James Graham Brown Foundation

720 Background: Quality-of-life (QoL) endpoints are vital for assessing patient-centered outcomes in genitourinary (GU) cancers, yet their inclusion and reporting remain inconsistent. This study evaluated alignment between prospectively registered QoL plans and published results in contemporary phase III GU randomized controlled trials (RCTs). Methods: Phase III GU RCTs published between January 2020 and December 2024 were identified via PubMed. Corresponding ClinicalTrials.gov records were reviewed to determine whether QoL endpoints were prospectively planned. For each trial, published results were examined in primary and secondary manuscripts to assess whether QoL data were reported. Trial characteristics included tumor site, therapy class, funding source, disease setting, study result, and journal impact factor (IF). Additional design and registry variables were explored for associations with QoL reporting. Significant differences in QoL reporting were determined based on Chi-squared or Fisher’s exact tests. Results: A total of 79 phase III GU RCTs were included; 32 (41%) reported QoL outcomes. Sites included prostate (32, 41%), kidney (26, 33%), and bladder (19, 24%). Industry funding and publication in journals with an IF ≥ 10 occurred in 55 (70%) trials; 46 (61%) had positive results. Of 77 trials with registry data, 45 (58%) prospectively planned QoL assessment, yet 17 (38%) failed to publish results. QoL findings appeared in primary manuscripts for 17 (53%) and in secondary publications for 15 (47%). RCTs with positive results were more likely to report QoL than negative trials (26/46 [57%] vs 5/30 [17%]; p = 0.001). High-impact journals reported QoL more often than lower-impact journals (27/55 [49%] vs 5/24 [21%]; p = 0.019). Reporting did not differ by tumor site, disease setting, therapy class, study design, masking, or geographic scope (all p > 0.05). Industry-funded RCTs showed a trend toward higher reporting rates (26/55 [47%] vs 6/24 [25%]; p = 0.064). Conclusions: QoL outcomes were inconsistently reported in contemporary phase III GU oncology RCTs. Despite prospective planning in over half of the studies, more than one-third failed to publish QoL results. Trials with positive efficacy findings were approximately three times more likely to report QoL outcomes, underscoring the need for improved transparency and adherence to prespecified patient-reported outcome measures and reporting standards.

Polychlorinated biphenyls (PCBs) have been associated with sex-dependent liver disease outcomes. Current mechanisms only partially explain these sex differences and alternative mechanisms including gut-liver toxicity warrant investigation. This study aims to identify PCB-induced changes in the hepatic proteome and gut microbiome and determine their contributions to sex-specific PCB toxicity. Male and female C57BL/6J mice were exposed to Aroclor1260 (20 mg/kg) and PCB126 (20 μg/kg) via oral gavage. After two weeks, hepatic and intestinal tissues were collected for peptide measurements (LC/MS) and 16S sequencing respectively. Proteomic analysis revealed that biological sex largely drove differences seen in the hepatic proteome and dictated PCB liver responses. PCB-exposed females manifested higher abundance of aryl hydrocarbon receptor (AHR) targets including CD36 vs. PCB-exposed males. Computational analysis also demonstrated enhanced AHR and liver-X-receptor (LXR) activation (higher z-scores) in PCB-exposed females vs. males. With regards to gut microbiome, both exposure and sex impacted the composition of microbial communities. Intriguingly, only PCB-exposed males exhibited increased Dehalobacterium abundance, and decreased mRNA levels for genes encoding gut barrier and antimicrobial proteins (Ocln, Reg3g). Overall, PCB-exposed females exhibited an altered proteome relevant to AHR and LXR responses, while PCB-exposed males exhibited more distinct changes in gut microbiota coupled with altered ileal gene expression. The findings suggest that, in addition to biological sex, organ-organ interactions should be considered when predicting toxicity outcomes, particularly for persistent compounds such as PCBs that can impact multiple organs simultaneously yet have tissue-specific toxic effects.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-23603-w.

The Center for Disease Control and Prevention (CDC) annually tracks American youth and adult smoking prevalence using data from the National Youth Tobacco Survey (NYTS) and the National Health Interview Survey (NHIS). The NYTS and the NHIS began collecting information on vaping in 2011 and 2014 respectively. However, since those years the CDC has only reported smoking and vaping rates separately, which presents a long-term and important information gap, given the decade-long debate about whether e-cigarettes help people who smoke reduce or quit, and whether they are a gateway to youth smoking. This short report provides joint smoking and vaping prevalence rates for American high school students from 2011 to 2022 from the NYTS, and rates for American adults 18–44 years old over the same period from the NHIS. The results show that cigarette smoking declined sharply, especially in high schoolers and emerging young adults (18–20 years) while vaping increased substantially. In addition, the prevalence of vaping among people who formerly smoked also increased. The importance of these trends is highlighted by sharp increases in quit ratios among emerging and junior (21–24 years) young adults, who had historically low levels of quitting.

Electronic cigarettes (e-cigarettes) and cardiovascular health risks have gained attention among tobacco researchers. While the cardiovascular risks from e-cigarettes are still unclear, a recent paper by Alzahrani in Cureus claimed that current usage of e-cigarettes increases the risks of cardiovascular diseases, such as myocardial infarction and stroke, in subjects who were never cigarette smokers. The National Health Interview Survey (NHIS) data from 2014 to 2021 and logistic regression models were used to replicate and extend Alzahrani's analysis. Only 12 never smokers who were current e-cigarette users had a myocardial infarction in all eight years. The crude odds ratio (OR) for e-cigarette use was 0.42 (95%CI: 0.24, 0.75). After adjusting for age and other confounding factors and health conditions, the OR of e-cigarette use increased to 2.48 (95%CI: 1.35, 4.55). The omission of age while adjusting for all other risk factors resulted in an OR of 0.80 (95%CI: 0.45, 1.43). In addition, the adjusted ORs for coronary heart disease and stroke were 1.12 (95%CI: 0.58, 2.17) and 1.13 (95%CI: 0.55, 2.29), respectively. The findings indicate that Alzahrani's study is scientifically unreliable. The association between e-cigarette use and heart attack reported by Alzahrani was substantially driven by age, and the very small number of exposed cases makes the association very unstable. Given the nature of cross-sectional NHIS data, it is impossible to establish a robust association or causal claim that e-cigarette use "increases" the risks of any disease.

Daily rhythms are primarily synchronized by the suprachiasmatic nucleus (SCN) in the hypothalamus, the body’s central circadian clock. The SCN aligns whole-body cellular, behavioral and phenomenological processes with the Earth’s 24-hour day/night rhythm. When disruptions to the SCN’s perceptual system occur (e.g., “jet-lag,” prolonged waking, chronic exposure to light at night or habit change as the result of becoming a parent), disrupted melatonin and glucocorticoid secretion can lead to widespread dysregulation of sleep and circadian cycling. The effects of circadian disruptions are often compounded by the homeostatic sleep drive, wherein sleep pressure accumulates with protracted wakefulness to affect mood, cognition, health and well-being.