tbuckley/cabot-search huggingface dataset:
Ultrafine particle mobile monitoring study designs for epidemiology: Cost and performance comparisons
Authors: Sun-Young Kim, Amanda J Gassett, Magali N Blanco, Lianne Sheppard
Journal: Environmental Health Perspectives (2025)

Given the difficulty of collecting air pollution measurements for individuals, researchers use mobile monitoring to develop accurate models that predict long-term average exposure to air pollution, allowing the investigation of its association with human health. Although recent mobile monitoring studies focused on predictive models' abilities to select optimal designs, cost is also an important feature. This study aimed to compare costs to predictive model performance for different mobile monitoring designs. We used data on ultrafine particle stationary roadside mobile monitoring and associated costs collected by the Adult Changes in Thought Air Pollution (ACT-AP) study. By assuming a single-instrument, local monitoring, and constant costs of equipment and investigator oversight, we focused on the incremental cost of staff work days composed mostly of sampling drives and quality control procedures. The ACT-AP complete design included data collection from 309 sites, ∼29 visits per site, during four seasons, every day of the week. We considered alternative designs by selecting subsets of fewer sites, visits, seasons, days of week, and hours of day. Then, we developed exposure prediction models from each alternative design and calculated cross-validation (CV) statistics using all observations from the complete design. Finally, we compared CV R-squared values and the numbers of staff work days from alternative designs to those from the complete design and demonstrate this exercise in a web application. For designs with fewer visits per site, the costs for number of work days were lower and model performance (CV R2) also worsened, but with mild decline above 12 visits per site. The costs were also less for designs with fewer sites when considering at least 100 sites, although the reduction in performance was minimal. For temporally restricted designs that were constrained to have the same number of work days and thus the same cost, restrictions on the number of seasons, days of week, and/or hours of the day adversely impacted model performance. Our study provides practical guidance to future mobile monitoring campaigns that have the ultimate goal of assessing the health effect of long-term air pollution. Temporally balanced designs with 12 visits per site are a cost-effective option that provide relatively good prediction accuracy with reduced costs. https://doi.org/10.1289/EHP15100.
Importance of Age and Sex in Carotid Artery Plaque Detection and Cardiovascular Disease Risk
Authors: Matthew C. Tattersall, Spencer L. Hansen, Robyn L. McClelland, Claudia E. Korcarz, Kristin M. Hansen, Wendy S. Post, Michael D. Shapiro, James H. Stein
Journal: JAMA Cardiology (2025)

Carotid artery plaque (CAP) is commonly encountered in clinical practice. Presence of CAP predicts future atherosclerotic cardiovascular disease (ASCVD) events; however, CAP prevalence increases with age, and it is unknown how age and sex affect the association of CAP presence and ASCVD risk. To describe CAP prevalence by age, sex, race, and ethnicity in a multiethnic population and to investigate whether the impact of CAP detection on relative ASCVD risk declines with age and differs by sex. This cohort study examines participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Adults aged 45 to 84 years who were free of clinical ASCVD at recruitment (2000-2002) were included, and follow-up for ASCVD events was conducted through December 2019. Data analysis was performed from July 2023 to April 2024. Presence of CAP. The primary outcome was ASCVD events (coronary heart disease events, stroke, and ASCVD death). Prevalence of CAP by age, sex, race, and ethnicity was calculated. Cox proportional hazards models with age interaction terms were used to investigate associations of CAP and incident ASCVD events across sexes. Among 6814 adults in the MESA cohort, 5689 participants had complete data and were included in this analysis. Among these 5689 participants, mean (SD) age was 62.0 (10.2) years, and 3002 participants (53%) were female. The cohort included 1551 Black participants (27%), 687 Chinese participants (12%), 1276 Hispanic participants (22%), and 2165 White participants (38%). In total, participants experienced 1043 ASCVD events over a median (IQR) period of 17.6 (10.5-18.4) years. Prevalence of CAP differed by age, sex, race, and ethnicity, ranging from 15% in Chinese women younger than 50 years to 95% in non-Hispanic White men aged 80 to 84 years. CAP independently predicted ASCVD events (hazard ratio, 1.38; 95% CI, 1.20-1.58; P < .001). The strength of this association was stronger among younger participants (≤60 years) vs older (>60 years) (P for interaction = .01), especially among women (P for interaction = .005) vs men (P for interaction = .66). CAP detection in younger individuals conferred higher relative ASCVD risk than in older participants, who had higher absolute risk regardless of CAP. CAP becomes very common with increasing age among individuals without clinical ASCVD, and the association of CAP with incident ASCVD events was strongest in younger ages, especially among women. These data can help guide ASCVD risk assessment in younger adults and provide perspective when CAP is detected on clinical imaging studies in older adults.
Targeting GOLPH3L improves glioblastoma radiotherapy by regulating STING-NLRP3–mediated tumor immune microenvironment reprogramming
Authors: Shuo Sun, Shiyu Qian, Ran Wang, Mengya Zhao, Ran Li, Wei Gu, Mengjie Zhao, Chunfa Qian, Liang Liu, Xianglong Tang, Yangyang Li, Hui Shi, Yunsong Pan, Hong Xiao, Kun Yang, Chupeng Hu, Yedi Huang, Liangnian Wei, Yuhan Zhang, Jing Ji, Yun Chen, Hongyi Liu
Journal: Science Translational Medicine (2025)

Radiotherapy (RT) has been the standard-of-care treatment for patients with glioblastoma (GBM); however, the clinical effectiveness is hindered by therapeutic resistance. Here, we demonstrated that the tumor immune microenvironment (TIME) exhibited immunosuppressive properties and high expression of Golgi phosphoprotein 3 like (GOLPH3L) in RT-resistant GBM. Our study showed that GOLPH3L interacted with stimulator of interferon genes (STING) at the aspartic acid residue 184 in Golgi after RT, leading to coat protein complex II-mediated retrograde transport of STING from Golgi to endoplasmic reticulum. This suppressed the STING-NOD-like receptor thermal protein domain associated protein 3 (NLRP3)-mediated pyroptosis, resulting in suppressive TIME, driving GBM resistance to RT. Genetic GOLPH3L ablation in RT-resistant GBM cells augmented antitumor immunity and overcame tumor resistance to RT. Moreover, we have identified a small molecular inhibitor of GOLPH3L, vitamin B5 calcium (VB5), which improved the therapeutic efficacy of RT and immune checkpoint blockade by inducing a robust antitumor immune response in mouse models. Clinically, patients with GBM treated with VB5 exhibited improved responses to RT. Thus, reprogramming the TIME by targeting GOLPH3L may offer a potential opportunity to improve RT in GBM.
Simultaneous or Rapid Initiation of Combination Therapy for Heart Failure With Preserved Ejection Fraction
Authors: Stephen J. Greene, Javed Butler, Gregg C. Fonarow
Journal: JAMA Cardiology (2025)

This Viewpoint recommends simultaneous or rapid sequence initiation of combination therapy with 3 specific classes of medication for heart failure with mildly reduced ejection fraction or preserved ejection fraction.
Finerenone for Heart Failure and Risk Estimated by the PREDICT-HFpEF Model
Authors: Kirsty McDowell, Kieran F. Docherty, Ross T. Campbell, Alasdair D. Henderson, Pardeep S. Jhund, Brian L. Claggett, Akshay S. Desai, James Lay-Flurrie, Lucas Hofmeister, Andrea Scalise, Carolyn S. P. Lam, Mark C. Petrie, Morten Schou, Michele Senni, Sanjiv J. Shah, Jacob A. Udell, Faiez Zannad, Bertram Pitt, Muthiah Vaduganathan, Scott D. Solomon, John J. V. McMurray
Journal: JAMA Cardiology (2025)

Patients with heart failure (HF) and mildly reduced ejection fraction (HFmrEF) or preserved ejection fraction (HFpEF) have a spectrum of risk, and the effect of therapies may vary by risk. To validate the Prognostic Models for Mortality and Morbidity in HFpEF (PREDICT-HFpEF) in the phase 3 randomized clinical trial Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure (FINEARTS-HF) and to evaluate the effect of finerenone, compared with placebo, across the spectrum of risk in these patients. The FINEARTS-HF trial was conducted across 653 sites in 37 countries. Participants were adults 40 years and older with symptomatic HF and left ventricular EF of 40% or greater randomized between September 2020 and January 2023. Finerenone (titrated to 20 mg or 40 mg) or placebo. The 3 PREDICT-HFpEF risk scores for the composite outcome of cardiovascular death or HF hospitalization, cardiovascular death, and all-cause death, respectively, were calculated. Predicted risk was compared with observed outcomes. Model performance was assessed using the Harrell C statistic. The rates of the predicted outcomes (plus the composite of cardiovascular death and worsening HF events, which was the primary end point in the trial) were examined according to quintiles of risk score, as was the effect of finerenone according to risk quintiles. A total of 6001 patients (mean [SD] age, 72 [9.6] years; 3269 male [54.5%]) were randomized in the FINEARTS-HF trial. The C statistics for cardiovascular death or HF hospitalization, cardiovascular death, and all-cause death at 2 years were 0.71 (95% CI, 0.69-0.72), 0.68 (95% CI, 0.66-0.71), and 0.69 (95% CI, 0.67-0.71), respectively. The risk of the composite outcomes was approximately 8- to 10-fold higher in those in the highest compared with the lowest risk quintile. The relative risk reduction with finerenone compared with placebo was consistent across the spectrum of risk for all outcomes examined (eg, interaction P value for primary outcome = .24). Results of the FINEARTS-HF randomized clinical trial demonstrate that the PREDICT-HFpEF models performed well in terms of calibration and discrimination. Baseline risk did not modify the benefit of finerenone. ClinicalTrials.gov Identifier: NCT04435626.
Sleep Characteristics and Long-Term Risk of Type 2 Diabetes Among Women With Gestational Diabetes
Authors: Xin Yin, Wei Bao, Sylvia H. Ley, Jiaxi Yang, Sherri Babaeian Cuffe, Guoqi Yu, Jorge E. Chavarro, Peipei Liu, Juan Helen Zhou, Deirdre K. Tobias, Frank B. Hu, Cuilin Zhang
Journal: JAMA Network Open (2025)

Women with a history of gestational diabetes (GD) are at high risk for developing type 2 diabetes (T2D). Sleep is a crucial lifestyle factor associated with cardiometabolic health, yet studies on its role in the progression from GD to T2D are sparse. To investigate the associations of sleep duration and quality with T2D risk and levels of glucose metabolism biomarkers in women with a history of GD. This cohort study used data from the Nurses' Health Study II, an ongoing longitudinal cohort that began in 1989 and initially included 116 429 female nurses with health status and lifestyle factors updated every 2 to 4 years. A subset of participants with a history of GD was followed up through June 2021. Sleep characteristics were assessed in the 2001 questionnaire (administered from June 2001 to June 2003), which served as the baseline for follow-up. Data were analyzed from November 2023 to August 2024. Snoring frequency, sleep duration, and daytime sleepiness. Physician-diagnosed incident T2D was ascertained biennially via questionnaires. Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and 95% CIs. Biomarkers (glycated hemoglobin [HbA1c], C-peptide, and insulin) were compared across sleep characteristic categories using multivariable-adjusted least-squares means (LSMs) and 95% CIs. During a total of 42 155 person-years of follow-up among 2891 women with a history of GD (mean [SD] age, 45.3 [4.4] years), 563 women (19.5%) developed T2D. Compared with women who reported rarely snoring, those with occasional or regular snoring had significantly higher T2D risk, with adjusted HRs of 1.54 (95% CI, 1.18-2.02) and 1.61 (95% CI, 1.21-2.13), respectively. Compared with women who slept 7 to 8 hours per day, shorter sleep duration (≤6 hours per day) was significantly associated with a higher risk of T2D (HR, 1.32; 95% CI, 1.06-1.64). Women who slept 6 or fewer hours per day and snored regularly had the highest risk of developing T2D (HR, 2.06; 95% CI, 1.38-3.07). Additionally, more frequent snoring was associated with higher HbA1c (LSM, 5.89; 95% CI, 5.75-6.02), C-peptide (LSM, 4.30; 95% CI, 3.70-4.99), and insulin (LSM, 11.25; 95% CI, 8.75-14.40) levels in the full adjusted models (P = .01 for trend for all). In this cohort study of women with a history of GD, shorter sleep duration and both occasional and regular snoring were significantly associated with an increased risk of T2D. These findings suggest that improving sleep health may be important to reduce T2D incidence in this high-risk population.
A single-cell atlas of circulating immune cells over the first 2 months of age in extremely premature infants
Authors: Oluwabunmi Olaloye, Weihong Gu, Arne Gehlhaar, Burhanuddin Sabuwala, Chino K. Eke, Yujia Li, Tessa Kehoe, Rohit Farmer, Gisela Gabernet, Carrie L. Lucas, John S. Tsang, Saquib A. Lakhani, Sarah N. Taylor, George Tseng, Steven H. Kleinstein, Liza Konnikova
Journal: Science Translational Medicine (2025)

Extremely premature infants (EPIs) who are born before 30 weeks of gestation are susceptible to infection; however, the trajectory of their peripheral immunity is poorly understood. Here, we undertook longitudinal analyses of immune cells from 250 μl of whole blood at 1 week, 1 month, and 2 months from 10 EPIs and compared these with samples from healthy adults and with preterm and full-term cord blood samples. Single-cell suspensions from individual samples were split to perform single-cell RNA sequencing, T and B cell receptor sequencing, and phosphoprotein mass cytometry. The trajectories of circulating T, B, myeloid, and natural killer cells in EPIs over the first 2 months of life were distinct from those of full-term infants. In EPIs, peripheral T cell development rapidly progressed over the first month of life, with an increase in the proportion of naïve CD4+, regulatory, and cycling T cells, accompanied by greater STAT5 (signal transducer and activator of transcription 5) signaling. EPI memory CD4+ T cells showed a T helper 1 (TH1) predominance compared with TH2 skewing of central memory-like T cells in full-term infants, and B cells from 2-month-old EPIs exhibited increased signatures of activation and differentiation. Both B and T cells from 2-month-old EPIs displayed increased interferon signatures compared with cells from full-term infants. In conclusion, we demonstrated the feasibility of longitudinal multiomic analyses in EPIs using minute amounts of blood and developed a resource describing peripheral immune development in EPIs that suggested ongoing activation in early life.
Estrogen influences class-switched memory B cell frequency only in humans with two X chromosomes
Authors: Hannah Peckham, Anna Radziszewska, Justyna Sikora, Nina M. de Gruijter, Restuadi Restuadi, Melissa Kartawinata, Lucia Martin-Gutierrez, George A. Robinson, Claire T. Deakin, Lucy R. Wedderburn, Elizabeth C. Jury, Gary Butler, Emma S. Chambers, Elizabeth C. Rosser, Coziana Ciurtin
Journal: The Journal of Experimental Medicine (2025)

Sex differences in immunity are well-documented, though mechanisms underpinning these differences remain ill-defined. Here, in a human-only ex vivo study, we demonstrate that postpubertal cisgender females have higher levels of CD19+CD27+IgD− class-switched memory B cells compared with age-matched cisgender males. This increase is only observed after puberty and before menopause, suggesting a strong influence for sex hormones. Accordingly, B cells express high levels of estrogen receptor 2 (ESR2), and class-switch–regulating genes are enriched for ESR2-binding sites. In a gender-diverse cohort, blockade of natal estrogen in transgender males (XX karyotype) reduced class-switched memory B cell frequency, while gender-affirming estradiol treatment in transgender females (XY karyotype) did not increase these levels. In postmenopausal cis-females, class-switched memory B cells were increased in those taking hormone replacement therapy (HRT) compared with those who were not. These data demonstrate that sex hormones and chromosomes work in tandem to impact immune responses, with estrogen only influencing the frequency of class-switched memory B cells in individuals with an XX chromosomal background.
An oral norovirus vaccine tablet was safe and elicited mucosal immunity in older adults in a phase 1b clinical trial
Authors: Becca A. Flitter, Susan N. Greco, Colin A. Lester, Elena D. Neuhaus, Sarah N. Tedjakusuma, Mallory Shriver, Esmeralda Cuevas-Juárez, Samanta Gutierrez, Molly R. Braun, Marcela F. Pasetti, Sean N. Tucker, James F. Cummings
Journal: Science Translational Medicine (2025)

Norovirus is a leading cause of acute gastroenteritis globally, with infections in older adults associated with heightened severity and increased risk of mortality. Currently, no licensed vaccines are available to prevent norovirus infection. We developed an orally administered vaccine tablet (VXA-G1.1-NN) that delivers a nonreplicating adenoviral vector expressing norovirus GI.1 major capsid protein VP1 to the small intestine. Here, we report safety and immunogenicity results of a randomized, double-blind, placebo-controlled clinical trial (NCT04854746) that investigated the oral administration of VXA-G1.1-NN in two groups of healthy older adults aged 55 to 65 and 66 to 80 years. VXA-G1.1-NN was administered orally at three dose levels by prime and boost, 28 days apart. Immunization was well tolerated regardless of dose, with mild to moderate reported solicited symptoms and no related serious or grade 3 adverse events. Oral delivery of VXA-G1.1-NN elicited VP1-specific serum immunoglobulin G (IgG) and IgA and functional antibodies in a dose-dependent manner 28 days postvaccination and remained above baseline for 210 days. Moreover, robust circulating VP1-specific IgA antibody-secreting cells were detected 1 week postvaccination along with IgA+ plasmablasts expressing the mucosal-homing marker α4β7. VP1-specific IgA increased in saliva and nasal lining fluid 28 days postvaccination in both age groups and remained above baseline concentrations through 210 days, demonstrating durable mucosal responses. This clinical trial established that oral administration of VXA-G1.1-NN is safe, well tolerated, and induces robust systemic and mucosal immune responses in adults up to 80 years old.
Metabolic reprogramming in cancer and senescence
Authors: Yuzhu Zhang, Jiaxi Tang, Can Jiang, Hanxi Yi, Shu Guang, Gang Yin, Maonan Wang
Journal: MedComm (2025)

The rising trend in global cancer incidence has caused widespread concern, one of the main reasons being the aging of the global population. Statistical data show that cancer incidence and mortality rates show a clear upward trend with age. Although there is a commonality between dysregulated nutrient sensing, which is one of the main features of aging, and metabolic reprogramming of tumor cells, the specific regulatory relationship is not clear. This manuscript intends to comprehensively analyze the relationship between senescence and tumor metabolic reprogramming; as well as reveal the impact of key factors leading to cellular senescence on tumorigenesis. In addition, this review summarizes the current intervention strategies targeting nutrient sensing pathways, as well as the clinical cases of treating tumors targeting the characteristics of senescence with the existing nanodelivery research strategies. Finally, it also suggests sensible dietary habits for those who wish to combat aging. In conclusion, this review attempts to sort out the link between aging and metabolism and provide new ideas for cancer treatment.
From Gestational Diabetes to Type 2 Diabetes—Is Poor Sleep to Blame?
Authors: Christian Benedict, Marie-Pierre St-Onge
Journal: JAMA Network Open (2025)

Xin Yin, PhD; Wei Bao, PhD; Sylvia H. Ley, PhD; Jiaxi Yang, PhD; Sherri Babaeian Cuffe, MS; Guoqi Yu, PhD; Jorge E. Chavarro, PhD; Peipei Liu, PhD; Juan Helen Zhou, PhD; Deirdre K. Tobias, PhD; Frank B. Hu, PhD; Cuilin Zhang, PhD
Vasomics of the liver
Authors: Chengyan Wang, Eric Felli, Jonathan Andrew Fallowfield, Christoph Frank Dietrich, Don Rockey, Jürgen Hennig, Gao-Jun Teng, Jordi Gracia-Sancho, Xiaolong Qi
Journal: Gut (2025)

Chronic liver disease is a cluster of disorders associated with complex haemodynamic alterations, which is characterised by structural and functional disruptions of the intrahepatic and extrahepatic vasculature. 'Vasomics' is an emerging omics discipline that comprehensively analyses and models the vascular system by integrating pathophysiology of disease, biomechanics, medical imaging, computational science and artificial intelligence. Vasomics is further typified by its multidimensional, multiscale and high-throughput nature, which depends on the rapid and robust extraction of well-defined vascular phenotypes with clear clinical and/or biological interpretability. By leveraging multimodality medical imaging techniques, vascular functional assessments, pathological image evaluation, and related computational methods, integrated vasomics provides a deeper understanding of the associations between the vascular system and disease. This in turn reveals the crucial role of the vascular system in disease occurrence, progression and treatment responses, thereby supporting precision medicine approaches. Pathological vascular features have already demonstrated their key role in different clinical scenarios. Despite this, vasomics is yet to be widely recognised. Therefore, we furnished a comprehensive definition of vasomics providing a classification of existing hepatic vascular phenotypes into the following categories: anatomical, biomechanical, biochemical, pathophysiological and composite.
Bacterial Vaginosis — Time to Treat Male Partners
Authors: Christina A Muzny, Jack D Sobel
Journal: New England Journal of Medicine (2025)

Bacterial vaginosis, the most common cause of vaginal discharge in reproductive-age women,1 is associated with multiple consequential adverse outcomes, including an increased risk of adverse birth outcomes, acquisition of human immunodeficiency virus and other sexually transmitted infections (STIs), pelvic inflammatory disease, and a high incidence of symptomatic recurrence.2 Bacterial vaginosis is characterized as a polymicrobial vaginal dysbiosis due to a decrease in protective lactobacillus species and an increase in facultative and strictly anaerobic bacteria.3 The incidence of symptomatic recurrence after treatment can be as high as 60% at 12 months.4 Despite substantial data supporting the role of sexual transmission of . . .