Nonacademic predictors of China medical licensing examination.

Background: National Medical Licensing Examination (NMLE) is the entrance exam for medical practice in China, and its general medical knowledge test (GMKT) evaluates abilities of medical students to comprehensively apply medical knowledge to clinical practice. This study aimed to identify nonacademic predictors of GMKT performance, which would benefit medical schools in designing appropriate strategies and techniques to facilitate the transition from medical students to qualified medical practitioners.

Methods: In 1202 medical students, we conducted the deletion-substitution-addition (DSA) and structural equation model (SEM) analyses to identify nonacademic predictors of GMKT performance from 98 candidate variables including early life events, physical conditions, psychological and personality assessments, cognitive abilities, and socioeconomic conditions.

Decoding the functional impact of the cancer genome through protein-protein interactions.

Acquisition of genomic mutations enables cancer cells to gain fitness advantages under selective pressure and, ultimately, leads to oncogenic transformation. Interestingly, driver mutations, even within the same gene, can yield distinct phenotypes and clinical outcomes, necessitating a mutation-focused approach. Conversely, cellular functions are governed by molecular machines and signalling networks that are mostly controlled by protein-protein interactions (PPIs).

Shenmai Injection Reduces Cardiomyocyte Apoptosis Induced by Doxorubicin through miR-30a/Bcl-2.

Objective: To explore the molecular mechanism of Shenmai Injection (SMI) against doxorubicin (DOX) induced cardiomyocyte apoptosis.

Methods: A total of 40 specific pathogen-free (SPF) male Sprague Dawley (SD) male rats were divided into 5 groups based on the random number table, including the control group, the model group, miR-30a agomir group, SMI low-dose (SMI-L) group, and SMI high-dose (SMI-H) group, with 8 rats in each group. Except for the control group, the rats were injected weekly with DOX (2 mg/kg) in the tail vein for 4 weeks to induce myocardial injury, and were given different regimens of continuous intervention for 2 weeks.

Optimizing the NGS-based discrimination of multiple lung cancers from the perspective of evolution.

Next-generation sequencing (NGS) offers a promising approach for differentiating multiple primary lung cancers (MPLC) from intrapulmonary metastasis (IPM), though panel selection and clonal interpretation remain challenging. Whole-exome sequencing (WES) data from 80 lung cancer samples were utilized to simulate MPLC and IPM, with various sequenced panels constructed through gene subsampling. Two clonal interpretation approaches primarily applied in clinical practice, MoleA (based on shared mutation comparison) and MoleB (based on probability calculation), were subsequently evaluated.

Catalytic-independent functions of the Integrator-PP2A complex (INTAC) confer sensitivity to BET inhibition.

Chromatin and transcription regulators are critical to defining cell identity through shaping epigenetic and transcriptional landscapes, with their misregulation being closely linked to oncogenesis. Pharmacologically targeting these regulators, particularly the transcription-activating BET proteins, has emerged as a promising approach in cancer therapy, yet intrinsic or acquired resistance frequently occurs, with poorly understood mechanisms. Here, using genome-wide CRISPR screens, we find that BET inhibitor efficacy in mediating transcriptional silencing and growth inhibition depends on the auxiliary/arm/tail module of the Integrator-PP2A complex (INTAC), a global regulator of RNA polymerase II pause-release dynamics.

Genome-wide CRISPR-Cas9 screening identifies ITGA8 responsible for abivertinib sensitivity in lung adenocarcinoma.

The emergence of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has improved the prognosis for lung cancer patients with EGFR-driven mutations. However, acquired resistance to EGFR-TKIs poses a significant challenge to the treatment. Overcoming the resistance has primarily focused on developing next-generation targeted therapies based on the molecular mechanisms of resistance or inhibiting the activation of bypass pathways to suppress or reverse the resistance.

Targeted dual biologic therapy for erythroderma of unknown etiology guided by high-parameter peripheral blood immunophenotyping.

Erythroderma is a severe and heterogeneous inflammatory skin condition with little guidance on the approach to management in cases of unknown etiology. To guide therapeutic selection, we sought to create an immunophenotyping platform able to identify aberrant cell populations and cytokines in subtypes of erythroderma. We performed high-parameter flow cytometry on peripheral blood mononuclear cells (PBMCs) and whole blood of a patient with refractory idiopathic erythroderma, erythrodermic patients with Sézary syndrome and pityriasis rubra pilaris, and healthy controls.

Decreased risk of cardiovascular disease mortality associated with occasional positive screens following cancer screenings.

Positive results from cancer screenings, like a cancer diagnosis, can increase the risk of cardiovascular disease (CVD) mortality due to heightened psychological stress. However, positive screening results may also serve as a teachable moment to encourage the adoption of a healthier lifestyle. Consequently, the overall association between positive screenings and CVD mortality risk remains unclear.

Enabling next-generation engineered TCR-T therapies based on high-throughput TCR discovery from diagnostic tumor biopsies.

Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) can mediate tumor regression, including complete and durable responses, in a range of solid cancers, most notably in melanoma. However, its wider application and efficacy has been restricted by the limited accessibility, proliferative capacity and effector function of tumor-specific TIL. Here, we develop a platform for the efficient identification of tumor-specific TCR genes from diagnostic tumor biopsies, including core-needle biopsies frozen in a non-viable format, to enable engineered T cell therapy.

Digestive cancers: mechanisms, therapeutics and management.

Cancers of the digestive system are major contributors to global cancer-associated morbidity and mortality, accounting for 35% of annual cases of cancer deaths. The etiologies, molecular features, and therapeutic management of these cancer entities are highly heterogeneous and complex. Over the last decade, genomic and functional studies have provided unprecedented insights into the biology of digestive cancers, identifying genetic drivers of tumor progression and key interaction points of tumor cells with the immune system.

DNA replication stress underpins the vulnerability to oxidative phosphorylation inhibition in colorectal cancer.

Mitochondrial oxidative phosphorylation (OXPHOS) is a therapeutic vulnerability in glycolysis-deficient cancers. Here we show that inhibiting OXPHOS similarly suppresses the proliferation and tumorigenicity of glycolytically competent colorectal cancer (CRC) cells in vitro and in patient-derived CRC xenografts. While the increased glycolytic activity rapidly replenished the ATP pool, it did not restore the reduced production of aspartate upon OXPHOS inhibition.

Genetic predisposition to altered blood cell homeostasis is associated with glioma risk and survival.

Glioma is a highly fatal and heterogeneous brain tumor with few known risk factors. Our study examines genetically predicted variability in blood cell indices in relation to glioma risk and survival in 3418 cases and 8156 controls. We find that increased platelet to lymphocyte ratio (PLR) confers an increased risk of glioma (odds ratio (OR) = 1.

Application of thrombopoietic agents in cancer therapy-induced thrombocytopenia: A comprehensive review.

Cancer therapy-induced thrombocytopenia (CT-IT) is one of the most common hematological toxicities of anti-cancer therapy, often leading to treatment dose reduced, postponed, or treatment plans altered or even discontinued. Thrombopoietin (TPO) is the only key regulatory factor in platelet production, and TPO receptor is considered an ideal target for the treatment of thrombocytopenia. Thrombopoietic agents, including recombinant human thrombopoietin (rhTPO) and thrombopoietin receptor agonists (TPO-RAs), bind to different regions of the TPO receptor, activating downstream signaling pathways to increase platelet levels.

Impact of Endorectal Coil Use on Extraprostatic Extension Detection in Prostate MRI: A Retrospective Monocentric Study.

Rationale And Objectives: Accurate preoperative mpMRI-based detection of extraprostatic extension (EPE) in prostate cancer (PCa) is critical for surgical planning and patient outcomes. This study aims to evaluate the impact of endorectal coil (ERC) use on the diagnostic performance of mpMRI in detecting EPE.

Materials And Methods: This retrospective study with prospectively collected data included participants who underwent mpMRI and subsequent radical prostatectomy for PCa between 2007 and 2024.

Neoadjuvant Intratumoral MBT(A) Immunotherapy Prevents Distant Metastases and Recurrence in Murine Models.

Neoadjuvant immunotherapy represents a pioneering approach in the preoperative treatment of cancer, offering novel avenues for tumor reduction and improved patient outcomes by modulating the immune response. This study investigated neoadjuvant immunotherapy using intratumoral administration of mannan-BAM, Toll-like receptor ligands, and antiCD40 antibody (MBTA therapy) followed by surgery in murine models of mouse tumor tissue (MTT) pheochromocytoma, B16-F10 melanoma, and 4T1 and E0771.lmb mammary carcinomas.

Centromere inactivation during aging can be rescued in human cells.

Aging involves a range of genetic, epigenetic, and physiological alterations. A key characteristic of aged cells is the loss of global heterochromatin, accompanied by a reduction in canonical histone levels. In this study, we track the fate of centromeres in aged human fibroblasts and tissues and in various cellular senescent models.

Genomic and phenotypic correlates of mosaic loss of chromosome Y in blood.

Mosaic loss of Y (mLOY) is the most common somatic chromosomal alteration detected in human blood. The presence of mLOY is associated with altered blood cell counts and increased risk of Alzheimer disease, solid tumors, and other age-related diseases. We sought to gain a better understanding of genetic drivers and associated phenotypes of mLOY through analyses of whole-genome sequencing (WGS) of a large set of genetically diverse males from the Trans-Omics for Precision Medicine (TOPMed) program.

The Association of Care Fragmentation on Overall Survival for Early Stage Breast Cancer.

Introduction: Optimal treatment of stage I-III breast cancer requires multimodal therapies. Patients can receive these therapies at one or multiple facilities. Herein, we evaluated the association of receiving treatment at more than one facility and distance to that facility on overall survival.

Molecular profiling of bladder cancer xenografts defines relevant molecular subtypes and provides a resource for biomarker discovery.

Bladder cancer (BLCA) genomic profiling has identified molecular subtypes with distinct clinical characteristics and variable sensitivities to frontline therapy. BLCAs can be categorized into luminal or basal subtypes based on their gene expression. We comprehensively characterized nine human BLCA cell lines (UC3, UC6, UC9, UC13, UC14, T24, SCaBER, RT4V6 and RT112) into molecular subtypes using orthotopic xenograft models.

Development of the Lee Symptom Scale-Skin Sclerosis for chronic GVHD-associated sclerosis.

Sclerosis is a highly morbid manifestation of chronic GVHD (cGVHD), associated with distressing symptoms and significant long-term disability. A patient-reported outcome measure (PRO) for cGVHD-associated sclerosis is essential to advance therapeutic trials. We aimed to develop a PRO for adults with cGVHD-associated sclerosis and evaluate and refine its content validity.

Large clones of Clonal Hematopoiesis affect outcome in Mantle Cell Lymphoma: Results from The FIL MCL0208 Clinical Trial.

Although recent evidence suggests that myeloid clonal hematopoiesis (M-CH) may influence lymphoma clinical outcome, its impact in mantle cell lymphoma (MCL) remains unclear. Here, we report a comprehensive NGS-based analysis of the M-CH mutational landscape at baseline and follow-up in patients enrolled in the Fondazione Italiana Linfomi (FIL) MCL0208 phase 3 trial (NCT02354313), evaluating lenalidomide maintenance versus observation after chemoimmunotherapy and autologous stem cell transplantation (ASCT) in untreated young MCL patients. Overall, 254/300 (85%) enrolled patients (median age 57 years [32-66]) had a baseline sample available for CH analysis.

How I Treat Anemia in Myelofibrosis.

Anemia is a common consequence of myelofibrosis. The treatment of myelofibrosis-associated anemia is complicated by a multifactorial pathobiology, as well as a lack of therapies that result in normalization of the bone marrow and complete restoration of its function. Established agents that are used to treat anemia in other bone marrow failure states such as myelodysplastic syndromes and aplastic anemia, are used for the treatment of myelofibrosis-associated anemia.

Validation of Clinical Dynamic Contrast-Enhanced Magnetic Resonance Imaging Perfusion Modeling and Neoadjuvant Chemotherapy Response Prediction in Breast Cancer Using FDG and Cu-DOTA-Trastuzumab Positron Emission Tomography Studies.

Purpose: Perfusion modeling presents significant opportunities for imaging biomarker development in breast cancer but has historically been held back by the need for data beyond the clinical standard of care (SoC) and uncertainty in the interpretability of results. We aimed to design a perfusion model applicable to breast cancer SoC dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) series with results stable to low temporal resolution imaging, comparable with published results using full-resolution DCE-MRI, and correlative with orthogonal imaging modalities indicative of biophysical markers.

Methods: Subsampled high-temporal-resolution DCE-MRI series were run through our perfusion model and resulting fits were compared for consistency.

Accelerating the Future of Oncology Drug Development: The Role of Consortia in the Delivery of Precision Oncology Early Phase Clinical Trials.

Purpose: Over the past 15 years, the landscape of early phase clinical trials (EPCTs) has undergone a remarkable expansion in both quantity and intricacy. The proliferation of sites, trials, sponsors, and contract research organizations has surged exponentially, marking a significant shift in research conduct. However, EPCT operations suffer from numerous inefficiencies, such as cumbersome start-up processes, which are particularly critical when drug safety and the recommended phase II dose need to be established in a timely manner.

EMPOWER PKD: Patient, Caregiver, and Researcher Priorities for Research in Polycystic Kidney Disease.

Background: Patient involvement in research can help to ensure that the evidence generated aligns with their needs and priorities. In the Establishing Meaningful Patient-Centered Outcomes With Relevance for Patients with Polycystic Kidney Disease (EMPOWER PKD) project we aimed to identify patient-important outcomes and discuss the impact of PKD on patients.

Methods: Nine focus groups were held with adult patients with PKD, caregivers, and clinical or research experts in PKD.