SEAD reference panel with 22,134 haplotypes boosts rare variant imputation and genome-wide association analysis in Asian populations.

Limited whole genome sequencing (WGS) studies in Asian populations result in a lack of representative reference panels, thus hindering the discovery of ancestry-specific variants. Here, we present the South and East Asian reference Database (SEAD) panel ( https://imputationserver.westlake.

Radiomics of Periprostatic Fat and Tumor Lesion Based on MRI Predicts the Pathological Upgrading of Prostate Cancer from Biopsy to Radical Prostatectomy.

Rationale And Objectives: To assess the predictive value of MRI-based radiomics of periprostatic fat (PPF) and tumor lesions for predicting Gleason score (GS) upgrading from biopsy to radical prostatectomy (RP) in prostate cancer (PCa).

Methods: A total of 314 patients with pathologically confirmed prostate cancer (PCa) after radical prostatectomy (RP) were included in the study. The patients were randomly assigned to the training cohort (n = 157) and the validating cohort (n = 157) in a 1:1 ratio.

Cardiovascular Events Associated with CDK4/6 Inhibitors: A Safety Meta-Analysis of Randomized Controlled Trials and a Pharmacovigilance Study of the FAERS Database.

Background: CDK4/6 inhibitors are highly valued, but the incidence of cardiovascular adverse events (CVAEs) associated with CDK4/6 inhibitors is not clear.

Objective: Our aim was therefore to assess the risk of developing CVAEs associated with CDK4/6 inhibitors, by conducting a systematic review and meta-analysis of randomized controlled trials (RCTs), along with a pharmacovigilance study of the FDA Adverse Event Reporting System (FAERS) database.

Methods: Eligible CVAEs were extracted from the ClinicalTrials.

Association Between Hypoglycemia Agents and Long-term Survival Outcomes for Patients with Non-muscle-invasive Bladder Cancer Treated with Intravesical Bacillus Calmette-Guérin Immunotherapy.

Background And Objective: There is a lack of data on the impact of hypoglycemia agents, especially metformin, on prognosis for non-muscle-invasive bladder cancer (NMIBC). Our aim was to investigate the association between hypoglycemia agents, especially metformin, and long-term survival outcomes for patients with NMIBC treated with bacillus Calmette-Guérin.

Methods: All patients with NMIBC treated with intravesical BCG therapy from 2001 to 2020 were identified in a territory-wide database in Hong Kong.

Targeting peptide antigens using a multiallelic MHC I-binding system.

Identifying highly specific T cell receptors (TCRs) or antibodies against epitopic peptides presented by class I major histocompatibility complex (MHC I) proteins remains a bottleneck in the development of targeted therapeutics. Here, we introduce targeted recognition of antigen-MHC complex reporter for MHC I (TRACeR-I), a generalizable platform for targeting peptides on polymorphic HLA-A*, HLA-B* and HLA-C* allotypes while overcoming the cross-reactivity challenges of TCRs. Our TRACeR-MHC I co-crystal structure reveals a unique antigen recognition mechanism, with TRACeR forming extensive contacts across the entire peptide length to confer single-residue specificity at the accessible positions.

A general system for targeting MHC class II-antigen complex via a single adaptable loop.

Major histocompatibility complex class II (MHCII) bound to a peptide antigen mediates interactions between CD4 T cells and antigen-presenting cells. Targeting peptide-MHCII with T cell antigen receptors (TCRs) and TCR-like antibodies has shown promise for autoimmune diseases and microbiome tolerance. To develop a general targeting approach, we introduce targeted recognition of antigen-MHC complex reporter for MHCII (TRACeR-II) for the rapid development of peptide-specific MHCII binders.

Gene editing without ex vivo culture evades genotoxicity in human hematopoietic stem cells.

Gene editing the BCL11A erythroid enhancer is a validated approach to fetal hemoglobin (HbF) induction for β-hemoglobinopathy therapy, though heterogeneity in edit allele distribution and HbF response may impact its safety and efficacy. Here, we compare combined CRISPR-Cas9 editing of the BCL11A +58 and +55 enhancers with leading gene modification approaches under clinical investigation. Dual targeting of the BCL11A +58 and +55 enhancers with 3xNLS-SpCas9 and two single guide RNAs (sgRNAs) resulted in superior HbF induction, including in sickle cell disease (SCD) patient xenografts, attributable to simultaneous disruption of core half E-box/GATA motifs at both enhancers.

Sulfur-functionalized sawdust biochar for enhanced cadmium adsorption and environmental remediation: A multidisciplinary approach and density functional theory insights.

Pristine biochar typically exhibits limited capacity for heavy metal adsorption due to its inadequate pore development and insufficient surface functionality. This study introduces an innovative chemical strategy to enhance the surface of sawdust biochar with sulfur-based functional groups (C=S, C-S, S-S, S, S-H, -SO, -SO) to significantly improve cadmium (Cd) adsorption. Sulfur-doping using HSO, NaS, and NaSO markedly increased the sulfur content from 0.

Moving Beyond Medical Statistics: A Systematic Review on Missing Data Handling in Electronic Health Records.

Missing data in electronic health records (EHRs) presents significant challenges in medical studies. Many methods have been proposed, but uncertainty exists regarding the current state of missing data addressing methods applied for EHR and which strategy performs better within specific contexts. All studies referencing EHR and missing data methods published from their inception until 2024 March 30 were searched via the MEDLINE, EMBASE, and Digital Bibliography and Library Project databases.

Cis-regulatory elements driving motor neuron-selective viral payload expression within the mammalian spinal cord.

Spinal motor neuron (MN) dysfunction is the cause of a number of clinically significant movement disorders. Despite the recent approval of gene therapeutics targeting these MN-related disorders, there are no viral delivery mechanisms that achieve MN-restricted transgene expression. In this study, chromatin accessibility profiling of genetically defined mouse MNs was used to identify candidate cis-regulatory elements (CREs) capable of driving MN-selective gene expression.

Comparative Evaluation of Clinical-MRI, Radiomics, and Integrated Nomogram Models for Preoperative Prediction of Placenta Accreta Spectrum.

Rationale And Objectives: The escalating incidence of placental accreta spectrum (PAS), a pregnancy complication, underscores the need for accurate prenatal diagnosis to guide optimal management strategies. This study aims to develop, validate, and compare various prenatal PAS prediction models integrating clinical data, MRI signs, and radiomics signatures.

Materials And Methods: A cohort comprising 111 patients (72 with PAS and 39 without, denoted as N-PAS) served as the training set, while another 47 patients (33 PAS and 14 N-PAS) constituted the validation set.

The early transcriptional and post-transcriptional responses to fluconazole in sensitive and resistant Candida albicans.

Candida albicans is a leading cause of fungal infections in immunocompromised patients. Management of candidemia relies on a few antifungal agents, with fluconazole being first line therapy. The emergence of fluconazole-resistant strains highlights the pressing need to improve our molecular understanding of the drug response mechanisms.

Disparities in Receipt of Medications for Opioid Use Disorder Before and During the COVID-19 Pandemic in the US Veterans Health Administration.

Background: Populations disproportionately impacted by the opioid epidemic are less likely to receive medications for opioid use disorder (MOUD; OUD). The COVID-19 pandemic exacerbated these disparities. We performed an ecological survey of subpopulations to compare differences in MOUD receipt among Veterans with OUD before versus during the pandemic.

Iron-Catalyzed Cross-Electrophile Coupling for the Formation of All-Carbon Quaternary Centers.

Quaternary carbon centers are desirable targets for drug discovery and complex molecule synthesis, yet the synthesis of these motifs within traditional cross-coupling paradigms remains a significant challenge due to competing β-hydride elimination pathways. In contrast, the bimolecular homolytic substitution (S2) mechanism offers a unique and attractive alternative pathway. Metal porphyrin complexes have emerged as privileged catalysts owing to their ability to selectively form primary metal-alkyl complexes, thereby eliminating the challenges associated with tertiary alkyl complexation with a metal center.

Neuroprotective role of CHCHD2 in Parkinson's disease: Insights into the GPX4-related ferroptosis pathway.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease, characterized by pathogenesis involving mitochondrial dysfunction, oxidative stress, and ferroptosis. Unfortunately, there are currently no effective interventions to slow down the progression of PD. The mitochondrial protein coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2), which is implicated in neurodegeneration and serves as a biomarker for PD, has been reported to have neuroprotective effects against oxidative stress, but the potential molecular mechanisms involved remain elusive.

Stratified analysis identifies HIF-2 as a therapeutic target for highly immune-infiltrated melanomas.

While immune-checkpoint blockade (ICB) has revolutionized treatment of metastatic melanoma over the last decade, the identification of broadly applicable robust biomarkers has been challenging, driven in large part by the heterogeneity of ICB regimens and patient and tumor characteristics. To disentangle these features, we performed a standardized meta-analysis of eight cohorts of patients treated with anti-PD-1 (n=290), anti-CTLA-4 (n=175), and combination anti-PD-1/anti-CTLA-4 (n=51) with RNA sequencing of pre-treatment tumor and clinical annotations. Stratifying by immune-high vs -low tumors, we found that surprisingly, high immune infiltrate was a biomarker for response to combination ICB, but not anti-PD-1 alone.

Determination and Application of Stress States Based on Finite Element Techniques: A Case Study of the Longmaxi Formation in the Luzhou Block, Sichuan Basin.

Knowledge of the present-day in situ stress field (PIS) has important theoretical and practical significance for shale gas exploration and development. The Wufeng-Longmaxi Formation in the Luzhou Block serves as the main reservoir of marine shale production in southern China. However, there is no clear understanding of PIS in the Luzhou area, which leads to a series of production problems.

Study of a coal fly ash-based integrated CO capture-mineralization material: Preparation method, modification mechanism, and CO mineralization property.

Utilizing industrial solid waste for CO mineralization not only reduces CO emissions but also promotes the resource utilization of solid waste. Additionally, it allows for the permanent sequestration of CO and enables green value-added utilization of the products. Coal fly ash (CFA) is one of the most abundant industrial solid wastes with significant carbon mineralization potential.

Ab Initio Neural Network Potential Energy Surface and Quantum Dynamics Calculations on Na(S) + H → NaH + H Reaction.

The collisions between Na atoms and H molecules are of great significance in the field of chemical reaction dynamics, but the corresponding dynamics results of ground-state reactions have not been reported experimentally or theoretically. Herein, a global and high-precision potential energy surface (PES) of NaH (1') is constructed by the neural network model based on 21,873 high-level ab initio points. On the newly constructed PES, the quantum dynamics calculations on the Na(S) + H( = 0, = 0) → NaH + H reaction are carried out using the time-dependent wave packet method to study the microscopic reaction mechanism at the state-to-state level.

An Ecological Survey of Chiggers (Acariformes: Trombiculidae) Associated with Small Mammals in an Epidemic Focus of Scrub Typhus on the China-Myanmar Border in Southwest China.

Chiggers (chigger mites) are a group of tiny arthropods, and they are the exclusive vector of (Ot), the causative agent of scrub typhus (tsutsugamushi disease). Dehong Prefecture in Yunnan Province of southwest China is located on the China-Myanmar border and is an important focus of scrub typhus. Based on the field surveys in Dehong between 2008 and 2022, the present paper reports the infestation and ecological distribution of chiggers on the body surface of rodents and other sympatric small mammals (shrews, tree shrews, etc.

Histopathologic pattern and molecular risk stratification are associated with prognosis in patients with stage IB lung adenocarcinoma.

Background: The benefit of adjuvant therapy remains controversial in completely resected (R0) stage IB non-small cell lung cancer (NCLSC) patients. In this study, we aimed to explore potential prognostic factors in stage IB NSCLC patients.

Methods: This study included 215 patients with R0 stage IB lung adenocarcinoma (LUAD) (tumor size: 3-4 cm).