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Gastrointestinal (GI) cancers, including colorectal, gastric, esophageal, pancreatic, and liver cancers, represent a significant global health burden, with high prevalence and mortality rates driven by aging, lifestyle factors, and infections. Emerging research highlights the role of vitamin D in cancer biology, particularly its potential in the prevention and management of GI cancers. Through its active form, calcitriol, vitamin D regulates cell proliferation, apoptosis, angiogenesis, and immune responses via the vitamin D receptor (VDR). Epidemiological studies suggest an inverse association between vitamin D deficiency and cancer risk, while experimental models demonstrate its anti-tumor effects. Additionally, vitamin D influences gut microbiota composition and immune regulation, potentially enhancing cancer immunity and response to immunotherapy. Despite promising evidence, clinical trials have yielded mixed results, underscoring the need for further research to determine optimal supplementation strategies, individual responses, and genetic influences. This review explores vitamin D’s mechanisms, epidemiological evidence, and therapeutic potential in GI cancers, advocating for personalized approaches in cancer prevention and treatment.

Background: This narrative review examines the role of artificial intelligence (AI) in bowel sound analysis for the diagnosis and management of inflammatory bowel disease (IBD). Inflammatory bowel disease (IBD), encompassing Crohn’s disease and ulcerative colitis, presents a significant clinical burden due to its unpredictable course, variable symptomatology, and reliance on invasive procedures for diagnosis and disease monitoring. Despite advances in imaging and biomarkers, tools such as colonoscopy and fecal calprotectin remain costly, uncomfortable, and impractical for frequent or real-time assessment. Meanwhile, bowel sounds—an overlooked physiologic signal—reflect underlying gastrointestinal motility and inflammation but have historically lacked objective quantification. With recent advances in artificial intelligence (AI) and acoustic signal processing, there is growing interest in leveraging bowel sound analysis as a novel, non-invasive biomarker for detecting IBD, monitoring disease activity, and predicting disease flares. This approach holds the promise of continuous, low-cost, and patient-friendly monitoring, which could transform IBD management. Objectives: This narrative review assesses the clinical utility, methodological rigor, and potential future integration of artificial intelligence (AI)-driven bowel sound analysis in inflammatory bowel disease (IBD), with a focus on its potential as a non-invasive biomarker for disease activity, flare prediction, and differential diagnosis. Methods: This manuscript reviews the potential of AI-powered bowel sound analysis as a non-invasive tool for diagnosing, monitoring, and managing inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis. Traditional diagnostic methods, such as colonoscopy and biomarkers, are often invasive, costly, and impractical for real-time monitoring. The manuscript explores bowel sounds, which reflect gastrointestinal motility and inflammation, as an alternative biomarker by utilizing AI techniques like convolutional neural networks (CNNs), transformers, and gradient boosting. We analyze data on acoustic signal acquisition (e.g., smart T-shirts, smartphones), signal processing methodologies (e.g., MFCCs, spectrograms, empirical mode decomposition), and validation metrics (e.g., accuracy, F1 scores, AUC). Studies were assessed for clinical relevance, methodological rigor, and translational potential. Results: Across studies enrolling 16–100 participants, AI models achieved diagnostic accuracies of 88–96%, with AUCs ≥ 0.83 and F1 scores ranging from 0.71 to 0.85 for differentiating IBD from healthy controls and IBS. Transformer-based approaches (e.g., HuBERT, Wav2Vec 2.0) consistently outperformed CNNs and tabular models, yielding F1 scores of 80–85%, while gradient boosting on wearable multi-microphone recordings demonstrated robustness to background noise. Distinct acoustic signatures were identified, including prolonged sound-to-sound intervals in Crohn’s disease (mean 1232 ms vs. 511 ms in IBS) and high-pitched tinkling in stricturing phenotypes. Despite promising performance, current models remain below established biomarkers such as fecal calprotectin (~90% sensitivity for active disease), and generalizability is limited by small, heterogeneous cohorts and the absence of prospective validation. Conclusions: AI-powered bowel sound analysis represents a promising, non-invasive tool for IBD monitoring. However, widespread clinical integration requires standardized data acquisition protocols, large multi-center datasets with clinical correlates, explainable AI frameworks, and ethical data governance. Future directions include wearable-enabled remote monitoring platforms and multi-modal decision support systems integrating bowel sounds with biomarker and symptom data. This manuscript emphasizes the need for large-scale, multi-center studies, the development of explainable AI frameworks, and the integration of these tools within clinical workflows. Future directions include remote monitoring using wearables and multi-modal systems that combine bowel sounds with biomarkers and patient symptoms, aiming to transform IBD care into a more personalized and proactive model.

Background: Venous malformations can cause substantial morbidity and long-term complications. There are no Food and Drug Administration (FDA)-approved therapies for the treatment of venous malformations. However, off-label use of sirolimus has demonstrated clinical benefit in these patients. This systematic review evaluates the efficacy and safety of sirolimus in the management of venous malformations. Methods and Results: A systematic literature search identified 26 studies comprising 98 patients treated with sirolimus for venous malformations. Most studies were case reports or case series (77%), with 15% prospective trials and 8% retrospective analyses. Sirolimus, primarily administered orally, yielded some level of clinical improvement in 72% of reported patients, with consistent symptomatic relief observed in coagulopathy, bleeding, anemia, pain, and improved function. However, reduction in the size of the malformation varied and treatment-limiting side effects were observed. Conclusions: Oral sirolimus is a promising treatment option for venous malformations, especially for those with deep venous malformations. A direct, targeted topical treatment could provide clinical benefit for the cutaneous manifestation without the risk of off-target effects as occur with oral sirolimus. Further prospective, controlled studies are warranted to elucidate sirolimus’s role in managing venous malformations.

Abstract Background Completing adjuvant chemotherapy and reducing toxicities are critical for maximizing survival after a colon cancer diagnosis. Sex, as a biological variable, may affect colon cancer chemotherapy completion, toxicities, and survival differently. Methods From a National Cancer Institute–sponsored trial conducted among patients with stage III colon cancer (Cancer and Leukemia Group B (Alliance)/Southwest Oncology Group 80702), we included 2201 patients receiving the standard adjuvant chemotherapy regimen of fluorouracil, leucovorin, and oxaliplatin. We calculated relative dose intensity to indicate chemotherapy completion and considered reduced relative dose intensity (values <85%) as a clinically significant deviation from standard fluorouracil, leucovorin, and oxaliplatin. Using National Cancer Institute’s Common Terminology Criteria for Adverse Events, we defined severe adverse events (grade ≥3) as the occurrence of any following event, including neutrophil count decrease, nausea, platelet count decrease, hypertension, peripheral neuropathy, diarrhea, fatigue, gastritis, creatinine level increase, gastric ulcer, myocardial ischemia, and cerebral ischemia. The primary survival outcome was disease-free survival (time from enrollment to colon cancer recurrence or death from any cause), and secondary survival outcomes were recurrence-free and overall survival. Results Compared with men, women were at statistically significantly higher risks of experiencing reduced relative dose intensity (adjusted odds ratio = 1.59, 95% CI = 1.29 to 1.96; P < .001) and severe advance events (adjusted odds ratio = 1.72, 95% CI = 1.41 to 2.11; P < .001). Yet, women had statistically significantly better disease-free survival (adjusted hazard ratio = 0.72, 95% CI = 0.59 to 0.87; P < .001) as well as better recurrence-free and overall survival. Conclusions Our findings suggested that women with colon cancer are more likely to have worse chemotherapy completion rates and more severe adverse events, but they have better survival. Sex as a biological variable warrants further consideration in chemotherapy administration and survivorship management after colon cancer diagnosis.

Abstract Introduction: The disproportionate prostate cancer (CaP) burden, which includes high mortality rates, is significantly attributed to the characteristics of the social determinants of the health status of the Black Male population. Designing targeted interventions to address poor health outcomes through a collaborative population-based approach could reduce CaP health disparities. The Community Living Lab (CoLLab) Learning Health System was developed to address ethnically sensitive, targeted approaches that will eliminate CaP health disparities among Black Men. This study assessed demographic factors and Knowledge on prostate cancer screening attitudes and research participation among black men. Method: The collab project employed a social ecological model to design intervention to address barriers to CaP screening and participation in clinical trials. A validated, pretested questionnaire was used to collect information on demographics, CaP knowledge, attitudes, testing, and a history of participation in research and clinical trials. Baseline data were collected from 3 American Legion posts (ALPs). The association between variables was evaluated using the Chi-square test. Results: Participants between 60-69 years were 28.38%, and those aged 40-49 were 12.16%. Most are US-born Black (89.8%), with others identifying as African-born Black (6.76%) and Caribbean-born Black (1.35%). Approximately 43.24% were retired, and 36.49% were working full-time. CaP knowledge was high in 43.9%, moderate in 46.6%, and low in 9.5%. Only 45% of the participants have undergone Prostate-Specific Antigen test, and 24.6% have had a Digital Rectal Examination. Reported past clinical trials and research participation were very low (9.38%). Participants with higher knowledge levels had higher information scores (p < .0001), favored various research settings (p = 0.0008), had favorable attitudes towards CaP testing (p < .0001), and were more likely to participate in research (p = 0.0117). Work status was found to impact CaP Knowledge (p = 0.0117). Participants with stronger beliefs about prostate cancer may have different attitudes toward testing (p = 0.0444). Age did not impact attitudes toward CaP testing (p = 0.4298). Conclusion: The knowledge of CaP was found to impact the attitudes, testing, and disposition of the participants towards research. The baseline data generated from the clinical study will curate insightful evidence that will create innovative approaches to prostate cancer education among males in Black communities. Citation Format: Opeyemi O. Bolajoko, Quincy A. Wimberly, Daniel W. Lee, Collisa Mahin, Michelle Fudge, Shaina E. Flynn, Arnold J. Merriweather, Trevanne R. Matthews Hew, Monica L. Albertie, Dery Greene, Wayne Ford, Toshiko Moultrie, Floyd B. Willis, Folakemi T. Odedina. Influence of demographic factors and knowledge on prostate cancer screening attitude and research participation among Black men [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr C138.

Abstract Background Lung adenocarcinoma in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve lung adenocarcinoma risk prediction. Methods PRSs were developed using genome-wide association study summary statistics from East Asian (8002 cases; 20 782 controls) and European (2058 cases; 5575 controls) populations. Single-ancestry models included a PRS with 25 single nucleotide variants (PRS-25), PRS clumping and thresholding (CT), and LDpred2; multi-ancestry models included LDpred2 plus European PRS-128, PRS-CSx, and clumping and thresholding, super learning, empirical Bayes (CT-SLEB). Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium and externally validated in the Nanjing Lung Cancer Cohort. We assessed predictive accuracy via area under the curve operating procedure (AUC), with 10-year and (ages 30-80 years) absolute risks estimates. Results The best multi-ancestry PRS, using East Asian and European data via CT-SLEB, outperformed the best East Asian-only (LDpred2; AUC = 0.629, 95% confidence interval [CI] = 0.618 to 0.641), achieving an AUC of 0.640 (95% CI = 0.629 to 0.653) and odds ratio of 1.71 (95% CI = 1.61 to 1.82) per standard deviation increase. Nanjing Lung Cancer Cohort validation confirmed robust performance (AUC = 0.649, 95% CI = 0.623 to 0.676). The top 20% PRS group had a 3.92-fold higher lung adenocarcinoma risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year lung adenocarcinoma risk at age 50 years (0.42%) by age 41 years, 9 years earlier. Conclusions Multi-ancestry PRS approaches enhance lung adenocarcinoma risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.

PURPOSE Preclinical studies suggest the combination of the poly(adenosine diphosphate[ADP]-ribose) polymerase (PARP) inhibitor olaparib and the ataxia telangiectasia–mutated and Rad3-related (ATR) inhibitor ceralasertib has synergistic antitumor activity in homologous recombination proficient (HRP) and homologous recombination repair gene mutation (HRRm) patients. This study aims to determine the efficacy of olaparib plus ceralasertib in metastatic castration-resistant prostate cancer (mCRPC) with and without HRRm. PATIENTS AND METHODS Thirty-five HRP and 12 HRRm PARP inhibitor–naïve patients with mCRPC progressing on ≥1 line of therapy or previous androgen receptor pathway inhibitor were enrolled. Patients received olaparib (300 mg twice daily) and ceralasertib (160 mg once daily, days 1-7) in 28-day cycles. HRRm was defined as biallelic inactivation of BRCA2 or BRCA1 , monoallelic inactivation of ATM , or germline inactivation of any of these genes. The primary end point was disease response rate (dRR; confirmed prostate-specific antigen decline ≥50% and/or complete/partial radiographic response by RECIST v1.1) in HRP patients. Secondary end points included dRR in HRRm patients, progression-free survival (PFS), and safety/toxicity. Two-stage designs were used. RESULTS Four of 35 (11%; 95% CI, 3.2 to 26.7) HRP and four of 12 HRRm patients responded. Median PFS was 8.2 months (95% CI, 5.3 to not reached) for HRP patients. Thirty-six percent of patients had ≥grade 3 toxicity, most commonly from anemia. Limitations include small, single-arm, nonrandomized trial design. CONCLUSION Combining ceralasertib with olaparib had limited activity in patients with HRP mCRPC. HRRm response rate was not greater than previous single-agent PARP inhibitor clinical trials.

Importance Advances in Alzheimer disease (AD) have shifted research focus to earlier disease stages, necessitating more scalable approaches to identify cognitively unimpaired individuals with amyloid β (Aβ) pathology. Objective To assess the utility of plasma phosphorylated tau 217 (p-tau217) for classifying Aβ status in cognitively unimpaired individuals, both as a stand-alone test and in a 2-step approach where positive plasma results were confirmed using a second modality (Aβ positron emission tomography [PET] or cerebrospinal fluid [CSF]). Design, Setting, and Participants This cross-sectional cohort study used data collected between June 2009 and March 2024. We included 2916 cognitively unimpaired participants from 12 international independent observational cohorts in the US, Europe, Australia, and Canada with available plasma p-tau217 levels and CSF or PET Aβ biomarkers. Performance comparisons between mass spectrometry and immunoassay-based p-tau217 measurements were also performed (n = 964). Exposures Plasma p-tau217 levels measured by immunoassay. Main Outcome and Measures Aβ status, determined by CSF or Aβ PET biomarkers. Results Participants had a mean (SD) age of 66.9 (9.9) years; 971 (33.3%) were Aβ positive by either CSF or PET, 1667 (57.2%) were women, and 1108 (38.1%) carried at least 1 APOE ε4 allele. As a stand-alone test, plasma p-tau217 achieved a positive predictive value (PPV) of 79% (95% CI, 74-84) and an overall accuracy of 81% (95% CI, 80-82). In a 2-step workflow, the PPV and accuracy significantly increased to 91% (95% CI, 86-95). While this approach required screening of 677 individuals with plasma p-tau217 to identify 100 Aβ-positive individuals, compared to 536 participants when using PET alone, it reduced the need for PET testing to 124. Immunoassays demonstrated comparable PPVs to mass spectrometry (80% [95% CI, 74-86] vs 85% [95% CI, 81-90]; P = .12) but significantly lower overall accuracy (82% [95% CI, 79-84]% vs 88 [95% CI, 86-90]; P < .001) and true Aβ-positive detection rate (49% [95% CI, 43-55] vs 69% [95% CI, 64-75]; P < .001). Conclusions and Relevance The findings highlight the potential of plasma p-tau217 as a stand-alone test—or when used in a sequential 2-step approach alongside PET or CSF testing—as a cost-effective, scalable, and minimally burdensome strategy for identifying preclinical AD. Tailored screening workflows that incorporate p-tau217 can improve efficiency in participant selection for preclinical AD trials and, in the future, help guide access to disease-modifying treatments.

Abstract 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) = 1.18, 95% confidence interval (95% CI): 1.05–1.33, p = .005]. This finding was consistent with Mendelian randomization analyses, which demonstrated a similar increased risk of DLBCL with higher genetically determined BMI (OR per SD = 1.12, 95% CI: 1.02–1.23, p = .03). No significant associations were observed with other NHL subtypes. Our study demonstrates a positive link between a genetically determined BMI and an increased risk of DLBCL, providing additional support for increased adiposity as a risk factor for DLBCL.