tbuckley/cabot-search huggingface dataset:
Utilization and Outcomes of Ex Vivo Heart Perfusion in Donation After Brain Death Heart Transplantation
Authors: Joseph B Lerman, Veraprapas Kittipibul, Cynthia L Green, Karen Flores Rosario, Chetan B Patel, Richa Agarwal, Jeffrey E Keenan, Carmelo A Milano, Jacob N Schroder, Adam D DeVore
Journal: JACC Heart Failure (2025)
Association of PM2.5 With Cardiac Mechanics Using Speckle-Tracking Echocardiography in the Cardiovascular Health Study
Authors: Andrew Y. Chang, Joel D. Kaufman, Annabel Xulin Tan, Sanjiv J. Shah, Ravi B. Patel, Helene Margolis, Bruce M. Psaty, Julius M. Gardin, Sadeer Al-Kindi, Thomas R. Austin, Michelle C. Odden
Journal: JACC. Cardiovascular imaging (2025)
5-Year Echocardiographic Results of Transcatheter Versus Surgical Aortic Valve Replacement in Low-Risk Patients
Authors: Rebecca T Hahn, Julien Ternacle, Iria Silva, Carlos Giuliani, Antonela Zanuttini, Alexis Théron, Nicole Cristell, Mathieu Bernier, Sabah Skaf, Jonathan Beaudoin, Susheel K Kodali, Mark Russo, Samir R Kapadia, Chris S Malaisrie, David J Cohen, Jonathon Leipsic, Philipp Blanke, Mathew R Williams, James M McCabe, David L Brown, Vasilis Babaliaros, Scott Goldman, Wilson Y Szeto, Philippe Généreux, Ashish Pershad, Brandon Park, Marissa Gunnarsson, John G Webb, Craig R Smith, Raj Makkar, Vinod H Thourani, Michael J Mack, Martin B Leon, Philippe Pibarot
Journal: JACC. Cardiovascular imaging (2025)
Evidence-based Emergency Tracheal Intubation
Authors: Stephanie C. DeMasi, Jonathan D Casey, Matthew W Semler
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

Millions of critically ill adults undergo tracheal intubation in an emergency department or intensive care unit each year, nearly 40% of whom experience hypoxemia, hypotension, or cardiac arrest during the procedure. Over the last two decades, a series of randomized trials have evaluated the tools, techniques, devices, and drugs used to perform emergency tracheal intubation to determine which interventions improve outcomes and which are ineffective or harmful. Results of these trials have demonstrated that: preoxygenation with noninvasive ventilation and administration of positive pressure ventilation between induction and laryngoscopy prevent hypoxemia during intubation; video laryngoscopy facilitates successful intubation on the first attempt and may prevent esophageal intubation; use of a stylet is superior to intubation with an endotracheal tube alone and is comparable to use of a bougie; and administration of a fluid bolus before induction does not prevent hypotension. Many additional decisions clinicians face during emergency tracheal intubation are not yet informed by rigorous evidence. Randomized trials must continue to examine systematically each aspect of this common and high-risk procedure to improve patient outcomes and bring forth an era of evidence-based emergency tracheal intubation. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
Associations of Pre-Pandemic Lung Function and Structure with COVID-19 Outcomes: The C4R Study
Authors: Pallavi P. Balte, John S. Kim, Yifei Sun, Nori Allen, Elsa Angelini, Alexander Arynchyn, R. Graham Barr, Michael Blaha, Russell Bowler, Jeff Carr, Shelley A. Cole, David Couper, Ryan T Demmer, Margaret Doyle, Mitchell Elkind, Raúl San José Estépar, Olga Garcia-Bedoya, Suresh Garudadri, Nadia N Hansel, Emilia A. Hermann, Eric A. Hoffman, Stephen M Humphries, Gary M Hunninghake, Robert Kaplan, Jerry A Krishnan, Andrew Laine, Joyce S Lee, David A. Lynch, Barry Make, Kunihiro Matsushita, Will McKleroy, Yuan-I Min, Sneha N Naik, George O'Connor, Olivia O'Driscoll, Eyal Oren, Anna J. Podolanczuk, Wendy S. Post, Tess Pottinger, Elizabeth Regan, Annie Rusk, Mary Salvatore, David A. Schwartz, Benjamin Smith, Daniela Sotres-Alvarez, Jason G Umans, Ramachandran S Vasan, George Washko, Sally Wenzel, Prescott Woodruff, Vanessa Xanthakis, Victor E. Ortega, Elizabeth C. Oelsner
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

Increased risk of COVID-19 hospitalization and death has been reported among patients with clinical lung disease. To test the association of objective measures of pre-pandemic lung function and structure with COVID-19 outcomes in US adults. Pre-pandemic obstruction (FEV1/FVC<0.70) and restriction (FEV1/FVC≥0.7, FVC<80%) were defined based on the most recent spirometry exam conducted in 11 prospective US general population-based cohorts. Severe obstruction was classified by FEV1<50%. Percent emphysema, percent high attenuation areas (HAA), and interstitial lung abnormalities (ILA) were defined on computed tomography (CT) in a subset. Incident COVID-19 was ascertained via questionnaires, serosurvey, and medical records from 2020-2023, and classified as severe (hospitalized or fatal) or non-severe. Cause-specific hazards models were adjusted for socio-demographics, anthropometry, smoking, comorbidities, and COVID-19 vaccination status. Among 29,323 participants (mean age, 67 years), there were 748 severe incident COVID-19 cases over median follow-up of 17.3 months from March 1, 2020. Greater hazards of severe COVID-19 were associated with severe obstruction (vs normal, aHR=2.11;95%CI:1.02-1.27), restriction (vs normal, aHR=1.40;95%CI:1.12-1.76), and percent emphysema (highest vs lowest quartile, aHR= 1.64;95%CI:1.03-2.61), but not greater HAA or ILAs. COVID-19 vaccination provided greater absolute risk reduction in these groups. Results were similar in participants without smoking, obesity, or clinical cardiopulmonary disease. Pre-pandemic severe spirometric obstruction, spirometric restriction, and greater percent emphysema lung on CT were associated with risk of severe COVID-19. These findings support enhanced COVID-19 risk mitigation for individuals with impaired lung health and warrant further mechanistic studies on interactions of lung function, structure, and vulnerability to acute respiratory illnesses. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
The association between multiple environmental exposures and symptoms of generalized anxiety disorder in a prospective, U.S.-based cohort study
Authors: Unnati V. Mehta, Grete E. Wilt, Charlotte Roscoe, O. I. Okereke, B. A. Coull, Peter James, Francine Laden, Hari S. Iyer, Jeff D. Yanosky, Joel Kaufman, Melissa R. Fiffer, Nicole V. DeVille, Isabel Holland, Jaime E. Hart
Journal: Environmental Health Perspectives (2025)

Emerging evidence has implicated built and natural environmental exposures in the etiology and exacerbation of anxiety symptoms. Our objective was to assess individual and joint associations between neighborhood socioeconomic status (nSES), walkability, greenness, fine particulate matter (PM2.5), nitrogen dioxide (NO2), and temperature and generalized anxiety disorder (GAD) symptoms. We included 81,897 participants of the Nurses' Health Study II. GAD symptoms were measured in 2013 and 2017 using the 7-item Generalized Anxiety Disorder scale (GAD-7). Walkability and nSES z-scores were calculated at the Census tract level. Normalized Difference Vegetation Index (NDVI) summer and annual average greenness at 270m and 1230m buffer sizes, and spatiotemporal models predicted one-, three-, and twelve-month averages of PM2.5, NO2, and temperature were calculated at the residence. Longitudinal logistic and generalized estimating equations (GEE) models estimated odds ratios and 95% confidence intervals for clinically relevant GAD symptoms (GAD-7 ≥ 5 points). We assessed effect modification by nSES, summer NDVI (1230m), and select covariates. We employed quantile g-computation to more directly assess the association between environmental exposure mixtures and GAD symptoms. In single exposure models, summer NDVI (e.g., for 1230m, OR: 0.96, 95% CI: 0.94, 0.98), NO2 (e.g., for twelve-month average NO2, OR: 1.03, 95% CI: 1.01, 1.04), twelve-month average temperature (OR: 1.05, 95% CI: 1.03, 1.07, and walkability (OR: 1.02, 95% CI: 1.01, 1.03) were associated with GAD symptoms. In the joint exposure model, nSES (OR: 0.96, 95% CI: 0.95, 0.98) and summer NDVI were associated (OR: 0.92, 95% CI: 0.88, 0.96); all other associations were attenuated. Associations with summer NDVI (1230m), temperature, and NO2 were modified by nSES, with stronger associations in socioeconomically deprived areas. In this population, higher levels of summer greenness and nSES may be protectively associated with GAD symptoms, while medium- and long-term NO2 exposure, long-term temperature, and walkability are adversely associated with GAD symptoms. Socioeconomically deprived areas may bear additional risks. The results of the quantile g-computation analysis suggest that environmental exposures may act antagonistically with one another in relation to GAD symptoms. https://doi.org/10.1289/EHP14458.
A qualitative study of the ethics of community scientists’ role in environmental health research from the perspective of community scientists and institutional review board staff
Authors: Sherry Baron, Isabel Cuervo, Ilene Wilets, Josy Cruz, Ana Gonzalez, Deysi Flores, Homero Harari
Journal: Environmental Health Perspectives (2025)

Community engagement in research, including community scientists' (CSs) participation in environmental exposure assessments, promotes the bidirectional flow of information between communities and researchers and improves the development of interventions to reduce environmental health inequities. Nonetheless, Institutional Review Boards (IRBs) with limited experience with CS research tend to struggle when reviewing protocols given CS participants' dual role as research participants and co-creators of data. We collected focus group data from 35 Latina housecleaners eliciting their bioethical reflections on their experience as CSs before and after participation in the collection of data about their exposures to chemical compounds in cleaning products. We shared findings from CS participants and collected impressions and challenges from IRB staff from five New York City (NYC) biomedical research institutions. We used a modified approach to conventional content analysis to guide data analysis and combined deductive and inductive approaches to generate codes. The CS participants emphasized their shared responsibility in the research process and bidirectional learning with the research team, which they saw as educating and empowering themselves and their broader community to create safer cleaning practices to improve the community's health and well-being. CS participants embraced the importance of sound science by their recognition that their community relied on the quality and accuracy of their work as CSs. Perspectives from IRB staff similarly recognized the value of participant engagement but emphasized the importance of disentangling CS activities as research participants from activities as research team members to better determine the appropriate mechanisms and authorities for assuring ethical protections. Findings suggest that existing bioethical principles of beneficence, respect for persons, and justice, when interpreted by participants as inclusive of protections and benefits for both the CSs and their community's collective good, reflect the bioethical values of our CS participants. However, better guidance and training is needed for researchers, IRBs and community collaborators to apply these values and respect and protect the full range of roles for community members participating in research. https://doi.org/10.1289/EHP15824.
Adjusting the P/F-Ratio for BMI in Acute Hypoxemic Respiratory Failure Mitigates but Does Not Eliminate the Obesity Paradox
Authors: Philipp Simon, David Petroff, Andrew J. Simpkin, Tài Pham, Giacomo Bellani, John G. Laffey, Hermann Wrigge
Journal: American Journal of Respiratory and Critical Care Medicine (2025)
Pentatricopeptide repeat protein targeting CUG repeat RNA ameliorates RNA toxicity in a myotonic dystrophy type 1 mouse model
Authors: Takayoshi Imai, Maiko Miyai, Joe Nemoto, Takayuki Tamai, Masaru Ohta, Yusuke Yagi, Osamu Nakanishi, Hideki Mochizuki, Masayuki Nakamori
Journal: Science Translational Medicine (2025)

Myotonic dystrophy type 1 (DM1) is an autosomal dominant multisystemic disorder caused by the expansion of a CTG-triplet repeat in the 3′ untranslated region of the dystrophia myotonica protein kinase ( DMPK ) gene. It results in the transcription of toxic RNAs that contain expanded CUG repeats (CUG exp ). Splicing factors, such as muscleblind-like 1 (MBNL1), are sequestered by CUG exp , thereby disrupting the normal splicing program that is essential for various cellular functions. Pentatricopeptide repeat (PPR) proteins, originally found in plants, regulate RNA in organelles by binding in a sequence-specific manner. Here, we designed PPR proteins that specifically bind to the hexamer of CUG repeat RNAs (CUG-PPRs) and showed that CUG-PPR1 could ameliorate RNA toxicity induced by CUG exp in cell models of DM1. A single systemic recombinant adeno-associated virus (AAV9) vector–mediated gene delivery of CUG-PPR1 demonstrated long-term therapeutic effects on myotonia and restored splicing activity in a mouse model of DM1. These results highlight the potential of PPR molecules to target pathogenic RNA sequences in DM1 and potentially other RNA-mediated disorders.
Preclinical development of anti-CD21 chimeric antigen receptor T cells to treat T cell acute lymphoblastic leukemia
Authors: Nicola Maciocia, Malika Hoekx, Ciaran Acuna, Brandon Wade, Amy Burley, Saumya Ramanayake, Francesco Nannini, Patrycja A. Wawrzyniecka, Thaneswari Karpanasamy, Maria Schuldt, Stephanie Ng, Mathieu Ferrari, Teresa Marafioti, Giuseppe Gritti, Shimobi Onuoha, David O’Connor, Lydia Lee, Marc Mansour, Asim Khwaja, Martin Pule, Paul Maciocia
Journal: Science Translational Medicine (2025)

Patients with relapsed/refractory (r/r) T cell acute lymphoblastic leukemia (T-ALL) have a dismal prognosis, highlighting the urgent need for effective therapies. Chimeric antigen receptor (CAR)–T cell approaches targeting pan–T cell antigens may be limited by T cell aplasia and fratricide, necessitating “rescue” allogeneic hematopoietic stem cell transplantation. In this study, we identify CD21, a pan–B cell marker, as a promising target for T-ALL immunotherapy. CD21 is expressed in 50% of T-ALL cases at diagnosis but in fewer than 10% of mature T cells. We observed that CAR-T cells targeting membrane-distal CD21 epitopes were ineffective, likely because of the bulky, glycosylated nature of the antigen. However, when we engineered CAR-T cells to target membrane-proximal CD21 epitopes using an antigen-binding fragment (Fab)–CAR design, we demonstrated robust activity against T-ALL cell lines, primary tumors, and patient-derived xenografts in both in vitro and in vivo models. The enhanced efficacy of this Fab-CAR design was driven by its high stability and reduced surface expression, addressing limitations of traditional CAR constructs. In addition, pharmacological inhibition of the phosphatidylinositol 3-kinase axis up-regulated CD21 expression in T-ALL, further enhancing the potency of anti-CD21 CAR-T cells in vitro and in a patient-derived xenograft in vivo model. This study establishes CD21 as a viable CAR-T target and highlights advances in CAR design for bulky antigens, as well as the potential for pharmacological strategies to augment target expression. Anti-CD21 CAR-T cells represent a promising therapeutic option for improving outcomes for patients with T-ALL.
Vaccinology in the artificial intelligence era
Authors: Gianmarco Gasperini, Norman Baylor, Steve Black, David E. Bloom, Jakob Cramer, Gaël de Lannoy, Philippe Denoel, Mark Feinberg, Thibault Helleputte, Gagandeep Kang, William R. Schief, Lynda Stuart, Charlie Weller, Magda Zwierzyna, Rino Rappuoli
Journal: Science Translational Medicine (2025)

Artificial intelligence (AI) has already transformed vaccine antigen design and could transform the entire vaccinology pipeline, including immune responses and emerging infectious disease prediction, manufacturing and regulatory processes, clinical trial design and implementation, and vaccine access and equity. However, realizing the promise of AI for vaccinology requires more high-quality data.
Condensation of cellular prion protein promotes renal fibrosis through the TBK1-IRF3 signaling axis
Authors: Tantan Long, Yumei Lu, Yuanyuan Ma, Yandong Song, Xiaoping Yi, Xiaomei Chen, Miaomiao Zhou, Jingyi Ma, Jiayuan Chen, Zhuoliang Liu, Fengxin Zhu, Zheng Hu, Zhanmei Zhou, Chaoyang Li, Fan Fan Hou, Lirong Zhang, Yupeng Chen, Jing Nie
Journal: Science Translational Medicine (2025)

Cellular prion protein (PrP C ), known for its pathological isoform in prion diseases such as Creutzfeldt-Jakob disease, is primarily expressed in the nervous system but has also been detected in the blood and urine of individuals with renal dysfunction. However, the role of PrP C in the development of renal disease is unexplored. Here, we showed that PrP C was up-regulated in fibrotic renal lesions in biopsies from patients with chronic kidney disease (CKD), predominantly in proximal tubular epithelial cells (PTECs). Furthermore, renal expression of PrP C was positively correlated with the severity of renal failure and the decline in estimated glomerular filtration rate in patients with CKD. In mice, tubular-specific deletion of PrP C mitigated renal fibrosis induced by unilateral ureteral obstruction (UUO) or unilateral ischemia-reperfusion injury (UIRI). Mechanistically, PrP C was up-regulated by transforming growth factor–β1–suppressor of mothers against decapentaplegic 3 signaling. PrP C activated TANK binding kinase 1 (TBK1)–interferon regulatory factor 3 (IRF3) signaling through its capacity for liquid-liquid phase separation, which promoted a profibrotic response in PTECs and fibroblasts. Treating mice with amlexanox, a US Food and Drug Administration–approved inhibitor of TBK1, either before the onset of renal fibrosis (in UUO and UIRI models) or after its establishment (in adenine- and aristolochic acid–induced CKD models), mitigated worsening of renal fibrosis and renal function. Collectively, our findings uncovered a mechanism involving phase separation of PrP C underlying renal fibrosis and support further study of the PrP C -TBK1-IRF3 axis as a potential therapeutic target for CKD.
Expansion of a bacterial operon during cancer treatment ameliorates fluoropyrimidine toxicity
Authors: Kai R. Trepka, Wesley A. Kidder, Than S. Kyaw, Taylor Halsey, Christine A. Olson, Edwin F. Ortega, Cecilia Noecker, Vaibhav Upadhyay, Dalila Stanfield, Paige Steiding, Benjamin G. H. Guthrie, Peter Spanogiannopoulos, Darren Dumlao, Jessie A. Turnbaugh, Matthew D. Stachler, Erin L. Van Blarigan, Alan P. Venook, Chloe E. Atreya, Peter J. Turnbaugh
Journal: Science Translational Medicine (2025)

Dose-limiting toxicities remain a major barrier to drug development and therapy, revealing the limited predictive power of human genetics. Here, we demonstrate the utility of a more comprehensive approach to studying drug toxicity through longitudinal profiling of the human gut microbiome during colorectal cancer (CRC) treatment (NCT04054908) coupled to cell culture and mouse experiments. Substantial shifts in gut microbial community structure during oral fluoropyrimidine treatment across multiple patient cohorts, in mouse small and large intestinal contents, and in patient-derived ex vivo communities were revealed by 16 S rRNA gene sequencing. Metagenomic sequencing revealed marked shifts in pyrimidine-related gene abundance during oral fluoropyrimidine treatment, including enrichment of the preTA operon, which was sufficient for the inactivation of active metabolite 5-fluorouracil (5-FU). preTA + bacteria depleted 5-FU in gut microbiota grown ex vivo and in the mouse distal gut. Germ-free and antibiotic-treated mice experienced increased fluoropyrimidine toxicity, which was rescued by colonization with the mouse gut microbiota, preTA + Escherichia coli , or preTA -high stool from patients with CRC. Last, preTA abundance was negatively associated with fluoropyrimidine toxicity in patients. Together, these data support a causal, clinically relevant interaction between a human gut bacterial operon and the dose-limiting side effects of cancer treatment. Our approach may be generalizable to other drugs, including cancer immunotherapies, and provides valuable insights into host-microbiome interactions in the context of disease.
PDL1-expressing macrophages infiltrate diffuse large B-cell lymphoma and promote lymphoma growth in a MYC-driven experimental model
Authors: Ningxuan Cui, Peter Leary, Vanesa-Sindi Ivanova, Kristin Stirm, Lydia Kirsche, Nicola Aceto, Frank Stenner, Lothar C Dieterich, Michael Detmar, Ekaterina Petrova, Sarah Mundt, Melanie Greter, Alexandar Tzankov, Anne Müller
Journal: Blood Cancer Journal (2025)
Long-term safety, tolerability, and efficacy of eptinezumab in chronic cluster headache (CHRONICLE): an open-label safety trial
Authors: Cristina Tassorelli, Rigmor H Jensen, Peter J Goadsby, Andrew C Charles, Stewart J Tepper, Agneta Henriette Snoer, Mette Krog Josiassen, Christine Borgen Linander, Anders Ettrup, Bjørn Sperling, Neli Boneva
Journal: The Lancet Neurology (2025)
Effect of a novel house design (star home) on indoor malaria mosquito abundance in rural Tanzania: secondary outcomes of an open-label, household, randomised controlled trial
Authors: Arnold S Mmbando, Amos J Ngonzi, Salum Mshamu, John Bradley, Thomas C Bøjstrup, Halfan S Ngowo, Jakob Knudsen, Lorenz von Seidlein, Fredros O Okumu, Steve W Lindsay
Journal: The Lancet Planetary Health (2025)

Screening houses can reduce malaria transmission in sub-Saharan Africa. Our study evaluated whether a novel screened house design (star home) with bedrooms on the second storey reduced indoor mosquito abundance compared with traditional houses in Mtwara, Tanzania. In this open-label, household, randomised controlled trial, indoor mosquito abundance was assessed in 110 star homes and 110 neighbouring traditional houses in 59 villages from Jan 5, 2022, to Dec 20, 2023. Mosquitoes were collected using US Centers for Disease Control light traps every 7 weeks. Anopheles gambiae and Anopheles funestus species were identified using PCR and Plasmodium falciparum sporozoites detected using ELISA. Nightly temperature, CO2 concentrations, and duration of door opening was recorded. Differences between study groups were analysed using generalised linear mixed-effects models. The trial is registered with ClinicalTrials.gov (NCT04529434). Of 9290 mosquitoes collected, 1899 were A gambiae, 69 were A funestus, and 7322 Culex species, mainly Culex quinquefasciatus. Star homes had 51% less A gambiae (adjusted risk ratio [RR] 0·49, 95% CI 0·35 to 0·69; p<0·0001) and 61% less Culex species (RR 0·39, 0·32 to 0·48; p<0·0001) than traditional houses. At night, star homes were 0·5°C cooler (95% CI 0·2 to 0·9; p=0·010), with similar concentrations of CO2 (-7 ppm, 95% CI -19 to 6; p=0·285) and had external doors open 53% less time than traditional houses (7·5 min/h vs 16·2 min/h; p<0·0001). Star homes reduced indoor mosquito abundance and malaria transmission risk compared with traditional houses, demonstrating the protective efficacy of houses that are well screened and air permeable in rural Africa. Hanako Foundation, Singapore.