Exploring the role of splicing in TP53 variant pathogenicity through predictions and minigene assays.

Background: TP53 variant classification benefits from the availability of large-scale functional data for missense variants generated using cDNA-based assays. However, absence of comprehensive splicing assay data for TP53 confounds the classification of the subset of predicted missense and synonymous variants that are also predicted to alter splicing. Our study aimed to generate and apply splicing assay data for a prioritised group of 59 TP53 predicted missense or synonymous variants that are also predicted to affect splicing by either SpliceAI or MaxEntScan.

CASP5 associated with PANoptosis promotes tumorigenesis and progression of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a globally severe cancer with an unfavorable prognosis. PANoptosis, a form of cell death regulated by PANoptosomes, plays a role in numerous cancer types. However, the specific roles of genes associated with PANoptosis in the development and advancement of ccRCC remain unclear.

Inflammatory markers link triglyceride-glucose index and obesity indicators with adverse cardiovascular events in patients with hypertension: insights from three cohorts.

Background: Among hypertensive cohorts across different nations, the relationship between the triglyceride-glucose index (TyG) and its conjunction with obesity metrics in relation to cardiovascular disease (CVD) incidence and mortality remains to be elucidated.

Methods: This study enrolled 9,283, 164,357, and 5,334 hypertensives from the National Health and Nutrition Examination Survey (NHANES), UK Biobank (UKBB), and Shanghai Pudong cohort. The related outcomes for CVD were defined by multivariate Cox proportional hazards models, Generalized Additive Models and Mendelian randomization analysis.

Investigation of the causal relationship between patient portal utilization and patient's self-care self-efficacy and satisfaction in care among patients with cancer.

Objective: The objective of this study was to examine the causal relationship between the usage of patient portals and patients' self-care self-efficacy and satisfaction in care outcomes in the context of cancer care.

Methods: The National Institute's HINTS 5 Cycle 1-4 (2017-2020) data were used to perform a secondary data analysis. Patients who reported being ever diagnosed with cancer were included in the study population.

Development of a prognostic nomogram and risk stratification system for elderly patients with esophageal squamous cell carcinoma undergoing definitive radiotherapy: a multicenter retrospective analysis (3JECROG R-03 A).

Background: Our goal is to develop a nomogram model to predict overall survival (OS) for elderly esophageal squamous cell carcinoma (ESCC) patients receiving definitive radiotherapy (RT) or concurrent chemoradiotherapy (CRT), aiding clinicians in personalized treatment planning with a risk stratification system.

Methods: A retrospective study was conducted on 718 elderly ESCC patients treated with RT or CRT at 10 medical centers (3JECROG) from January 2004 to November 2016. We identified independent prognostic factors using univariate and multifactorial Cox regression to construct a nomogram model.

Association of remote work with tobacco and alcohol use: a cross-sectional study in Japan.

Background: Remote work allows one to work free from workplace policy, but it may negatively affect health-related behaviors such as tobacco product use and alcohol drinking. Our study aimed to investigate the association of remote work with tobacco dependence and hazardous alcohol use.

Methods: This nationwide Internet-based survey was conducted in Japan in February 2023.

Cross-cultural adaptation of the simple Chinese version of the medication adherence reasons scale in patients undergoing adjuvant endocrine therapy for breast cancer.

Adjuvant endocrine therapy (AET) is essential for improving survival and reducing mortality and recurrence rates in breast cancer (BrCa) patients. However, the adherence to AET among BrCa patients is poor, and there is no scale to measure adherence to AET or the reasons for non-adherence among BrCa patients in mainland China. The aim of this study was to assess the psychometric properties of the simple Chinese version of the Medication Adherence Reasons (MAR) scale in BrCa patients undergoing AET.

Association between physical multimorbidity in middle adulthood and mortality: findings from two large cohort studies in Japan.

Background: While previous literature suggests that multimorbidity is linked to a higher risk of mortality, evidence is scarce among individuals in middle adulthood. We aimed to examine the association between physical multimorbidity and all-cause mortality among individuals aged 40-64 years at baseline in Japan.

Methods: Data were obtained from two cohort studies, the Japan Public Health Center-based Prospective Study (JPHC) and the Japan Epidemiology Collaboration on Occupational Health Study (J-ECOH).

Development and validation of a five-year cardiovascular risk assessment tool for Asian adults aged 75 years and older.

Background: To identify cardiovascular (CV) risk factors in Asian elderly aged 75 years and older and subsequently develop and validate a sex-specific five-year CV risk assessment tool for this population.

Methods: This study included 12,174 patients aged ≥ 75 years without a prior history of cardiovascular disease at a single hospital in Taiwan. Electronic health records were linked to the National Health Insurance Research Database and the National Death Registry to ensure comprehensive health information.

Postdiagnostic use of antihypertensive medications and survival in colorectal, lung, corpus uteri, melanoma and kidney cancer patients with hypertension.

Background: Arterial hypertension is one of the most frequent comorbidities in patients with cancer. Studies have indicated that drugs used to control hypertension may alter cancer patient survival; however, epidemiological findings for their impact on cancer survival remain inconsistent. The aim of this study was to examine the effect of the consumption of antihypertensive (AH) medication on the risk of death in cancer patients.

Chromosome mis-segregation triggers cell cycle arrest through a mechanosensitive nuclear envelope checkpoint.

Errors during cell division lead to aneuploidy, which is associated with genomic instability and cell transformation. In response to aneuploidy, cells activate the tumour suppressor p53 to elicit a surveillance mechanism that halts proliferation and promotes senescence. The molecular sensors that trigger this checkpoint are unclear.

The TRIPOD-LLM reporting guideline for studies using large language models.

Large language models (LLMs) are rapidly being adopted in healthcare, necessitating standardized reporting guidelines. We present transparent reporting of a multivariable model for individual prognosis or diagnosis (TRIPOD)-LLM, an extension of the TRIPOD + artificial intelligence statement, addressing the unique challenges of LLMs in biomedical applications. TRIPOD-LLM provides a comprehensive checklist of 19 main items and 50 subitems, covering key aspects from title to discussion.

Lymphatic collection and cell isolation from mouse models for multiomic profiling.

Premetastatic cancer cells often spread from the primary lesion through the lymphatic vasculature and, clinically, the presence or absence of lymph node metastases impacts treatment decisions. However, little is known about cancer progression via the lymphatic system or of the effect that the lymphatic environment has on cancer progression. This is due, in part, to the technical challenge of studying lymphatic vessels and collecting lymph fluid.

A hybrid machine learning approach for the personalized prognostication of aggressive skin cancers.

Accurate prognostication guides optimal clinical management in skin cancer. Merkel cell carcinoma (MCC) is the most aggressive form of skin cancer that often presents in advanced stages and is associated with poor survival rates. There are no personalized prognostic tools in use in MCC.

Saturation genome editing-based clinical classification of BRCA2 variants.

Sequencing-based genetic tests have uncovered a vast array of BRCA2 sequence variants. Owing to limited clinical, familial and epidemiological data, thousands of variants are considered to be variants of uncertain significance (VUS). Here we have utilized CRISPR-Cas9-based saturation genome editing in a humanized mouse embryonic stem cell line to determine the functional effect of VUS.

Novel metabolic prognostic score for predicting survival in patients with cancer.

Cancer is a fatal disease with a high global prevalence and is associated with an increased incidence of metabolic disorders. This study aimed to develop a novel metabolic prognostic system to evaluate the overall metabolic disorder burden in cancer patients and its relationship with their prognosis. The patients in this study were enrolled from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) project.

Boosting skin cancer diagnosis accuracy with ensemble approach.

Skin cancer is common and deadly, hence a correct diagnosis at an early age is essential. Effective therapy depends on precise classification of the several skin cancer forms, each with special traits. Because dermoscopy and other sophisticated imaging methods produce detailed lesion images, early detection has been enhanced.

Identifying ADME-related gene signature for immune landscape and prognosis in KIRC by single-cell and spatial transcriptome analysis.

Kidney renal clear cell carcinoma (KIRC) is the most prevalent subtype of kidney cancer. Although multiple therapeutic agents have been proven effective in KIRC, their clinical application has been hindered by a lack of reliable biomarkers. This study focused on the prognostic value and function of drug absorption, distribution, metabolism, and excretion- (ADME-) related genes (ARGs) in KIRC to enhance personalized therapy.

Microglia depletion reduces neurodegeneration and remodels extracellular matrix in a mouse Parkinson's disease model triggered by α-synuclein overexpression.

Chronic neuroinflammation with sustained microglial activation occurs in Parkinson's disease (PD), yet the mechanisms and exact contribution of these cells to the neurodegeneration remains poorly understood. In this study, we induced progressive dopaminergic neuron loss in mice via rAAV-hSYN injection to cause the neuronal expression of α-synuclein, which produced neuroinflammation and behavioral alterations. We administered PLX5622, a colony-stimulating factor 1 receptor inhibitor, for 3 weeks prior to rAAV-hSYN injection, maintaining it for 8 weeks to eliminate microglia.

Diet-wide analyses for risk of colorectal cancer: prospective study of 12,251 incident cases among 542,778 women in the UK.

Uncertainty remains regarding the role of diet in colorectal cancer development. We examined associations of 97 dietary factors with colorectal cancer risk in 542,778 Million Women Study participants (12,251 incident cases over 16.6 years), and conducted a targeted genetic analysis in the ColoRectal Transdisciplinary Study, Colon Cancer Family Registry, and Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO).

Prognostic significance of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio in uterine carcinosarcoma.

Introduction: Uterine carcinosarcoma (UCS) and uterine sarcomas (US) are rare but aggressive cancer with poor prognoses. The prognostic value of systemic inflammatory response (SIR) indicators, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), in predicting outcomes of UCS and US remains unclear. This study investigated the prognostic significance of SIR indicators for UCS and US.

Eligibility for and reach of the National Breast and Cervical Cancer Early Detection Program, 2018-2021.

Purpose: The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) provides access to timely breast and cervical cancer screening and diagnostic services to women who have low incomes and are uninsured or underinsured. Documenting the number of women eligible and the proportion of eligible women who receive NBCCEDP-funded services is important for identifying opportunities to increase screening and diagnostic services among those who would not otherwise have access.

Methods: Using the Census Bureau's Small Area Health Insurance Estimates data, we estimated the number of women who met the NBCCEDP eligibility criteria based on age, income, and insurance status.

Development of Tc-Labeled Complexes with a Niraparib HYNIC Derivative for PARP-Positive Tumor Imaging.

As an enzyme that plays an important role in DNA repair, poly(ADP-ribose) polymerase-1 (PARP-1) has become a popular target for cancer therapy. Nuclear medicine molecular imaging technology, supplemented by radiolabeled PARP-1 inhibitors, can accurately determine the expression level of PARP-1 at lesion sites to help patients choose an appropriate treatment plan. In this work, niraparib was modified with a hydrazinonicotinamide (HYNIC) group to generate the ligand NPBHYNIC, which has an affinity (IC) of 450.

Early life factors and later metabolic syndrome in European children and adolescents.

Background And Aims: Early life factors have been suggested to be associated with later cardiometabolic risk in children, adolescents and adults. Our study aimed to investigate the associations between early life factors and metabolic syndrome (MetS) in children and adolescents.

Methods And Results: Our analysis sample comprised of 8852 children aged 2-9 years at baseline that participated in up to three examination waves of the pan-European IDEFICS/I.