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Dispensable regulation of brain development and myelination by the immune-related protein Serpina3n.

Serine protease inhibitor clade A member 3n (Serpina3n) or its human orthologue SERPINA3 is a secretory immune-related molecule produced primarily in the liver and brain under homeostatic conditions and up-regulated in response to system inflammation. Yet, it remains elusive regarding its cellular identity and physiological significance in the development of the postnatal brain. Here, we reported that oligodendroglial lineage cells are the major cell population expressing Serpina3n protein in the postnatal murine CNS.

Prediabetes persistence or remission and subsequent risk of gallbladder cancer: A nationwide cohort study.

Background & Aims: Hyperglycemia is associated with an increased risk of gallbladder cancer (GBC), potentially by inhibiting gallbladder motility and inducing prolonged cholestasis. Although intermediate hyperglycemia (or prediabetes) is highly reversible, evidence is lacking about whether prediabetes persistence or remission is associated with an altered GBC risk.

Methods: This nationwide cohort study included 6058,662 adults without diabetes or cancer who underwent national health examinations twice in 2-year intervals between 2009 (S1) and 2011 (S2) and were followed-up until 2018.

Identification and characterisation of pathogenic and non-pathogenic FGF14 repeat expansions.

Repeat expansions in FGF14 cause autosomal dominant late-onset cerebellar ataxia (SCA27B) with estimated pathogenic thresholds of 250 (incomplete penetrance) and 300 AAG repeats (full penetrance), but the sequence of pathogenic and non-pathogenic expansions remains unexplored. Here, we demonstrate that STRling and ExpansionHunter accurately detect FGF14 expansions from short-read genome data using outlier approaches. By combining long-range PCR and nanopore sequencing in 169 patients with cerebellar ataxia and 802 controls, we compare FGF14 expansion alleles, including interruptions and flanking regions.

Association between Liver Function Markers and Menstrual Cycle Irregularity in Korean Female Population.

Background: The liver plays an important role in gonadal steroid hormone metabolism, which can affect reproductive health, including the menstrual cycle. However, evidence from large population-based studies is limited. Therefore, this study aimed to investigate the association between liver function markers and menstrual cycle irregularities in premenopausal Korean women using nationwide data.

Modulating monocyte-derived macrophage polarization in cerebral ischemic injury with hyperglycemia.

Ischemic stroke (IS), characterized by high mortality rate, occurs owing to diminished or blocked blood flow to the brain. Hyperglycemia (HG) is a major contributor to the risk of IS. HG induces augmented oxidative stress and Blood-Brain Barrier breakdown, which increases the influx of blood-derived myeloid cells into the brain parenchyma.

Cost-effectiveness of mask mandates on subways to prevent SARS-CoV-2 transmission in the United States.

Background: Community-based mask wearing has been shown to reduce the transmission of SARS-CoV-2. However, few studies have conducted an economic evaluation of mask mandates, specifically in public transportation settings. This study evaluated the cost-effectiveness of implementing mask mandates for subway passengers in the United States by evaluating its potential to reduce COVID-19 transmission during subway travel.

Control of OPC proliferation and repopulation by the intellectual disability gene PAK1 under homeostatic and demyelinating conditions.

Appropriate proliferation and repopulation of oligodendrocyte progenitor cells (OPCs) determine successful (re)myelination in homeostatic and demyelinating brains. Activating mutations in p21-activated kinase 1 (PAK1) cause intellectual disability, neurodevelopmental abnormality, and white matter anomaly in children. It remains unclear if and how PAK1 regulates oligodendroglial development.

A GGC-repeat expansion in ZFHX3 encoding polyglycine causes spinocerebellar ataxia type 4 and impairs autophagy.

Despite linkage to chromosome 16q in 1996, the mutation causing spinocerebellar ataxia type 4 (SCA4), a late-onset sensory and cerebellar ataxia, remained unknown. Here, using long-read single-strand whole-genome sequencing (LR-GS), we identified a heterozygous GGC-repeat expansion in a large Utah pedigree encoding polyglycine (polyG) in zinc finger homeobox protein 3 (ZFHX3), also known as AT-binding transcription factor 1 (ATBF1). We queried 6,495 genome sequencing datasets and identified the repeat expansion in seven additional pedigrees.

Regulation of CNS pathology by Serpina3n/SERPINA3: The knowns and the puzzles.

Neuroinflammation, blood-brain barrier (BBB) dysfunction, neuron and glia injury/death and myelin damage are common central nervous system (CNS) pathologies observed in various neurological diseases and injuries. Serine protease inhibitor (Serpin) clade A member 3n (Serpina3n), and its human orthologue SERPINA3, is an acute-phase inflammatory glycoprotein secreted primarily by the liver into the bloodstream in response to systemic inflammation. Clinically, SERPINA3 is dysregulated in brain cells, cerebrospinal fluid and plasma in various neurological conditions.

Dispensable regulation of brain development and myelination by the immune-related protein Serpina3n.

Serine protease inhibitor clade A member 3n (Serpina3n) or its human orthologue SERPINA3 is a secretory immune-related molecule produced primarily in the liver and brain under homeostatic conditions and upregulated in response to system inflammation. Yet it remains elusive regarding its cellular identity and physiological significance in the development of the postnatal brain. Here, we reported that oligodendroglial lineage cells are the major cell population expressing Serpina3n protein in the postnatal murine CNS.

Lessons Learned from Translating Genome Sequencing to Clinical Routine: Understanding the Accuracy of a Diagnostic Pipeline.

The potential of genome sequencing (GS), which allows detection of almost all types of genetic variation across nearly the entire genome of an individual, greatly expands the possibility for diagnosing genetic disorders. The opportunities provided with this single test are enticing to researchers and clinicians worldwide for human genetic research as well as clinical application. Multiple studies have highlighted the advantages of GS for genetic variant discovery, emphasizing its added value for routine clinical use.

Association between Smoking Cessation and the Risk of Cholangiocarcinoma and Ampulla of Vater Cancer: A Nationwide Cohort Study.

Introduction: The association between smoking cessation and intrahepatic and extrahepatic cholangiocarcinoma (iCCA and eCCA) risk is unclear. Furthermore, the association in individuals with preexisting risk factors is unknown. We aimed to investigate the association between smoking status (especially smoking cessation) and CCA risk according to individuals' glycemic status.

HNRNPC haploinsufficiency affects alternative splicing of intellectual disability-associated genes and causes a neurodevelopmental disorder.

Heterogeneous nuclear ribonucleoprotein C (HNRNPC) is an essential, ubiquitously abundant protein involved in mRNA processing. Genetic variants in other members of the HNRNP family have been associated with neurodevelopmental disorders. Here, we describe 13 individuals with global developmental delay, intellectual disability, behavioral abnormalities, and subtle facial dysmorphology with heterozygous HNRNPC germline variants.

Productivity costs associated with reactive school closures related to influenza or influenza-like illness in the United States from 2011 to 2019.

Introduction: Schools close in reaction to seasonal influenza outbreaks and, on occasion, pandemic influenza. The unintended costs of reactive school closures associated with influenza or influenza-like illness (ILI) has not been studied previously. We estimated the costs of ILI-related reactive school closures in the United States over eight academic years.

Costs of malaria treatment in the United States.

We estimated inpatient and outpatient payments for malaria treatment in the USA. The mean cost per hospitalized patient was significantly higher than for non-hospitalized patients (e.g.

Threshold dose-response association between smoking pack-years and the risk of gallbladder cancer: A nationwide cohort study.

Background And Aims: The association between smoking and gallbladder cancer (GBC) risk is unclear. We investigated the association between smoking (including pack-years) and GBC risk. We also examined the combined effects of smoking and diabetes or prediabetes on GBC risk.