Asparagine availability controls germinal center B cell homeostasis.

The rapid proliferation of germinal center (GC) B cells requires metabolic reprogramming to meet energy demands, yet these metabolic processes are poorly understood. By integrating metabolomic and transcriptomic profiling of GC B cells, we identified that asparagine (Asn) metabolism was highly up-regulated and essential for B cell function. Asparagine synthetase (ASNS) was up-regulated after B cell activation through the integrated stress response sensor GCN2.

Trends and Complications of Medial Patellofemoral Ligament Reconstruction Among Applicants for the American Board of Orthopaedic Surgery Part II and Maintenance of Certification Examinations: Analysis of Data Over a 15-Year Period.

Background: Medial patellofemoral ligament reconstruction (MPFLR) and tibial tubercle osteotomy (TTO) are commonly performed surgical procedures that often have a high learning curve.

Purpose: To review the American Board of Orthopaedic Surgery (ABOS) Part II oral examination case list and the Maintenance of Certification (MOC) examination case list databases for trends in MPFLR (isolated and with concurrent TTO) and complication rates.

Study Design: Cross-sectional study; Level of evidence, 3.

Impact of Female Sex and Mild Cortisol Secretion on Coagulation Profile in Adrenal Incidentalomas.

Context: Studies describing the coagulation profile in adrenal adenomas still need to be added.

Objective: We explored how sex and mild autonomous cortisol secretion (MACS) affect coagulation parameters in patients with adrenal adenomas.

Design: Cross-sectional study.

Role of Image-guided Platelet-rich Plasma Injection in the Management of Patients of Supraspinatus Tendon Tear.

Introduction: Supraspinatus tendinopathy is a common reason for shoulder pain, with or without an associated cuff tear. Various modalities of treatment have been described in literature such as physiotherapy, analgesics, corticosteroid injection, surgical repair (open or arthroscopic), and platelet-rich plasma (PRP) injection. Recently, there has been an increasing trend of PRP injection for rotator cuff arthropathy.

Prevalence and treatment of perinatal anxiety: diagnostic interview study.

Background: Anxiety affects around one in five women during pregnancy and after birth. However, there is no systematic information on the proportion of women with perinatal anxiety disorders who want or receive treatment.

Aims: To examine (a) the prevalence of anxiety disorders during pregnancy and after birth in a population-based sample, and (b) the proportion of women with anxiety disorders who want treatment and receive treatment.

Independent SAGE as an example of effective public dialogue on scientific research.

The World Health Organization declared COVID-19 to be a public health emergency of international concern on 30 January 2020 and then a pandemic on 11 March 2020. In early 2020, a group of UK scientists volunteered to provide the public with up-to-date and transparent scientific information. The group formed the Independent Scientific Advisory Group for Emergencies (Independent SAGE) and provided live weekly briefings to the public via YouTube.

scTrends: A living review of commercial single-cell and spatial 'omic technologies.

Understanding the rapidly evolving landscape of single-cell and spatial omic technologies is crucial for advancing biomedical research and drug development. We provide a living review of both mature and emerging commercial platforms, highlighting key methodologies and trends shaping the field. This review spans from foundational single-cell technologies such as microfluidics and plate-based methods to newer approaches like combinatorial indexing; on the spatial side, we consider next-generation sequencing and imaging-based spatial transcriptomics.

Association of the Cervical Canal Area With Disability and Progression in People With Multiple Sclerosis.

Background And Objectives: In multiple sclerosis (MS), brain reserve serves as a protective factor against cognitive impairment. Previous research has suggested a structural counterpart in the spine-spinal cord reserve-seemed to be associated with physical disability. This study aimed to investigate the potential of the cervical canal area (CCaA) as a proxy for spinal cord reserve in a multicentric cohort of people with MS (PwMS).

Extracellular Vesicles From Preeclampsia Disrupt the Blood-Brain Barrier by Reducing CLDN5.

Background: The physiopathology of life-threatening cerebrovascular complications in preeclampsia is unknown. We investigated whether disruption of the blood-brain barrier, generated using circulating small extracellular vesicles (sEVs) from women with preeclampsia or placentae cultured under hypoxic conditions, impairs the expression of tight junction proteins, such as CLDN5 (claudin-5), mediated by VEGF (vascular endothelial growth factor), and activation of KDR (VEGFR2 [VEGF receptor 2]).

Methods: We perform a preclinical mechanistic study using sEVs isolated from plasma of pregnant women with normal pregnancy (sEVs-NP; n=9), sEVs isolated from plasma of women with preeclampsia (sEVs-PE; n=9), or sEVs isolated from placentas cultured in normoxia (sEVs-Nor; n=10) or sEVs isolated from placentas cultured in hypoxia (sEVs-Hyp; n=10).

Current data science capacity building initiatives for health researchers in LMICs: global & regional efforts.

Background: Data science approaches have proved crucial for generating major insights to address public health challenges. While such approaches have played significant roles during the COVID-19 pandemic, there has been limited investment in capacity building in data science skills and infrastructure for health researchers in LMICs.

Objectives: This review aims to identify current health data science capacity building initiatives and gaps in Africa, Asia, and Latin America and the Caribbean (LAC), to support knowledge sharing and collaborations, and inform future initiatives and associated investment.

Neutralizing GDF-15 can overcome anti-PD-1 and anti-PD-L1 resistance in solid tumours.

Cancer immunotherapies with antibodies blocking immune checkpoint molecules are clinically active across multiple cancer entities and have markedly improved cancer treatment. Yet, response rates are still limited, and tumour progression commonly occurs. Soluble and cell-bound factors in the tumour microenvironment negatively affect cancer immunity.

Routine Capsular Closure Outperforms Incomplete Capsular Closure After Hip Arthroscopy: A Meta-analysis and Expected-Value Decision Analysis.

Purpose: To determine the optimal treatment decision for capsular management after primary hip arthroscopy for femoroacetabular impingement syndrome.

Methods: An expected-value decision analysis was performed (1) organizing the decision problem, (2) determining outcome probabilities, (3) determining outcome utilities, (4) performing fold-back analyses, and (5) performing sensitivity analyses. A decision tree was constructed (complete capsule closure vs incomplete closure) and a meta-analysis was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework, a systematic review was conducted to determine outcome probabilities.

Structure and mechanism of the Zorya anti-phage defense system.

Zorya is a recently identified and widely distributed bacterial immune system that protects bacteria from viral (phage) infections. Three Zorya subtypes have been discovered, each containing predicted membrane-embedded ZorAB complexes paired with soluble subunits that differ among Zorya subtypes, notably ZorC and ZorD in type I Zorya systems. Here, we investigate the molecular basis of Zorya defense using cryo-electron microscopy, mutagenesis, fluorescence microscopy, proteomics, and functional studies.

Energy-Efficient Integrated Electro-Optic Memristors.

Neuromorphic photonic processors are redefining the boundaries of classical computing by enabling high-speed multidimensional information processing within the memory. Memristors, the backbone of neuromorphic processors, retain their state after programming without static power consumption. Among them, electro-optic memristors are of great interest, as they enable dual electrical-optical functionality that bridges the efficiency of electronics and the bandwidth of photonics.

Surrogate endpoints in mature B-cell neoplasms - meaningful or misleading?

Indolent mature B-cell neoplasms are a group of diseases in which recent therapeutic advances have led to an improved overall survival (OS) extending beyond several years. While cause of celebration for patients and caregivers, the increasingly long observation periods necessary to capture treatment effects are complicating trial design and possibly hindering swift access to more effective therapies. Surrogate endpoints are a tool with the potential of earlier study readouts, however, their validity needs to be proven in each individual disease and therapeutic setting.

Genomic perspective on the bacillus causing paratyphoid B fever.

Paratyphoid B fever (PTB) is caused by an invasive lineage (phylogroup 1, PG1) of Salmonella enterica serotype Paratyphi B (SPB). However, little was known about the global population structure, geographic distribution, and evolution of this pathogen. Here, we report a whole-genome analysis of 568 historical and contemporary SPB PG1 isolates, obtained globally, between 1898 and 2021.

Pancreas Preservation: Hypothermic Oxygenated Perfusion to Improve Graft Reperfusion.

Background: The clinical standard for pancreas preservation for transplantation is static cold storage (SCS). Oxygenation during preservation has been shown to be advantageous in clinical studies. This study evaluates the efficiency of different oxygenation modalities during hypothermic pancreas preservation.

The contributions of vascular comorbidities on self-reported functional issues in persons with multiple sclerosis.

Purpose: This study aimed to evaluate 1) whether having a vascular comorbidity (i.e., hypertension, hyperlipidemia, heart disease, and diabetes) was associated with self-reported issues with functional activities among persons with multiple sclerosis (MS) and 2) if certain contributing factors (i.

Leptomeningeal metastatic disease: new frontiers and future directions.

Leptomeningeal metastatic disease (LMD), encompassing entities of 'meningeal carcinomatosis', neoplastic meningitis' and 'leukaemic/lymphomatous meningitis', arises secondary to the metastatic dissemination of cancer cells from extracranial and certain intracranial malignancies into the leptomeninges and cerebrospinal fluid. The clinical burden of LMD has been increasing secondary to more sensitive diagnostics, aggressive local therapies for discrete brain metastases, and improved management of extracranial disease with targeted and immunotherapeutic agents, resulting in improved survival. However, owing to drug delivery challenges and the unique microenvironment of LMD, novel therapies against systemic disease have not yet translated into improved outcomes for these patients.