tbuckley/cabot-search huggingface dataset:
Trends in Launch Prices and Price Increases for Self-Administered Anticancer Drugs in Medicare
Authors: Stacie B. Dusetzina, Shelley A. Jazowski, Rahul K. Nayak, Haiden A. Huskamp, Nancy L. Keating
Journal: JAMA (2025)

This study examines trends in launch prices and price increases for anticancer therapies covered under Medicare Part D and approved from 2010 to 2024.
Use of Biologics During Pregnancy Among Patients With Autoimmune Conditions
Authors: Celeste L. Y. Ewig, Yanning Wang, Nicole E. Smolinski, Thuy Nhu Thai, Sonja A. Rasmussen, Almut G. Winterstein
Journal: JAMA Network Open (2025)

Importance Continuation of biologics in patients with an autoimmune condition who become pregnant involves weighing consequences of pregnancy-related changes in disease severity and potential teratogenic effects of medications. Characterization of biologic treatment patterns during pregnancy may provide insight into maternal and fetal risks and benefits. Objective To describe the utilization pattern of biologics in pregnant individuals with autoimmune conditions. Design, Setting, and Participants This cohort study used data from Merative MarketScan Research Databases, which contain administrative claims of commercially insured individuals in the US. Pregnant patients aged 16 to 55 years with an autoimmune condition and biologic use 6 months before conception between January 1, 2011, and December 31, 2022, were included. The data were analyzed between October 15, 2024, and February 28, 2025. Exposure Use of biologics for autoimmune disease after conception. Main Outcomes and Measures The proportion of patients who used biologics for Crohn disease, ulcerative colitis, psoriasis or psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, and multiple sclerosis was assessed, and the association between underlying autoimmune disease and use of biologics during pregnancy was measured using multivariable logistic regression. Results A total of 6131 pregnant patients (median [IQR] age, 32 [29-36] years) with an autoimmune condition were included. The most prevalent conditions were Crohn disease (1372 patients [25.6%]) and rheumatoid arthritis (1295 patients [24.1%]). Of all patients, 4393 (71.6%; 95% CI, 70.5%-72.8%) used biologics at least once during pregnancy. Among pregnancies with live birth outcomes, biologic use declined throughout gestation, with 2981 patients (68.6% [95% CI, 67.2%-70.0%]), 2555 patients (58.8% [95% CI, 57.3%-60.3%]), and 2113 patients (48.6% [95% CI, 47.1%-50.1%]) using biologics during the first, second, and third trimesters, respectively, and 3350 patients (77.1% [95% CI, 75.8%-78.3%]) using them post partum. Compared with pregnant patients with rheumatoid arthritis, those with Crohn disease (odds ratio [OR], 7.88 [95% CI, 5.93-10.47]) and ulcerative colitis (OR, 5.35 [95% CI, 3.73-7.66]) were more likely to use biologics, while those with psoriasis or psoriatic arthritis (OR, 0.65 [95% CI, 0.52-0.80]) were less likely. Conclusions and Relevance In this cohort study, a decline in the use of biologics for autoimmune disease was observed during the pregnancy period that rebounded only partially thereafter. Notable variations in use across autoimmune conditions suggest that indication-specific risk-benefit assessments of biologic use are needed.
Trends in Cystic Fibrosis–Related Diabetes Epidemiology Between 2003 and 2018 From the U.S. Cystic Fibrosis Foundation Patient Registry
Authors: Celia L. Kohler, Tim Vigers, Laura Pyle, Kristen Miller, Edith T. Zemanick, Antoinette Moran, Scott D. Sagel, Christine L. Chan
Journal: Diabetes Care (2025)

OBJECTIVE A number of disease-modifying therapies have been introduced for people with cystic fibrosis (CF) over the past two decades. The cumulative effects of this changing landscape on CF–related diabetes (CFRD) are unclear. We examined trends in CFRD epidemiology over time using data from the U.S. Cystic Fibrosis Foundation Patient Registry (CFFPR). RESEARCH DESIGN AND METHODS CFFPR data from 2003 to 2018 were queried to determine annual screening, incidence, and prevalence rates of CFRD. Individuals with incident CFRD were compared with individuals without CFRD. Survival analyses were performed to estimate the cumulative hazard of CFRD given predictors of interest over the 15 years of study. Data were also grouped into three time periods (2003–2008, 2009–2013, and 2014–2018) to investigate whether the hazard of developing CFRD varied over time. RESULTS CFRD screening rates increased from 2003 to 2018, particularly in 10- to 18-year-olds. Although screening rates increased in adults, overall rates remained low. In 10- to 18-year-olds, the incidence of CFRD was stable over time, while incident cases in adults steadily decreased, approaching incident rates in adolescents. Despite this, the prevalence of CFRD has gradually increased in adults, likely reflecting increased longevity. Age, female sex, Black race, severe mutation class, liver disease, poorer lung function, pancreatic insufficiency, enteric feeds, and low and high BMI were all risk factors associated with CFRD. CONCLUSIONS Findings support the need for the development of tailored CFRD screening algorithms and increased subspecialists to care for a growing population of adults with CF and CF-associated comorbidities.
Artificial lipids and macrophage membranes coassembled biomimetic nanovesicles for thoracic aortic dissection treatment
Authors: Yanlin Gao, Li Rong, Jin Cui, Wei Cheng, Lin Fu, Guangpu Fan, Haiyan Wang, Jiaqi Yu, Zhen Li, Dinghong Liu, Sheng Zhao, Houliang Chen, Junchao Qin, Miaomiao Tao, Zhechuan Jin, Yu Chen, Yuyu Li
Journal: Journal of Controlled Release (2025)

Thoracic aortic dissection (TAD) is a life-threatening cardiovascular disease characterized by rapid progression and high morbidity. Current efforts to develop effective treatment strategies focus on targeting apoptotic aortic endothelial cells and mitigating inflammation. Here, inspired by the inflammation-neutralizing capacity of functional cells, we present multifunctional biomimetic nanovesicles (MM-LPs) co-assembled from macrophage membranes and synthetic lipids for the targeted delivery of Senkyunolide I (SEI) in TAD treatment. The integration of macrophage membranes endows MM-LPs with the ability to selectively target activated vascular endothelial cells (VECs) while adsorbing proinflammatory cytokines to suppress inflammation. Additionally, these nanoparticles enable the controlled release of SEI, leading to significant anti-apoptotic effects. Leveraging these advantages, MM-LPs effectively mitigated VEC activation, reduced apoptosis, and prevented disease progression and rupture in a BAPN-induced mouse model of TAD. Furthermore, this system significantly reduced SEI-associated toxicity and adverse effects on the liver and kidneys. These findings highlight the potential of combining natural macrophage membranes with synthetic lipids to develop a multifunctional biomimetic drug delivery system for treating VEC dysfunction while minimizing drug-related side effects.
Targeting processive transcription for Myc-driven circuitry in medulloblastoma
Authors: Lays Martin Sobral, Faye M Walker, Krishna Madhavan, Elizabeth Janko, Sahiti Donthula, Etienne Danis, Pradeep Bompada, Ilango Balakrishnan, Dong Wang, Angela Pierce, Mary M Haag, Billie J Carstens, Natalie J Serkova, Nicholas K Foreman, Sujatha Venkataraman, Bethany Veo, Rajeev Vibhakar, Nathan A Dahl
Journal: Neuro-Oncology (2025)

Abstract Background Medulloblastoma is the most common malignant brain tumor of childhood. The highest-risk tumors are driven by recurrent Myc amplifications (Myc-MB) and experience poorer outcomes despite intensive multimodal therapy. The Myc transcription factor defines core regulatory circuitry for these tumors and acts to broadly amplify downstream pro-survival transcriptional programs. Therapeutic targeting of Myc directly has proven elusive, but inhibiting transcriptional cofactors may present an indirect means of drugging the oncogenic transcriptional circuitry sustaining Myc-MB. Methods Independent CRISPR-Cas9 screens were pooled to identify conserved dependencies in Myc-MB. We performed chromatin conformation capture (Hi-C) from primary patient Myc-MB samples to map enhancer-promoter interactions. We then treated in vitro and xenograft models with CDK9/7 inhibitors to evaluate effect on Myc-driven programs and tumor growth Results Eight CRISPR-Cas9 screens performed across three independent labs identify CDK9 as a conserved dependency in Myc-MB. Myc-MB cells are susceptible to CDK9 inhibition, which is synergistic with concurrent inhibition of CDK7. Inhibition of transcriptional CDKs disrupts enhancer-promoter activity in Myc-MB and downregulates Myc-driven transcriptional programs, exerting potent anti-tumor effect. Conclusions Our findings identify CDK9 inhibition as a translationally promising strategy for the treatment of Myc-MB.
Mechanical Wave Velocities in Acute Myocardial Infarction: An Exploratory Study Using Three-Dimensional High Frame Rate Echocardiography
Authors: Marlene Iversen Halvorsrød, Mohammad Mohajery, Torvald Espeland, Sebastien Salles, Asbjørn Støylen, Lasse Løvstakken, Bjørnar Grenne
Journal:  (2025)

Abstract Aims High frame rate (HFR) echocardiography captures myocardial mechanical waves (MW), reflecting critical tissue properties. The aim was to assess the feasibility of 3D HFR echocardiography for estimating MW velocities in acute myocardial infarction (AMI) patients, and to compare MW velocities with those in controls. Methods and results Twenty patients with ST-elevation AMI were included within 48 hours of reperfusion therapy. 3D high-quality recordings (∼20 volumes/s) were acquired for myocardial segmentation and 3D HFR recordings (750 volumes/s) for measuring the atrial kick wave propagation velocity. MW velocities were compared to 20 controls. MW velocities were successfully measured in 93% of subjects (17 patients and 20 controls). The segmental feasibility was 97%. Global MW velocities were significantly higher in AMI patients than controls (2.1±0.6m/s vs. 1.5±0.2m/s, p&amp;lt;0.001). Infarcted territories had higher velocities when compared to the corresponding territories in controls: right coronary artery: 1.9±0.7m/s vs. 1.4±0.3m/s, p&amp;lt;0.05; circumflex artery: 3.1±1.5m/s vs. 1.7±0.4m/s, p&amp;lt;0.01; left anterior descending artery: 1.8±0.5m/s vs. 1.4±0.2m/s, p&amp;lt;0.01. There was a strong correlation between global MW velocities and wall motion score index (r=0.70, p&amp;lt;0.001). MW velocities were higher in segments with wall motion abnormalities than in healthy segments (2.3±1.1 vs. 1.6±0.7m/s, p&amp;lt;0.001). Conclusions Estimation of MW velocities using 3D HFR echocardiography had excellent feasibility. MW velocities were higher in patients with AMI than in controls, in infarcted compared to healthy territories, and in segments with wall motion abnormalities. Future work should evaluate the clinical value in larger populations.
Dental and Vision Services Among Veterans in Medicare Advantage vs Traditional Medicare
Authors: Adam L. Beckman, Dannie Dai, Hawazin W. Elani, Christopher L. Cai, E. John Orav, José F. Figueroa
Journal: JAMA (2025)

This cross-sectional study compares medical spending on vision and dental care among veterans enrolled in Medicare Advantage vs veterans enrolled in traditional Medicare.
The pharmacokinetics of antibiotics in patients with obesity: a systematic review and consensus guidelines for dose adjustments
Authors: Anne-Grete Märtson, Katie E Barber, Ryan L Crass, Maya Hites, Charlotte Kloft, Joseph L Kuti, Elisabet I Nielsen, Manjunath P Pai, Markus Zeitlinger, Jason A Roberts, Thomas Tängdén
Journal: The Lancet Infectious Diseases (2025)
General population-based lung function trajectories over the life course: an accelerated cohort study
Authors: Judith Garcia-Aymerich, Martí de Las Heras, Anne-Elie Carsin, Simone Accordini, Alvar Agustí, Dinh Bui, Shyamali C Dharmage, James W Dodd, Ikenna Eze, Ulrike Gehring, Thorarinn Gislason, Raquel Granell, Medea Imboden, Carmen Íñiguez, Ayoung Jeong, Sarah Koch, Gerard H Koppelman, Bénédicte Leynaert, Erik Melén, Jennifer Perret, Nicole Probst-Hensch, Loreto Santa-Marina, Maties Torrent, Don Vicendese, Judith M Vonk, Maaike de Vries, E Haydn Walters, Gang Wang, Jadwiga A Wedzicha, Deborah Jarvis, Rosa Faner
Journal: The Lancet Respiratory Medicine (2025)
Safety and efficacy of a novel ANGPTL4 inhibitory antibody for lipid lowering: results from phase 1 and phase 1b/2a clinical studies
Authors: Beryl B Cummings, Mark P Joing, Page R Bouchard, Mark N Milton, Peter F Moesta, Vyas Ramanan, Andrew Lane, Joe Hirman, John W Trauger, Eleftheria Maratos-Flier, Andrei Voznesensky, Igor Splawski, Amitabh V Nimonkar, Meghan M Flaherty, B Alexander Yi, Daniel Meyers, Francois Huet, Sukhdeep K Sahambi, Denise P Yates, Douglas Hom, Markus Hinder, Craig T Basson, Chris O'Donnell, Evan S Siegelman, Chris E Garrett, Joshua Lehrer-Graiwer, Rebecca A Juliano, Ethan J Weiss
Journal: The Lancet (2025)
Durvalumab plus chemotherapy in advanced biliary tract cancer: 3-year overall survival update from the phase III TOPAZ-1 study
Authors: Do-Youn Oh, Aiwu Ruth He, Shukui Qin, Li-Tzong Chen, Takuji Okusaka, Jin Won Kim, Thatthan Suksombooncharoen, Myung Ah Lee, Masayuki Kitano, Howard A Burris, Mohamed Bouattour, Suebpong Tanasanvimon, Renata Zaucha, Antonio Avallone, Juan Cundom, Aleksandra Kuzko, Julie Wang, Ioannis Xynos, Arndt Vogel, Juan W Valle
Journal: Journal of Hepatology (2025)
Long term outcomes in drug resistant tuberculosis with Bedaquiline, Pretomanid and varying doses of Linezolid
Authors: Bella Devaleenal Daniel, Sivakumar Shanmugam, Rashi Mehta, Manpreet Bhalla, Muthu Vijayalakshmi, Balaji Ramraj, Avijit Kumar Awasthi, Pranav Patel, Amita Jain, Parul Jain, Chetan Kumar, Vikas Oswal, Neeta Singla, Santosh Kumar, Jigna Dave, Parul Vadgama, Anuj Bhatnagar, Surya Kant, Rathinam Prabhakaran, Grinish Tamakuwala, Rishikesh Nath Mukherjee, Ramesh Kumar Santhanakrishnan, Dhandapani Ravikumar, Naveen Kumar Nagarajan, Shanmugapriya Kumaravadivelu, Jeyadeepa Bharathi, Anand Sridhar, Ranjani Ramachandran, Sanjay K Matoo, Chinnaiyan Ponnuraja, Jyoti Jaju, Chandrasekaran Padmapriyadarsini
Journal: Journal of Infection (2025)

Assess the effectiveness of bedaquiline, pretomanid and linezolid (BPaL) regimens with varying doses and duration of linezolid at the end of 48 weeks post treatment among drug resistant tuberculosis (DR TB) patients. Multicentric pragmatic randomized clinical trial in which BPaL regimens were given for 26 weeks for pulmonary pre extensively drug resistant tuberculosis (PreXDR TB); bedaquiline, pretomanid and linezolid 600mg for 26 weeks (arm1), structured dose reduction arms with linezolid dose reduction from 600 to 300mg after nine weeks (arm2) and 13 weeks (arm3). Participants were followed up for recurrence free cure up to 48 weeks post treatment. Whole genome sequencing in sputum samples at baseline and recurrence differentiated relapse and reinfection. Of 403 enrolled, 378 were included for the modified intent to treat analysis based on baseline sputum culture positivity and sensitivity to medications in the study regimen. Among them, 331(88%) had recurrence free cure at the end of 48 weeks of post treatment follow-up; arm1:112(87%), arm2:110(88%), arm3:109(88%). Overall, 14 (12 bacteriological and 2 clinical) recurrences (arm1-four, 2-six and 3-four) occurred; 11 recurrences occurred within 24 weeks after treatment completion; four out of 11 within the first 12 weeks. Of the 10 paired sputum samples available at baseline and recurrence for comparison of lineages, there were two reinfections and eight relapses. Structured dose reduction arms had comparable recurrence free cure rates as linezolid 600mg arm when given along with bedaquiline and pretomanid for 26 weeks in PreXDR TB. Most of the recurrences occurred within the first six months.
External exposome and incident asthma across the life course in 14 European cohorts: a prospective analysis within the EXPANSE project
Authors: Zhebin Yu, Sara Kress, Natalia Blay, Petr Gregor, Hanna-Maria Kukk, Miriam Leskien, Renata Majewska, Max J. Oosterwegel, Daniel Szabó, Margreet ten Have, Jana Klánová, Ondřej Mikeš, Anna Bergström, Alonso Bussalleu, Rafael de Cid, Andrea Dalecka, Payam Dadvand, Saskia van Dorsselaer, Krista Fischer, Kees de Hoogh, Gerard H. Koppelman, Jaanika Kronberg, Andres Metspalu, Lili Milani, Tõnu Esko, Mait Metspalu, Jeroen Lakerveld, Petter Ljungman, Simon Kebede Merid, Pawel Macek, Marta Manczuk, Anne-Sophie Merritt, Agnieszka Pac, Priit Palta, Göran Pershagen, Annette Peters, Hynek Pikhart, Apolline Saucy, Tamara Schikowski, Youchen Shen, Marie Standl, Cathryn Tonne, Roel Vermeulen, Jelle Vlaanderen, Judith M. Vonk, Kathrin Wolf, Carl Henrik Ek, Olena Gruzieva, Ulrike Gehring, Erik Melén
Journal: The Lancet Regional Health - Europe (2025)
Association of metabolic comorbidities with fibrosis severity and fibrosis regression in patients with chronic hepatitis B
Authors: Lisa M van Velsen, Lesley A Patmore, Jordan J Feld, Henry L Y Chan, Teerha Piratvisuth, Rong-Nan Chien, Edo J Dongelmans, Vedran Pavlovic, Leland J Yee, Willem Pieter Brouwer, Audrey Lau, Bettina E Hansen, Maria Buti, Qing Xie, Keyur Patel, Scott K Fung, Harry L A Janssen, Milan J Sonneveld
Journal: Clinical Gastroenterology and Hepatology (2025)

Presence of metabolic comorbidities is associated with a higher risk of liver-related events in chronic hepatitis B (CHB) patients. However, the association between presence of metabolic comorbidities and the severity of biopsy-proven liver fibrosis is yet unknown. Data from CHB patients from 2 tertiary clinics and 8 clinical trials was analyzed. We studied the association between presence of metabolic comorbidities with severity of liver fibrosis in untreated patients, and with fibrosis regression or progression in biopsies taken after initiation of antiviral therapy (AVT). We analyzed biopsies from 3179 untreated CHB patients. Median age was 37 years, 57.6% HBeAg positive, with median HBV DNA of 7.30 logIU/mL. Overweight (29.4 vs 19.0%;p<0.001), hypertension (40.7 vs 23.2%,p<0.001), diabetes (42.2 vs 23.6%,p<0.001) and dyslipidemia (42.9 vs 23.6%,p<0.001) were associated with a higher risk of advanced fibrosis, with the highest risk observed in patients with multiple comorbidities. Findings were consistent in multivariable analysis (1 comorbidity aOR:1.115, ≥2 comorbidities aOR:1.627,p=0.006). Regression to non-advanced fibrosis, after treatment initiation, was more often observed in patients without metabolic comorbidities (43.1%), compared to patients with 1 (31.6%) or ≥2 comorbidities (17.0%,p=0.005). Findings were consistent in multivariable analysis (1 comorbidity aOR:0.792, ≥2 comorbidities aOR:0.260,p=0.025). The risk of progression to advanced fibrosis was highest in patients with ≥2 comorbidities (14.3% vs 4.6%,p=0.001). Presence of metabolic comorbidities in untreated CHB patients is associated with more severe liver fibrosis and, after initiation of AVT, with less fibrosis regression and a higher risk of fibrosis progression.
Household fuel use and kidney disease-related mortality: the Golestan Cohort Study
Authors: Michele Sassano, Monireh Sadat Seyyedsalehi, Sudabeh Alatab, Hossein Poustchi, Mahdi Sheikh, Arash Etemadi, Reza Malekzadeh, Paolo Boffetta
Journal: Environmental Health Perspectives (2025)

A large proportion of global population use solid fuels for household purposes, and limited evidence from previous studies suggests that it might be associated with reduced renal function. To investigate the association between household use of different types of fuels and kidney disease-related mortality. We analyzed data from the Golestan Cohort Study, a population-based prospective cohort study conducted in northeastern Iran, with 50,045 individuals aged 40-75 years enrolled in the period 2004-2008 and followed through April 2023. Information on household fuel use was collected using validated questionnaires. We estimated adjusted hazards ratios (HRs) and corresponding 95% confidence intervals (CIs) using Cox proportional hazards models. The outcome of interest was death due to any kidney disease, excluding kidney cancer (ICD-10 codes: N00-N19, N25-N29). During 724,063.62 person-years of follow-up, 262 participants died due to kidney disease. The risk of kidney disease-related mortality was higher with increasing duration of biomass use for cooking or house heating (HR for every 10-year increase: 1.20; 95% CI: 1.04-1.37), while it was not associated with increased duration of using kerosene (10-y HR: 1.09; 95% CI: 0.95-1.24), or gas (10-y HR: 1.00; 95% CI: 0.86-1.16). Estimates for lifetime duration of fuel burning for both cooking and house heating (exclusive fuel use) did not differ according to whether used heating stoves were chimney-equipped or not for kerosene, while they differed for biomass (10-y HR, chimney-equipped: 1.06 [95% CI: 0.95-1.18]; 10-y HR, not chimney-equipped: 1.19 [95% CI: 1.06-1.34]; Pdifference=0.025). The findings of our study suggest that burning biomass for household purposes under poor ventilating conditions is associated with kidney disease-related mortality. https://doi.org/10.1289/EHP15629.
A phase 2 Trial of CHOP with Anti-CCR4 Antibody Mogamulizumab for older Patients with Adult T-Cell Leukemia/Lymphoma
Authors: Makoto Yoshimitsu, Ilseung Choi, Shigeru Kusumoto, Mototsugu Shimokawa, Atae Utsunomiya, Youko Suehiro, Tomonori Hidaka, Kisato Nosaka, Hidenori Sasaki, Shinya Rai, Shinobu Tamura, Satsuki Owatari, Ki-Ryang Koh, Daisuke Nakamura, Masahito Tokunaga, Masaaki Sekine, Yuma Sakamoto, Hiroshi Inagaki, Takashi Ishida, Kenji Ishitsuka
Journal: Blood (2025)
Selection on the epigenome: small RNA inheritance in animal evolution
Authors: Isaac Harris, Simone Immler, Tracey Chapman, Alexei A Maklakov
Journal: Trends in Genetics (2025)

The inheritance of small RNAs (sRNAs) is taxonomically widespread. Changing environments alter the production and presence of sRNAs in the germline, and this can in theory either increase offspring phenotypic variance as an evolutionary bet-hedging strategy or elicit predictive and adaptive phenotypic responses that increase offspring fitness. Nevertheless, the putative role of sRNA inheritance systems in adaptive evolution is still debated and it is currently unclear how selection acts on sRNAs. We outline two adaptive sRNA inheritance strategies - specialist and generalist - and discuss non-adaptive alternatives and the evolutionary implications of different strategies. Our review suggests that the role of natural selection in sRNA inheritance has been significantly overlooked, potentially leading to misinterpretations of the causal agents and the evolutionary implications of sRNA inheritance.