The association between glyphosate use and mosaic loss of chromosome Y in buccal samples among male pesticide applicators in the Agricultural Health Study.

Glyphosate-based herbicides are the most widely applied pesticides worldwide and have been implicated in the development of certain hematologic malignancies; however, the underlying biological mechanisms are not well-understood. High lifetime use of glyphosate-based herbicides, hereafter referred to as glyphosate, was previously associated with mosaic loss of chromosome Y (mLOY), a biomarker of genomic instability potentially linked to cancer and immune dysregulation, in circulating blood of male farmers from a subcohort of the Agricultural Health Study (AHS). Here, we further investigated the association between glyphosate use and mLOY using buccal-derived DNA among 1,868 male pesticide applicators in an independent AHS study.

Expression profiling of KRAS and NOXA genes as prospective biomarkers in ovarian carcinoma.

Background: Ovarian cancer (OC) is a leading cause of cancer deaths in women. Comprehensive molecular studies are required to understand OC pathogenesis. KRAS and NOXA genes are involved in tumorigenesis and disease progression.

Phenotyping and Clinical Utility of Phagocytic Polyploid Giant Cancer Macrophages in Blood.

Historically, polyploid giant cancer cells (PGCCs) within tumors have been ignored as superfluous inflammatory refuse with no intrinsic clinical or biological relevance. However recently, multiple studies have described the existence PGCCs in solid tumor masses that appear to correlate with tumor progression, and can also appear in blood circulation as cancer associated macrophage like cells (CAMLs). In an effort to understand the clinical and biological role of CAMLs (i.

Pde5a deficiency prevents diet-induced obesity via adipose cAMP-PKA activation enhancing fat browning.

Cyclic nucleotides are critical regulators of adaptive thermogenesis and adipogenesis, with their intracellular levels finely tuned by phosphodiesterases. Phosphodiesterase type 5 (PDE5A) modulates cyclic guanosine monophosphate (cGMP) levels in adipocytes. While PDE5A inhibition has shown promise in patients with diabetes, its role in metabolism remains unclear.

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.

A multicenter retrospective analysis of recurrent/metastatic nasopharyngeal cancer from non-endemic areas: Results in the pre-immunotherapy era.

Aim Of The Study: The aim of the study is to describe clinical features, treatment approach and outcomes of recurrent/metastatic (R/M) NPC in non-endemic areas MATERIALS AND METHODS: This observational, retrospective and multicenter study was conducted within 36 referral hospital in non-endemic areas including Europe, Jordan, Kuwait, Turkey and United States of America. All NPC patients diagnosed between 2004 and 2016 and with a minimum 12 months of follow-up were included. Data entry started in January 2018 and closed in December 2023.

Advancing preclinical biology for Ewing Sarcoma: an international effort.

Ewing sarcoma (EwS) is an aggressive bone and soft tissue cancer affecting adolescents and young adults. In vitro and in vivo models of EwS have been instrumental in advancing our understanding of EwS biology and essential in evaluating potential therapies, particularly for metastatic or relapsed disease where effective treatment options remain limited. Through an international collaborative effort between the Children's Oncology Group (COG) Bone Tumor Committee and the Euro Ewing Consortium (EEC), we review the current landscape of preclinical modeling used in EwS research encompassing both in vitro (cell lines and tumor organoids) and in vivo (mouse and non-mammalian xenografts) model systems.

Incorporating Heterogeneity in Mixed Hidden Markov Models With an Application to the Sleep-Wake Cycle.

The sleep-wake cycle plays an important and far-reaching role in health. By utilizing personal physical activity monitors (PAMs), inferences about the sleep-wake cycle can be made. Hidden Markov models (HMMs) have been applied in this area as an accurate unsupervised approach.

Exploring the Topoisomerase II Inhibitory Potential of Steroidal Drugs as a Recommended Mechanism of Action for Their Anticancer Activity: In Silico and In Vitro Assessments.

Herein, and based on the pharmacophoric features of doxorubicin (Dox); 133 steroids were screened to assess their ability to act as TOP II inhibitors for the discovery of those with promising anticancer activity. The cytotoxic inhibitory concentration 50 (IC) of the investigated steroids was determined against H1299, CaCo2, MDA-MB-468, and FaDu cancer cell lines and compared to Dox. Fluticasone propionate and fusidic acid exhibited the most potent antiproliferative effect against the MDA-MB-468 with IC values of 10.

Advanced robotic surgery in obese patients with gynecological cancers: tips and tricks from literature to clinical practice.

Obesity is closely linked to an increased incidence of several gynecological conditions and poses significant challenges to their surgical management. Among these, endometrial cancer stands out due to its high prevalence in patients with elevated body mass index, with nearly 60% of those requiring primary surgical treatment classified as obese or morbidly obese. The coexistence of multiple comorbidities in this population contributes to a heightened risk of perioperative and postoperative complications.

Cancer-related cognitive impairment: a review of National Institutes of Health‑Funded grants (2017-2024).

Purpose: Cancer-related cognitive impairment (CRCI) adversely affects cancer survivors' academic, occupational, and psychosocial functioning. Analyzing the National Institutes of Health (NIH) portfolio of funded research provides insight into current efforts, trends, and gaps in CRCI research.

Methods: We queried the internal NIH iSearch database to identify awards focused on CRCI.

Genetically determined body mass index is associated with diffuse large B-cell lymphoma in polygenic and Mendelian randomization analyses.

Obesity has been associated with non-Hodgkin lymphoma (NHL), but the evidence is inconclusive. We examined the association between genetically determined adiposity and four common NHL subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic leukemia, and marginal zone lymphoma, using eight genome-wide association studies of European ancestry (N = 10,629 cases, 9505 controls) and constructing polygenic scores for body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-hip ratio adjusted for BMI (WHRadjBMI). Higher genetically determined BMI was associated with an increased risk of DLBCL [odds ratio (OR) per standard deviation (SD) = 1.

Ten-Year Trends in Digital Rectal Exam Results and Prostate Cancer Detection: Insights from the PLCO Trial.

Objective: Digital Rectal Examination (DRE) remains an important preventive measure in primary care settings, but a single screening may produce false positives. We sought to explore the trend of abnormal DRE (suspicious and non-suspicious) findings in men with and without prostate cancer.

Methods: We utilized data on 34,756 men (1,713 Black and 33,043 White) from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.

Recent Advances in Bioanalytical Methods for Quantification and Pharmacokinetic Analyses of Antibody-Drug Conjugates.

Antibody-drug conjugates (ADCs) represent a rapidly expanding class of therapeutics, uniquely combining the specificity of monoclonal antibodies with the potency of cytotoxic small-molecule payloads. Due to their inherent structural complexity and heterogeneous composition, accurate characterization and quantification of ADCs pose significant bioanalytical challenges. This review discusses recent advancements in bioanalytical methodologies, including ligand binding assays (LBAs), liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based approaches, and emerging hybrid LBA-LC-MS/MS platforms.

Role of Metabolic Nuclear Receptors in Acute Liver Injury and Drug-Induced Hepatotoxicity.

Metabolic nuclear receptors (NRs) are ligand-activated transcription factors central to metabolic homeostasis and detoxification. While their roles in chronic liver diseases have been extensively reviewed, comprehensive review of metabolic NRs in acute liver injury (ALI) is scarce. This review summarizes the current knowledge on how metabolic NRs modulate ALI, with particular focus on those frequently-studied NRs including farnesoid X receptor, peroxisome proliferator-activated receptors and pregnane X receptor, as well as on the less-characterized liver X receptor and constitutive androstane receptor.

Analysis of TERT association with clinical outcome in meningiomas: a multi-institutional cohort study.

Background: TERT promoter mutation is a rare biomarker in meningiomas associated with aberrant TERT expression and reduced progression-free survival. Although high TERT expression is characteristic of tumours with TERT promoter mutations, it has also been observed in tumours with wildtype TERT promoters. This study aimed to investigate the prevalence and prognostic association of TERT expression in meningiomas.

Localized high-risk prostate cancer harbors an androgen receptor activity-low subpopulation susceptible to HER2 inhibition.

Background: Localized high-risk prostate cancer (PCa) often recurs despite neoadjuvant androgen deprivation therapy (ADT). We sought to identify baseline molecular programs that predict pathologic response and reveal targetable vulnerabilities.

Methods: We profiled 147 biopsy foci from 48 MRI-visible lesions in 37 patients before 6 months of ADT plus enzalutamide and radical prostatectomy.

County-level socioeconomic status, rurality, and second primary cancer risk among breast cancer survivors in the United States.

Background: Breast cancer survivors have an increased risk of second primary cancers (SPCs), the role of county-level socioeconomic status and rurality-factors that may influence access to treatment, surveillance, and preventive care-remains understudied.

Methods: We identified 721,957 women with localized/regional first primary breast cancer who survived ≥ 1 year in 17 Surveillance, Epidemiology, and End Results registries (2000-2018). We used Cox regression to assess associations between county-level median household income (proxy for socioeconomic status), rurality, and their joint effects on invasive SPC risk, adjusting for demographic and clinical factors.

Cytotoxic CD4⁺ T cells exhibit an immunosuppressive shift in checkpoint immunotherapy resistance in melanoma patients.

Although checkpoint immunotherapy has primarily focused on CD8⁺ T cells, emerging evidence highlights an important role for cytotoxic CD4⁺ T cells in mediating therapeutic responses. However, research on the functional properties of cytotoxic CD4⁺ T cells in the context of immunotherapy is still at an early stage and remains insufficiently defined. Utilizing single-cell RNA-sequencing datasets obtained from metastatic melanoma patients treated with checkpoint inhibitors targeting PD-1 and/or CTLA-4, we performed transcriptomic profiling of conventional CD4⁺ T cells, excluding proliferative and regulatory (FOXP3⁺) subsets, and compared responders and non-responders as distinct groups.

Cardiopulmonary changes and its association with clinical features in noncirrhotic portal hypertension.

Background: Cardiopulmonary changes in noncirrhotic portal hypertension (NCPH) are poorly understood.

Aim: To investigate cardiopulmonary changes using transthoracic echocardiography (TTE) in NCPH and their correlation with clinical features.

Methods: Prospective cohort including 10 preclinical NCPH [without portal hypertension (PH)] and 32 NCPH subjects who underwent TTE with agitated saline injection and comprehensive clinical evaluation were assessed.

Atypical cadherin FAT1 promotes tumorigenesis by suppressing autophagic cell death in glioblastoma under hypoxia or nutrient stress.

Background: Autophagy, a conserved intracellular degradation process, plays dual roles in cancer, promoting survival under stress or mediating cell death through deregulated autophagy. Atypical cadherin FAT1 functions as an oncogene or tumor suppressor in a context-dependent manner. Our previous work identifies the oncogenic role of FAT1 in glioblastoma.

4D-printed microdevices for spatiotemporal detection of ctDNA and miRNA in pancreatic cancer: an in-depth review.

Pancreatic cancer is among the most lethal forms of cancer, with a five-year survival rate under 7%, primarily due to its late clinical presentation and rapid disease progression. Although the oncogenic development of pancreatic tumors can span over a decade, early diagnosis remains a major clinical challenge, as current diagnostic approaches-including imaging modalities and blood-based markers like CA19-9-lack the requisite sensitivity for detecting early-stage disease. Liquid biopsy has emerged as a promising, non-invasive diagnostic technique by enabling the detection of circulating tumor-specific nucleic acids, particularly circulating tumor DNA (ctDNA) and microRNAs (miRNAs).

What makes genes burst.

Genes burst. Instead of being monotonously transcribed by a steady stream of RNA polymerases, active genes undergo transient and random pulses of transcription that are referred to as gene bursting. This property is ubiquitous and evolutionarily conserved from bacteria to humans, and reflects the inherent stochastic nature of most biological processes.

Integrated iodine biokinetic models for pregnancy and lactation based on the ICRP reference adult model.

Exposure to radioactive iodine (radioiodine) during pregnancy and lactation poses unique risks to both mothers and their offspring due to altered iodine metabolism and heightened radiosensitivity. Existing biokinetic models, such as those developed by Berkovski, have provided a foundation for understanding iodine kinetics in these physiological states but lack integration with the latest International Commission on Radiological Protection (ICRP) reference model for non-pregnant adults. In this study, we developed integrated biokinetic models for pregnancy and lactation that are structurally consistent with the ICRP Publication 137 adult iodine model.