Refining breast cancer genetic risk and biology through multi-ancestry fine-mapping analyses of 192 risk regions.

Genome-wide association studies have identified approximately 200 genetic risk loci for breast cancer, but the causal variants and target genes are mostly unknown. We sought to fine-map all known breast cancer risk loci using genome-wide association study data from 172,737 female breast cancer cases and 242,009 controls of African, Asian and European ancestry. We identified 332 independent association signals for breast cancer risk, including 131 signals not reported previously, and for 50 of them, we narrowed the credible causal variants down to a single variant.

Blood DNA virome associates with autoimmune diseases and COVID-19.

Aberrant immune responses to viral pathogens contribute to pathogenesis, but our understanding of pathological immune responses caused by viruses within the human virome, especially at a population scale, remains limited. We analyzed whole-genome sequencing datasets of 6,321 Japanese individuals, including patients with autoimmune diseases (psoriasis vulgaris, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), pulmonary alveolar proteinosis (PAP) or multiple sclerosis) and coronavirus disease 2019 (COVID-19), or healthy controls. We systematically quantified two constituents of the blood DNA virome, endogenous HHV-6 (eHHV-6) and anellovirus.

ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip.

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma).

Demonstration of active neutron interrogation of special nuclear materials using a high-intensity short-pulse-laser-driven neutron source.

Detecting shielded special nuclear material, such as nuclear explosives, is a difficult challenge pursued by non-proliferation, anti-terrorism, and nuclear security programs worldwide. Interrogation with intense fast-neutron pulses is a promising method to characterize concealed nuclear material rapidly but is limited by suitable source availability and proven instrumentation. In this study we have pioneered a demonstration of such an interrogation method using a high-intensity, short-pulse, laser-driven neutron source that offers potential benefits compared to conventional neutron sources.

Infiltrating plasma cells maintain glioblastoma stem cells through IgG-Tumor binding.

Glioblastoma is a highly aggressive primary brain tumor with glioblastoma stem cells (GSCs) enforcing the intra-tumoral hierarchy. Plasma cells (PCs) are critical effectors of the B-lineage immune system, but their roles in glioblastoma remain largely unexplored. Here, we leverage single-cell RNA and B cell receptor sequencing of tumor-infiltrating B-lineage cells and reveal that PCs are aberrantly enriched in the glioblastoma-infiltrating B-lineage population, experience low level of somatic hypermutation, and are associated with poor prognosis.

Latent epigenetic programs in Müller glia contribute to stress and disease response in the retina.

Previous studies have demonstrated the dynamic changes in chromatin structure during retinal development correlate with changes in gene expression. However, those studies lack cellular resolution. Here, we integrate single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) with bulk data to identify cell-type-specific changes in chromatin structure during human and murine development.

Evaluation of water environmental capacity in a northern river-reservoir continuum using environmental fluid dynamics code.

The hydrodynamics, water temperature, and water quality model for the Dan River and Renzhuang Reservoir continuum were developed using field monitoring data and the Environmental Fluid Dynamics Code (EFDC). An in-situ water discharge experiment enabled the calculation of water propagation time using a simulated flood progression method and the hydrodynamics module of EFDC. Based on these model results, degradation coefficients for chemical oxygen demand, biochemical oxygen demand, nitrogen (N), phosphorus (P), fluoride, arsenic were determined, revealing significantly higher values when the wetland barrage was opening.

Evaluation of testing approaches for constituent leaching from electric arc furnace (EAF) slags.

Increased usage of electric arc furnace (EAF) slags as soil amendments and surface aggregates raises concerns regarding heavy metal release. However, no standardized leaching characterization approach exists for EAF slags and other industrial materials. This study compares test results for three EAF slags using several testing approaches: (i) total content analysis, (ii) single-batch extractions (i.

Inorganic bioelectric system for nitrate removal with low NO production at cold temperatures of 4 and 10 °C.

Groundwater, essential for ecological stability and freshwater supply, faces escalating nitrate contamination. Traditional biological methods struggle with organic carbon scarcity and low temperatures, leading to an urgent need to explore efficient approaches for groundwater remediation. In this work, we proposed an inorganic bioelectric system designed to confront these challenges.

Vascular endothelial growth factor receptor-1 (FLT1) interactions with amyloid-beta in Alzheimer's disease: A putative biomarker of amyloid-induced vascular damage.

We have identified FLT1 as a protein that changes during Alzheimer's disease (AD) whereby higher brain protein levels are associated with more amyloid, more tau, and faster longitudinal cognitive decline. Given FLT1's role in angiogenesis and immune activation, we hypothesized that FLT1 is upregulated in response to amyloid pathology, driving a vascular-immune cascade resulting in neurodegeneration and cognitive decline. We sought to determine (1) if in vivo FLT1 levels (CSF and plasma) associate with biomarkers of AD neuropathology or differ between diagnostic staging in an aged cohort enriched for early disease, and (2) whether FLT1 expression interacts with amyloid on downstream outcomes, such as phosphorylated tau levels and cognitive performance.

Coastal redox shifts over the past 167 years and preservation of total organic carbon and total nitrogen.

This study reconstructs the environmental history of Xincun Lagoon over the past 167 years using sediment core XCW, employing Cu/Zn as a proxy for redox changes. Time-series analysis of Cu/Zn ratios reveals a significant decline (linear regression slope = -0.00082, p < 0.

Improved Patient-Reported Outcomes With Post-Transplant Cyclophosphamide: A Quality-of-Life Evaluation and 2-Year Outcomes of BMT CTN 1703.

The BMT CTN 1703 phase III trial confirmed that graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF) results in superior GVHD-free, relapse-free survival (GRFS) compared with Tac/methotrexate (MTX) prophylaxis. This companion study assesses the effect of these regimens on patient-reported outcomes (PROs). Using the Lee Chronic GVHD Symptom Score and PROMIS subscales (physical function, GI symptoms, social role satisfaction) as primary end points and hemorrhagic cystitis symptoms and Lee subscales as secondary end points, responses from English and Spanish speakers were analyzed at baseline and days 100, 180, and 365 after transplant.

Trends in childhood cancer: Incidence and survival analysis over 45 years of SEER data.

Background: The SEER Registry contains U.S. cancer statistics.

Laparoscopic Warshaw Procedure for Solid Pseudopapillary Neoplasms in Children.

Background: Solid pseudopapillary neoplasms (SPNs) arising in the body or tail of the pancreas can be amenable to laparoscopic distal pancreatectomy with or without concomitant splenectomy. The purpose of this study was to evaluate laparoscopic distal pancreatectomy for SPN using the Warshaw technique as a means to preserve spleens in children.

Methods: We reviewed our database of SPN patients 19 years and younger (January 2006-December 2023).

Impact of APOE and MAPT genetic profile on the cognitive functions among Amyotrophic Lateral Sclerosis Tunisian patients.

Amyotrophic Lateral Sclerosis(ALS) has traditionally been managed as a neuromuscular disorder. However, recent evidence suggests involvement of non-motor domains. This study aims to evaluate the impact of APOE and MAPT genotypes on the cognitive features of ALS.

Human Footprint and Forest Disturbance Reduce Space Use of Brown Bears (Ursus arctos) Across Europe.

Three-quarters of the planet's land surface has been altered by humans, with consequences for animal ecology, movements and related ecosystem functioning. Species often occupy wide geographical ranges with contrasting human disturbance and environmental conditions, yet, limited data availability across species' ranges has constrained our understanding of how human pressure and resource availability jointly shape intraspecific variation of animal space use. Leveraging a unique dataset of 758 annual GPS movement trajectories from 375 brown bears (Ursus arctos) across the species' range in Europe, we investigated the effects of human pressure (i.

Structural and magnetic phase transitions in EuLaFe(BO) (x = 0, 0.18).

The crystal structures and hyperfine magnetic parameters of EuFe(BO) and mixed EuLaFe(BO) were studied over a wide temperature range in order to analyze correlations of the structural and magnetic features and the phase transitions in multiferroic compounds of the rare-earth iron borate family. The chemical compositions of the crystals are reported from X-ray fluorescence analysis. The crystal structures of EuFe(BO) and EuLaFe(BO) were determined using single-crystal X-ray diffraction in the temperature range 25-500 K.

Integrating Pharmacogenomics into the Broader Construct of Genomic Medicine: Efforts by the ClinGen Pharmacogenomics Working Group (PGxWG).

Pharmacogenomics (PGx) is focused on the relationship between an individual's genetic makeup and their response to medications, with the overarching aim of guiding prescribing decisions to improve drug efficacy and reduce adverse events. The PGx and genomic medicine communities have worked independently for over 2 decades, developing separate standards and terminology, making implementation of PGx across all areas of genomic medicine difficult. To address this issue, the Clinical Genome Resource (ClinGen) Pharmacogenomics Working Group (PGxWG) was established by the National Institutes of Health (NIH)-funded ClinGen to initially create frameworks for evaluating gene-drug response clinical validity and actionability aligned with the ClinGen frameworks for evaluating monogenic gene-disease relationships, and a framework for classifying germline PGx variants similar to the American College of Medical Genetics (ACMG) and Association of Molecular Pathology (AMP) system for interpretation of disease-causing variants.

Racial, Socioeconomic, and Geographic Disparities in Preamputation Vascular Care for Patients With Chronic Limb-Threatening Ischemia.

Background: Black patients, those with low socioeconomic status (SES), and those living in rural areas have elevated rates of major lower extremity amputation, which may be related to a lack of subspecialty chronic limb-threatening ischemia care. We evaluated the association between race, rurality, SES, and preamputation vascular care.

Methods: Among patients aged 66 to 86 years with fee-for-service Medicare who underwent major lower extremity amputation for chronic limb-threatening ischemia from July 2010 to December 2019, we compared the proportion who received vascular care in the 12 months before amputation by race (Black versus White), rurality, and SES (dual eligibility for Medicaid versus no dual eligibility) using multivariable logistic regression adjusting for clinical and demographic covariates.

Disparities in Advanced Stage Colorectal Cancer Outcomes in Appalachia: A Comprehensive Review.

The Appalachian region consists of over 26 million Americans, of whom almost 2.5 million live in rural areas. Various social determinants of health including but not limited to rural living conditions and geographic isolation, food insecurity, and low income contribute to disparate health outcomes compared to the rest of the country.