Integrated multi-omic characterizations of the synapse reveal RNA processing factors and ubiquitin ligases associated with neurodevelopmental disorders.

The molecular composition of the excitatory synapse is incompletely defined due to its dynamic nature across developmental stages and neuronal populations. To address this gap, we apply proteomic mass spectrometry to characterize the synapse in multiple biological models, including the fetal human brain and human induced pluripotent stem cell (hiPSC)-derived neurons. To prioritize the identified proteins, we develop an orthogonal multi-omic screen of genomic, transcriptomic, interactomic, and structural data.

Evaluation of Immunosuppression Levels and Risk of Graft-Versus-Host Disease in Allogeneic Blood or Marrow Transplantation with Post-Transplant Cyclophosphamide.

Post-transplantation cyclophosphamide (PTCy) is standard graft-versus-host disease (GVHD) prophylaxis for allogeneic blood or marrow transplantation (alloBMT), although optimal therapeutic levels of immunosuppression (IS) therapy combined with PTCy remain contested. Previously, with tacrolimus and methotrexate GVHD prophylaxis, week 1 tacrolimus levels >12 ng/mL were associated with a decreased incidence of grade 2-4 acute GVHD (aGVHD). We evaluated if associations between aGVHD and early IS levels were observed amongst patients receiving PTCy.

Defined cellular reprogramming of androgen receptor-active prostate cancer to neuroendocrine prostate cancer.

Neuroendocrine prostate cancer (NEPC) arises primarily through neuroendocrine transdifferentiation (NEtD) as an adaptive mechanism of therapeutic resistance. Models to define the functional effects of putative drivers of this process on androgen receptor (AR) signaling and NE cancer lineage programs are lacking. We adapted a genetically defined strategy from the field of cellular reprogramming to directly convert AR-active prostate cancer (ARPC) to AR-independent NEPC using candidate factors.

Precision measurements of brain oxygen utilization with positron emission tomography.

Oxygen utilization is important for studies of brain metabolism, alongside other measurements such as for glucose metabolism. Oxygen and other measurements with [ O] tracers and PET, however, are significantly more challenging than measurements of [ F]fluorodeoxyglucose, the standard for probing tissue glucose metabolism in vivo, in part due to the much shorter radioactive half-life of [ O]. This work examines details of precision measurement of [ O] tracers and their kinetics.

TLR4 downregulation protects against cisplatin-induced ototoxicity in adult and pediatric patients with cancer.

Cisplatin causes permanent hearing loss or cisplatin-induced ototoxicity in over 50% of treated patients with cancer, leading to significant social and functional limitations. Interindividual variability in developing hearing loss suggests the role of genetic predispositions to cisplatin-induced hearing loss. We investigated genetic associations between cisplatin-induced ototoxicity and toll-like receptor 4 (TLR4), an immune receptor known to mediate inflammatory responses to cisplatin.

Towards faster plan adaptation for proton arc therapy using initial treatment plan information.

Background And Purpose: Proton arc therapy (PAT) is an emerging modality delivering continuously rotating proton beams. Current PAT planning approaches are time-consuming, making them unsuitable for online adaptation. This study proposes an accelerated workflow for adapting PAT plans.

Metabolic rate and insulin-independent glucose uptake increase in a TDP-43 mouse model of amyotrophic lateral sclerosis.

Impaired glucose regulation is increasingly recognised in amyotrophic lateral sclerosis (ALS), yet the precise mechanisms remain unclear. Here, we investigated energy balance and glucose control in TAR DNA-binding protein 43 (TDP-43) mice, a model of ALS, at both the early and late symptomatic stages of disease. Mutant TDP-43 mice and non-transgenic controls underwent indirect calorimetry, as well as intraperitoneal glucose, insulin, and glucagon tolerance testing.

Anticipating potential bottlenecks in adaptive proton FLASH therapy: a ridge filter reuse strategy.

Achieving FLASH dose rate with pencil beam scanning intensity modulated proton therapy is challenging. However, utilizing a single energy layer with a ridge filter (RF) can maintain dose rate and conformality. Yet, changes in patient anatomy over the treatment course can render the RF obsolete.

Anaplastic meningioma in a 6-year-old with somatic YAP1::MAML2 fusion and multiple endocrine neoplasia type 4 (MEN4) syndrome.

Meningiomas are the most common primary brain tumors in adults but much less frequent in children. Many subtypes exist, including anaplastic (malignant) meningioma, which accounts for less than 20% of pediatric tumors. Meningiomas can arise in association with cancer predisposition syndromes due to germline variants in genes such as NF2, MEN1 and SMARCE1.

Performance of 8 Smoking Metrics for Modeling Survival in Head and Neck Squamous Cell Carcinoma.

Importance: Cigarette smoking is a strong risk factor for mortality in patients diagnosed with head and neck squamous cell carcinoma (HNSCC). However, little evidence supports which smoking metric best models the association between smoking and survival in HNSCC.

Objective: To determine which smoking metric best models a linear association between smoking exposure and overall survival (OS) in patients with HNSCC.

Pregnancy Reduces COVID-19 Vaccine Immunity Against Novel Variants.

Pregnant women are at heightened risk for severe outcomes from many infectious diseases, including COVID-19. However, they were not included in the initial COVID-19 vaccine clinical trials and current rates of vaccine uptake among pregnant women remain below 15%. We explored the serological and cellular responses to COVID-19 mRNA booster vaccines (i.

Effective coverage for reproductive, maternal, neonatal and newborn health: an analysis of geographical and socioeconomic inequalities in 39 low- and middle-income countries.

Background: Inadequate access to quality maternal and child health services leads to poor health outcomes for millions of women, particularly in low- and middle-income countries (LMICs). This study aims to explore the effective coverage of reproductive, maternal, neonatal and newborn health (RMNCH) services and examines socioeconomic and rural and urban disparities in 39 LMICs.

Methods: Using Demographic and Health Surveys (DHS) data, the research assesses RMNCH service quality by applying an effective coverage framework, which measures service contact, crude coverage, quality-adjusted coverage and user adherence-adjusted coverage.

Fluorescence-Guided Surgery Using 5-Aminolevulinic Acid/Protoporphyrin IX in Brain Metastases.

Background And Objectives: The purpose of this systematic review was to provide a comprehensive overview of the available literature on 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence-guided surgery (FGS) for the resection of brain metastases (BMs).

Methods: A comprehensive search of the PubMed database for literature on 5-ALA use in BMs surgery was performed. For inclusion, BMs studies had to have data on the observed intraoperative fluorescence available.

Lipopolysaccharide structural modification in Salmonella Gallinarum targeting lipid a deacylation and O-antigen reduces virulence and endotoxicity with competitive protection against a wild-type challenge in chickens.

Fowl typhoid (FT), caused by Salmonella Gallinarum (SG), inflicts a significant economic burden on the poultry industry. Our study focused on a non-reversible gene deletion to develop a safe and effective SG vaccine strain through lipopolysaccharide (LPS) structural modification. The virulence-attenuated SG JOL914 strain, generated by deleting the global regulator lon gene, was engineered by in-frame deletions targeting the LPS structure.

ZINQ-L: a zero-inflated quantile approach for differential abundance analysis of longitudinal microbiome data.

Background: Identifying bacterial taxa associated with disease phenotypes or clinical treatments over time is critical for understanding the underlying biological mechanism. Association testing for microbiome data is already challenging due to its complex distribution that involves sparsity, over-dispersion, heavy tails, etc. The longitudinal nature of the data adds another layer of complexity - one needs to account for the within-subject correlations to avoid biased results.

The Effects of Presenting AI Uncertainty Information on Pharmacists' Trust in Automated Pill Recognition Technology: Exploratory Mixed Subjects Study.

Background: Dispensing errors significantly contribute to adverse drug events, resulting in substantial health care costs and patient harm. Automated pill verification technologies have been developed to aid pharmacists with medication dispensing. However, pharmacists' trust in such automated technologies remains unexplored.

Understanding the Association Between Home Broadband Connection and Well-Being Among Middle-Aged and Older Adults in China: Nationally Representative Panel Data Study.

Background: Access to digital technology is among the major social determinants of health, and digital divide impacts health inequality. Yet, the impact of digital connectivity on the well-being and psychosocial outcomes in adults has not been fully studied.

Objective: The aim of this study was to investigate the association of home broadband connection with health and well-being of middle-aged adults and adults older than 45 years in China.

Peripheral and central elevation of IL-8 in patients with Huntington's disease.

Objectives: Huntington's Disease (HD) is a debilitating neurodegenerative condition characterized by motor, cognitive and psychiatric abnormalities. Immune hyperactivity and dysregulation are common in HD. In addition to the central nervous system, HD patients exhibit systemic innate immune activation and inflammation, which has been shown to contribute to the pathogenic effects of the Huntingtin gene mutation.

A third COVID-19 vaccine dose in kidney transplant recipients induces antibody response to vaccine and Omicron variants but shows limited Ig subclass switching.

Solid organ transplant recipients (SOTRs) suffer more frequent and more severe infections due to their compromised immune responses resulting from immunosuppressive treatments designed to prevent organ rejection. Pharmacological immunosuppression can adversely affect immune responses to vaccination. A cohort of kidney transplant recipients (KTRs) received their third dose of ancestral, monovalent COVID-19 vaccine in the context of a clinical trial and antibody responses to the vaccine strain, as well as two Omicron variants BA.

A Framework for Assessing Viral Pathogens: A Key Element of the BARDA Emerging Infectious Diseases Strategy.

The COVID-19 pandemic has revealed the need for nations to prepare more effectively for emerging infectious diseases. Preparing for these threats requires a multifaceted approach that includes assessing pathogen threat, building flexible capabilities for rapid medical countermeasure (MCM) development, and exercising, maintaining, and improving those response capabilities. The Biomedical Advanced Research and Development Authority (BARDA) promotes the advanced development of MCMs in response to natural and manmade threats.

Living donor uterus transplant research project in Singapore: Progress of the first case.

Introduction: To report the progress of the human living uterus transplant research project in Singapore.

Material And Methods: The uterus transplant research project began in 2012 with a collaboration between the Swedish and Singapore teams. Ethics approval was obtained from the SingHealth Centralised Institutional Review Board, the SingHealth Transplant and the Singapore General Hospital Biomedical Ethics Committee to perform 5 uterus transplant procedures in a collaborative multi-site research study at the Singapore General Hospital.

Advancing vaccine technology through the manipulation of pathogenic and commensal bacteria.

Advancements in vaccine technology are increasingly focused on leveraging the unique properties of both pathogenic and commensal bacteria. This revolutionary approach harnesses the diverse immune modulatory mechanisms and bacterial biology inherent in different bacterial species enhancing vaccine efficacy and safety. Pathogenic bacteria, known for their ability to induce robust immune responses, are being studied for their potential to be engineered into safe, attenuated vectors that can target specific diseases with high precision.

Corneal Stromal Stem Cell-Derived Extracellular Vesicles Attenuate ANGPTL7 Expression in the Human Trabecular Meshwork.

Purpose: Regulating intraocular pressure (IOP), mainly via the trabecular meshwork (TM), is critical in developing glaucoma. Whereas current treatments aim to lower IOP, directly targeting the dysfunctional TM tissue for therapeutic intervention has proven challenging. In our study, we utilized Dexamethasone (Dex)-treated TM cells as a model to investigate how extracellular vesicles (EVs) from immortalized corneal stromal stem cells (imCSSCs) could influence ANGPTL7 and MYOC genes expression within TM cells.