tbuckley/cabot-search huggingface dataset:
Asthma Treatment Response Modified by PM2.5, NO2, and O3 Among African American Children: A Reanalysis of the AsthmaNet’s BARD Trial
Authors: Lizbeth F Gómez, Ellen Kinnee, Michael T Young, Joel D Kaufman, Anne M Fitzpatrick, Sharmilee M Nyenhuis, Julian Solway, Steven R White, Edward T Naureckas, Wanda Phipatanakul, Michael E Wechsler, Susan J Kunselman, David T Mauger, Leslie A McClure, Usama Bilal, Stephen C Lazarus, Fernando Holguin, Jane E Clougherty
Journal: Journal of Allergy and Clinical Immunology (2025)

Asthma morbidity significantly affects children of all racial backgrounds; however, African American children experience a greater disease burden than children from other racial groups. Despite the known influence of air pollution on asthma outcomes, its role in the efficacy of asthma treatments remains underexplored. To examine how exposure to particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) influenced treatment outcomes in the NIH AsthmaNet Best African American Response to Asthma Drugs (BARD) trial. The BARD trial randomized 224 African American children to four asthma treatments consisting of inhaled corticosteroids (ICS) and long-acting beta antagonists (LABA) administered in a randomized crossover fashion. Treatment efficacy was assessed by the frequency of asthma exacerbations, percent predicted FEV1 (%PFEV1), and annualized asthma control days. Residential exposures to PM2.5, NO2, and O3 were estimated using a validated spatiotemporal model. Mixed effects models were used to evaluate the interaction between pollution exposure and treatment efficacy, adjusting for age, household triggers and trial site. PM2.5, NO2, and O3 exposures ranged substantially across participants: from 2.28 - 15.3 μg/m3, 2.34 - 63.7 ppm, and 2.57 - 23.7 ppb, respectively. NO2 and PM2.5 exposures were not associated with increased exacerbations post-treatment (p for interaction = 0.15 and 0.08, respectively). However, NO2 exposure significantly modified the effect of high-dose ICS+LABA therapy on lung function. Children with below median NO2 exposures while on ICS + LABA had a reduction of 5.86 (1.16, 10.56) in %PFEV1 compared to those with above-median NO2 exposures. Residential high NO2 exposure may significantly attenuate the efficacy of ICS+LABA therapy on lung function in African American children. These findings suggest the need to consider environmental factors in clinical trials and asthma management strategies.
A Metal-Semimetal Zn–Ge Alloy with Modified Biodegradation Behavior and Enhanced Osteogenic Activity Mediated by Eutectic Ge Phases-induced Microgalvanic Cells
Authors: Kai Chen, Shan Gao, Xuenan Gu, Li Zhao, Yunan Lu, Jinwu Bai, Linjun Huang, Hongtao Yang, Yu Qin, Fang Zhou, Yongcan Huang, Yang Lv, Yufeng Zheng
Journal: Biomaterials (2025)
The novel brain penetrant ATM inhibitor WSD0628 provides robust radiosensitization of brain tumor patient derived xenografts
Authors: Zhiyi Xue, Ann C Mladek, Sneha Rathi, Sonia Jain, Rachael A Vaubel, Lateef A Odukoya, Darwin A Garcia, Lily Liu, Katrina K Bakken, Brett L Carlson, Lauren L Ott, Danielle M Burgenske, Zeng Hu, Sonja Dragojevic, Paul A Decker, Matthew L Kosel, William G Breen, Shiv K Gupta, Jeanette E Eckel-Passow, William F Elmquist, Wei Zhong, Jann N Sarkaria
Journal: Neuro-Oncology (2025)

Abstract Background The ataxia telangiectasia mutated (ATM) protein coordinates the cellular response to therapeutic radiation, and ATM inhibitors can potentially enhance the efficacy of radiation in otherwise radiation-resistant tumors. Methods The small molecule ATM kinase inhibitor WSD0628 was specifically designed for enhanced distribution across the blood brain barrier to more effectively treat glioblastoma (GBM) and brain metastases in combination with radiation therapy (RT). GBM and brain metastasis patient-derived xenograft (PDX) models were used to understand target inhibition, radiosensitization, inhibition of the DNA damage response, and in vivo efficacy. Results Initial in vitro characterization of WSD0628 demonstrate a high-level of selectivity across kinase families, limited aldehyde oxidase liability, and low risk of hERG interactions. Consistent with a central role for ATM in radiation response, WSD0628 blocked radiation-induced signaling and enhanced radiosensitivity in U251 glioma cells and brain tumor PDXs GBM120 and M12. In comparison to control or RT alone in orthotopic PDXs, the combination of WSD0628 with RT markedly prolonged median survival – GBM12 (19, 55 and 408 days, respectively); GBM43 (26, 44 and 143 days, respectively); GBM120 (51, 89 and 231 days, respectively); M12 (17, 39 and 190 days, respectively). Pharmacokinetic and pharmacodynamic testing after treatment in orthotopic GBM43 tumors showed inhibitory levels of WSD0628 and a reduction of γH2AX foci in the combination-treated tumors. Conclusion Collectively, these results suggest a promising role for WSD0628 in combination with RT in brain tumors and provide the rationale for an ongoing Phase 0/1A clinical trial testing this combination in recurrent GBM.
High peritumoral network connectedness in glioblastoma reveals a distinct epigenetic signature and is associated with decreased overall survival
Authors: Kerstin Jütten, Jonas Ort, Julius M Kernbach, Anke Meyer-Baese, Uwe Meyer-Baese, Hussam Aldin Hamou, Hans Clusmann, Martin Wiesmann, Juliane Bremer, Henner Koch, Aniella Bak, Franz Ricklefs, Richard Drexler, Dieter-Henrik Heiland, Daniel Delev
Journal: Neuro-Oncology (2025)

Abstract Background Glioblastomas are functionally integrated into their peritumoral neural environment, and the dynamic functional interaction can be analyzed using network theory, providing insights into the tumor-brain interface. We investigated peritumoral network connectedness of glioblastomas, revealing its association with distinct epigenetic signatures, its influence on survival, and its susceptibility to modification through surgical treatment. Methods Resting-state fMRI was performed on 48 glioblastoma patients. Tumor lesions were segmented, and networks were constructed at 10mm and 40mm distances from the tumor margin. These networks were mirrored to the healthy hemisphere to compare lesional and contralesional networks. The difference between lesional and contralesional mean degree centrality was calculated to assess peritumoral network connectedness. Its correlation with epigenetic signatures and effect on overall survival were analyzed. Surgery-induced changes in peritumoral network connectedness were evaluated in seven patients with follow-up data. Results Mean degree centrality was significantly higher in the lesional compared to the contralesional network (p=.032), indicating a tumor-induced effect on its local environment and reflecting high peritumoral network connectedness. Glioblastomas with a neural high epigenetic signature exhibited increased peritumoral network connectedness (p=.010), which was associated with decreased survival (p=.036). Postoperative peritumoral network connectedness tended to decrease, suggesting that surgical resection disrupts the functional communication between the tumor and its peritumoral environment. Conclusions The role of network features in predicting patient survival suggests their clinical relevance as imaging biomarkers for assessing personalized treatment strategies, which may include targeting crucial nodes for disconnection or even neuromodulation of neural circuits.
Mixed adeno-neuroendocrine carcinoma on dual-tracer 18F-FDG and 68Ga-DOTATATE PET/CT
Authors: Xuezhi Lin, Guojian Zhang
Journal: Clinical Nuclear Medicine (2025)

Tumor heterogeneity is not effortlessly detected. We present the case of a 66-year-old man with a history of rectal adenocarcinoma diagnosed four years ago, where mixed adeno-neuroendocrine carcinoma were identified via dual-tracer 18 F-FDG and 68 Ga-DOTATATE PET/CT. This case highlights the value of dual-tracer PET/CT imaging in assessing tumor heterogeneity and compensating for potential pathological sampling bias.
Prevalence, trends and outcomes from smoking in elective surgical systems: a secondary analysis of a prospective observational cohort study across 442 hospitals from 29 countries across Europe
Authors: Sivesh K. Kamarajah, Ieva Jakaityte, Setthasorn Ooi Zhi Yang, Omar Kouli, Kariem El-Boghdadly, Amanda Farley, James Glasbey, Dion Morton, Krishnarajah Nirantharakumar, Thomas Pinkney, David Thickett, Joyce Yeung, Aneel Bhangu, Dmitri Nepogodiev
Journal: The Lancet Regional Health - Europe (2025)
Side-by-side placement of a novel slim 6-mm multi-hole covered self-expandable metallic stent for malignant hilar biliary obstruction
Authors: Sho Takahashi, Toshio Fujisawa, Yusuke Takasaki, Daisuke Namima, Ko Tomishima, Shigeto Ishii, Hiroyuki Isayama
Journal: Endoscopy (2025)
Endoscopic direct diverticulitis therapy for acute uncomplicated diverticulitis
Authors: Jianzhen Ren, Jun Cai, Bo Li, Guang Yang, Suhuan Liao, Jia-Kuan Chen, Yitian Guo, Yang-Bor Lu, Silin Huang
Journal: Endoscopy (2025)

Background and study aims The global prevalence of acute uncomplicated diverticulitis is increasing, and patient care for this condition is experiencing a paradigm shift. This study evaluated the diagnostic and therapeutic value of endoscopic direct diverticulitis therapy (EDDT) using cholangioscope-assisted colonoscopy for acute uncomplicated diverticulitis. Patient and methods Patients with CT-confirmed acute uncomplicated diverticulitis (Hinchey stage Ia or Ib) between July 2023 and December 2024 who underwent EDDT were included. The technique success rate of EDDT, procedural time, endoscopic findings, symptom resolution, and recurrence were documented. Results Twelve patients (10 males; mean age 45.2 ± 10.1 years) underwent EDDT. Technical success was achieved in all 12 patients (100%). Cholangioscope-assisted colonoscopy revealed fecaliths with pus in 7 patients, copious purulent collection in 4, edematous inflammatory mucosa in 5, and bleeding in 1. Corresponding treatments were applied without complications. Abdominal pain resolved immediately after EDDT, and inflammatory parameters normalized. No recurrences were reported over a mean follow-up of 4 months (range 1–10 months). Conclusions EDDT utilizing cholangioscope-assisted colonoscopy is a feasible alternative treatment for acute uncomplicated diverticulitis, offering diagnostic and therapeutic advantages through direct visualization. With promising preliminary results, further studies with larger cohorts are warranted to confirm its efficacy and long-term outcomes.
Precancerous Cells Initiate Glioblastoma Evolution and Contribute to Intratumoral Heterogeneity
Authors: Hyun Jung Kim, Keon Woo Kim, Do Hyeon Cha, Jihwan Yoo, Eui Hyun Kim, Jong Hee Chang, Seok-Gu Kang, Jung Won Park, Ja Hye Kim, Yeonhee Lee, Eunha Lim, Yiseul Kim, Myeong Heui Kim, Xue Li, Joo Ho Lee, Jeong Ho Lee
Journal: Cancer Discovery (2025)

Abstract Neural stem cells (NSCs) in the subventricular zone (SVZ) are identified as cells-of-origin harboring driver mutations in glioblastoma (GBM), which is the most devastating brain tumor with highly heterogeneous nature. However, the sequential transformation of a limited number of mutation-harboring NSCs into a distant tumor with high intratumoral heterogeneity remains poorly understood. In this study, we have identified transcriptionally distinct types of mutation-harboring precancerous cells in our spontaneous, somatic mouse model recapitulating human GBM evolution as well as in tumor-free SVZ tissues from patients. These precancerous cells emerge via oligodendrocyte lineage specification, exhibiting unique transcriptional programs involving dysregulated translations and extracellular matrix remodeling. Subsequently, they give rise to heterogeneous tumor cell populations by activating multiple programs crucial for gliomagenesis. Our findings highlight the pivotal role of precancerous cells in tumor evolution and intratumoral heterogeneity, suggesting their potential as a novel therapeutic target for GBM.
Negative pressure wound therapy versus usual care in patients with surgical wound healing by secondary intention in the UK (SWHSI-2): an open-label, multicentre, parallel-group, randomised controlled trial
Authors: Catherine Arundel, Laura Mandefield, Caroline Fairhurst, Kalpita Baird, Athanasios Gkekas, Pedro Saramago, Ian Chetter
Journal: The Lancet (2025)
A proposed framework for monitoring and evaluating progress at the intersection of women, power, and cancer
Authors: Elise M Garton, Gavin Allman, Hyo Sook Bae, Kalina Duncan, Ibithal Fadhil, Nazik Hammad, Shirin Heidari, Erica Liebermann, Meritxell Mallafré-Larrosa, Jennifer Moodley, Rachel Nugent, Isabelle Soerjomataram, Carolyn D Taylor, Karla Unger-Saldaña, Verna Vanderpuye, Ophira Ginsburg
Journal: The Lancet (2025)
Live-attenuated Mycobacterium tuberculosis vaccine, MTBVAC, in adults with or without M tuberculosis sensitisation: a single-centre, phase 1b–2a, double-blind, dose-escalation, randomised controlled trial
Authors: Angelique Kany Kany Luabeya, Virginie Rozot, Claire Imbratta, Frances Ratangee, Justin Shenje, Michele Tameris, Simon C Mendelsohn, Hennie Geldenhuys, Michelle Fisher, Munyaradzi Musvosvi, Carly Young, Humphrey Mulenga, Nicole Bilek, Simbarashe Mabwe, Ingrid Murillo Jelsbak, Esteban Rodríguez, Eugenia Puentes, Juana Doce, Nacho Aguilo, Carlos Martin, Cadwill Pillay, Dereck Tait, Marisa Russell, Arrie Van Der Merve, Kathryn Rutkowski, Devin Hunt, Ann Ginsberg, Thomas J Scriba, Mark Hatherill
Journal: The Lancet Global Health (2025)
Multi‐parametric profiling of circulating immune cells identifies an expansion of <scp>CD25<sup>hi</sup></scp> switched memory B cells in Osteoarthritis
Authors: Neety Sahu, Yudhisthar Singh Bedi, Fiorella Grandi, William J. Maloney, Constance R. Chu, Nidhi Bhutani
Journal: Arthritis & Rheumatology (2025)

Objective Osteoarthritis (OA) is a chronic, debilitating disease with no available disease‐modifying drugs. Biomarker identification in OA patients has hitherto been limited to serum proteins and bulk epigenomic feature identification. Methods Peripheral blood mononuclear cells (PBMC) from 21 healthy donors, 17 OA patients, and 10 patients with degenerative meniscal tears (DMT) were immunophenotyped at single‐cell resolution by mass cytometry by time‐of‐flight (cyTOF) using a 29‐marker panel to identify OA‐associated features in the circulating immune cells. Single‐cell RNA sequencing was utilized to discern mechanistic attributes of perturbed immune cell populations in OA. Results Comparison of healthy donors and OA patients’ PBMC revealed distinct perturbations in OA. While subsets of naive B cells were depleted, switched memory B cells were significantly expanded in OA including a CD25 hi CXCR5 hi CD27 + IgD ‐ subpopulation. Single cell‐RNA sequencing revealed a dysfunction of IL2/Stat3 and TNF signaling in the CD25 hi switched memory B cells in OA. A similar expansion of CD25 hi switched memory B cells was observed in patients with DMT, a population at enhanced risk for OA. Conclusions A CD25 hi switched memory B cell population was identified to be a potential cellular biomarker for OA that can be detected in early stages of OA in the readily accessible circulating blood cells. image
Breakthrough hemolysis in paroxysmal nocturnal hemoglobinuria throughout clinical trials: from definition to clinical practice
Authors: Bruno Fattizzo, Francesco Versino, Wilma Barcellini
Journal: Blood (2025)

Breakthrough hemolysis (BTH) is the hemolytic exacerbation occurring in a patient with paroxysmal nocturnal hemoglobinuria (PNH) on treatment with anti-complement therapies. In this review article we analysed the definition, frequency and severity of BTH events across phase 3 clinical trials with terminal (anti-C5 ravulizumab and crovalimab) and complement inhibitors upstream C5 (anti-C3 pegcetacoplan, alternative-pathway inhibitors iptacopan and danicopan), as well as from real-world reports. Furthermore, we reviewed the impact of the various compounds on quality of life and patients reported outcomes. In particular, BTH may occur with all complement inhibitors, with a frequency of 10-15% over 6 months with eculizumab, crovalimab, and pegcetacoplan, and &amp;lt;5% with ravulizumab, iptacopan, and danicopan plus anti-C5. By prolonging the follow-up, the frequency of BTH appeared increased in pegcetacoplan treated patients (nearly 24% at 1 year) as compared to both anti-C5, iptacopan, and double inhibition with danicopan plus anti-C5. BTH risk appears associated with patients' features, particularly suboptimal response/failure of previous complement inhibitor. Transfusions were required in about half of cases and modifications of anti-complement therapy included anticipation of the next anti-C5 dose and addition of eculizumab in patients on proximal inhibitors. Breakthrough thromboses were rare, though anti-coagulant prophylaxis should be considered during severe episodes. Complement amplifying conditions were observed in about half of cases and were more frequently infections. Treatment adherence, optimization of the administration schedule, anticoagulant prophylaxis, as well as education of patients and physicians remain important factors to prevent BTH and its complications.
Maternal Tmprss6 is required for hepcidin suppression and fetal health
Authors: Katherine Louise Fielding, Cavan Bennett, Anne Pettikiriarachchi, Naomi Jones, Rebecca Harding, Alistair R.D. McLean, Louise M Randall, Ute Schaeper, Alberto Martinez, Ricardo Ataide, Sant-Rayn Pasricha
Journal: Blood (2025)

The antenatal role of the hepcidin-regulating protease Tmprss6 has never been elucidated as knockout dams are infertile. Utilising an in vivo knockdown approach, we confirm Tmprsss6 is critical for hepcidin suppression in pregnancy, and Tmprss6 inhibition drives deleterious fetal outcomes.
Outcomes of PLAT-02 and PLAT-03: Evaluating CD19 CAR T-Cell Therapy and CD19-expressing T-APC Support in Pediatric B-ALL
Authors: Colleen Annesley, Kristy D. Seidel, Qian Wu, Corinne Summers, Alan S. Wayne, Michael A. Pulsipher, Anurag K Agrawal, Christopher T Brown, Stephanie Mgebroff, Catherine G Lindgren, Stephanie D. Rawlings-Rhea, Wenjun Huang, Ashley Wilson, Michael C Jensen, Julie R Park, Rebecca A Gardner
Journal: Blood (2025)
The ENHANCE-3 study: venetoclax and azacitidine plus magrolimab or placebo for untreated AML unfit for intensive therapy
Authors: Naval G. Daver, Paresh Vyas, Gerwin A Huls, Hartmut Döhner, Sebastien Maury, Jan Novak, Cristina Papayannidis, Carmen Martinez Chamorro, Pau Montesinos, Rabin Niroula, Pierre Fenaux, Jordi Esteve, Shang-Ju Wu, Adrien De Voeght, Jiri Mayer, Peter J.M. Valk, Lisa Johnson, Mei Dong, Ke Liu, Sowmya Banda Kuwahara, Kenneth Caldwell, Guru Subramanian Guru Murthy
Journal: Blood (2025)

Patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy (IC) have limited treatment options. The phase 3 ENHANCE-3 study aimed to determine whether magrolimab (magrolimab arm) was superior to placebo (control arm) when either was combined with venetoclax and azacitidine. Adults with previously untreated AML who were ineligible for IC were randomized to receive magrolimab (1 mg/kg on days 1 and 4, 15 mg/kg on day 8, 30 mg/kg on days 11 and 15, then weekly for 5 weeks, then every 2 weeks) or placebo, venetoclax (100 mg on day 1, 200 mg on day 2, and 400 mg daily thereafter), and azacitidine (75 mg/m2 days 1-7) in 28-day cycles. The primary endpoint was overall survival (OS); key secondary endpoints included complete remission (CR) rate and safety. After randomization of 378 patients, the trial was stopped at a prespecified interim analysis due to futility. At final analysis, with median follow-up of 7.6 months (magrolimab arm) vs 7.4 months (control arm), median OS was 10.7 vs 14.1 months (HR, 1.178 [95% CI, 0.848-1.637]). The CR rate within 6 cycles was 41.3% vs 46.0%. Addition of magrolimab to venetoclax and azacitidine resulted in more fatal adverse events (19.0% vs 11.4%), primarily driven by grade 5 infections (11.1% vs 6.5%) and respiratory events (2.6% vs 0%). There were similar incidences of any-grade infections, febrile neutropenia, and neutropenia between arms. These results highlight the difficulty in improving outcomes for patients with AML ineligible for IC. This trial was registered at www.clinicaltrials.gov as #NCT05079230.
Outdoor exposure to artificial light at night and breast cancer risk: A case-control study nested in the E3N-Generations Cohort
Authors: Nirmala Prajapati, Delphine Praud, Claire Perrin, Béatrice Fervers, Thomas Coudon, Elodie Faure, Pascal Guénel
Journal: Environmental Health Perspectives (2025)

Exposure to light at night (LAN), particularly blue light, is suspected to disrupt circadian rhythm, inhibit melatonin production, and eventually increase the risk of breast cancer. We assessed the association between exposure to outdoor LAN and breast cancer risk in the E3N-Générations cohort, a large population-based cohort study of French women followed-up from 1990 to 2011. We conducted a nested case-control study in the cohort, including 5222 incident breast cancer cases and 5222 matched controls. Outdoor LAN exposure at residential addresses was assessed using radiance-calibrated satellite images from the Defense Meteorological Satellite Program (DMSP). Logistic regression models were used to obtain odds ratios (OR) and 95% confidence intervals (CI), adjusting for socio-demographic, reproductive, hormonal, and lifestyle-related factors, as well as exposure to air pollutants (NO2, PM2.5) evaluated from land use regression and chemistry transport models, and proximity to greenspaces estimated from the Normalized Difference Vegetation Index (NDVI) in a buffer of 300 m. Before adjustment for environmental covariates, the ORs associated for LAN exposure increased monotonically from the first to the fourth quartile. This increasing trend was less pronounced after adjustment for air pollutants (NO2 and PM2.5) and NDVI, but the fully adjusted OR per interquartile-range of LAN exposure (261 nW/cm2/sr) remained slightly elevated (ORIQR 1.11; 95% CI: 1.02, 1.20). The adjusted ORs were slightly more elevated in postmenopausal (ORIQR 1.10; 95% CI 1.02-1.18) than in pre-menopausal women, and in women living in urban areas with low greenness. The weak positive associations observed in this study that persist after adjustment for environmental covariates, support the hypothesis that outdoor LAN may increase breast cancer risk. Our results, suggesting that urban greenness could mitigate the role of LAN exposure in breast cancer risk, should be investigated further. Future studies on cancer risk in relation to outdoor LAN should assess exposure to indoor sources, including electronic devices, and characterize the light spectrum, particularly the blue light. https://doi.org/10.1289/EHP15105.