tbuckley/cabot-search huggingface dataset:
Adoption of Broad Genomic Profiling in Patients With Cancer
Authors: Xiao Wang, John Rothen, Sida Huang, Jessica B. Long, Pamela R. Soulos, Sarah B. Goldberg, Ronac Mamtani, Carolyn J. Presley, Natalia Kunst, Shuangge Ma, Shi-Yi Wang, Cary P. Gross, Michaela A. Dinan
Journal: JAMA Oncology (2025)

This cross-sectional study examines the use of broad genomic profiling in patients with metastatic cancer.
Atezolizumab and Trastuzumab Plus Chemotherapy for <i>ERBB2</i>-Positive Locally Advanced Resectable Gastric Cancer
Authors: Zhi Peng, Xiaotian Zhang, Han Liang, Zhichao Zheng, Zhenning Wang, Hao Liu, Jiankun Hu, Yihong Sun, Yanqiao Zhang, Han Yan, Lin Tong, Jiahui Xu, Jiafu Ji, Lin Shen
Journal: JAMA Oncology (2025)

Importance Effective treatment of locally advanced gastric cancer (GC) or gastroesophageal junction (GEJ) cancer remains a challenge. Objective To compare the efficacy and safety of atezolizumab plus trastuzumab plus capecitabine and oxaliplatin chemotherapy (XELOX) vs trastuzumab plus XELOX in Chinese patients with locally advanced human epidermal growth factor receptor 2 ( ERBB2 ; formerly HER2 )–positive GC or adenocarcinoma of the GEJ. Design, Setting, and Participants This was an open-label phase 2 randomized clinical trial conducted at 8 study sites in China. Patient recruitment started on February 25, 2021, and this study is ongoing as participants are still being actively followed up. Chinese patients eligible for surgery with locally advanced ERBB2 -positive GC or adenocarcinoma of the GEJ were included. Data were analyzed from March 2021 to October 2023. Interventions Eligible patients were enrolled and randomly assigned 1:1 to perioperative treatment with either atezolizumab plus trastuzumab plus XELOX (arm A) or trastuzumab plus XELOX (arm B) for 3 neoadjuvant cycles (3 weeks per cycle) and 5 adjuvant cycles. Main Outcomes and Measures The primary efficacy end point was the pathological complete response (pCR) rate following completion of neoadjuvant therapy and surgery. Results In total, 42 patients were screened and randomly assigned to arm A (n = 21) or arm B (n = 21). The median (range) ages were 61 (33-72) years and 65 (49-72) years in arm A and arm B, respectively, and 39 patients (93%) were male. The pCR rate was significantly higher in arm A (8 [38%]) than arm B (3 [14%]; difference, 23.8%; 90% CI, 1.3-44.7). Age younger than 65 years, male sex, and intestinal Lauren classification were significantly associated with a better pCR rate in arm A. Median event-free survival, disease-free survival, and overall survival were not reached. Based on the same way of interpretation, major pathologic response should be statistically significantly different between the 2 arms, while other outcome measures remained not significantly different. The incidence of treatment-emergent adverse events was 100% (21 of 21) and 100% (21 of 21) in arms A and B, respectively; grade 3 or higher TEAEs, 57% (12 of 21) and 67% (14 of 21), respectively; and serious TEAEs, 29% (6 of 21) and 10% (2 of 21), respectively. Conclusions and Relevance In this randomized clinical trial, add-on atezolizumab to trastuzumab plus XELOX therapy demonstrated promising efficacy in this patient population, and no new safety concerns were raised. Trial Registration ClinicalTrials.gov Identifier: NCT04661150
Circular RMST cooperates with lineage-driving transcription factors to govern neuroendocrine transdifferentiation
Authors: Mona Teng, Jiacheng Guo, Xin Xu, Xinpei Ci, Yulin Mo, Yakup Kohen, Zuyao Ni, Sujun Chen, Wang Yuan Guo, Martin Bakht, Shengyu Ku, Michael Sigouros, Wenqin Luo, Colette Maya Macarios, Ziting Xia, Moliang Chen, Sami Ul Haq, Wen Yang, Alejandro Berlin, Theo van der Kwast, Leigh Ellis, Amina Zoubeidi, Gang Zheng, Jie Ming, Yuzhuo Wang, Haissi Cui, Benjamin H Lok, Brian Raught, Himisha Beltran, Jun Qin, Housheng Hansen He
Journal: Cancer Cell (2025)

Circular RNA (circRNA) is a class of noncoding RNA with regulatory potentials. Its role in the transdifferentiation of prostate and lung adenocarcinoma into neuroendocrine prostate cancer (NEPC) and small cell lung cancer (SCLC) remains unexplored. Here, we identified circRMST as an exceptionally abundant circRNA predominantly expressed in NEPC and SCLC, with strong conservation between humans and mice. Functional studies using shRNA, siRNA, CRISPR-Cas13, and Cas9 consistently demonstrate that circRMST is essential for tumor growth and the expression of ASCL1, a master regulator of neuroendocrine fate. Genetic knockout of Rmst in NEPC genetic engineered mouse models prevents neuroendocrine transdifferentiation, maintaining tumors in an adenocarcinoma state. Mechanistically, circRMST physically interacts with lineage transcription factors NKX2-1 and SOX2. Loss of circRMST induces NKX2-1 protein degradation through autophagy-lysosomal pathway and alters the genomic binding of SOX2, collectively leading to the loss of ASCL1 transcription.
Dasatinib and CAR T-Cell Therapy in Newly Diagnosed Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia
Authors: Mingming Zhang, Shan Fu, Jingjing Feng, Ruimin Hong, Guoqing Wei, Houli Zhao, Mengyu Zhao, Huijun Xu, Jiazhen Cui, Simao Huang, Xiaoyu Wu, Lianxuan Liu, Jie Sun, Wenjun Wu, Yuanyuan Zhu, Jingsong He, Yi Zhao, Zhen Cai, Weiyan Zheng, Xiujin Ye, Jimin Shi, Yi Luo, Dongrui Wang, Alex H. Chang, Yongxian Hu, He Huang
Journal: JAMA Oncology (2025)

Importance A combination of tyrosine kinase inhibitors and chimeric antigen receptor (CAR) T cells has made a breakthrough in refractory or relapsed Philadelphia chromosome (Ph)–positive acute lymphoblastic leukemia (ALL). However, it remains unclear if this treatment in newly diagnosed Ph-positive ALL is associated with high rates of complete molecular remission (CMR) and leukemia-free survival. Objective To evaluate the efficacy and safety of dasatinib in combination with CAR T cells as frontline therapy in adults with newly diagnosed Ph-positive ALL. Design, Setting, and Participants This trial was conducted at a single center, the First Affiliated Hospital of Zhejiang University School of Medicine. Patients were enrolled in this phase 2, single-arm nonrandomized clinical trial between March 5, 2021, and April 13, 2024. The data cutoff date was February 10, 2025. The data analysis was conducted on February 11, 2025. The median duration of follow-up was 23.9 (range, 7.3-47.7) months. A total of 29 adults with newly diagnosed Ph-positive ALL and adequate organ function were screened for eligibility, and 1 patient who received a diagnosis of blast-phase chronic myeloid leukemia was excluded. Intervention Dasatinib was administered with a 2-week vindesine and dexamethasone regimen as induction, followed by sequential CD19 and CD22 CAR T-cell therapies and single-agent dasatinib maintenance. Main Outcomes and Measures The primary end point was CMR rate after CD19 CAR T-cell therapy. CMR was defined as undetectable BCR/ABL1 transcripts as measured by quantitative reverse transcription polymerase chain reaction with a sensitivity of 10 −4 in the bone marrow. Results Twenty-eight patients (median [range] age, 48.5 [18.0-69.0] years; 10 female individuals [36%]) were enrolled, and 1 patient withdrew after induction. The CMR rate was 25% (7 of 28) after induction and increased to 85% (23 of 27) after CD19 CAR T-cell therapy. Twenty-five patients (89.3%) received sequential CD22 CAR T-cell therapy, and the CMR rate was 76% (19 of 25). Of the 52 CAR T-cell therapies, only 21 cases of grade 1 cytokine release syndrome occurred. After a median follow-up of 23.9 (range, 7.3-47.7) months, the 2-year overall survival and leukemia-free survival were 92%. Conclusions and Relevance The results of this nonrandomized clinical trial suggest that the combination of dasatinib and CAR T-cell therapy showed encouraging efficacy in newly diagnosed Ph-positive ALL with acceptable toxic effects. Further studies with larger cohorts and longer follow-up durations are needed. Trial Registration ClinicalTrials.gov Identifier: NCT04788472
Integrated liver-secreted and plasma proteomics identify a predictive model that stratifies MASH
Authors: William De Nardo, Olivia Lee, Yazmin Johari, Jacqueline Bayliss, Marcus Pensa, Paula M Miotto, Stacey N Keenan, Andrew Ryan, Amber Rucinski, Tessa M Svinos, Geraldine J Ooi, Wendy A Brown, William Kemp, Stuart K Roberts, Benjamin L Parker, Magdalene K Montgomery, Mark Larance, Paul R Burton, Matthew J Watt
Journal: Cell Reports Medicine (2025)

Obesity is a major risk factor for metabolic-associated steatotic liver disease (MASLD), which can progress to metabolic-associated steatohepatitis (MASH). There are no validated non-invasive tests to stratify persons with obesity with a greater risk for MASH. Herein, we assess plasma and liver from 266 obese individuals spanning the MASLD spectrum. Ninety-six human livers were precision-cut, and mass spectrometry-based proteomics identifies 3,333 proteins in the liver-secretion medium, of which 107 are differentially secreted in MASH compared with no pathology. The plasma proteome is markedly remodeled in MASH but is not different between patients with steatosis and no pathology. The APASHA model, comprising plasma apolipoprotein F (APOF), proprotein convertase subtilisin/kexin type 9 (PCSK9), afamin (AFM), S100 calcium-binding protein A6 (S100A6), HbA1c, and zinc-alpha-2-glycoprotein (AZGP1), stratifies MASH (area under receiver operating characteristic [AUROC] = 0.88). Our investigations detail the evolution of liver-secreted and plasma proteins with MASLD progression, providing a rich resource defining human liver-secreted proteins and creating a predictive model to stratify patients with obesity at risk of MASH.
The Financial Toxicity Tumor Board: 5-Year Update on Practice and a Guide to Implementation
Authors: Thomas G. Knight, Caitlin Hensel, Kris Blackley, Mellisa Wheeler, Hughes R. Warden, Wendy Jo Turan, Jaynie Moroe, Seungjean Chai, Donna Feild, Ruben Mesa, Derek Raghavan
Journal: Journal of the National Comprehensive Cancer Network (2025)

Background: Financial toxicity has been increasingly recognized as a major driver of negative outcomes for patients with cancer, with prior interventions focused primarily on patient-level support. The Financial Toxicity Tumor Board (FTTB), established in 2019, is the first institutional-level intervention addressing these challenges. We report on its function and outcomes over 5 years of operation. Methods: Drawing on expertise from across the cancer center, the FTTB was designed to operate similarly to traditional, disease-focused multidisciplinary tumor boards but with a focus on issues related to financial distress. Over time, this system-level intervention has evolved, with major changes including a shift to disease-focused meetings and the developing refinement of process to an Archetype system—categorizing cases as Immediate Assistance Required, System-Level Issue Identified, or Policy/Legislative Issue Identified—which has enhanced its function and effectiveness. In tandem, the pharmacy-based patient assistance program (PAP) arm of the FTTB, formerly focused only on drug approvals, has expanded to address routine financial challenges associated with broader cancer care. Results: Over the past 5 years, &gt;70 cases have been presented to the tumor board, with most resulting in immediate solutions for the individual patient as well as numerous systemic changes. The PAP arm of the FTTB has provided 9,321 patients with copay assistance, totalling &gt;$10,316,695. Furthermore, 16,495 patients have received free medications, amounting to $392,895,101 in patient benefits. Conclusions: The success of the FTTB—both through the tumor board and PAP arms—demonstrates that focused systemic intervention can lead to sustained, substantial improvements in financial toxicity. This model should be further developed as a new standard of care.
AI-driven predictive biomarker discovery with contrastive learning to improve clinical trial outcomes
Authors: Gustavo Arango-Argoty, Damian E Bikiel, Gerald J Sun, Elly Kipkogei, Kaitlin M Smith, Sebastian Carrasco Pro, Elizabeth Y Choe, Etai Jacob
Journal: Cancer Cell (2025)

Modern clinical trials can capture tens of thousands of clinicogenomic measurements per individual. Discovering predictive biomarkers, as opposed to prognostic markers, remains challenging. To address this, we present a neural network framework based on contrastive learning-the Predictive Biomarker Modeling Framework (PBMF)-that explores potential predictive biomarkers in an automated, systematic, and unbiased manner. Applied retrospectively to real clinicogenomic datasets, particularly for immuno-oncology (IO) trials, our algorithm identifies biomarkers of IO-treated individuals who survive longer than those treated with other therapies. We demonstrate how our framework retrospectively contributes to a phase 3 clinical trial by uncovering a predictive, interpretable biomarker based solely on early study data. Patients identified with this predictive biomarker show a 15% improvement in survival risk compared to those in the original trial. The PBMF offers a general-purpose, rapid, and robust approach to inform biomarker strategy, providing actionable outcomes for clinical decision-making.
Abstract 071: Association Between Proximity to Hazardous Waste Sites and Cardiometabolic Diseases: Coronary Heart Disease, Stroke, Hypertension, and Diabetes
Authors: Azar Abadi, Kelley Gabriel, Jeffrey Wickliffe, Emily Levitan, Qasim Hussaini
Journal: Circulation (2025)

Introduction: Proximity to hazardous waste sites may increase cardiometabolic risk. However, differences in these associations by socioeconomic status and urban-rural residency is underexplored. We estimated the associations of proximity to hazardous waste sites with prevalence of coronary heart disease (CHD), stroke, hypertension, and diabetes, while exploring the moderating roles of the Social Vulnerability Index (SVI) and Rural-Urban status. Hypothesis: We hypothesized that neighborhoods closer in proximity to hazardous waste sites have an incrementally higher prevalence of the selected disease outcomes compared to neighborhoods furthest away. Methods: We used data from 57,845 (~70%) U.S. census tracts, creating a percentile-ranked score based on proximity to hazardous waste sites from the Environmental Justice Index, classified into quartiles (Q4 = closest). Prevalence of health outcomes were obtained from the Centers for Disease Control and Prevention (CDC) PLACES dataset, and SVI and Rural-Urban Commuting Area (RUCA) codes were obtained from the CDC and U.S. Department of Agriculture, respectively. A linear mixed-effects model assessed prevalence differences between quartiles, adjusting for percentages of uninsured, race/ethnicity minority, aged ≥65, and &lt;17, with county-level random effects. We also evaluated the moderating role of SVI and urbanicity. Results: After adjustment, neighborhoods closest to hazardous waste sites (Q4) had a significantly higher prevalence of each of the cardiometabolic diseases when compared to Q1: CHD (0.35%; 95% CI, 0.33-0.38), Stroke (0.19%; 95% CI, 0.17-0.21), Hypertension (0.44%; 95% CI, 0.35-0.54) and Diabetes (0.48%; 95% CI, 0.43-0.53). The interaction term between SVI, RUCA, and our exposure was significant for all health outcomes (p&lt;0.05), based on the Wald chi-square test. The magnitude of the associations were stronger in higher socially vulnerable neighborhoods (compared with low) (Figure 1). Although the prevalence of cardiometabolic diseases was higher in non-metro tracts, there was a weaker association with proximity to hazardous waste sites, compared to metropolitan tracts. Conclusion: These findings highlight the potential role of environmental factors in shaping community-level cardiometabolic health disparities. While individual inferences are limited by the study's ecological nature, the results emphasize addressing environmental and social vulnerabilities to promote health equity at a population level.
Abstract P1079: Association Between Blood Sugar Counseling at Dental Visits and Diabetes Status: Findings from the 2011-2020 National Health and Nutrition Examination Survey
Authors: India Washington, Chelsea Akubo, Maya Kramer, Shanshan Song, Ruth-Alma Turkson-Ocran, Bunmi Ogungbe
Journal: Circulation (2025)

Almost 10 million adults across the United States are unaware that they have diabetes. Despite the strong link between diabetes and adverse oral health outcomes, blood sugar screening is not routine procedure in dental offices. To examine the association between receiving blood glucose counseling from dentist. Cross-sectional data from the 2011-2020 National Health and Nutrition Examination Survey assessed the relationship between blood sugar screening advice by dentists, and diabetes status. The primary exposure was defined as whether individuals were advised by their dentist to check their blood sugar, assessed with the survey question: “In the past 12 months, did a dentist, hygienist, or other dental professional have a direct conversation with you about the dental health benefits of checking your blood sugar?” The outcome variable was categorized into four levels of diabetes status: no diabetes, prediabetes, undiagnosed diabetes, and diagnosed diabetes. We fitted weighted multinomial logistic regression models; first conducting an overall analysis, then performing race-specific analyses to examine how the association between dental blood sugar counseling and diabetes status varied across four racial/ethnic groups. The sample included 14,057 U.S. adults, mean age 53 (±16) years; 52% were female. With prediabetes as the reference group, those with no diabetes had a lower relative risk of receiving blood glucose counseling from dentists (RRR:0.49, 95% CI:0.27, 0.89), while those with diagnosed diabetes were more likely to receive this counseling (RRR:13.71, 95% CI:7.51, 25.03). Race-specific analyses showed variations in this association. For diagnosed diabetes, non-Hispanic White adults showed the strongest association (RRR:13.71, 95% CI:7.51, 25.03), followed by non-Hispanic Asian adults (RRR:10.28, 95% CI: 3.63, 29.08), Hispanic adults (RRR:4.50, 95% CI:2.69, 7.51), and non-Hispanic Black adults (RRR:3.09, 95% CI:1.89, 5.06). Notably, among non-Hispanic Asian adults, undiagnosed diabetes was also strongly associated with counseling (RRR:7.06, 95% CI:1.97, 25.26). Receiving blood glucose counseling during dental visits showed strong associations with diagnosed diabetes, suggesting dentists’ potential to contribute significantly to diabetes management. The varying strengths of this association across racial and ethnic groups may be opportunities for targeted interventions, such as integrating blood sugar screening and counseling into routine dental care.
Abstract P2167: Racial and Ethnic Disparities in Neighborhood Socioeconomic Status Associated with Cardiovascular Disease and Stroke
Authors: Jeremey Shropshire, Shawna Follis
Journal: Circulation (2025)

Introduction: The role of socioeconomic status (SES) across cardiovascular diseases (CVD) is well researched at the individual-level but fails to explain the greater CVD rates among Black and American Indian and Alaska Native (AIAN) groups at every level of SES. This research investigated whether lower Neighborhood SES (NSES), a structural determinant of health, was associated with racial and ethnic disparities in CVD or stroke among aging women. Methods: The data came from the Women’s Health Initiative (WHI) cohort, consisting of 161,808 postmenopausal women with 30 years of data on stroke and CVD incidence. The NSES data were obtained from the US Census based on participant’s census tract of residence. We evaluated racial and ethnic disparities in the exposure and outcome prevalence using ANOVA. Associations between NSES and time to stroke and CVD were evaluated using multivariate adjusted Cox Regression models, and models were stratified by race and ethnicity to evaluate disparities. Results: NSES differed by race and ethnicity. Black, AIAN, and Latina groups were significantly (P&lt;0.01) more likely to live in neighborhoods with NSES Z-scores below the population mean (Z-score=0) compared with White and Asian groups. The mean NSES Z-score among Black participants was -5.21 standard deviations below the population mean. Thirty-year CVD and stroke incidence followed the same trajectory of racial disparities. Preliminary analysis suggests results from Cox regression models will identify lower NSES to be longitudinally associated with greater stroke and CVD incidence overall, and greater effect sizes among groups experiencing structural racism. Conclusion: This research evaluates racial disparities in NSES as a structural determinant of stroke and CVD. These findings provide evidence emphasizing the urgent need for neighborhood-level interventions to address CVD disparities that coalesce in marginalized communities.
Abstract MP76: Joint Associations of Physical Activity and Sedentary Behavior with Cardiovascular Disease Risk (Pooled Analysis of Six NHLBI Cohorts)
Authors: Francis Ryan Avenido, Zachary Pope, Christine Prissel, Nathan Mitchell, Mahesh Mathew, Pamela Schreiner, David Jacobs, Lin Yee Chen, Susan Heckbert, Elsayed Soliman, Donald Lloyd-Jones, Kelley Gabriel, David Siscovick, Bruce Psaty, Phyllis Stein, Mercedes Carnethon, Daniel Levy, Mark Pereira
Journal: Circulation (2025)

Introduction: Many studies report physical activity (PA) and sedentary behavior (SB) to be independently associated with lower and higher cardiovascular disease (CVD) risk, respectively. We evaluated a combined exposure of PA and SB in association with CVD risk. Methods: Data were gathered from 35,844 participants from six NHLBI cohorts: Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Heart Study, Jackson Heart Study, and the Multi-Ethnic Study of Atherosclerosis. We harmonized time-varying PA and SB into quintiles, considering the cumulative average over all timepoints prior to a first CVD event (fatal and non-fatal) or end of follow-up. We created a 6-level ‘PASB index’ based on combining the PA and SB quintiles. We performed Cox regression to examine the associations of PA and SB quintiles, and the PASB index with incident CVD risk. Covariates were age, sex, race/ethnicity, study center, education, smoking, alcohol use, and dietary quality. A random effects model was used for the pooled results. Results: Across cohorts, there were 10,913 CVD events. In pooled analyses, PA had a graded inverse association with CVD risk (HR=0.92 per quintile increment; 95% CI: 0.89, 0.95), and SB had a non-linear threshold association with CVD with the highest SB quintile having a greater risk relative to the lowest quintile (HR=1.13; 95% CI: 1.01, 1.26). Results for the six-level PASB index are shown in Figure 1, with the lowest HRs for those with low to moderate SB and either moderate or high PA. Conclusion: The combined behaviors of moderate to high PA and low SB were associated with the lowest risk for CVD. These findings support current public guidelines to engage in regular PA of at least moderate intensity and to avoid high levels of SB.