tbuckley/cabot-search huggingface dataset:
Regulatory T cell depletion promotes myeloid cell activation and glioblastoma response to anti-PD1 and tumor-targeting antibodies
Authors: Felipe Galvez-Cancino, Mariela Navarrete, Gordon Beattie, Simone Puccio, Enrique Conde-Gallastegi, Kane Foster, Yasmin Morris, Teerapon Sahwangarrom, Despoina Karagianni, Jiali Liu, Alvin J X Lee, Dimitrios A Garyfallos, Alexander P Simpson, Gerasimos-Theodoros Mastrokalos, Francesco Nannini, Cristobal Costoya, Varshaa Anantharam, Beatrice Claudia Cianciotti, Leanne Bradley, Claudia Garcia-Diaz, Melanie Clements, Aditya Shroff, Fatemeh Vahid Dastjerdi, Enrique Miranda Rota, Shahida Sheraz, Robert Bentham, Imran Uddin, Henning Walczak, Alvaro Lladser, James L Reading, Kerry A Chester, Martin A Pule, Paul M Brennan, Samuel Marguerat, Simona Parrinello, Karl S Peggs, Nicholas McGranahan, Enrico Lugli, Kevin Litchfield, Steven M Pollard, Sergio A Quezada
Journal: Immunity (2025)

Glioblastoma is invariably lethal and responds poorly to immune checkpoint blockade. Here, we examined the impact of regulatory T (Treg) cell depletion on glioblastoma progression and immunotherapy responsiveness. In human glioblastoma, elevated Treg cell signatures correlated with poorer survival outcomes, with these cells expressing high levels of CD25. In Nf1-/-Pten-/-EGFRvIII+ glioblastoma-bearing mice, a single dose of non-interleukin-2 (IL-2) blocking (NIB) anti-CD25 (anti-CD25NIB) antibody depleted Treg cells and promoted CD8+ T cell clonal expansion and partial tumor control, further enhanced by programmed cell death-1 (PD1)-blockade. Treg cell depletion induced interferon-γ (IFN-γ)-dependent tumor microenvironment remodeling, increasing Fcγ receptor (FcγR) expression on intratumoral myeloid cells and enhancing phagocytosis. Combination of anti-CD25NIB with anti-EGFRvIII tumor-targeting antibodies resulted in complete tumor control. Anti-human CD25NIB treatment of glioblastoma patient-derived tumor fragments effectively depleted Treg cells and activated CD8+ T cells. These findings underscore the therapeutic relevance of Treg targeting in glioblastoma and unveil potent combination strategies for anti-CD25NIB based on innate cell activation.
The gut microbiota promotes pain in fibromyalgia
Authors: Weihua Cai, May Haddad, Rana Haddad, Inbar Kesten, Tseela Hoffman, Reut Laan, Susan Westfall, Manon Defaye, Nasser S Abdullah, Calvin Wong, Nicole Brown, Shannon Tansley, Kevin C Lister, Mehdi Hooshmandi, Feng Wang, Louis-Etienne Lorenzo, Volodya Hovhannisyan, David Ho-Tieng, Vibhu Kumar, Behrang Sharif, Bavanitha Thurairajah, Jonathan Fan, Tali Sahar, Charlotte Clayton, Neil Wu, Ji Zhang, Haggai Bar-Yoseph, Milena Pitashny, Emerson Krock, Jeffrey S Mogil, Masha Prager-Khoutorsky, Philippe Séguéla, Christophe Altier, Irah L King, Yves De Koninck, Nicholas J B Brereton, Emmanuel Gonzalez, Yoram Shir, Amir Minerbi, Arkady Khoutorsky
Journal: Neuron (2025)

Fibromyalgia is a prevalent syndrome characterized by widespread pain in the absence of evident tissue injury or pathology, making it one of the most mysterious chronic pain conditions. The composition of the gut microbiota in individuals with fibromyalgia differs from that of healthy controls, but its functional role in the syndrome is unknown. Here, we show that fecal microbiota transplantation from fibromyalgia patients, but not from healthy controls, into germ-free mice induces pain and numerous molecular phenotypes that parallel known changes in fibromyalgia patients, including immune activation and metabolomic profile alterations. Replacing the fibromyalgia microbiota with a healthy microbiota substantially alleviated pain in mice. An open-label trial in women with fibromyalgia (Registry MOH_2021-11-04_010374) showed that transplantation of a healthy microbiota is associated with reduced pain and improved quality of life. We conclude that altered gut microbiota has a role in fibromyalgia pain, highlighting it as a promising target for therapeutic interventions.
Where is my mind? A neurocognitive investigation of mind blanking
Authors: Thomas Andrillon, Antoine Lutz, Jennifer Windt, Athena Demertzi
Journal: Trends in Cognitive Sciences (2025)

During wakefulness, our thoughts transition between different contents. However, there are moments that are seemingly devoid of reportable content, referred to as mind blanking (MB). It remains unclear what these blanks represent, highlighting the definitional and phenomenological ambiguities surrounding MB. We map out MB in terms of its reportable expressions, neurophysiology, and relationship to adjacent phenomenology, including meditative practices and sleep. We propose a mechanistic account linking MB to changes at the physiological, neural, and cognitive levels. We suggest that ongoing experiences are characterized by degrees of richness, and that contentless events represent distinct mental states with their own diversity. We encourage future research to acknowledge MB as a reportable mental category, leading to a comprehensive understanding of ongoing experience.
Race, Ethnicity, and Outcomes Among Adults With Atrial Fibrillation Treated With Drug Therapy vs Ablation
Authors: Larry R. Jackson, Rahul Khanna, Sonia Maccioni, Dongyu Zhang, Kevin L. Thomas
Journal: JAMA Network Open (2025)

This comparative effectiveness study evaluates effectiveness and safety outcomes associated with antiarrhythmic drug therapy compared with catheter ablation for Black, Hispanic, and White adults with atrial fibrillation.
Dwell Time and Risk of Bloodstream Infection With Peripheral Intravenous Catheters
Authors: Marie-Céline Zanella, Gaud Catho, Holly Jackson, Nasim Lotfinejad, Valérie Sauvan, Marie-Noëlle Chraiti, Walter Zingg, Stephan Harbarth, Niccolò Buetti
Journal: JAMA Network Open (2025)

Importance Bloodstream infections (BSIs) associated with peripheral intravenous catheters (PIVCs) are rare but preventable adverse events. The association of dwell time with the risk of BSIs with PIVCs remains controversial. Objective To analyze the risk of BSIs during PIVC maintenance therapy. Design, Setting, and Participants In this observational cohort study, all patients hospitalized at Geneva University Hospitals with at least 1 PIVC insertion on the upper extremity (N = 371 061) between January 1, 2016, and February 29, 2020, were evaluated. Statistical analysis was performed from January 2023 to January 2025. Exposure At least 1 PIVC insertion on the upper extremity. Main Outcomes and Measures The primary outcome was BSIs with PIVCs; data were collected by prospective BSI surveillance. The daily risk of BSIs with PIVCs was analyzed using the hazard rate function by kernel-based methods. Multivariable logistic models were performed to evaluate the risk of BSIs with PIVCs comparing different cutoff values of dwell times (&amp;amp;gt;3 vs ≤3 days, &amp;amp;gt;4 vs ≤4 days, &amp;amp;gt;5 vs ≤5 days, and &amp;amp;gt;6 vs ≤6 days). Results A total of 371 061 PIVCs (median patient age, 63 years [IQR, 41-79 years]; 187 786 women [51%]) with documented catheter duration were included. A total of 140 178 PIVCs (38%) had a dwell time of 1 to 2 days, 119 252 (32%) had a dwell time of 3 to 4 days, and 111 631 (30%) had a dwell time of more than 4 days. The instantaneous risk of BSIs with PIVCs was low in the first 2 days of dwell time and increased rapidly thereafter. The risk of BSIs was significantly increased after 3 days of catheter maintenance (adjusted odds ratio [AOR], 13.55; 95% CI, 5.44-34.00). This risk was the highest after 3 days and remained increased thereafter (&amp;amp;gt;4 days: AOR, 8.53; 95% CI, 4.47-16.28; &amp;amp;gt;5 days: AOR, 5.38; 95% CI, 3.23-8.96; and &amp;amp;gt;6 days: AOR, 7.63; 95% CI, 4.57-12.74). Conclusions and Relevance In this cohort study of 371 061 PIVCs, dwell time was associated with the development of BSIs with PIVCs. After day 3, PIVC indication should be reviewed and PIVC replacement considered.
Cooking methods affect advanced glycation end products and lipid profiles: A randomized cross-over study in healthy subjects
Authors: Judith Wellens, Eva Vissers, Anaïs Dumoulin, Sien Hoekx, Julie Vanderstappen, Joke Verbeke, Roman Vangoitsenhoven, Muriel Derrien, Bram Verstockt, Marc Ferrante, Christophe Matthys, Jeroen Raes, Kristin Verbeke, Séverine Vermeire, João Sabino
Journal: Cell Reports Medicine (2025)

Thermal treatments used in ultra-processed foods (UPFs) lead to advanced glycation end products (AGEs). UPFs and serum AGEs are associated with cardiometabolic disease. We explore differential cooking methods as a mechanistic link between UPFs and detrimental health outcomes through a randomized cross-over cooking method trial in healthy subjects using identical ingredients and a deep profiling analysis. We show that low-AGE-generating cooking methods such as boiling and steaming decrease serum AGEs, improve lipid profiles, and increase serum protein 4E-BP1. In contrast, high-AGE-generating cooking methods such as grilling and baking increase fecal butyrate. In sum, this suggests that low-AGE-generating cooking methods should be considered in cardiovascular risk prevention. Since current dietary guidelines focus on ingredients, but not cooking methods, our results suggest that culinary techniques should be considered as an important factor in cardiometabolic preventive strategies and future dietary trial design. This study was registered at ClinicalTrials.gov (NCT06547190).
Intravenous Magnesium and Cisplatin-Associated Acute Kidney Injury
Authors: Shruti Gupta, Ilya G. Glezerman, Jamie S. Hirsch, Api Chewcharat, Sophia L. Wells, Jessica L. Ortega, Marta Pirovano, Raphael Kim, Kevin L. Chen, Kenar D. Jhaveri, Valda D. Page, Matthew H. Abramson, Anip Bansal, Avisek Ghimire, Melanie S. Joy, Ala Abudayyeh, David E. Leaf
Journal: JAMA Oncology (2025)

Importance Cisplatin-associated acute kidney injury (CP-AKI) is a frequent complication of cisplatin chemotherapy and is associated with considerable morbidity and mortality. Prophylactic administration of intravenous (IV) magnesium attenuates CP-AKI in animal models; however, its association with CP-AKI in humans has not been rigorously evaluated. Objective To evaluate the association of prophylactic IV magnesium administration with CP-AKI in patients with cancer undergoing cisplatin chemotherapy. Design, Settings, and Participants This multicenter study was conducted at 5 major cancer centers across the US and included adult patients with cancer who were treated with a first dose of IV cisplatin between 2006 to 2022. Data analyses were performed from February to December 2024. Exposure IV magnesium vs no IV magnesium receipt on the first day of cisplatin treatment. Main Outcomes and Measures Composite outcome of CP-AKI or death, with CP-AKI defined as a 2-fold or greater increase in serum creatinine levels from baseline or receipt of kidney replacement therapy within 14 days after first dose of IV cisplatin. Secondary outcomes were CP-AKI or death, defined using alternative definitions, as well as major adverse kidney events at 90 days. Inverse probability treatment weighting was used to estimate the association between IV magnesium receipt and CP-AKI. Models were adjusted for demographics, comorbidities, laboratory values, receipt of concurrent nephrotoxic anticancer therapies, site, year of cisplatin administration, and cisplatin dose. Results A total of 13 719 patients were included (median [IQR] age, 59 [49-67] years; 7817 male [57%]), of whom 3893 (28.4%) received IV magnesium on the first day of cisplatin chemotherapy. The median (IQR) dose of IV magnesium was 2 (1-2) g. CP-AKI or death occurred in 104 of 3893 patients (2.7%) who received IV magnesium, and in 520 of 9826 (5.3%) who did not (adjusted odds ratio, 0.80; 95% CI, 0.66-0.97). Results were similar across a number of sensitivity analyses and secondary outcomes, including major adverse kidney events at 90 days. Conclusions and Relevance This multicenter cohort study found that patients with cancer who received prophylactic IV magnesium before initiating treatment with IV cisplatin had a lower risk of CP-AKI compared to those who did not receive magnesium. Randomized clinical trials are needed to confirm these findings.
Health Care Cost Concerns and Hardships for Families of Children With Disabilities
Authors: Amy J. Houtrow, Chloe S. Shearer, Gina McKernan, Karen Kuhlthau, Rishi Agrawal
Journal: JAMA Network Open (2025)

This survey study uses data from the 2019-2022 National Health Interview Survey to estimate heath care–related financial hardships experienced by families of children with disabilities.
Patient-Centered Research Through Artificial Intelligence to Identify Priorities in Cancer Care
Authors: Jiyeong Kim, Michael L. Chen, Shawheen J. Rezaei, Mariana Ramirez-Posada, Jennifer L. Caswell-Jin, Allison W. Kurian, Fauzia Riaz, Kavita Y. Sarin, Jean Y. Tang, Steven M. Asch, Eleni Linos
Journal: JAMA Oncology (2025)

Importance Patient-centered research is essential for bridging the gap between research and patient care, yet patient perspectives are often inadequately represented in health research. Objective To leverage artificial intelligence (AI) and natural language processing (NLP) to analyze a large dataset of patient messages, defining patient concerns and generating relevant research topics, and to quantify the quality of these AI-generated topics. Design, Setting, and Participants This case series was conducted using an automated framework involving a 2-staged unsupervised NLP topic model and AI-generated research topic suggestions. The study was based on deidentified patient portal message data from individuals with breast or skin cancer at Stanford Health Care and 22 affiliated centers over July 2013 to April 2024. Exposures A widely used large language model (ChatGPT-4o [OpenAI]; April 2024) was used and guided through multiple prompt-engineering strategies to perform multilevel tasks, including knowledge interpretation and summarization (eg, interpreting and summarizing the NLP-defined topics), knowledge generation (eg, generating research ideas corresponding to patients’ issues), self-reflection and correction (eg, ensuring and revising the research ideas after searching for scientific articles), and self-reassurance (eg, confirming and finalizing the research ideas). Main Outcomes and Measures Three breast oncologists (J.L.C., A.W.K., F.R) and 3 dermatologists (K.Y.S, J.Y.T., E.L.) evaluated the meaningfulness and novelty of the AI-generated research topics using a 5-point Likert scale (1 representing exceptional to 5 representing poor). Mean (SD) scores for meaningfulness and novelty were computed for each topic. Results A total of 614 464 patient messages were analyzed from 25 549 individuals, 10 665 with breast cancer (98.6% female) and 14 884 had skin cancer (49.0% female). The overall mean (SD) scores for meaningfulness and novelty were 3.00 (0.50) and 3.29 (0.74), respectively, for breast cancer topics and 2.67 (0.45) and 3.09 (0.68), respectively, for skin cancer topics. One-third of the AI-suggested research topics were highly meaningful and novel when both scores were lower than the average (5 of 15 for breast cancer and 6 of 15 for skin cancer). Notably, two-thirds of the AI-suggested topics were novel (10 of 15 for breast cancer and 11 of 15 for skin cancer). Conclusions and Relevance This case series demonstrates that AI/NLP-driven analysis of large volumes of patient messages can generate quality research topics in cancer care that reflect patient perspectives, providing valuable guidance for future patient-centered health research endeavors.
Trends in Mental Health Diagnoses Among Publicly Insured Children
Authors: Janet R. Cummings, Xin Hu, Jordan Marchak, Cristian Ramos, Ilana Graetz, Xu Ji
Journal: JAMA (2025)

Importance Children living in poverty are at increased risk of mental health and neurodevelopmental disorders. Little is known about the trends in diagnoses of these disorders among children enrolled in public insurance programs, such as Medicaid, which insure more than 1 in 3 US children. Objective To provide comprehensive, multistate estimates of changes in the percentage of publicly insured children with mental health and/or neurodevelopmental disorder diagnoses. Design, Setting, and Participants This serial, cross-sectional study used administrative claims data from 22 states to test trends from 2010 to 2019 in the percentage of publicly insured children aged 3 to 17 years with mental health or neurodevelopmental disorder diagnoses. Regression models included a dummy variable for each year, controlled for child demographics, county-level metropolitan status, median household income, and US Census region. Adjusted risk differences were estimated, with standard errors clustered at the state level. Exposure Calendar year. Main Outcomes Any mental health or neurodevelopmental disorder diagnosis in the calendar year, and any diagnosis in 1 of 13 specific diagnostic categories. Results A total of 129 306 637 child-year observations (29 925 633 unique publicly insured children) were included. The percentage of publicly insured children with any diagnosed mental health or neurodevelopmental disorder increased from 10.7% in 2010 to 16.5% in 2019; this change remained significant after adjustment for covariates (adjusted risk difference [aRD], 6.7 percentage points [95% CI, 5.0-8.4]). Statistically significant increases were also observed in 9 of the 13 diagnostic categories examined. The largest absolute increases were observed for attention-deficit/hyperactivity disorder (aRD, 2.3 percentage points [95% CI, 1.4-3.3]), trauma- and stressor-related disorders (aRD, 1.7 percentage points [95% CI, 0.9-2.5]), anxiety disorders (aRD, 1.6 percentage points [95% CI, 1.2-2.1]), autism spectrum disorders (aRD, 1.1 percentage points [95% CI, 0.9-1.4]), depressive disorders (aRD, 0.9 percentage points [95% CI, 0.6-1.3]), and other neurodevelopmental disorders (aRD, 2.6 percentage points [95% CI, 1.8-3.5]). Conclusions and Relevance The percentage of publicly insured children receiving any mental health or neurodevelopmental disorder diagnosis significantly increased between 2010 and 2019, with increases observed for most diagnostic categories examined. These findings highlight the need for access to appropriate services in safety net systems and other settings that serve this population.
Placental and Fetal In Utero Growth Among Fetuses With Congenital Heart Disease
Authors: Marin Jacobwitz, Kushal Kapse, Julius Ngwa, Josepheen De Asis-Cruz, Yao Wu, Mary T. Donofrio, Caitlin McDermott, Adre du Plessis, Catherine Limperopoulos, Nickie Andescavage
Journal: JAMA Network Open (2025)

Importance At birth, neonates with congenital heart disease (CHD) have smaller placentas, lower birth weight, and smaller head circumferences compared with healthy neonates. The onset of feto-placental growth disturbances, however, is not well known. Objective To compare fetal body volumes, assess differences in the fetal to placental volume ratios (placental growth relative to the fetus), and investigate the association between in utero fetal body and total brain volume in fetuses with and without CHD. Design, Setting, and Participants This case-control study enrolled pregnant women with a fetal diagnosis of CHD and those with healthy pregnancies at Children’s National Hospital in Washington, DC, from April 2018 to July 2023. Fetal magnetic resonance imaging was obtained up to 2 time points during pregnancy. The fetal to placental ratio was calculated using 3-dimensional magnetic resonance image fetal body volumes and placental volumes. Exposure In utero environment CHD. Main Outcomes and Measures The main outcomes were the trajectories of body, brain, and placental volumetric growth in fetuses with CHD and in control fetuses. Generalized linear regression and mixed-effects models were applied to identify associations for fetal body volume and fetal to placental volume ratios between CHD and control groups adjusting for fetal sex and gestational age at the time of the magnetic resonance imaging scan. Results The study included 108 fetuses (59 male [54.6%]), of which 55 were in the healthy control group (with 55 scans), and 53 had CHD (with 77 scans). Fetal body volumes in fetuses with CHD were smaller compared with control fetuses (β = −193.60 [SE, 44.42]; P &amp;amp;lt; .001) with larger fetal to placental volume ratios (β = 0.23 [SE, 0.10]; P = .02). The total brain volume was smaller in fetuses with CHD compared with control fetuses (β = −10.87 [SE, 5.09]; P = .04). Conclusions and Relevance In this case-control study of fetuses with and without CHD, those with CHD demonstrated impaired fetal body growth with higher fetal to placental volume ratios and smaller total brain volume, suggesting that placental failure was associated with growth disturbances in CHD, as demonstrated by the large fetal to placental volume ratios. Additional studies should assess the onset and progression of placental dysfunction and how the timing of placental failure may contribute to neurodevelopmental disability in survivors of CHD.
Imaging Surveillance Adherence After Endovascular Abdominal Aortic Aneurysm Repair at VA Hospitals
Authors: Laura E. Newton, Aravind Ponukumati, Gabrielle Zwain, Caroline Korves, Jialin Mao, Kayla Moore, Shipra Arya, Olamide Alabi, Salvatore Scali, Erin Greenleaf, David Stone, Emily Spangler, Philip Goodney
Journal: JAMA Network Open (2025)

Importance Guidelines recommend annual imaging surveillance after endovascular abdominal aortic aneurysm repair (EVAR). How these guidelines translate into practice among veterans remains poorly described. Objective To characterize post-EVAR surveillance among veterans. Design, Setting, and Participants This retrospective cohort study evaluated veterans who underwent EVAR between January 1, 2000, and December 31, 2023, at US Department of Veterans Affairs (VA) hospitals and received follow-up care at VA and non-VA hospitals and imaging centers with payment via Medicare or the VA. Veterans treated with EVAR in VA hospitals during the study period were included. Exposure Years after EVAR. Main Outcomes and Measures The primary outcome was annual surveillance adherence, measured as 1 or more imaging studies in the abdomen or pelvis each year after EVAR. Stepwise logistic regression modeling was used to determine factors associated with poor adherence. Secondary outcomes were imaging type (cross-sectional, ultrasonography, or ultrasonography followed by cross-sectional imaging) and factors associated with lower adherence. Results The cohort included 27 792 veterans (27 624 male [99.4%]; 22 521 aged ≥65 years [81.0%]). Mean (SD) follow-up was 6.0 (4.0) years. The mean (SD) proportion of time that veterans were surveillance adherent was 71.1% (28.5%). Surveillance was initially high, with 25 026 of 27 792 veterans (90.0%) undergoing surveillance imaging in year 1 after EVAR. However, this proportion decreased further out from EVAR, with 12 401 of 21 384 veterans (58.0%) undergoing surveillance imaging by year 4 after EVAR. Veterans were most likely to undergo imaging with computed tomography scans (21 911 veterans [78.8%]). However, the proportion with surveillance via ultrasonography alone increased from 823 of 25 026 veterans (3.3%) in year 1 after EVAR to 2567 of 12 401 veterans (20.7%) in year 4 after EVAR. White race (odds ratio [OR] vs all other racial groups, 0.84; 95% CI, 0.72-0.98), married status (OR vs all other social status categories, 0.80; 95% CI, 0.71-0.89), having a service-connected disability (OR, 0.69; 95% CI, 0.62-0.77), and a higher Charlson Comorbidity Index score (OR per 1-unit increase, 0.93; 95% CI, 0.91-0.95) were associated with lower odds of poor surveillance adherence. Conclusions and Relevance In this study, post-EVAR imaging surveillance was high, although surveillance lapses were more likely further out from EVAR and for patients with certain characteristics. This information may inform future patient-centered efforts to improve post-EVAR imaging adherence.