Cdk1-dependent lamin aggregation underlies oxidative stress-induced nuclear shape abnormalities.

Altered nuclear morphology, one of the characteristics of cancer cells, is often indicative of tumor prognosis. While reactive oxygen species (ROS) are known to induce nuclear morphology changes, mechanisms underlying these effects remain elusive, particularly regarding nuclear assembly. We hypothesized that mitotic cells might exhibit increased susceptibility to ROSinduced nuclear deformation due to the dynamic nature of nuclear envelope during mitosis, i.

Comparison of Underlying Risk of Developing and Dying from Lung Cancer in Screened Populations.

Background: Trial participants are typically healthier than the general population. Differences in underlying characteristics between the population undergoing lung cancer screening (LCS) and LCS trial participants may alter the benefits of LCS.

Research Question: Does the risk of developing and dying from lung cancer differ between trial participants and the general population?

Study Design And Methods: Using data from the i) North Carolina Lung Screening Registry (NCLSR), ii) 2022 Center for Disease Control and Prevention's Behavioral Risk Factor Surveillance System (BRFSS) Lung Cancer Screening Module, and iii) National Lung Screening Trial (NLST), we estimated the 5-year probability of developing and dying from lung cancer if not screened using publicly available macros.

Comfort With Sharing Food Insecurity Risk for Clinical Care Among Individuals With and Without a Cancer History: Findings From a National Survey.

Introduction: Food insecurity negatively affects timely access to care, treatment adherence, quality of life, and survival among cancer survivors. There is limited knowledge about cancer survivors' comfort with sharing food insecurity risk for clinical care on a national scale. This study aims to assess comfort with sharing food insecurity risk for clinical care among adults with and without a cancer history and to identify factors that may be associated with comfort for sharing food insecurity risk.

Peripheral immune patterns enable robust cross-platform prediction of ALS onset and progression.

Amyotrophic lateral sclerosis (ALS) progression rates vary dramatically between patients, yet the basis of this heterogeneity remains elusive, with no prognostic biomarkers existing to guide clinical decisions or stratify patients for therapeutic trials. Here, we identify a network of coordinated immune cell types, which exhibit differential disruption across progression groups. Using mass cytometry (CyTOF) to profile 2.

Assessing the impact of TET2 and TET3 deletion in TCRalpha and TCRbeta repertoire in murine CD4 T cells in physiological and pathophysiological conditions.

Ten Eleven Translocation (TET) proteins can oxidize 5-methylcytosine to generate in sequential steps oxidized forms of cytosine: 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine. Through their catalytic activity TET proteins promote active DNA demethylation. There are three TET proteins: TET1, TET2 and TET3.

Feasibility of Intravaginal Artesunate as an Adjuvant HPV & Cervical Precancer Treatment Among Women Living With HIV in Kenya: Study Protocol for a Phase II Clinical Trial.

IntroductionCervical cancer disproportionately affects women in low- and middle-income countries (LMICs), who account for 90% of deaths from the disease. Human papillomavirus (HPV) is responsible for 99% of cervical cancer cases. Women living with HIV (WLWH) have a higher risk of persistent HPV infection and a greater likelihood of developing cervical cancer.

Real-World Validation of the Purity Independent Subtyping of Tumors Classifier for Informing Therapy Selection in Pancreatic Ductal Adenocarcinoma.

Purpose: FOLFIRINOX (FFX) and gemcitabine + nab-paclitaxel (GnP) are the most commonly administered first-line (1L) regimens for advanced, nonresectable, pancreatic ductal adenocarcinoma (PDAC). In the absence of biomarkers to predict response, clinical covariates such as age and performance status are often used by clinicians to select optimal treatment regimens. Purity independent subtyping of tumors (PurIST) is a molecular subtyping algorithm that classifies tumors as classical or basal.

What's hidden in plain sight? Impact of clonal hematopoiesis on the risk and progression of non-hematologic cancers.

Clonal hematopoiesis (CH) is a frequently observed phenomenon in aging individuals without apparent illness and exhibits an increased prevalence in cancer patients. Mechanistic studies indicate that mutant immune cells alter the tumor microenvironment, leading to increased inflammation, blood vessel formation, and immune cell exhaustion. Paradoxically, these changes also preserve stem-like T-cell pools that can be utilized by immunotherapy.

A soft-stiff patterned bioengineering model reveals kinase pathways driving directional cell migration in pulmonary arterial hypertension.

Directional cell migration by pulmonary arterial cells (PACs) is one of the important features of diseases involving arterial remodeling, such as pulmonary arterial hypertension (PAH), a disease that is often characterized by reduced arterial compliance and increased extracellular matrix (ECM) stiffening. However, there are no therapeutics that can halt the directional cell migration of PACs in PAH. The inability to identify drug targets or drugs against the directional cell migration during PAH pathogenesis stems from an incomplete understanding of the process and a lack of effective translational models for screening of candidate small molecules.

An allele-agnostic mutant-KRAS inhibitor suppresses tumor maintenance signals and reprograms tumor immunity in pancreatic cancer.

is among the most frequently mutated oncogenes in cancer, and for decades, efforts at pharmacological blockade of its function in solid cancers have been unsuccessful. A notable advance in this endeavor is the recent development of small-molecule KRAS inhibitors, which enable direct targeting of the mutant oncoprotein. Here, we comprehensively evaluated the preclinical efficacy of BI-2493, a first-in-class allele-agnostic mutant-KRAS inhibitor (panKRASi), in pancreatic ductal adenocarcinoma (PDAC).

The landscape of microbial associations in human cancer.

Oncomicrobes are estimated to cause 15% of cancers worldwide. When cancer whole-genome sequencing (WGS) data are collected, the microbes present are also sequenced, allowing the investigation of potential etiological and clinical associations. Interrogating the microbial community for 8908 patients encompassing 22 cancer types from the Genomics England WGS dataset revealed that only colorectal tumors exhibited unmistakably distinct microbial communities that can reliably be used to distinguish anatomical site [positive predictive value (PPV) = 0.

Better health and less stress: an elicitation survey on quitting little cigars and cigarillos by young adults.

Introduction: Little cigars and cigarillos (LCCs) pose health risks similar to cigarettes yet remain popular among US young adults (YAs), particularly Black or African American YAs. While previous studies have explored beliefs surrounding LCC prevention and use, no research has yet focused on LCC cessation beliefs.

Aims And Methods: This study examined the beliefs of 134 YAs who currently or formerly used LCC aged 18-29, recruited via Qualtrics panels.

Open-Label, Phase II Trial of Extracellular Regulated Kinase Inhibition Alone and in Combination With Autophagy Inhibition in Patients With Metastatic Pancreatic Cancer.

Purpose: Oncogenic mutations in Kirsten rat sarcoma virus are present in over 90% of pancreatic ductal adenocarcinomas (PDACs). Preclinical data suggest that PDAC cells treated with inhibitors of the mitogen-activated protein kinase pathway demonstrate elevated autophagic flux. In this study, we evaluate the clinical efficacy of combining LY3214996 (extracellular regulated kinase inhibitor) with hydroxychloroquine (HCQ; autophagy inhibitor) in patients with metastatic PDAC.

Association of Patient Comorbidities with Treatment Regret Among Patients with Localized Prostate Cancer - Results from a Population-Based Cohort.

Objectives: Decision regret is a well-established, negative outcome in prostate cancer. We hypothesized that baseline comorbidities, which impact treatment tolerability, are associated with regret.

Materials And Methods: In a prospective, population-based cohort of prostate cancer patients, patient-reported regret was assessed at 12 months after treatment using a validated measure.

Carbon isotopic labelling of carboxylic acids enabled by organic photoredox-catalysed cyanation.

The application of molecular imaging has advanced personalized medicine and generated a profound impact on patient care. Positron emission tomography and magnetic resonance imaging are among the most widely used imaging modalities, often requiring the isotopic labelling of bioactive molecules to generate the desired imaging probes. Unfortunately, radiochemistry often limits the development of novel agents due to complicated syntheses and the incompatibility of complex molecules.

Persistent Type I Interferon Signaling Impairs Innate Lymphoid Cells During HIV-1 Infection Under Suppressive ART.

Persistent type I interferon (IFN-I) signaling compromises adaptive anti-HIV-1 T cell immunity and promotes viral reservoir persistence, yet its effects on innate lymphoid cells during chronic infection remain unclear. Through integrated single-cell RNA sequencing and functional validation in HIV-1-infected humanized mice with combination antiretroviral therapy (cART) and IFN-I signaling blockade, we reveal IFN-I-induced dysfunction of natural killer (NK) cells and group 3 innate lymphoid cells (ILC3s). Mechanistically, the IFN-I-CD9 axis drives NK cells toward a decidual NK cell-like phenotype, impairing their cytotoxic activity.

Response splicing quantitative trait loci in primary human chondrocytes identify putative osteoarthritis risk genes.

Osteoarthritis affects millions worldwide, yet effective treatments remain elusive due to poorly understood molecular mechanisms. While genome-wide association studies (GWAS) have identified hundreds of osteoarthritis-associated loci, identifying the genes impacted at each locus remains challenging. We investigate alternative splicing using RNA-sequencing data from 101 human chondrocyte samples treated with phosphate-buffered saline or fibronectin fragment, an osteoarthritis trigger.

Interindividual genetic differences drive discordance between serum calcidiol and calcitriol concentrations in females.

Vitamin D insufficiency (VDI) is primarily determined by serum levels of calcidiol (25(OH)D3), which serves as a biomarker for the less abundant but most potent bioactive metabolite, calcitriol (1,25(OH)2D3). However, population studies often show discordance between calcidiol and calcitriol. Here, a genetically diverse population of seven inbred mouse strains was used to investigate the role of interindividual genetic differences in driving calcidiol-to-calcitriol discordance under vitamin D sufficient (VDS) vs.

Changes in Price, Consumption, Prevalence and State Revenue of Transitioning Cigarette Sales to State-Controlled Outlets.

Introduction: Policies that phase out the retail sale of tobacco products have been recommended to accelerate the tobacco endgame and reach negligible tobacco use rates. Using simulation modeling, this study assessed how a policy that transitions cigarette sales to state-controlled outlets may change prices, and thus affect state revenue, cigarette pack sales and smoking prevalence.

Methods: Using data from the Behavioral Risk Factor Surveillance System and Tax Burden On Tobacco, models were developed to examine three potential scenarios resulting from a policy that transitions the sales of cigarette products to state-controlled outlets in Oregon, Pennsylvania, Vermont and Virginia.

Chitosan-Glycerol Injectable Hydrogel for Intratumoral Delivery of Macromolecules.

Intratumoral injections of macromolecules, such as biologics and immunotherapeutics, show promise in overcoming dose-limiting side effects associated with systemic injections and improve treatment efficacy. However, the retention of injectates in the tumor microenvironment is a major underappreciated challenge. High interstitial pressures and dense tumor architectures create shear forces that rapidly expel low-viscosity solutions post-injection.

Shared Decision Making Interventions for Deprescribing in Older Adults With Polypharmacy: A Scoping Review.

Background: Despite being integral to the deprescribing process, integration of shared decision making (SDM) into structured deprescribing interventions and its relation to patient outcomes remain understudied.

Methods: We conducted a scoping review of PubMed/MEDLINE, Embase, Scopus, and PsycInfo (through September 2023) with a medical librarian's guidance. Studies of SDM interventions for deprescribing in older adults with polypharmacy were included.

The case for stronger regulation of deceptive nutrition-related claims on unhealthy food.

Deceptive nutrition-related claims are pervasive on unhealthy packaged foods. This Perspective describes the potential for these claims to harm consumer health and advocates for tighter regulation of misleading claims to empower individuals to make more nutritious choices.

Patient-Reported Side Effect Bother: Understanding the Value of the Baseline Report.

Aim: Patient-perceived treatment tolerability can affect patient ability and willingness to remain on therapy. We sought to examine completion rates for a single item of overall side effect bother at baseline and at the first on-treatment assessment, the association between this item with other patient-reported outcomes (PROs) and the odds of early discontinuation due to clinician-assessed adverse events or reasons other than disease progression.

Methods: Data were from three commercial cancer trials in solid tumours, focusing on the safety population.

Ultra-long-acting injectable, biodegradable, and removable in-situ forming implant with cabotegravir for HIV prevention.

HIV is a global health issue affecting approximately 40 million people worldwide, with low patient adherence being the primary challenge for maintaining effective pre-exposure prophylaxis (PrEP). Limitations of oral PrEP are mainly attributed to lack of adherence due to pill fatigue or stigma [1, 2]. Recently introduced long-acting injectables offer several advantages over daily PrEP, namely by improving adherence and improving efficacy [3-5].