Disrupted callosal connectivity underlies long-lasting sensory-motor deficits in an NMDAreceptor antibody encephalitis mouse model.

NMDA receptor mediated autoimmune encephalitis (NMDAR-AE) frequently results in persistent sensory-motor deficits, especially in children, yet the underlying mechanisms remain unclear. This study investigated the long- term effects of exposure to a patient-derived GluN1-specific monoclonal antibody (mAb) during a critical developmental period (from postnatal day 3 to day 12) in mice. We observed long-lasting sensory-motor deficits characteristic of NMDAR-AE, along with permanent changes in callosal axons within the primary somatosensory cortex (S1) in adulthood, including increased terminal branch complexity.

Association of maxillofacial injuries with traumatic brain injuries in paediatric patients: a case-control study.

Background: Traumatic brain injuries (TBIs) are among the most challenging conditions to accurately diagnose in children, and many TBIs are underdiagnosed. Patients with maxillofacial injury may be at risk for TBI. The objective of this study was to analyse the association between maxillofacial injuries and TBI among paediatric patients.

repeat expansion creates the unstable folate-sensitive fragile site FRA9A.

The hyper-unstable Chr9p21 locus, harbouring the interferon gene cluster, oncogenes and , is linked to multiple diseases. (GGGGCC)n expansions (Exp) are associated with incompletely penetrant amyotrophic lateral sclerosis, frontotemporal dementia and autoimmune disorders. Exp patients display hyperactive cGAS-STING-linked interferon immune and DNA damage responses, but the source of immunostimulatory or damaged DNA is unknown.

An updated reference genome sequence and annotation reveals gene losses and gains underlying naked mole-rat biology.

The naked mole-rat (NMR; ) is a eusocial subterranean rodent with a highly unusual set of physiological traits that has attracted great interest amongst the scientific community. However, the genetic basis of most of these traits has not been elucidated. To facilitate our understanding of the molecular mechanisms underlying NMR physiology and behaviour, we generated a long-read chromosomal-level genome assembly of the NMR.

Unraveling SARS-CoV-2 Host-Response Heterogeneity through Longitudinal Molecular Subtyping.

Hospitalized COVID-19 patients exhibit diverse immune responses during acute infection, which are associated with a wide range of clinical outcomes. However, understanding these immune heterogeneities and their links to various clinical complications, especially long COVID, remains a challenge. In this study, we performed unsupervised subtyping of longitudinal multi-omics immunophenotyping in over 1,000 hospitalized patients, identifying two critical subtypes linked to mortality or mechanical ventilation with prolonged hospital stay and three severe subtypes associated with timely acute recovery.

Discovery of novel cyclopentane carboxylic acids as potent and selective inhibitors of Na1.7.

Discovery efforts leading to the identification of cyclopentane carboxylic acid 31, a potent inhibitor of Na1.7 that showed high selectivity over Na1.5 and exhibited robust analgesic effects in an inherited erythromelalgia (IEM) transgenic mouse assay, are described herein.

Antigen-Specific T Cell Receptor Discovery for Treating Progressive Multifocal Leukoencephalopathy.

Background: Progressive multifocal leukoencephalopathy (PML) is a frequently fatal disease of the central nervous system caused by JC virus (JCV). Survival is dependent on early diagnosis and ability to re-establish anti-viral T cell immunity. Adoptive transfer of polyomavirus-specific T cells has shown promise; however, there are no readily available HLA-matched anti-viral T cells to facilitate rapid treatment.

expansion creates the unstable folate-sensitive fragile site FRA9A.

The hyper-unstable Chr9p21 locus, harbouring the interferon gene cluster, oncogenes and is linked to multiple diseases. (GGGGCC)n expansions ( Exp) are associated with incompletely penetrant amyotrophic lateral sclerosis, frontotemporal dementia and autoimmune disorders. Exp patients display hyperactive cGAS-STING-linked interferon immune and DNA damage responses, but the source of immuno-stimulatory or damaged DNA is unknown.

Inter-chromosomal contacts demarcate genome topology along a spatial gradient.

Non-homologous chromosomal contacts (NHCCs) between different chromosomes participate considerably in gene and genome regulation. Due to analytical challenges, NHCCs are currently considered as singular, stochastic events, and their extent and fundamental principles across cell types remain controversial. We develop a supervised and unsupervised learning algorithm, termed Signature, to call NHCCs in Hi-C datasets to advance our understanding of genome topology.

Seven-year performance of a clinical metagenomic next-generation sequencing test for diagnosis of central nervous system infections.

Metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) is an agnostic method for broad-based diagnosis of central nervous system (CNS) infections. Here we analyzed the 7-year performance of clinical CSF mNGS testing of 4,828 samples from June 2016 to April 2023 performed by the University of California, San Francisco (UCSF) clinical microbiology laboratory. Overall, mNGS testing detected 797 organisms from 697 (14.

Inferring allele-specific copy number aberrations and tumor phylogeography from spatially resolved transcriptomics.

Analyzing somatic evolution within a tumor over time and across space is a key challenge in cancer research. Spatially resolved transcriptomics (SRT) measures gene expression at thousands of spatial locations in a tumor, but does not directly reveal genomic aberrations. We introduce CalicoST, an algorithm to simultaneously infer allele-specific copy number aberrations (CNAs) and reconstruct spatial tumor evolution, or phylogeography, from SRT data.

Age, sex, and cell type-resolved hypothalamic gene expression across the pubertal transition in mice.

Background: The hypothalamus plays a central role in regulating puberty. However, our knowledge of the postnatal gene regulatory networks that control the pubertal transition in males and females is incomplete. Here, we investigate the age-, sex- and cell-type-specific gene regulation in the hypothalamus across the pubertal transition.

Autosomal-dominant macular dystrophy linked to a chromosome 17 tandem duplication.

Hereditary macular dystrophies (HMDs) are a genetically diverse group of disorders that cause central vision loss due to photoreceptor and retinal pigment epithelium (RPE) damage. We investigated a family with a presumed novel autosomal-dominant HMD characterized by faint, hypopigmented RPE changes involving the central retina. Genome and RNA sequencing identified the disease-causing variant to be a 560 kb tandem duplication on chromosome 17 [NC_000017.

Etiology and Outcomes of Acute Infectious Conjunctivitis in Children.

Objective: To determine the causes of conjunctivitis and whether clinical presentations and outcomes differ by pathogen.

Study Design: This multicenter, case-control study enrolled 390 children (194 cases, 196 controls) whose conjunctival samples were tested for bacterial and viral pathogens. Caregivers completed surveys tracking symptoms, antibiotic use, school attendance, and adverse events.

Whom Do I Trust to Represent Me? Long-Term Care Resident and Family Perspectives on Legitimate Representation.

Introduction: Public engagement in long-term care policy making in Canada has primarily focused on "intermediary agents" who speak on behalf of long-term care (LTC) residents and their family caregivers. Yet the legitimacy of these intermediaries, as perceived by those they represent, has gone largely unexplored. This study examines LTC resident and family perspectives on who can legitimately represent them in LTC policy making.

Factors That Influence Access to Medical Assistance in Dying Services: An Integrative Review.

Background: In nearly all jurisdictions where it is permitted, Medical Assistance in Dying is situated in a healthcare system. Currently, limited evidence demonstrates how supply and demand factors influence access to Medical Assistance in Dying.

Objective: The aim of this study is to synthesise empirical research from jurisdictions where Medical Assistance in Dying is legal to identify how supply and demand factors influence access for eligible adults.

Protoporphyrin IX iron(II) revisited. An overview of the Mössbauer spectroscopic parameters of low-spin porphyrin iron(II) complexes.

Mössbauer parameters of low-spin six-coordinate [Fe(II)(Por)L] complexes (where Por is a synthetic porphyrin; L is a nitrogenous aliphatic, an aromatic base or a heterocyclic ligand, a P-bonding ligand, CO or CN) and low-spin [Fe(Por)LX] complexes (where L and X are different ligands) are reported. A known point charge calculation approach was extended to investigate how the axial ligands and the four porphyrinato-N atoms generate the observed quadrupole splittings (ΔE) for the complexes. Partial quadrupole splitting (p.

Local cryptic diversity in salinity adaptation mechanisms in the wild outcrossing .

It is normally supposed that populations of the same species should evolve shared mechanisms of adaptation to common stressors due to evolutionary constraint. Here, we describe a system of within-species local adaptation to coastal habitats, and detail surprising strategic variability in adaptive responses to high salinity. These different adaptive responses in neighboring populations are evidenced by transcriptomes, diverse physiological outputs, and distinct genomic selective landscapes.

Sexual minority men's experiences of, and strategies for emotional intimacy in intimate partner relationships.

Emotional intimacy is key to intimate partner relationship quality and satisfaction. For sexual minority men, queer and feminist theorists consistently link emotional intimacy to diverse sexual practices and partnership dynamics formulated within the relationship. This Photovoice study adds to those insights by drawing on individual photovoice interviews with 16 sexual minority men to describe participant's experiences of, and strategies for emotional intimacy in their intimate relationships.