tbuckley/cabot-search huggingface dataset:
Early Childhood Food Insecurity and Cardiovascular Health in Young Adulthood
Authors: Emily L. Lam, Abigail M. Gauen, Namratha R. Kandula, Daniel A. Notterman, Noreen Goldman, Donald M. Lloyd-Jones, Norrina B. Allen, Nilay S. Shah
Journal: JAMA Cardiology (2025)

Importance Food insecurity is a social risk factor that may be associated with cardiovascular health across the life course. Objective To evaluate the association of food insecurity in early childhood with cardiovascular health (CVH) in young adulthood and whether associations are modified by participation during childhood in the Supplemental Nutrition Assistance Program (SNAP). Design, Setting, and Participants The Future of Families–Cardiovascular Health Among Young Adults cohort study was conducted in 20 US cities among 1071 individuals enrolled at birth (February 1998 to September 2000), evaluated in childhood (age, 3-5 years), and followed up to young adulthood (September 2021 to September 2023; mean [SD] participant age, 22.3 [0.7] years). Main Outcomes and Measures Household food insecurity (assessed by the US Department of Agriculture Food Insecurity survey) and SNAP participation at ages 3 to 5 years and CVH (assessed by the American Heart Association Life’s Essential 8 [LE8] score, component LE8 scores, and clinical CVH risk factors). Results Of the 1071 participants, 570 were female (53%), 422 (39%) lived in households with food insecurity, and 475 (44%) participated in SNAP. Early childhood food insecurity was associated with having a lower LE8 score in young adulthood (β, −2.2 [95% CI, −4.0 to −0.4]). Among component LE8 scores and clinical CVH risk factors, food insecurity was associated with a lower LE8 score for body mass index (BMI; β, −4.9 [95% CI, −9.6 to −0.3]) and higher odds of having a BMI of 30 or more (adjusted odds ratio, 1.40 [95% CI, 1.07-1.84]). Food insecurity was more strongly associated with a lower LE8 score among those whose households did not participate in SNAP (β, −4.9 [95% CI, −7.6 to −2.3]) compared with those whose households participated in SNAP (β, 1.0 [95% CI, −1.6 to 3.7]). Conclusions and Significance This study suggests that early childhood food insecurity is associated with a higher BMI in young adulthood, which is associated with a worse overall LE8 score, especially among children whose families did not participate in SNAP. Policies to promote food security among children may promote healthy BMIs and better CVH across the life course.
A New International Scheme for the Classification and Management of Clinical Outcomes Post-Gastric Peroral Endoscopic Myotomy
Authors: Yervant Ichkhanian, Marita Salame, John M Wo, Thomas V Nowak, Sarah Stainko, Akira Saito, Robert M Siwiec, Amr Kais, Joo Ha Hwang, Andrew A Li, Juliana Yang, Joseph R Broucek, Tuba Esfandyari, Stephanie Joseph, Michael B Ujiki, Ashley E Williams, Jacob Moremen, Zane Gouda, Alexander Schlachterman, Kristina Hugova, Jan Martinek, Calvin X Geng, Alexander Podboy, Andrew Y Wang, Michael Lajin, Lennon Gregor, Payton M Miller, Hashem Al Bunni, John M DeWitt, Mohammad Al-Haddad
Journal: Clinical Gastroenterology and Hepatology (2025)
Proactive Drug Monitoring versus Clinically-based Dosing for Endoscopic Healing in Pediatric Crohn’s Disease Receiving Infliximab
Authors: Ben Kang, Eun Sil Kim, Sujin Choi, Byung-Ho Choe, Jin Soo Moon, Jae Sung Ko, Sangjun Sohn, Yeoun Joo Lee, Yiyoung Kwon, Mi Jin Kim, Tae Yeon Jeon, So Mi Lee, Seunghyun Lee, Youngcheol Ju, Yon Ho Choe
Journal: Clinical Gastroenterology and Hepatology (2025)
Long-term Benefits of Resilience-Based Integrated Care: Reduced Unplanned Care, Opioid, and Steroid Use in the GRITT-IBD Study
Authors: Yenamala Reddy, Michelle Mendiolaza, Tina Siganporia, Anthony Biello, Ksenia Gorbenko, Laurie Keefer
Journal: Clinical Gastroenterology and Hepatology (2025)
Integrating Transcriptomic and Targeted New Approach Methodologies into a Tiered Framework for Chemical Bioactivity Screening
Authors: Jesse D. Rogers, Joseph L. Bundy, Joshua A. Harrill, Richard J. Judson, Katie Paul-Friedman, Logan J. Everett
Journal: Environmental Health Perspectives (2025)

With thousands of chemicals in commerce and the environment, rapid identification of potential hazards is a critical need. Combining broad molecular profiling with targeted in vitro assays, such as high-throughput transcriptomics (HTTr) and receptor screening assays, could improve identification of chemicals that perturb key molecular targets associated with adverse outcomes. We aimed to link transcriptomic readouts to individual molecular targets and integrate transcriptomic predictions with orthogonal receptor-level assays in a proof-of-concept framework for chemical hazard prioritization. Transcriptomic profiles generated via TempO-Seq in U-2 OS and HepaRG cell lines were used to develop signatures comprised of genes uniquely responsive to reference chemicals for distinct molecular targets. These signatures were applied to 75 reference and 1,126 non-reference chemicals screened via HTTr in both cell lines. Selective bioactivity towards each signature was determined by comparing potency estimates against the bulk of transcriptomic bioactivity for each chemical. Chemicals predicted by transcriptomics were confirmed for target bioactivity and selectivity using available orthogonal assay data from US EPA's ToxCast program. A subset of 37 selectively acting chemicals from HTTr that did not have sufficient orthogonal data were prospectively tested using one of five receptor-level assays. Of the 1,126 non-reference chemicals screened, 201 demonstrated selective bioactivity in at least one transcriptomic signature, and 57 were confirmed as selective nuclear receptor agonists. Chemicals bioactive for each signature were significantly associated with orthogonal assay bioactivity, and signature-based points-of-departure were equally or more sensitive than biological pathway altering concentrations in 95.4% of signature-prioritized chemicals. Prospective profiling found that 18 of 37 (49%) chemicals without prior orthogonal assay data were bioactive against the predicted receptor. Our work demonstrates that integrating transcriptomics with targeted orthogonal assays in a tiered framework can support Next Generation Risk Assessment by informing putative molecular targets and prioritizing chemicals for further testing. https://doi.org/10.1289/EHPXXXXX.
A Woman With Facial, Neck, and Chest Swelling During Dental Cleaning
Authors: Ali Bilal Ulas, Yener Aydin, Mehmet Zubeyr Egilmez
Journal: JAMA (2025)

A 37-year-old woman with no history of lung disease experienced sudden-onset tearing pain in her jaw several minutes into a routine air-powder dental polishing; chest radiography and computed tomography showed air located in the fascial planes of her neck and mediastinum. What is the diagnosis and what would you do next?
Psychiatric Prognosis Following Index Suicide Attempts in Early Adolescents
Authors: Tanner J. Bommersbach, Grace Johnson, Vanessa K. Pazdernik, J. Michael Bostwick, Alastair J. S. McKean
Journal: JAMA Psychiatry (2025)

Importance The rates of suicide and suicide attempts are rising precipitously among early adolescents aged 10 to 14 years in the US. While suicide attempts in this age group are more common and associated with lower lethality than in older age groups, very little is known about these individuals’ long-term social and psychiatric outcomes. Objectives To examine the adult outcomes of individuals making index suicide attempts that came to medical attention between the ages of 10 and 14 years. Design, Setting, and Participants This population-based cohort constitutes a subsample (n = 164) of a previously reported retrospective-prospective study examining individuals who made index suicide attempts during a 22-year period (1986-2007) in Olmsted County, Minnesota. Main Outcomes and Measures To collect outcome measures, the medical records of all individuals were queried until March 31, 2023, comprising up to 36 years of follow-up data after the index attempt. Measures included current social, psychiatric, and mortality outcomes as well as lifetime measures of psychiatric hospitalizations and repeat suicide attempts. K-means clustering generated adult groupings based on aggregates of psychiatric hospitalizations and repeat attempts. Multivariable logistic regression identified index attempt factors associated with poor adult outcomes. Results Of 164 individuals aged 10 to 14 years who made index attempts (128 [78.0%] female; mean [SD] age at index attempt, 13.7 [1.1] years), 3 (1.8%) died on the index attempt. In the follow-up period, no individuals died by suicide. K-means clustering generated a 2-group solution reflecting low (120 [80%]) and high (30 [20%]) rates of adult psychopathology. While a minority of the sample belonged to the high-rate group, characterized by multiple repeat attempts and hospitalizations, the majority had favorable social indicators and fewer reattempts and hospitalizations. Poor adult outcomes were associated with being male (odds ratio, 2.44; 95% CI, 1.00-5.80; P = .04) and having a psychiatric diagnosis prior to the index attempt (odds ratio, 3.27; 95% CI, 1.42-8.07; P = .007). Conclusions and Relevance In this sample of early adolescents with index suicide attempts followed into adulthood, all who died by suicide did so on the index attempt. While a small number of individuals went on to develop chronic severe psychopathology, the majority demonstrated little evidence of long-term impairment. Given this discrepancy, future studies should focus on using risk stratification after index attempts to direct postvention resources toward adolescents more susceptible to poor outcomes.
scPrediXcan integrates deep learning methods and single-cell data into a cell-type-specific transcriptome-wide association study framework
Authors: Yichao Zhou, Temidayo Adeluwa, Lisha Zhu, Sofia Salazar-Magaña, Sarah Sumner, Hyunki Kim, Saideep Gona, Festus Nyasimi, Rohit Kulkarni, Joseph E Powell, Ravi Madduri, Boxiang Liu, Mengjie Chen, Hae Kyung Im
Journal: Cell Genomics (2025)

Transcriptome-wide association studies (TWASs) help identify disease-causing genes but often fail to pinpoint disease mechanisms at the cellular level because of the limited sample sizes and sparsity of cell-type-specific expression data. Here, we propose scPrediXcan, which integrates state-of-the-art deep learning approaches that predict epigenetic features from DNA sequences with the canonical TWAS framework. Our prediction approach, ctPred, predicts cell-type-specific expression with high accuracy and captures complex gene-regulatory grammar that linear models overlook. Applied to type 2 diabetes (T2D) and systemic lupus erythematosus (SLE), scPrediXcan outperformed the canonical TWAS framework by identifying more candidate causal genes, explaining more genome-wide association study (GWAS) loci and providing insights into the cellular specificity of TWAS hits. Overall, our results demonstrate that scPrediXcan represents a significant advance, promising to deepen our understanding of the cellular mechanisms underlying complex diseases.
Providing Equitable Surgical Care to Patients in Law Enforcement Custody
Authors: Elinore J. Kaufman, Jesse E. Passman, Rucha Alur, Randi Smith, Anwar Osborne, Sara Scarlet, Kimberly Sue, Robert Wright, Rebecca Maine, Nephetari Smith, Nia Holston, Emily Zhu, Jessica H. Beard
Journal: JAMA Surgery (2025)

Importance Approximately 2 million individuals are incarcerated in the US. Surgical needs increase with age, and an aging prison population means an increasing need for surgical care for incarcerated individuals. Challenges in logistics, privacy, communication, and comorbidities put people in law enforcement custody at risk for suboptimal care and outcomes. Little guidance exists for surgeons seeking to provide equitable care for these patients. Observations No national statistics are available on the need for surgery among incarcerated people. Autopsy data suggest that nearly a quarter of deaths among incarcerated individuals were attributable to causes that could have been treated with surgery, yet few received surgical care before death. Across the spectrum of custody, including police detention, jail, prison, probation, and parole, access to consistent preoperative and postoperative care are major challenges, as is sustaining appropriate levels of privacy and communication. Incarcerated people are often accompanied by guards, preventing privacy. Patients are shackled to hospital beds, restricting mobility. For incarcerated individuals, access to postoperative medication may be curtailed when they return to jail or prison. To be effective advocates for patient-centered care and to achieve the best outcomes, surgeons must remain vigilant to specific barriers to care. Conclusions and Relevance Individuals in law enforcement custody have particular needs regarding communication, surgical planning, and perioperative and postoperative care. Clinicians must remain alert to these challenges and serve as advocates for these marginalized patients, even adjusting their care practices. Professional societies and health systems can bolster care for this marginalized population by developing and disseminating guidelines and pathways for patient-centered surgical care for individuals in law enforcement custody.
Long-Term Oncologic Outcome of Breast-Conserving Treatment in Patients With Breast Cancer With <i>BRCA </i>Variants
Authors: Janghee Lee, Jai Min Ryu, Hong Kyu Kim, Hyung Seok Park, Byeongju Kang, Sung Gwe Ahn, Min Sung Chung, Seon-Hi Shin, Junwon Go, Sanghwa Kim, Eun Young Kim, Young-Joon Kang, Sun Young Min, Moohyun Lee, Eunju Shin, Jisoo Shin, Sae Byul Lee, Chihwan David Cha
Journal: JAMA Network Open (2025)

Importance Patients with sporadic breast cancer have comparable prognoses after undergoing either breast-conserving treatment (BCT) or mastectomy. However, there are limited and inconsistent data on the assessment of oncologic outcomes between BCT and mastectomy in patients with pathogenic variants in BRCA1 or BRCA2 . Objective To investigate the outcomes of BCT on recurrence and survival in patients with breast cancer with BRCA1 or BRCA2 pathogenic variants. Design, Setting, and Participants This retrospective multicenter cohort study analyzed patients from 13 institutions in South Korea with primary breast cancer with BRCA1 or BRCA2 pathogenic variants who underwent either BCT or mastectomy from January 2008 through December 2015. The median (IQR) follow-up period was 8.3 (6.4-9.6) years. Data were analyzed from September 2023 to August 2024. Exposure BRCA1 or BRCA2 pathogenic variant and BCT. Main Outcomes and Measures Primary outcomes were logoregional recurrence–free survival, distant recurrence–free survival, and overall survival. Propensity score matching (PSM) using the greedy nearest neighbor method was performed to match covariates to minimize potential selection bias. Results A total of 575 female patients with BRCA1 or BRCA2 pathogenic variants were identified, all of whom were South Korean with a mean (SD) age of 42.0 (9.7) years. Among them, 367 patients (66.2%) received BCT and 186 (33.8%) were treated with mastectomy. BCT was not a factor associated with oncologic outcomes, including locoregional recurrence, compared with mastectomy. After adjusting for clinicopathologic characteristics through 1:1 PSM, there were still no statistically significant differences in oncologic outcomes between the BCT group and the mastectomy group. Multivariate analysis showed that the type of breast surgery was not significantly associated with oncologic outcomes. In subgroup analysis among matched patients based on BRCA1 or BRCA2 status, tumor size, lymph node metastasis, histologic grade, and subtype, BCT was also not a factor associated with risk for recurrence. Conclusions and Relevance The findings from this cohort study of patients with BRCA1 or BRCA2 pathogenic variants suggested that there were no significant differences in oncologic outcomes between patients who underwent BCT and those who underwent mastectomy. Therefore, breast conservation with close surveillance can be considered a viable treatment option for BRCA1 or BRCA2 pathogenic variant carriers. Further studies incorporating prospectively collected data are warranted to validate our findings.
Overweight or Obesity and Outcomes in Children With Acute Lymphoblastic Leukemia
Authors: Elena J. Ladas, Haiyang Sheng, Uma H. Athale, Barbara L. Asselin, Luis A. Clavell, Peter D. Cole, Yael Flamand, Jean-Marie Leclerc, Caroline Laverdiere, Bruno Michon, Stephen E. Sallan, Lewis B. Silverman, Jennifer J. G. Welch, Song Yao, Kara M. Kelly
Journal: JAMA Network Open (2025)

Importance There are conflicting data on the association of overweight or obesity with clinical outcomes in childhood acute lymphoblastic leukemia (ALL). The duration of exposure to overweight or obesity may be a better indicator of the risk of poorer outcomes. Objective To determine the association of the duration of overweight or obesity with treatment-related toxic effects, minimal residual disease, relapse, and survival in childhood ALL. Design, Setting, and Participants In this prospective cohort study, fluctuations in z scores of body mass index (BMI) for age from diagnosis to the end of treatment (EOT) were examined in 794 children registered on a Dana Farber Cancer Institute ALL Consortium protocol from May 31, 2005, to December 15, 2011. Height and weight were abstracted from the medical record for classification of BMI z scores at diagnosis through EOT and into survivorship. Data were analyzed from July 1 to 31, 2024. Main Outcomes and Measures The duration of overweight or obesity was defined as having overweight or obesity at 2 or more time points and compared with having overweight or obesity at no more than 1 time point. Kaplan-Meier survival curves were generated to examine association of overweight or obesity with overall survival (OS), event-free survival (EFS), and cumulative incidence of relapse. Results Among the 794 patients included in the analysis, the mean age at diagnosis was 6.7 (range, 1.0-17.9) years, with 441 (55.5%) being male, 136 (17.1%) Hispanic, and 553 (69.6%) non-Hispanic. The prevalence of overweight or obesity increased from 234 of 793 (29.5%) at diagnosis to 346 of 715 (48.4%) by EOT. Having overweight or obesity at baseline or developing overweight or obesity during induction was not associated with treatment-related toxic effects or higher minimal residual disease. Children with overweight or obesity at 2 or more time points experienced inferior OS (3-year OS, 93.8% vs 98.0%; P = .01), increased relapse (3-year relapse rate, 10.5% vs 5.8%; P = .02), and lower EFS (3-year EFS, 89.0% vs 93.7%; P = .02), compared with children with overweight or obesity at no more than 1 time point. Multivariable Cox proportional hazards regression models revealed an association between increased risk of death (hazard ratio [HR], 3.49; 95% CI, 1.28-9.51; P = .01) and relapse (HR, 1.92; 95% CI, 1.07-3.46; P = .03) among children with overweight or obesity at 2 or more time points. Conclusions and Relevance In this prospective cohort study of children with ALL, longer duration of overweight or obesity was associated with lower OS and EFS and higher rates of relapse, underscoring the need for interventions targeting overweight or obesity during treatment of children with ALL.
Tumor Suppressor Genes with Segmental Duplications are Prone to Somatic Deletions and Structural Variations
Authors: Ziheng Huang, Lin Zhang, Huarong Chen, Xiaodong Liu, Likai Tan, Dan Huang, Yingzhi Liu, Yushan Wang, Xinyi Zhang, Alfred Sze Lok. Cheng, Maggie Haitian. Wang, Wei Kang, Ka-Fai To, Jun Yu, Ho Ko, Le Yu, Sunny H. Wong, Tony Gin, Matthew Tak Vai. Chan, Xiansong Wang, William Ka Kei. Wu
Journal: Cancer Research (2025)

Abstract Segmental duplications (SDs) are blocks of genomic DNA with high sequence homology that are hotspots for chromosomal rearrangements, coinciding with copy-number and single-nucleotide variations in the population. SDs could represent unstable genomic regions that are susceptible to somatic alterations in human cancers. Here, we aimed to elucidate the genomic locations of SDs in relation to cancer-related genes and their propensity for somatic alterations in cancer. The analysis showed that tumor suppressor genes (TSGs) were less associated with SDs compared to non-cancer genes in nearly all mammalian species. TSGs with SDs were larger in size in humans but only modestly conserved among mammals. In humans, the proportion of non-cancer genes with SDs decreased as the gene age increased. However, for TSGs, a loss of association with SDs was apparent among young genes. Pan-cancer analysis revealed that TSGs with SDs were more prone to deletions and structural variations independently of gene size. Re-analysis of publicly available experimental data further revealed that genes with SDs tended to replicate late and were more likely to undergo the error-prone mitotic DNA synthesis upon replication stress. In conclusion, the loss of SDs from TSGs during mammalian evolution protects against tumor formation by reducing somatic alterations.
SMARCA4 loss increases RNA Polymerase II pausing and elevates R-loops to inhibit BRCA1-mediated repair in ovarian cancer
Authors: Xianbing Zhu, Zheng Fu, Giulio Aceto, Jonathan St-Germain, Kexin Liu, Azadeh Arabzadeh, Yuxuan Qi, Yibo Xue, Leora Witkowski, Elise Graulich, Jutta Steinberger, Selim Misirlioglu, Nicklas Bassani, Racim Sansal, Amber Yasmeen, Geneviève Morin, Jingjie Guo, Anie Monast, Virginie Pilon, Alica Valachová, Kitty Pavlakis, Lili Fu, Walter H. Gotlieb, W. Glenn McCluggage, David Huntsman, Alexander J. R. Bishop, Douglas A. Levine, Morag Park, Yemin Wang, Brian Raught, William D. Foulkes, Sidong Huang
Journal: Cancer Research (2025)

Abstract Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare, aggressive cancer affecting young women, driven by inactivating mutations in SMARCA4, a key SWI/SNF chromatin remodeling gene. To uncover its druggable vulnerabilities, we performed a compound screen and found that SCCOHT cells and tumors were sensitive to PARP inhibitors. Paradoxically, SCCOHT displayed BRCA-deficient traits despite retaining wild-type BRCA1 expression. Elevated R-loop in SCCOHT sequestered BRCA1, limiting its availability for DNA damage repair. Proximity-dependent biotin identification revealed that wild-type SMARCA4, but not its pathogenic variants, promoted RNA polymerase II (Pol II) elongation by mediating the assembly of the polymerase-associated factor 1 (PAF1) complex. Thus, SMARCA4 loss increased Pol II pausing, resulting in elevated R-loops and BRCA1 redistribution. The suppression of BRCA1 activity sensitized SMARCA4-deficient SCCOHT cells and tumors to PARP inhibitors, which was further enhanced by the addition of a CDK9 inhibitor targeting Pol II elongation. Co-targeting PARP/CDK9 also elicited synergistic effects against other undifferentiated ovarian cancer cells with SMARCA4 loss. These findings link SMARCA4 loss to perturbed Pol II elongation and compromised DNA repair by BRCA1, providing a therapeutic opportunity to target SCCOHT and other SWI/SNF-deficient ovarian cancers.