HapCNV: A Comprehensive Framework for CNV Detection in Low-input DNA Sequencing Data.

Copy number variants (CNVs) are prevalent in both diploid and haploid genomes, with the latter containing a single copy of each gene. Studying CNVs in genomes from single or few cells is significantly advancing our knowledge in human disorders and disease susceptibility. Low-input including low-cell and single-cell sequencing data for haploid and diploid organisms generally displays shallow and highly non-uniform read counts resulting from the whole genome amplification steps that introduce amplification biases.

Pathogens spread by high-altitude windborne mosquitoes.

Recent studies have revealed that many mosquito species regularly engage in high-altitude windborne migration, but its epidemiological significance was debated. The hypothesis that high-altitude mosquitoes spread pathogens over large distances has not been directly tested. Here, we report for the first time that high-altitude windborne mosquitoes are commonly infected with arboviruses, protozoans, and helminths affecting vertebrates and humans, and provide the first description of this pathogen-vector aerial network.

Predicting protein curvature sensing across membrane compositions with a bilayer continuum model.

Cytoplasmic proteins must recruit to membranes to function in processes such as endocytosis and cell division. Many of these proteins recognize not only the chemical structure of the membrane lipids, but the curvature of the surface, binding more strongly to more highly curved surfaces, or 'curvature sensing'. Curvature sensing by amphipathic helices is known to vary with membrane bending rigidity, but changes to lipid composition can simultaneously alter membrane thickness, spontaneous curvature, and leaflet symmetry, thus far preventing a systematic characterization of lipid composition on such curvature sensing through either experiment or simulation.

Prediction of checkpoint inhibitor immunotherapy efficacy for cancer using routine blood tests and clinical data.

Predicting whether a patient with cancer will benefit from immune checkpoint inhibitors (ICIs) without resorting to advanced genomic or immunologic assays is an important clinical need. To address this, we developed and evaluated SCORPIO, a machine learning system that utilizes routine blood tests (complete blood count and comprehensive metabolic profile) alongside clinical characteristics from 9,745 ICI-treated patients across 21 cancer types. SCORPIO was trained on data from 1,628 patients across 17 cancer types from Memorial Sloan Kettering Cancer Center.

Adverse childhood experiences and adult alcohol use during pregnancy - 41 U.S. jurisdictions, 2019-2023.

Introduction: Adverse childhood experiences (ACEs) are preventable, potentially traumatic events that occur in childhood. Alcohol use during pregnancy can result in miscarriage, stillbirth, preterm birth, and a range of lifelong behavioral, intellectual, and physical disabilities in the child. Limited research has examined the relationship between ACEs and alcohol use in pregnancy; available studies might not reflect current trends in this relationship.

Bivalent SMAC mimetic APG-1387 reduces HIV reservoirs and limits viral rebound in humanized mice.

Latent viral reservoirs (VRs) represent a main barrier to HIV cure. Thus, developing new approaches that can purge and eliminate VRs paves the path toward achieving an HIV-1 cure. APG-1387, a bivalent SMAC mimetic (SM), efficiently reactivates latent HIV expression in T cell line models and enhances active caspase 3 expression, a condition that typically leads to apoptosis.

Severe maternal morbidity contributed by obstetric hemorrhage: Maryland, 2020-2022.

Background: Obstetric hemorrhage is the leading cause of maternal mortality and severe maternal morbidity (SMM) in Maryland and nationally. Currently, through a quality collaborative, the state is implementing the Alliance for Innovation on Maternal Health (AIM) patient safety bundle on obstetric hemorrhage.

Objective: To describe SMM events contributed by obstetric hemorrhage and their preventability in Maryland.

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.

Social Risks and Nonadherence to Recommended Cancer Screening Among US Adults.

Importance: Research indicates that social drivers of health are associated with cancer screening adherence, although the exact magnitude of these associations remains unclear.

Objective: To investigate the associations between individual-level social risks and nonadherence to guideline-recommended cancer screenings.

Design, Setting, And Participants: This cross-sectional study used 2022 Behavioral Risk Factor Surveillance System data from 39 US states and Washington, DC.

Rotavirus vaccine coverage, completion, and compliance: A systematic literature review.

Rotavirus, a leading cause of severe acute gastroenteritis in children, is largely preventable through immunization with two internationally licensed oral rotavirus vaccines (RVVs) included in national programs across over 100 countries. These RVVs are administered in either two (Rotarix™; 2D-RV) or three (RotaTeq®; 3D-RV) doses. We aimed to assess the global coverage, completion, and compliance of 2D-RV and 3D-RV in various settings, and to identify factors influencing vaccine coverage.

Recognition of Self and Viral Ligands by NK Cell Receptors.

Natural killer (NK) cells are essential elements of the innate immune response against tumors and viral infections. NK cell activation is governed by NK cell receptors that recognize both cellular (self) and viral (non-self) ligands, including MHC, MHC-related, and non-MHC molecules. These diverse receptors belong to two distinct structural families, the C-type lectin superfamily and the immunoglobulin superfamily.

The spatially informed mFISHseq assay resolves biomarker discordance and predicts treatment response in breast cancer.

Current assays fail to address breast cancer's complex biology and accurately predict treatment response. On a retrospective cohort of 1082 female breast tissues, we develop and validate mFISHseq, which integrates multiplexed RNA fluorescent in situ hybridization with RNA-sequencing, guided by laser capture microdissection. This technique ensures tumor purity, unbiased whole transcriptome profiling, and explicitly quantifies intratumoral heterogeneity.

Deep learning-based aberration compensation improves contrast and resolution in fluorescence microscopy.

Optical aberrations hinder fluorescence microscopy of thick samples, reducing image signal, contrast, and resolution. Here we introduce a deep learning-based strategy for aberration compensation, improving image quality without slowing image acquisition, applying additional dose, or introducing more optics. Our method (i) introduces synthetic aberrations to images acquired on the shallow side of image stacks, making them resemble those acquired deeper into the volume and (ii) trains neural networks to reverse the effect of these aberrations.

Estimated exposure to endotoxin and circulating immunological markers among male farmers in the Biomarkers of Exposure and Effect in Agriculture study.

Background: Occupational exposure to endotoxin has been associated with reduced lung cancer risk. The mechanisms underlying this association are unclear, though immunological alterations likely play a role. Farmers who perform certain tasks (eg, raising hogs) can be highly exposed to endotoxin.

Protective antibodies target cryptic epitope unmasked by cleavage of malaria sporozoite protein.

The most advanced monoclonal antibodies (mAbs) and vaccines against malaria target the central repeat region or closely related sequences within the circumsporozoite protein (PfCSP). Here, using an antigen-agnostic strategy to investigate human antibody responses to whole sporozoites, we identified a class of mAbs that target a cryptic PfCSP epitope that is only exposed after cleavage and subsequent pyroglutamylation (pGlu) of the newly formed N terminus. This pGlu-CSP epitope is not targeted by current anti-PfCSP mAbs and is not included in the licensed malaria vaccines.

Long-term impact of Diabetes Prevention Program interventions on walking endurance.

Objectives: Type 2 diabetes (T2D) and prediabetes are associated with poor walking endurance, a marker of physical function. We aimed to examine the long-term effects of metformin or intensive lifestyle intervention in adults at high risk of T2D on their 6-min walk test (6MWT) performance.

Methods: Participants were randomized in the 3-year Diabetes Prevention Program (DPP) to one of the three groups: lifestyle intervention, metformin, or placebo, and were subsequently followed in the DPP Outcomes Study.

The role of patient ergonomics in improving health research participation.

Patient ergonomics advances understanding of patient work to support individuals in managing health and health care, which can be expanded to include health research. While health research enables improvements in care delivery and health outcomes, participant recruitment, enrollment, and retention challenges hamper effective research participation, impede success of research studies, and influence the validity and generalizability of findings. Recent trends in health research create new opportunities to engage patients in research but require careful attention to patient ergonomics and human factors considerations to ensure they successfully address participant needs and contexts.