevelopmental conditions often exhibit overlapping symptoms, posing challenges for differential diagnosis. Developmental Coordination Disorder (DCD) manifests as fundamental motor impairments, often along with co-occurring visuospatial difficulties. Nonverbal Learning Disorder (NLD) features visuospatial core challenges, with a less consistent characterization of its motor profile.

Intergenerational transmission of childhood interpersonal trauma in adults entering therapy for intimate partner violence: The role of identity diffusion.

Background: Childhood Interpersonal Trauma (CIT) is a major public health issue that increases the risk of perpetrating and sustaining intimate partner violence (IPV) in adulthood, perpetuating intergenerational cycles of violence. Yet, the explanatory mechanisms behind the intergenerational transmission of trauma warrant further exploration.

Objective: This study explored identity diffusion as an explanatory mechanism linking cumulative and individual CIT (sexual, physical and psychological abuse, physical and psychological neglect, witnessing parental physical or psychological IPV, bullying) to IPV (sexual, physical, psychological, coercive control) and to the next generation's exposure to family violence.

Elevated glycocalyx shedding components as the early predictors of unfavorable outcomes in patients after cardiac arrest: A single-center observational study.

Objective: To assess the association of serum glycocalyx shedding components (Heparan sulfate, HS; Hyaluronic acid, HA; Syndecan-1, Sdc-1) with outcomes after CA.

Methods: Patients who were comatose for >24 h after CA in the intensive care unit (ICU) of the Affiliated Hospital of Xuzhou Medical University from 9/2021 to 04/2023 were enrolled. Serum samples were collected 24 h after CA to measure the concentrations of glycocalyx shedding components.

Prediction of growth and feed efficiency in mink using machine learning algorithms.

The feed efficiency (FE) expresses as the amount of feed required per unit of BW gain. Since feed cost is the major input cost in the mink industry, evaluating of FE is a crucial step for competitiveness of the mink industry. However, the FE measures have not been widely adopted for the mink due to the high cost of periodically measuring BW and daily feed intake.

Effect of head size, head material, and radiation dose on the repeatability of CT-RSA measurements of femoral head penetration.

Background: The risk of early revision of total hip arthroplasty (THA) for polyethylene wear is now low, but there remains a need to perform wear measurements in patients for clinical surveillance. The gold standard of wear measurements has been radiostereometric analysis (RSA), which has limited availability. The use of computed tomography (CT) to perform THA wear measurement was described a decade ago and found to have acceptable accuracy and precision, but high radiation dose was a concern.

Risks associated with opioid prescriptions for headache in the emergency department.

Study Hypothesis: Use of opioids for treatment of headache in the emergency department (ED) is associated with an increased 1-year risk of opioid-related adverse events.

Objective: To assess the safety and efficacy of opioid prescribing for ED patients with headache.

Methods: We performed a multicenter observational cohort study using linked administrative data.

You better keep an eye on your contacts.

Membrane contact sites (MCS) are specialized compartments found in all eukaryotic cells that are formed between membranes of different organelles that are in close proximity. MCS have important functions as they are sites of efficient transfer of molecules between neighboring organelles. Two recent articles have used the splitFAST system to mark and follow the dynamics of membrane contact sites and used the method to highlight the importance of MCS between the endoplasmic reticulum (ER) and lipid droplets in metabolic adaptation and MCS between the ER and mitochondria in Ca signal propagation.

The Hao-Fountain syndrome protein USP7 regulates neuronal connectivity in the brain via a novel p53-independent ubiquitin signaling pathway.

Mutation or deletion of the deubiquitinase USP7 causes Hao-Fountain syndrome (HAFOUS), which is characterized by speech delay, intellectual disability, and aggressive behavior and highlights important unknown roles of USP7 in the nervous system. Here, we conditionally delete USP7 in glutamatergic neurons in the mouse forebrain, triggering disease-relevant phenotypes, including sensorimotor deficits, impaired cognition, and aggressive behavior. Although USP7 deletion induces p53-dependent neuronal apoptosis, most behavioral abnormalities in USP7 conditional knockout mice persist following p53 loss.

Evaluation of Biodentine® and Calcium Hydroxide in the Formation of Dentin Bridge in Deep Carious Lesions.

Background: Indirect pulp capping is the main treatment modality for reversible pulpitis.

Objective: To evaluate the efficacy of Biodentine® and Calcium hydroxide in the formation of dentin bridge.

Materials And Methods: A double blinded, randomized clinical control trial involving 50 consenting subjects, aged 16 to 55 years with deep carious vital teeth.

Association Between Early Childhood P300 Deficits and Risk for Preadolescence Depressive Disorder Mediated by Responsiveness to PCIT-ED Treatment.

Preschool-onset major depressive disorder (PO-MDD) is an impairing pediatric mental health disorder that impacts children as young as three years old. There is limited work dedicated to uncovering neural measures of this early childhood disorder which could be leveraged to further understand both treatment responsiveness and future depression risk. Event-related potentials (ERPs) such as the P300 have been employed extensively in adult populations to examine depression-related deficits in cognitive and motivational systems.

A rare case of primary testicular follicular lymphoma in a pediatric patient.

Testicular follicular lymphoma (TFL) is an exceedingly rare lymphoma that typically occurs in young male patients and is now recognized as a distinct diagnostic entity in the International Consensus Classification. TFL shows some clinicopathologic and genetic overlap with pediatric-type follicular lymphoma (PTFL). We report a case of TFL occurring in an otherwise healthy 4-year-old boy who presented with painless scrotal swelling.

The Pediatric Hip Physical Exam.

Purpose Of Review: Atraumatic hip pain in children is one of the most common orthopaedic complaints in this population. This review details the important elements of the pediatric hip physical exam and provides an overview of pertinent clinical exam findings in specific diagnoses of common pediatric hip pathology.

Recent Findings: A thorough physical exam is critical for the diagnosis of pediatric hip pathology, as many conditions have exam findings that are very commonly associated with the pathology, if not pathognomonic for the disorder.

From Vision to Reality: The EU's Pharmaceutical Reforms and the Path to Improved Access.

Disparities in access to oncology medicines in European Union (EU) member states can impact patient outcomes profoundly, with availability and timely access varying significantly across and within member states. This paper discusses the intersection of the new European Health Technology Assessment Regulation (HTAR), the provisions of the proposed pharmaceutical legislation and their potential impacts on access to oncology medicines across EU member states. The HTAR, seeking to standardise the clinical evaluation of new medicines, has the potential to streamline the evaluation process but also risks oversimplifying diverse national healthcare needs.

Pituitary adenomas: biology, nomenclature and clinical classification.

An 'adenoma' is a benign neoplasm composed of epithelial tissue, and has been standard nomenclature for primary pituitary neoplasms. In 2022, the fifth edition of the WHO Classification of Endocrine Tumours and of Central Nervous System Tumours, renamed pituitary adenomas as neuroendocrine tumours (NETs), assigning an oncology label to pituitary invariably benign neoplasms. Multidisciplinary workshops convened by the Pituitary Society have questioned the process, validity, and merit of this arbitrary change, while addressing the adverse clinical implications of the proposed new nomenclature.

Survival disparities among Asian, Native Hawaiian and Pacific Islander (ANHPI) patients with non-Hodgkin lymphoma (NHL) in the United States.

Background: Non-Hodgkin lymphoma (NHL) is the seventh most common cancer among Asian, Native Hawaiian and Pacific Islanders (ANHPIs), yet the risk of death in specific ANHPI subgroups in the US is unknown.

Methods: We used Surveillance, Epidemiology, and End Results data to investigate relative survival and the risk of death among NHL patients in ANHPI subgroups. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals (CI), comparing ANHPI subgroups to non-Hispanic White (NHW) NHL patients for all-cause death and NHL-specific death.

MAPK1IP1L::TFE3-rearranged renal cell carcinoma: a novel fusion adding to the differential diagnosis of oncocytic renal neoplasms.

Beyond the more common TFE3 fusion partners PRCC, ASPSCR1, and SFPQ, additional less common fusion partners of TFE3-rearranged renal cell carcinoma (RCC) have been described. Herein, we present an example of TFE3-rearranged renal cell carcinoma harboring fusion partner MAPK1IP1L, a rare rearrangement with only one other reported tumor found in the literature. The currently reported TFE3-rearranged RCC demonstrates unique histological features compared to the previously reported tumor including dense eosinophilic cytoplasm and nuclear pseudoinclusions (corroborated by electron microscopic evaluation), with features not typically seen in other TFE3-rearranged RCCs.