tbuckley/cabot-search huggingface dataset:
Racial and Ethnic Disparities in Use of Helicopter Transport After Severe Trauma in the US
Authors: Christian Mpody, Maíra I. Rudolph, Alexandra Bastien, Ibraheem M. Karaye, Tracey Straker, Felix Borngaesser, Matthias Eikermann, Olubukola O. Nafiu
Journal: JAMA Surgery (2025)

In the US, traumatic injuries are a leading cause of mortality across all age groups. Patients with severe trauma often require time-sensitive, specialized medical care to reduce mortality; air transport is associated with improved survival in many cases. However, it is unknown whether the provision of and access to air transport are influenced by factors extrinsic to medical needs, such as race or ethnicity. To examine the current trends of racial and ethnic disparities in air transport use for patients who sustain severe trauma. This population-based cohort study used data from the National Trauma Data Bank from 2016 to 2022. Participants were patients older than 15 years who sustained a severe injury and required an urgent surgical procedure or intensive care unit (ICU) admission at level I or II trauma centers with helicopter service. Severe injury requiring treatment at a level I or II trauma center. The primary mode of transport, categorized as either helicopter ambulance or ground ambulance. A multifaceted approach was used to narrow the observed racial and ethnic disparities in helicopter deployment. The secondary outcome was mortality after helicopter transport vs ground ambulance transport. Data were included for 341 286 patients at 458 level I or II trauma centers with helicopter service. Their mean (SD) age was 47 (20) years; 243 936 patients (71.6%) were male and 96 633 (28.4%) female. Asian individuals were less likely to receive helicopter transport compared with White individuals (6.8% vs 21.8%; aRR, 0.38; 95% CI, 0.30-0.48; P < .001), driven by lower use for Asian patients in teaching hospitals (aRR, 0.29; 95% CI, 0.21-0.40; P < .001) and level I trauma centers (aRR, 0.33; 95% CI, 0.24-0.44; P < .001). In addition, Black patients were less likely to receive helicopter transport (8.7% vs 21.8%; aRR, 0.42; 95% CI, 0.36-0.49; P < .001), particularly in teaching hospitals (aRR, 0.41; 95% CI, 0.33-0.50; P < .001) and level I trauma centers (aRR, 0.40; 95% CI, 0.34-0.49; P < .001). A similar but less pronounced disparity was noted for Hispanic patients. Helicopter transport was associated with a lower mortality risk compared with ground transport (37.7% vs 42.6%; adjusted relative risk [aRR], 0.87; 95% CI, 0.85-0.89; P < .001). This study found that racial and ethnic minority patients, particularly Asian and Black patients, and notably those treated at level I teaching hospitals were less likely to receive airlift services compared with White patients. The current expansion of helicopter emergency medical services has yet to translate into equitable care for patients of all races and ethnicities.
Polygenic Risk Score Added to Conventional Case Finding to Identify Undiagnosed Chronic Obstructive Pulmonary Disease
Authors: Jingzhou Zhang, Brian D. Hobbs, Edwin K. Silverman, David Sparrow, Victor E. Ortega, Hanfei Xu, Chengyue Zhang, Josée Dupuis, Allan J. Walkey, George T. O’Connor, Michael H. Cho, Matthew Moll
Journal: JAMA (2025)

Importance Chronic obstructive pulmonary disease (COPD) is often undiagnosed. Although genetic risk plays a significant role in COPD susceptibility, its utility in guiding spirometry testing and identifying undiagnosed cases is unclear. Objective To determine whether a COPD polygenic risk score (PRS) enhances the identification of undiagnosed COPD beyond a case-finding questionnaire (eg, the Lung Function Questionnaire) using conventional risk factors and respiratory symptoms. Design, Setting, and Participants This cross-sectional analysis of participants 35 years or older who reported no history of physician-diagnosed COPD was conducted using data from 2 observational studies: the community-based Framingham Heart Study (FHS) and the COPD-enriched Genetic Epidemiology of COPD (COPDGene) study. Exposures Modified Lung Function Questionnaire (mLFQ) scores and COPD PRS. Main Outcomes and Measures The primary outcome was spirometry-defined moderate to severe COPD (forced expiratory volume in the first second of expiration/forced vital capacity [FEV 1 /FVC] &amp;amp;lt;0.7 and FEV 1 [percent predicted] &amp;amp;lt;80%). The performance of logistic models was assessed using the PRS, mLFQ score, and PRS plus mLFQ score for predicting spirometry-defined COPD. Results Among 3385 FHS participants (median age, 52.0 years; 45.9% male) and 4095 COPDGene participants (median age, 56.8 years; 55.5% male) who reported no history of COPD, 160 (4.7%) FHS and 775 (18.9%) COPDGene participants had spirometry-defined COPD. Adding the PRS to the mLFQ score significantly improved the area under the curve from 0.78 to 0.84 ( P &amp;amp;lt; .001) in FHS, 0.69 to 0.72 ( P = .04) in COPDGene non-Hispanic African American, and 0.75 to 0.78 ( P &amp;amp;lt; .001) in COPDGene non-Hispanic White participants. At a risk threshold for spirometry referral of 10%, the addition of the PRS to the mLFQ score correctly reclassified 13.8% (95% CI, 6.6%-21.0%) of COPD cases in FHS, but not in COPDGene. Conclusions and Relevance A COPD PRS enhances the identification of undiagnosed COPD beyond a conventional case-finding approach in the general population. Further research is needed to assess its impact on COPD diagnosis and outcomes.
Dupilumab treatment restores lesional and non-lesional skin barrier function in adults and adolescents with atopic dermatitis irrespective of the filaggrin genotype: Results from an open-label, healthy-control–matched, phase 4 clinical study (BALISTAD)
Authors: Robert Bissonnette, Elena Goleva, Evgeny Berdyshev, Shannon Garcia, Marco Ramirez-Gama, Patricia A Taylor, Gabriel Bologna, Amy H Praestgaard, Lei Chen, Noah A Levit, Joseph Zahn, Ana B Rossi, Annie Zhang, Donald Y M Leung
Journal: Journal of the American Academy of Dermatology (2025)
<i>Faecalibacterium prausnitzii</i> regulates carbohydrate metabolic functions of the gut microbiome in C57BL/6 mice
Authors: Peiling Geng, Ni Zhao, Yufan Zhou, Reuben S. Harris, Yong Ge
Journal: Gut Microbes (2025)

The probiotic impact of microbes on host metabolism and health depends on both host genetics and bacterial genomic variation. Faecalibacterium prausnitzii is the predominant human gut commensal emerging as a next-generation probiotic. Although this bacterium exhibits substantial intraspecies diversity, it is unclear whether genetically distinct F. prausnitzii strains might lead to functional differences in the gut microbiome. Here, we isolated and characterized a novel F. prausnitzii strain (UT1) that belongs to the most prevalent but underappreciated phylogenetic clade in the global human population. Genome analysis showed that this butyrate-producing isolate carries multiple putative mobile genetic elements, a clade-specific defense system, and a range of carbohydrate catabolic enzymes. Multiomic approaches were used to profile the impact of UT1 on the gut microbiome and associated metabolic activity of C57BL/6 mice at homeostasis. Both 16S rRNA and metagenomic sequencing demonstrated that oral administration of UT1 resulted in profound microbial compositional changes including a significant enrichment of Lactobacillus, Bifidobacterium, and Turicibacter. Functional profiling of the fecal metagenomes revealed a markedly higher abundance of carbohydrate-active enzymes (CAZymes) in UT1-gavaged mice. Accordingly, UT1-conditioned microbiota possessed the elevated capability of utilizing starch in vitro and exhibited a lower availability of microbiota-accessible carbohydrates in the gut. Further analysis uncovered a functional network wherein UT1 reduced the abundance of mucin-degrading CAZymes and microbes, which correlated with a concomitant reduction of fecal mucin glycans. Collectively, our results reveal a crucial role of UT1 in facilitating the carbohydrate metabolism of the gut microbiome and expand our understanding of the genetic and phenotypic diversity of F. prausnitzii.
The Access to Dialysis in Low- and Middle-Income Countries Commission: lessons for universal health coverage
Authors: Yot Teerawattananon, Kinanti Khansa Chavarina, Jeerath Phannajit, Jiratorn Sutawong, Natcha Yongphiphatwong, Sydney C W Tang, Talerngsak Kanjanabuch, Tanainan Chuanchaiyakul, Thunyarat Anothaisintawee, Valerie Luyckx, Wanrudee Isaranuwatchai, Kearkiat Praditpornsilpa, Kriang Tungsanga, Vivekanand Jha
Journal: Nature Medicine (2025)
Impact of visual presentation of atherosclerotic carotid plaque on cardiovascular risk profile using mHealth technologies
Authors: Greta Ullrich, Alexander Bäuerle, Lisa Maria Jahre, Katrin Paldán, Jana Rosemeyer, Chiara Kalaitzidis, Christos Rammos, Martin Teufel, Tienush Rassaf, Julia Lortz
Journal: npj Digital Medicine (2025)

Abstract This randomized, controlled trial evaluated the impact of plaque visualization combined with daily tasks on cardiovascular risk profile and included 240 participants with coronary arterial disease. The intervention group received the PreventiPlaque app during the 12-month study period in addition to standard care. The app contained daily tasks that promoted lifestyle modifications and adherence to prescribed medication. It included ultrasound images of participants´ individual carotid plaque, which were updated regularly. The impact of plaque visualization and personalized app usage was evaluated, using a change in the SCORE2 as a primary endpoint. In the intervention group, the SCORE2 was significantly lower after the study period ( t (120) = 6.43, p adj &lt; 0.001, d RM = 0.58). This demonstrates the efficacy of the PreventiPlaque app in supporting lifestyle modifications and medication adherence. These findings suggest that personalized mHealth interventions in combination with visual risk communication are valuable tools in secondary prevention. Trial Registration : The study was registered at ClinicalTrials.gov under the identifier NCT05096637 on 27 October 2021 and was approved by the local ethics committee of the University of Duisburg-Essen (20-9157-BO).
Novel clinical trial designs emerging from the molecular reclassification of cancer
Authors: Mina Nikanjam, Shumei Kato, Teresa Allen, Jason K. Sicklick, Razelle Kurzrock
Journal: CA A Cancer Journal for Clinicians (2025)

Abstract Next‐generation sequencing has revealed the disruptive reality that advanced/metastatic cancers have complex and individually distinct genomic landscapes, necessitating a rethinking of treatment strategies and clinical trial designs. Indeed, the molecular reclassification of cancer suggests that it is the molecular underpinnings of the disease, rather than the tissue of origin, that mostly drives outcomes. Consequently, oncology clinical trials have evolved from standard phase 1, 2, and 3 tissue‐specific studies; to tissue‐specific, biomarker‐driven trials; to tissue‐agnostic trials untethered from histology (all drug‐centered designs ); and, ultimately, to patient‐centered , N‐of‐1 precision medicine studies in which each patient receives a personalized, biomarker‐matched therapy/combination of drugs. Innovative technologies beyond genomics, including those that address transcriptomics, immunomics, proteomics, functional impact, epigenetic changes, and metabolomics, are enabling further refinement and customization of therapy. Decentralized studies have the potential to improve access to trials and precision medicine approaches for underserved minorities. Evaluation of real‐world data, assessment of patient‐reported outcomes, use of registry protocols, interrogation of exceptional responders, and exploitation of synthetic arms have all contributed to personalized therapeutic approaches. With greater than 1 × 10 12 potential patterns of genomic alterations and greater than 4.5 million possible three‐drug combinations, the deployment of artificial intelligence/machine learning may be necessary for the optimization of individual therapy and, in the near future, also may permit the discovery of new treatments in real time.
Microbiota translocation following intestinal barrier disruption promotes Mincle-mediated training of myeloid progenitors in the bone marrow
Authors: Iñaki Robles-Vera, Aitor Jarit-Cabanillas, Paola Brandi, María Martínez-López, Sarai Martínez-Cano, Manuel Rodrigo-Tapias, Marcos Femenía-Muiña, Ana Redondo-Urzainqui, Vanesa Nuñez, Cristina González-Correa, Javier Moleón, Juan Duarte, Laura Conejero, Pablo Mata-Martínez, Carmen María Díez-Rivero, Marta Bergón-Gutiérrez, Iván Fernández-López, Manuel J Gómez, Ana Quintas, Ana Dopazo, Fátima Sánchez-Cabo, Esther Pariente, Carlos Del Fresno, José Luis Subiza, Salvador Iborra, David Sancho
Journal: Immunity (2025)

Impairment of the intestinal barrier allows the systemic translocation of commensal bacteria, inducing a proinflammatory state in the host. Here, we investigated innate immune responses following increased gut permeability upon administration of dextran sulfate sodium (DSS) in mice. We found that Enterococcus faecalis translocated to the bone marrow following DSS treatment and induced trained immunity (TI) hallmarks in bone-marrow-derived mouse macrophages and human monocytes. DSS treatment or heat-killed E. faecalis reprogrammed bone marrow progenitors (BMPs), resulting in enhanced inflammatory responses in vitro and in vivo and protection against subsequent pathogen infections. The C-type lectin receptor Mincle (Clec4e) was essential for E. faecalis-induced TI in BMPs. Clec4e-/- mice showed impaired TI upon E. faecalis administration and reduced pathology following DSS treatment. Thus, Mincle sensing of E. faecalis induces TI that may have long-term effects on pathologies associated with increased gut permeability.
A genome-wide association study identified PRKCB as a causal gene and therapeutic target for Mycobacterium avium complex disease
Authors: Ruijuan Zheng, Zhiqiang Li, Weijun Fang, Hai Lou, Feng Liu, Qin Sun, Xiang Shi, Hua Liu, Qing Chen, Xiaona Shen, Lan Yao, Liru Guan, Jianxia Chen, Yingzhou Xie, Yifan Yang, Hua Yang, Ling Wang, Lianhua Qin, Xiaochen Huang, Jie Wang, Zhonghua Liu, Haipeng Liu, Baoxue Ge, Jinfu Xu, Wei Sha
Journal: Cell Reports Medicine (2025)

Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic progressive lung disease that is increasing in incidence. Host genetic factors are associated with NTM-PD susceptibility. However, the heritability of NTM-PD is not well understood. Here, we perform a two-stage genome-wide association study (GWAS) and discover a susceptibility locus at 16p21 associated with NTM-PD, especially with pulmonary Mycobacterium avium complex (MAC) disease. As the lead variant, rs194800 C allele augments protein kinase C beta (PRKCB) gene expression and associates with severer NTM-PD. The functional studies show that PRKCB exacerbates M. avium infection and promotes intracellular survival of M. avium in macrophages by inhibiting phagosomal acidification. Mechanistically, PRKCB interacts with subunit G of the vacuolar-H+-ATPase (V-ATPase) and vacuolar protein sorting-associated protein 16 homolog (VPS16), blocking the fusion between lysosomes and mycobacterial phagosomes. PRKCB inhibitor has therapeutic potential against M. avium infection. These findings provide insights into the genetic etiology of NTM-PD and highlight PRKCB as an attractive target for host-directed therapy of MAC disease.
Multimodal integration using a machine learning approach facilitates risk stratification in HR+/HER2− breast cancer
Authors: Hang Zhang, Fan Yang, Ying Xu, Shen Zhao, Yi-Zhou Jiang, Zhi-Ming Shao, Yi Xiao
Journal: Cell Reports Medicine (2025)

Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer is the most common type of breast cancer, with continuous recurrence remaining an important clinical issue. Current relapse predictive models in HR+/HER2- breast cancer patients still have limitations. The integration of multidimensional data represents a promising alternative for predicting relapse. In this study, we leverage our multi-omics cohort comprising 579 HR+/HER2- breast cancer patients (200 patients with complete data across 7 modalities) and develop a machine-learning-based model, namely CIMPTGV, which integrates clinical information, immunohistochemistry, metabolomics, pathomics, transcriptomics, genomics, and copy number variations to predict recurrence risk of HR+/HER2- breast cancer. This model achieves concordance indices (C-indices) of 0.871 and 0.869 in the train and test sets, respectively. The risk population predicted by the CIMPTGV model encompasses those identified by single-modality models. Feature analysis reveals that synergistic and complementary effects exist in different modalities. Simultaneously, we develop a simplified model with a mean area under the curve (AUC) of 0.840, presenting a useful approach for clinical applications.
A Multipotent PROX1+ Tumor Stem/Progenitor Cell Population Emerges During Intestinal Tumorigenesis and Mediates Radioresistance in Colorectal Cancer
Authors: Pauliina Kallio, Cinzia Bessone, Fatemeh Seyednasrollah, Jefim Brodkin, Marika Lassila, Jenny Högström, Alejandra González-Loyola, Tatiana V. Petrova, Caj Haglund, Kari Alitalo
Journal: Cancer Research (2025)

Abstract Colorectal carcinoma (CRC) progression is associated with an increase in PROX1+ tumor cells, which exhibit features of CRC stem cells and contribute to metastasis. Here, we aimed to provide a better understanding to the function of PROX1+ cells in CRC, investigating their progeny and their role in therapy resistance. PROX1+ cells in intestinal adenomas of ApcMin/+ mice expressed intestinal epithelial and CRC stem cell markers, and cells with high PROX1 expression could both self-renew tumor stem/progenitor cells and contribute to differentiated tumor cells. Most PROX1-lineage traced tumor cells were stem/progenitor cells, which can supply cells to multiple intestinal tumor cell lineages, whereas most lineage-traced LGR5+ tumor cells were enterocytes, indicating that PROX1+ and LGR5+ tumor stem cells have distinct differentiation programs. Although the PROX1+ tumor cells proliferated slower than PROX1- cells, irradiation increased the proportion of PROX1+ cells in human CRC cell lines, patient-derived organoids, and tumor xenografts. Furthermore, transcripts related to DNA damage repair (DDR) were enriched in PROX1+ vs. PROX1- cells in adenomas and in CRC tumor cells from patients. Experiments with PROX1 silencing and overexpression indicated that PROX1 expression enhances CRC cell colony formation following irradiation. PROX1 interacted with DDR proteins, including components of non-homologous end-joining (NHEJ) and base excision repair, and inhibition of NHEJ repair led to a decreased proportion of PROX1+ cells following irradiation. In conclusion, PROX1+ cells are irradiation-resistant tumor stem/progenitor cells capable of self-renewal and differentiation. DDR inhibitors could represent a strategy to target the treatment-resistant PROX1+ tumor stem cells.
Targeting ARPC1B Overcomes Immune Checkpoint Inhibitor Resistance in Glioblastoma by Reversing Pro-tumorigenic Macrophage Polarization
Authors: Tianqi Liu, Tao Sun, Xin Chen, Jianqi Wu, Xiaoqian Sun, Xing Liu, Haixu Yan, Qiang Fu, Zirong Fan, Xiangyu Wang, Peng Cheng, Wen Cheng, Anhua Wu
Journal: Cancer Research (2025)

Abstract Immunotherapy has elicited significant improvements in outcomes for patients with several tumor types. However, the immunosuppressive microenvironment in glioblastoma restricts the therapeutic efficacy of immune checkpoint blockade (ICB). In this study, we investigated which components of the immune microenvironment contribute to ICB failure in glioblastoma to elucidate the underlying causes of immunotherapeutic resistance. Macrophages were identified as a main contributor to ICB resistance. Expression of ARPC1B, a regulatory subunit of the Arp2/3 complex, was elevated in glioblastoma and correlated with macrophage enrichment and prognosis. ARPC1B in tumor cells increased STAT1 expression and subsequent IL10 production, which induced a pro-tumorigenic macrophage state. Mechanistically, ARPC1B inhibited the ubiquitination and degradation of STAT1 by preventing the E3 ubiquitin ligase NEDD4L from binding to STAT1 and by supporting the interaction between STAT1 and the deubiquitinase USP7. Inhibiting ARPC1B reshaped the immunosuppressive microenvironment and increased the efficacy of ICB in glioblastoma models. This study highlights the important role of ARPC1B in macrophage-mediated immunosuppression and proposes a combination treatment regimen for glioblastoma immunotherapy.
Associations of Short-Term Ozone Exposure With Hypoxia and Arterial Stiffness
Authors: Qiaoyi Hua, Xin Meng, Wu Chen, Yifan Xu, Ruiwei Xu, Yunxiu Shi, Jiajianghui Li, Xueling Meng, Ailin Li, Qianqian Chai, Mengshuang Sheng, Yuan Yao, Yunfei Fan, Ruohong Qiao, Yi Zhang, Teng Wang, Yidan Zhang, Xiaoyu Cui, Yaqi Yu, Haonan Li, Rui Tang, Meilin Yan, Bu Duo, Danzeng Dunzhu, Zhuo Ga, Lei Hou, Yingjun Liu, Jing Shang, Qi Chen, Xinghua Qiu, Chunxiang Ye, Jicheng Gong, Tong Zhu
Journal: Journal of the American College of Cardiology (2025)

Epidemiological studies reported associations between ozone (O3) exposure and cardiovascular diseases, yet the biological mechanisms remain underexplored. Hypoxia is a shared pathogenesis of O3-associated diseases; therefore, we hypothesized that O3 exposure may induce changes in hypoxia-related markers, leading to adverse cardiovascular effects. This study aimed to investigate associations of short-term O3 exposure with hypoxic biomarkers and arterial stiffness. We conducted a panel study involving 210 young healthy residents in 2 cities at different altitudes on the Qinghai-Tibetan Plateau in China, where O3 concentrations are high and particulate pollution is low. Participants underwent 4 repeated visits to assess ambient O3 exposure levels, hypoxic biomarkers, and arterial stiffness. We applied linear mixed-effects models to assess the associations of O3 exposure (lag1 to lag1-7 days) with hypoxic biomarkers and arterial stiffness, adjusted for confounders. Mediation analyses explored the hypoxia's role in O3-related arterial stiffness changes. We further examined effect modification by residence altitude and the robustness of results by including PM2.5 (particulate matter ≤2.5 μm in aerodynamic diameter) or NO2 in 2-pollutant models. O3 exposure 1 to 7 days before visits was significantly associated with changes in multiple hypoxic biomarkers. A 10-ppb increase in O3 exposure was linked to significant decreases in oxygen saturation (SpO2) and increases in red blood cell count (RBC), hemoglobin concentration, and hematocrit, with maximum changes by -0.42%, 0.92%, 0.97%, and 1.92%, respectively. Laboratory analysis of mRNA and protein markers consistently indicated that O3 exposure activated the hypoxia-inducible factor 1 (HIF-1) signaling pathway. Additionally, a 10-ppb increase in O3 corresponded to a 1.04% to 1.33% increase in carotid-femoral pulse wave velocity (cfPWV), indicating increased arterial stiffness. RBC, hemoglobin concentration, and hematocrit increases significantly mediated the O3-cfPWV association, whereas the SpO2 reduction had an insignificant mediating effect. Associations of O3 with hypoxic biomarkers varied by altitude. The higher altitude group showed delayed associations with SpO₂ and HIF-1 expression but stronger associations with RBC indices. These associations remained robust after adjusting for copollutants. O3 exposure may reduce oxygen availability, prompting compensatory increases in red blood cells and hemoglobin, which exacerbate arterial stiffening. These findings provide new insights into the mechanisms underlying O3-induced cardiovascular injury.