tbuckley/cabot-search huggingface dataset:
Statistical methods for chemical mixtures: a roadmap for practitioners using simulation studies and a sample data analysis in the PROTECT cohort
Authors: Wei Hao, Amber L. Cathey, Max M. Aung, Jonathan Boss, John D. Meeker, Bhramar Mukherjee
Journal: Environmental Health Perspectives (2025)

Quantitative characterization of the health impacts associated with exposure to chemical mixtures has received considerable attention in current environmental and epidemiological studies. With many existing statistical methods and emerging approaches, it is important for practitioners to understand which method is best suited for their inferential goals. The goal of this paper is to provide empirical simulation-based evidence regarding performance of mixture methods to help guide researchers on selecting the best available methods to address three scientific questions in mixtures analysis: identifying important components of a mixture, identifying interactions among mixture components and creating a summary score for risk stratification and prediction. We conduct a review and comparison of 11 analytical methods available for use in mixtures research, through extensive simulation studies for continuous and binary outcomes. In addition, we carry out an illustrative data analysis using the PROTECT birth cohort from Puerto Rico, to examine the associations between exposure to chemical mixtures-metals, polycyclic aromatic hydrocarbons (PAHs), phthalates and phenols-and birth outcomes. Our simulation results suggest that the choice of methods depends on the goal of analysis and there is no clear winner across the board. For selection of important toxicants in the mixtures and for identifying interactions, Elastic net by Zou et al. (Enet), Lasso for Hierarchical Interactions by Bien et al.(HierNet), Selection of nonlinear interactions by a forward stepwise algorithm by Narisetty et al. (SNIF) have the most stable performance across simulation settings. For overall summary or a cumulative measure, we find that using the Super Learner to combine multiple Environmental Risk Scores can lead to improved risk stratification and prediction properties. We develop an integrated R package "CompMix" that provides a platform for mixtures analysis where the practitioners can implement a pipeline that includes several approaches for mixtures analysis. Our study offers guidelines for selecting appropriate statistical methods for addressing specific scientific questions related to mixtures research. We identify critical gaps where new and better methods are needed. https://doi.org/10.1289/EHP15305.
A prospective exposome-based gene-environment interaction study on the effects of prenatal environmental exposure on fetal growth in the Shanghai Birth Cohort
Authors: Wen Jiang, Yun Huang, Hong Jin, Yuexin Gan, Qingli Zhang, Xiaoqing He, Ying Tian, Jun Zhang, None the Shanghai Birth Cohort
Journal: Environmental Health Perspectives (2025)

Both environmental exposure and type 2 diabetes (T2D) genetic susceptibility affect fetal growth. However, most previous studies used single exposure rather than an exposome strategy to explore the association between environmental factors and fetal growth, and the interactions of environmental exposures with maternal and fetal genes were often overlooked. To explore the associations between a broad range of prenatal environmental factors and fetal growth and further evaluate the effect modification of maternal and fetal T2D genetic susceptibility on the identified exposures. From 1,933 mother-neonate pairs from the Shanghai Birth Cohort, we estimated the associations between 70 prenatal exposure measures (including outdoor environment, residential environment, chemical exposures, lifestyle factors, and psychosocial status) and fetal growth, measured by birth-weight-for-gestational-age z-score (WAZ). Single-exposure analysis, elastic net regression, sparse partial least squares regression, extreme gradient boosting, and random forest were applied jointly to screen for WAZ-associated exposures. Multivariable linear regression models were used to assess the interactions of WAZ-associated exposures with maternal and fetal T2D polygenetic risk score (PRS). Sixteen prenatal exposures were associated with fetal growth, of which manganese, strontium, and residential greenspace showed a positive association while bisphenol A (BPA), 2,4-dihydroxy benzophenone (BP-1), ethyl 4-hydroxybenzoate (EtP), 4-hydroxybenzophenone (4-HBP), artificial light at night, noise, nitrogen dioxide, rubidium, thallium, silver, and humidity had a negative association. Temperature had an inverse U-shaped association with WAZ. The interactions of BPA and silver with maternal and fetal T2D PRS and rubidium with fetal T2D PRS were statistically significant, with more pronounced exposure effects in individuals with high T2D genetic risks. Our study identified several prenatal environmental exposures within the outdoor environment, phenols, and metal(loid)s that were associated with fetal growth. Mother-neonate pairs with high T2D genetic susceptibility were particularly vulnerable to the environmental insults. https://doi.org/10.1289/EHP15902.
From Niche to Norm: A Multi-Action Plan to Close Gaps and Mainstream Incremental Hemodialysis
Authors: Mariana Murea, Massimo Torreggiani, Javier Deira, Tammy L Sirich, Andrea K Viecelli, Enric Vilar, Miguel Á Suárez-Santisteban, John T Daugirdas, Ken Farrington, Kamyar Kalantar-Zadeh, Patrick Saudan, David A Jaques, Kristie L Foley, Ucheoma C Nwaozuru, Andrew Davenport, Elizabeth J Lindley, James Tattersall, Carlo Basile, Francesco G Casino, Giorgina B Piccoli
Journal: Kidney International (2025)
IKBKB gain of function: An inborn error with clinical heterogeneity progressing toward combined immunodeficiency
Authors: Julia Körholz, Samantha A M Tromp, Virgil A S H Dalm, Maaike de Bie, Godelieve J de Bree, Ester M M van Leeuwen, Pieter L A Fraaij, Machiel H Jansen, Iris H I M Hollink, Sietse Q Nagelkerke, Susanne Russ, Anne-Kathleen Scholze, Maarja Soomann, Ralf Wiedemuth, Jana Pachlopnik Schmid, Leif G Hanitsch, Catharina Schuetz, Taco W Kuijpers, Hanna IJspeert
Journal: Journal of Allergy and Clinical Immunology (2025)
In Vivo Assessment of iPSC-Cardiomyocyte Loaded Auxetic Cardiac Patches Following Chronic Myocardial Infarction
Authors: Olga Brazhkina, Jeong Hun Park, Milton Brown, Jelisha C Walcott, Jonghyeuk Han, Arianna Turchetti, Swarnima Roychowdhury, Ria Soni Prasad, Matthew J Kim, Ilanit Itzhaki, Kenneth J De Jesus Morales, Scott J Hollister, Michael E Davis
Journal: Biomaterials (2025)
Human Physiologic Responses to Insulin in Indigenous Americans Identify a Metabolic Susceptibility Profile Linked to Diabetes
Authors: Venkatesh L. Murthy, Paolo Piaggi, Phillip Lin, Shilin Zhao, Lindsey K. Stolze, Andrew S. Perry, Robert L. Hanson, John Jeffrey Carr, James G. Terry, Leslie J. Baier, Clifton Bogardus, Clary Clish, Eric R. Gamazon, Jonathan Krakoff, Ravi V. Shah
Journal: Diabetes Care (2025)

OBJECTIVE To identify metabolic signatures of insulin action/secretion in Indigenous Americans (IAs) and their association with diabetes. RESEARCH DESIGN AND METHODS We defined circulating metabolomic signatures of insulin action/secretion in 446 IAs, including glucose disposal rate during low-dose insulin clamp (Mlow) and endogenous glucose production (EGP) during insulin infusion (suppression of hepatic glucose production). We then determined associations of these metabolic scores with glucose tolerance (in a separate set of ∼700 IAs) and diabetes/metabolic risk in ∼2,000 individuals (from Coronary Artery Risk Development in Young Adults [CARDIA] study). We used tissue-specific gene–metabolite mapping to pinpoint genetic pathways of type 2 diabetes (T2D) implicated by metabolomic signatures. RESULTS In young IAs (mean age 29 years; mean BMI 34.9 kg/m2) without diabetes, phenotype–metabolome associations across multiple insulin action phenotypes were linked to mechanisms of fatty acid and amino acid metabolism and inflammation (among others). Metabolite-based scores of insulin action were strongly related to incident diabetes in our discovery IA population (Mlow; 49 metabolites; standardized hazard ratio [HR] 0.49; 95% CI 0.35–0.69; P &amp;lt; 0.0001) and also associated with measures of insulin resistance in a distinct IA population (|ρ| ∼0.3–0.5 correlation) and in the CARDIA group (median age 33 years). At ∼20 years of follow-up in CARDIA, we observed a strong BMI- and glucose-independent association of the metabolite profile of Mlow (HR 0.65; 95% CI 0.56–0.74; P &amp;lt; 0.0001) and EGP suppression (HR 0.66; 95% CI 0.57–0.76; P &amp;lt; 0.0001) with incident diabetes, directionally opposed to BMI and glucose. Genes implicated by the metabolomic signatures were strongly linked to T2D. CONCLUSIONS Metabolic signatures of clamp-determined insulin action are strongly associated with incident diabetes, suggesting causal–functional pathways of T2D.
Endometrial aging is accompanied by H3K27ac and PGR loss
Authors: Yue Wang, Ping Zhou, Hongying Shan, Xiyao Liu, Ming Cheng, Zhenhong Ye, Xiunan Chen, Baoying Liao, Tianliu Peng, Chenxi Xiao, Ziying Huang, Yunshu Dong, Yang Yu, Heng Pan, Rong Li
Journal: Nature Aging (2025)
Lu-177 DOTATATE Therapy in a Treatment Naive Metastatic NET Pineal Gland With Drop Metastasis to Spinal Cord: A Great Leap Forward in Oncology
Authors: Srinivas Ananth Kumar, Madhur Kumar Srivastava, Megha S. Uppin
Journal: Clinical Nuclear Medicine (2025)

Neuroendocrine tumors (NETs) are a heterogeneous group of tumors, which are usually indolent with metastatic disease at the initial presentation in most clinical situations. Intramedullary spinal cord metastasis (ICSM) is usually rare in the case of neuroendocrine tumors. Peptide receptor radionuclide therapy (PRRT) with Lu-177 DOTATATE has been in use for treatment of metastatic NETs for a long time. Here, the authors present favorable response to PRRT in a treatment-naive patient with metastatic NET of the pineal gland with brain and spinal cord metastases.
Exposure Therapy in Mixed Reality for Obsessive-Compulsive Disorder
Authors: Franziska Miegel, Lena Jelinek, Luzie Lohse, Steffen Moritz, Jannik Blömer, Kim Juckoff, Amir Yassari, Lara Rolvien
Journal: JAMA Network Open (2025)

Importance Exposure therapy in virtual reality (VR) is well established for anxiety disorders. While early studies show promise for VR-based exposure and response prevention (ERP) in obsessive-compulsive disorder (OCD), a key challenge of traditional VR is the weak sense of presence, deemed crucial for effectiveness. Objective To evaluate the feasibility and efficacy of ERP in mixed reality (MERP). Design, Setting, and Participants This randomized clinical trial (RCT) included 2 outpatient treatment groups, MERP vs self-guided ERP (SERP) from March 15, 2022, to October 26, 2024. Participants were required to be 18 to 80 years of age and have contamination-related OCD (C-OCD). Exclusion criteria consisted of schizophrenia or bipolar disorder, severe substance use disorder, acute suicidality, and ongoing inpatient treatment. Patients’ symptom severity was assessed by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) before (baseline) and after the 6-week intervention period as well as 3 months after posttreatment (follow-up). Intervention Six sessions of MERP or SERP. Main Outcomes and Measures Main outcome was the severity of OCD symptoms in the past 7 days on the Y-BOCS. Sense of presence and subjective appraisal were the secondary outcomes. Results Thirty-six participants fulfilled inclusion criteria. Twenty-four participants (66.7%) were female; mean (SD) age was 35.42 (14.03) years. Both groups had severe OCD symptoms, with major depressive disorder as the most common comorbidity (23 [63.9%]). Twenty-nine participants (80.6%) completed the postintervention and follow-up assessments. At baseline, patients in the MERP group had a mean (SD) Y-BOCS score of 26.94 (5.83), while the SERP group had a mean (SD) score of 24.22 (4.12). The decline in patients’ OCD symptoms (Y-BOCS) was similar in the MERP (mean difference, 3.15) and the SERP groups (mean difference, 1.47) (η p 2 = 0.002; 95% CI, –3.187 to 3.893). Significant improvements were observed within the MERP group from baseline to post treatment across several psychopathological variables, including OCD symptoms, with a medium to large effect (Cohen d , 0.584-0.931; 95% CI, 0.026-1.551). Sense of presence was moderate (mean [SD], ≤3.24 [≤2.07]). Subjective appraisal was heterogeneous. Conclusions This RCT on MERP in C-OCD provided important insights. While there were no significant between-group differences, changes in psychopathology within the MERP group suggest some level of effectiveness. However, the limited impact indicates that the full potential of MERP has not yet been realized, and future research should aim to improve immersion and overall effectiveness. Trial Registration German Clinical Trial Registry: DRKS00020969
99mTc-FAPI-46 Scintigraphy in Recurrence of Low-Grade Myofibroblastic Sarcoma
Authors: Nasrin Raeisi, Amin Saber Tanha, Kamran Aryana, Ehsan Soltani, Somaye Barashki
Journal: Clinical Nuclear Medicine (2025)

Low-grade myofibroblastic sarcoma (LGMFS) is a rare mesenchymal tumor, infrequently found in the abdominal cavity, where it may exhibit more aggressive behavior. This case report presents a 15-year-old boy with LGMFS manifesting as a large abdominal mass. Following neoadjuvant therapy and surgical resection, recurrence was detected via follow-up imaging. We employed 99m Tc-FAPI-46 scintigraphy, representing its first reported application in LGMFS. The FAPI scintigraphy exhibited uptake in all tumoral lesions identified on contrast-enhanced CT scan, underscoring the potential of FAPI in the evaluation of this rare entity.
The impacts of the <i>Dobbs</i> ruling on US cancer care delivery
Authors: Margaret Katana Ogongo, Nicole Huberfeld, Karen Basen Engquist, Julie R Gralow, Farhad Islami, Beth Y Karlan, K Robin Yabroff
Journal: JNCI Journal of the National Cancer Institute (2025)

Abstract The US Supreme Court’s ruling on Dobbs v Jackson Women’s Health Organization (Dobbs) in 2022 eliminated federal constitutional protection for abortion access. Dobbs has clinical and practical implications throughout the cancer control continuum. In abortion access-restrictive states, providers and patients with cancer who are pregnant will need to consider less efficacious cancer treatments, criminal or civil penalties for providers, and/or travel to abortion access-protective states. Provider shortages as well as closures of clinics that offer abortion services and cancer screening will likely contribute to screening declines. Limited access to and delays in reproductive health-care services, including fertility preservation, will likely widen existing gaps in cancer care and outcomes, disproportionately affecting marginalized populations and further perpetuating health inequities. In 2023, the National Cancer Policy Forum of the National Academies of Sciences, Engineering, and Medicine conducted a webinar series to examine the implications of Dobbs on cancer care delivery. This commentary summarizes presentations and discussions related to (1) cancer treatment in pregnant persons and all people of reproductive age, (2) the cancer care workforce and care delivery, and (3) access to fertility preservation. Where relevant, we discuss how abortion restrictions affect patients with cancer and cancer care delivery; describe how Dobbs affects the health system and workforce; and discuss the ethical, legal, and social implications of overturning Roe v Wade. We also make recommendations for patients, health-care workforce, cancer centers, payers, professional societies, and data and for mitigating the impact of the evolving patchwork of state laws and restrictions for cancer care and outcomes.
A randomized controlled trial of a digital lifestyle intervention involving postoperative patients with colorectal cancer
Authors: Young Il Kim, In Ja Park, Jun-Soo Ro, Jong Lyul Lee, Chan Wook Kim, Yong Sik Yoon, Seok-Byung Lim, Chang Sik Yu, Yura Lee, Yae Won Tak, Seockhoon Chung, Kyung Won Kim, Yousun Ko, Sung-Cheol Yun, Min-Woo Jo, Jong Won Lee
Journal: npj Digital Medicine (2025)
Ga-68-DOTATOC PET/CT Reveals Meningeal Metastasized Uveal Melanoma
Authors: Ferdinand Ndum, Martin Freesmeyer, Philipp Seifert, Falk Gühne
Journal: Clinical Nuclear Medicine (2025)

Upon suspicion of meningioma, a Ga-68-DOTATOC PET/CT was performed to further investigate newly detected cerebral MRI findings. Imaging showed relevant uptake in the right eye, as well as multiple intracranial and extracranial lesions. A uveal melanoma had been treated curatively 2 years prior. Histologic examination of present findings confirmed melanoma metastasis. The PET/CT results were, therefore, consistent with melanoma recurrence and advanced metastatic disease instead of meningioma. PET imaging with 68 Ga-labelled somatostatin receptor analogs can be a useful tool and alternative for staging uveal melanoma, especially regarding cranial findings, which are often undetectable in F-18-FDG-PET/CT.
Postdischarge Alcohol Cessation and Psychiatric Referrals in Alcoholic Liver Disease
Authors: Shu-Yen Chan, Yee Hui Yeo, Hyunseok Kim, Natchaya Polpichai, Yueh-Ting Tsai, Peng-Sheng Ting
Journal: JAMA Network Open (2025)

This cohort study evaluates nationwide trends of postdischarge alcohol relapse prevention treatment for hospitalized individuals.
18F-FDG PET/CT in a Giant Cell Tumor of Bone Masquerading as a Retroperitoneal Soft Tissue Sarcoma
Authors: Yamini Dharmashaktu, Shamim A. Shamim, Sameer Rastogi, Ritwik Wakankar, Adarsh Barwad
Journal: Clinical Nuclear Medicine (2025)

Giant cell tumor of bone (GCTB) is a rare, benign but locally aggressive neoplasm that typically arises in the epiphysis of long bones. GCTB occurrence in the axial skeleton is less common. Due to its variable radiological appearance and unusual location, GCTB can be misdiagnosed as a soft tissue or retroperitoneal mass, leading to delays in diagnosis and inappropriate treatment. We present the case of a 36-year-old woman who was misdiagnosed as a case of spinal tuberculosis and was started on ATT. Initial imaging, including ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), revealed a large, retroperitoneal mass involving the L2 vertebral body, raising suspicion of a malignant soft tissue tumor. Further evaluation with 18 F-FDG PET/CT suggested a retroperitoneal metabolically active lesion, reinforcing the need for histopathological confirmation.
Safety and Efficacy of Peptide Receptor Radionuclide Therapy in Multiple Endocrine Neoplasia Syndrome: A Single-center Experience
Authors: Piyush Aggarwal, Swayamjeet Satapathy, Gurjeet Kaur, Ashwani Sood, Sanjay Kumar Bhadada, Rama Walia, Rajesh Gupta, Bhagwant Rai Mittal
Journal: Clinical Nuclear Medicine (2025)

Purpose: Peptide receptor radionuclide therapy (PRRT) is recommended and approved in advanced neuroendocrine tumors (NETs). There is a lack of data on the utility of PRRT in multiple endocrine neoplasia (MEN) syndrome. This study explores the utility of PRRT in MEN syndrome patients with inoperable/metastatic NETs. Methods: A single-center retrospective analysis of MEN syndrome patients with advanced NETs referred for PRRT was done. Upto 4 cycles of 177 Lu-DOTATATE (5.5–7.4 GBq/cycle) were administered every 8–12 weeks. Treatment-related adverse events were assessed using CTCAE v5. The best response to PRRT was evaluated using RECIST 1.1. Follow-up was done to calculate the progression-free survival (PFS) and overall survival (OS). Results: The data of 15 patients with a median age of 36 years (IQR: 32–49) was analyzed. Fourteen patients had MEN-1 syndrome, and 1 had MEN-2 syndrome. Thirteen patients with MEN-1 syndrome had gastroenteropancreatic (GEP) NET, with the multifocal primary as the most common finding (n=7). One patient had thymic carcinoid. All patients had hyperparathyroidism, while 6 had pituitary adenoma. Fifty-three cycles of 177 Lu-DOTATATE (range: 1–4) were administered with a median cumulative activity of 27.8 GBq. Twelve patients (80%) showed grade 1/2 adverse events, with leukopenia being the most common. Six patients achieved partial response (43% ORR), 6 showed stable disease (86% DCR), 2 (14%) showed disease progression during PRRT, while 1 patient was lost to follow-up. The median PFS was 32.6 months (95% CI: 14.7–not reached) with an estimated 1- and 5-year PFS rate of 86.2% (95% CI: 68–100) and 46.3% (95% CI: 13–80), and estimated 5-year OS rate of 76.2% (95% CI: 52.1–100). Conclusion: 177 Lu-DOTATATE is a safe and effective treatment option for advanced NETs in MEN syndrome. However, large-sized multicentric prospective studies are required.
Substance Use Screening, Brief Intervention, and Referral to Treatment Among Youth-Serving Clinicians
Authors: Kathleen Ragan-Burnett, Lyna Schieber, Andrew Terranella, Christina Mikosz
Journal: JAMA Network Open (2025)

Importance Despite decreasing substance use by adolescents in recent years, overdose rates continue to rise. Morbidity and mortality from substance use is preventable if detected; however, screening practices among youth-serving clinicians are unknown. Objective To describe youth-serving clinicians’ screening, brief intervention, and referral to treatment practices for substance use disorders (SUDs) among adolescents. Design, Setting, and Participants This cross-sectional study used DocStyles data from September 5 to October 12, 2023, on clinical practice settings in the US. Responding clinicians included family physicians, internal medicine physicians, pediatricians, nurse practitioners, and physician assistants. Exposure Delivery of services to youths aged 17 years or younger. Main Outcomes and Measures Screening, brief intervention, and referral to treatment practices, including screening frequency and type of screening tool used, and screening at every well visit using a screening tool were assessed using descriptive statistics and multivariable logistic regression. Results Of 1047 youth-serving clinicians (mean [SD] age, 45.3 [11.4] years; 555 male [53.0%]), 467 (44.6%) were family physicians, 250 (23.9%) were pediatricians, 132 (12.6%) were internal medicine physicians, 107 (10.2%) were nurse practitioners, and 91 (8.7%) were physician assistants (survey response rate, 57%). Median years in practice was 13 (IQR, 7-23 years). Most clinicians (634 [60.6%]) reported that skills in SUD diagnosis were relevant to their practice, and 800 (76.4%) reported seeing at least 1 adolescent with an SUD monthly. A majority of clinicians (596 [56.9%]) reported screening for SUDs at every well visit, with a high proportion of pediatricians reporting screening at every well visit (173 of 250 [69.2%]). Clinicians who screened at every well visit were more likely to use a screening tool (odds ratio, 1.87 [95% CI, 1.44-2.44]). Only 411 clinicians (39.3%) reported screening at every well visit using a screening tool; 321 clinicians (30.7%) offered all components of screening, brief intervention, and referral to treatment practice. Clinicians who reported seeing 5 or more adolescents with an SUD per month had a higher odds of screening with a standardized tool at every annual well visit (adjusted odds ratio, 2.19 [95% CI, 1.30-3.71]). Conclusions and Relevance These findings suggest that while most clinicians report screening youths for SUDs at least sometimes, a substantial proportion screened only intermittently. Efforts to improve screening rates through education and systems-based practice changes may facilitate offering anticipatory guidance and SUD treatment in all youth-serving clinical settings.