tbuckley/cabot-search huggingface dataset:
Machine learning identifies clinical tumor mutation landscape pathways of resistance to checkpoint inhibitor therapy in NSCLC
Authors: Vitalay Fomin, WeiQing Venus So, Richard Alex Barbieri, Kenley Hiller-Bittrolff, Elina Koletou, Tiffany Tu, Bruno Gomes, James Cai, Jehad Charo
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Immune checkpoint inhibitors (CPIs) have revolutionized cancer therapy for several tumor indications. However, a substantial fraction of patients treated with CPIs derive no benefit or have short-lived responses to CPI therapy. Identifying patients who are most likely to benefit from CPIs and deciphering resistance mechanisms is therefore essential for developing adjunct treatments that can abrogate tumor resistance. Patients and methods In this study, we used a machine learning approach that used the US-based nationwide de-identified Flatiron Health and Foundation Medicine non-small cell lung carcinoma (NSCLC) clinico-genomic database to identify genomic markers that predict clinical responses to CPI therapy. In total, we analyzed data from 4,433 patients with NSCLC. Results Analysis of pretreatment genomic data from 1,511 patients with NSCLC identified. Of the 36 genomic signatures identified, 33 exhibited strong predictive capacity for CPI response (n=1150) compared with chemotherapy response (n=361), while three signatures were prognostic. These 36 genetic signatures had in common a core set of four genes ( BRAF, BRIP1, FGF10, and FLT1 ). Interestingly, we observed that some (n=19) of the genes in the signatures (eg, TP53, EZH2, KEAP1 and FGFR2 ) had alternative mutations with contrasting clinical outcomes to CPI therapy. Finally, the genetic signatures revealed multiple biological pathways involved in CPI response, including MAPK, PDGF, IL-6 and EGFR signaling. Conclusions In summary, we found several genomic markers and pathways that provide insight into biological mechanisms affecting response to CPI therapy. The analyses identified novel targets and biomarkers that have the potential to provide candidates for combination therapies or patient enrichment strategies, which could increase response rates to CPI therapy in patients with NSCLC.
Home, school, and retail food environments driving obesity among adolescent girls in South Asia
Authors: Oliver Huse, Vani Sethi, Dhammica Rowel, Aishath Shahula Ahmed, Navoda Liyana Pathirana, Monika Arora, Kathryn Backholer
Journal: BMJ (2025)

Urgent action is required to tackle the rising prevalence of overweight and obesity among adolescent girls in South Asia by improving food environments and countering the influence of powerful commercial organisations, argue <b>Kathryn Backholer and colleagues</b>
Socioeconomic and Geographic Disparities in the Reported U.S. Amyloidosis Mortality From 2018-2022
Authors: Gracia Fahed, John Isaiah Jimenez, Nixuan Cai, Xiaokang Wu, Alexis Edmonds, Khushali Shah, Hiroki Kitakata, Francois Haddad, Ronald M Witteles, Kevin M Alexander
Journal: JACC Heart Failure (2025)
Heart Transplant and Pregnancy
Authors: Vanessa Kirschner, Ophelia Yin, Lisa Coscia, Prisca C Diala, Negeen Shahandeh, Roxanna A Irani, Serban Constantinescu, Michael J Moritz, Yalda Afshar
Journal: JACC Heart Failure (2025)

Heart transplant recipients (HTRs) during pregnancy are at greater risk for maternal and obstetrical complications and hypertensive disease of pregnancy exacerbates these risks. The impact of preeclampsia on HTRs is unknown. The authors describe characteristics of HTRs who developed preeclampsia and the effect of preeclampsia on graft and pregnancy outcomes. This is a retrospective group study of adult HTRs with subsequent pregnancy outcomes of ≥20 weeks' gestation enrolled in the Transplant Pregnancy Registry International between 1986 and 2022. The primary outcome was graft loss within 2 years from delivery. Secondary outcomes included maternal and neonatal outcomes. A total of 146 pregnancies and 149 neonates met inclusion criteria. All were livebirths. Forty-two pregnancies (28.8%) were complicated by preeclampsia. HTRs in the preeclampsia group were more likely to be nulliparous (81.0% vs 54.8%; P < 0.01), and have chronic hypertension (73.8% vs 34.6%; P < 0.01). There was no difference in incidence of graft loss at 2 years with (4.8%) or without (2.9%) preeclampsia (P = 0.72). There was no clinically important difference in graft survival in pregnancies with preeclampsia compared with pregnancies without preeclampsia (adjusted HR: 0.79 [95% CI: 0.37-1.69]; P = 0.54). However, rates of severe maternal morbidity were high in both groups: 16.7% in the preeclampsia group and 10.6% in those without preeclampsia. Furthermore, preeclampsia was associated with earlier gestational age at birth (35.0 vs 37.0 weeks; P < 0.01) and lower birth weight (2,310 vs 2,801 grams; P < 0.01). There was no difference in graft loss from delivery in HTRs who developed preeclampsia during pregnancy. Regardless of preeclampsia, pregnant HTRs are more likely than the general population to experience severe maternal morbidity. These findings provide pertinent information for counseling heart transplant recipients who pursue pregnancy.
The Impact of Social Determinants of Health on Timely Detection in Transthyretin Cardiac Amyloidosis
Authors: Gracia Fahed, John Isaiah Jimenez, Marina I Adrianzen Fonseca, Jonathan Hu, Gabriela Spencer-Bonilla, Francois Haddad, Jesus E Pino Moreno, Ronald M Witteles, Kevin M Alexander
Journal: JACC Heart Failure (2025)
Supporting policy action to reduce adolescent anaemia in South Asia
Authors: Vani Sethi, Zivai Murira, Kapil Yadav, Preetu Mishra, Ireen Akhter Chowdhury, Ahmadwali Aminee
Journal: BMJ (2025)

<b>Vani Sethi and colleagues</b> highlight country efforts on evidence based policy making, strengthening implementation and institutional capacity, and inclusive strategies to accelerate reductions in anaemia in adolescent girls
99mTc-PSMA Uptake in Neurofibroma
Authors: Mohammad Hadi Samadi, Pegah Sahafi, Haniye Elahifard, Sima Davoodi, Emran Askari
Journal: Clinical Nuclear Medicine (2025)

We present a 74-year-old man with a history of very high-risk prostate cancer (Gleason score: 5+4 in 11 of 14 cores) who was referred for initial staging with 99mTc-HYNIC-PSMA. The scan was reported as miT2m N2(REI, ROB) M1b(uni) M1c(skin?), PRIMARY score: 4, PSMA expression score: 1-3. We incidentally discovered increased uptake in the left skull region on whole-body images. Subsequent SPECT/CT imaging localized this uptake to a subcutaneous nodule in the scalp, which pathologic analysis confirmed to be a neurofibroma. Several lesions of neurological origin may exhibit significant PSMA avidity, which is reviewed here.
Impact of COPD on cardiovascular risk factors and outcomes in people with established cardiovascular disease
Authors: Eunice Eunae Cho, Laura C Maclagan, Anna Chu, Ruth Croxford, Don D Sin, Jacob A Udell, Douglas Lee, Peter C Austin, Andrea S Gershon
Journal: Thorax (2025)

Background Little is known about the association between chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) in people with established CVD. Knowing if COPD is associated with a higher risk of cardiovascular events would guide appropriate secondary prevention. Objective To examine the risk of COPD on major adverse cardiac events (MACEs, acute myocardial infarction, stroke and cardiovascular death) in a complete real-world population of a large province, with known CVD. Methods We conducted a retrospective population cohort study using health administration, medication, laboratory, electronic medical record and other data from Ontario, Canada. All people with a history of CVD with and without physician-diagnosed COPD as of 2008 were followed until 2016 and cardiac risk factors, sociodemographic factors, comorbidities and other factors were compared. Sequential cause-specific hazard models adjusting for these factors determined the risk of MACE in people with COPD. Results Of 496 056 individuals with CVD in Ontario on 1 January 2008, 69 161 (13.9%) had COPD. MACE occurred more frequently among those with CVD (45.3 per 1000 person-years) and COPD compared with those with CVD alone (28.6 per 1000 person-years) (HR 1.24, 95% CI 1.21–1.26) after adjustment for cardiac risk factors, comorbidities, socioeconomic status and other factors. People with COPD were less likely to receive preventive CVD medications or see a cardiologist. Conclusion In a large, real-world population of people with established CVD, COPD was associated with a higher rate of cardiovascular events but a lower rate of preventive therapy. Strategies are needed to improve secondary CVD prevention in the COPD population.
Bioprinting functional hepatocyte organoids derived from human chemically induced pluripotent stem cells to treat liver failure
Authors: Guangya Li, Jianyu He, Jihang Shi, Xinyi Li, Lulu Liu, Xinlan Ge, Wenhan Chen, Jun Jia, Jinlin Wang, Ming Yin, Yasuyuki Sakai, Wei Sun, Hongkui Deng, Yuan Pang
Journal: Gut (2025)

Background To treat liver failure, three-dimensional (3D) bioprinting is a promising technology used to construct hepatic tissue models. However, current research on bioprinting of hepatic tissue models primarily relies on conventional single-cell-based bioprinting, where individual functional hepatocytes are dispersed and isolated within hydrogels, leading to insufficient treatment outcomes due to inadequate cell functionality. Objective Here, we aim to bioprint a hepatic tissue model using functional hepatocyte organoids (HOs) and evaluate its liver-specific functions in vitro and in vivo . Design Human chemically induced pluripotent stem cells (hCiPSCs) were used as a robust and non-genome-integrative cell source to produce highly viable and functional HOs (hCiPSC-HOs). An oxygen-permeable microwell device was used to enhance oxygen supply, ensuring high cell viability and promoting hCiPSC-HOs maturation. To maintain the long-term biofunction of hCiPSC-HOs, spheroid-based bioprinting was employed to construct hepatic tissue models (3DP-HOs). 3DP-HOs were intraperitoneally implanted in mice with liver failure. Results 3DP-HOs demonstrated enhanced cell viability when compared with a model fabricated using single-cell-based bioprinting and exhibited gene profiles closely resembling hCiPSC-HOs while maintaining liver-specific functionality. Moreover, 3DP-HOs implantation significantly improved survival in mice with CCl 4 -induced acute-on-chronic liver failure and also Fah−/− mice with liver failure. 3DP-HOs significantly reduced liver injury, inflammation and fibrosis indices while promoting liver regeneration and biofunction expression. Conclusion Our bioprinted hepatic tissue model exhibits remarkable therapeutic efficacy for liver failure and holds great potential for clinical research in the field of liver regenerative medicine.
24-Nor-ursodeoxycholic acid improves intestinal inflammation by targeting T<sub>H</sub>17 pathogenicity and transdifferentiation
Authors: Ci Zhu, Nicole Boucheron, Osamah Al-Rubaye, Brian K Chung, Liv Wenche Thorbjørnsen, Thomas Köcher, Michael Schuster, Thierry Claudel, Emina Halilbasic, Victoria Kunczer, Fanziska Muscate, Lois L Cavanagh, Darina Waltenberger, Alexander Lercher, Anna Ohradanova-Repic, Philipp Schatzlmaier, Tatjana Stojakovic, Hubert Scharnagl, Andreas Bergthaler, Hannes Stockinger, Samuel Huber, Christoph Bock, Lukas Kenner, Tom H Karlsen, Wilfried Ellmeier, Michael Trauner
Journal: Gut (2025)

Background 24-Nor-ursodeoxycholic acid (NorUDCA) is a novel therapeutic bile acid for treating immune-mediated cholestatic liver diseases, such as primary sclerosing cholangitis (PSC). Objective Since PSC strongly associates with T helper-type-like 17 (T H 17)-mediated intestinal inflammation, we explored NorUDCA’s immunomodulatory potential on T H 17 cells. Design NorUDCA’s impact on T H 17 differentiation was assessed using a CD4 + T Naive adoptive transfer mouse model, and on intraepithelial T H 17 pathogenicity and transdifferentiation using an αCD3 stimulation model combined with interleukin-17A-fate-mapping. Mechanistic studies used molecular and multiomics approaches, flow cytometry and metabolic assays with pathogenic (p) T H 17. Pathogenicity of pT H 17 exposed to NorUDCA in vitro was evaluated following adoptive transfer in intestinal tissues or the central nervous system (CNS). Key findings were validated in an αCD3-stimulated humanised NSG mouse model reconstituted with peripheral blood mononuclear cells from patients with PSC. Results NorUDCA suppressed T H 17 effector function and enriched regulatory T cell (Treg) abundance upon CD4 + T Naive cell transfer. NorUDCA mitigated intraepithelial T H 17 pathogenicity and decreased the generation of proinflammatory ‘T H 1-like-T H 17’ cells, and enhanced T H 17 transdifferentiation into Treg and Tr1 (regulatory type 1) cells in the αCD3-model. In vivo ablation revealed that Treg induction is crucial for NorUDCA’s anti-inflammatory effect on T H 17 pathogenicity. Mechanistically, NorUDCA restrained pT H 17 effector function and simultaneously promoted functional Treg formation in vitro , by attenuating a glutamine-mTORC1-glycolysis signalling axis. Exposure of pT H 17 to NorUDCA dampened their pathogenicity and expansion in the intestine or CNS upon transfer. NorUDCA’s impact on T H 17 inflammation was corroborated in the humanised NSG mouse model. Conclusion NorUDCA restricts T H 17 inflammation in multiple mouse models, potentiating future clinical applications for treating T H 17-mediated intestinal diseases and beyond.
Effect of intravenous iron therapy on exercise performance, fatigue scores and mood states in iron-deficient recreationally active females of reproductive age: a double-blind, randomised control trial (IRONWOMAN Trial)
Authors: Cory Dugan, Peter Peeling, Paige Buissink, Beth MacLean, Jayne Lim, Pradeep Jayasuriya, Toby Richards
Journal: British Journal of Sports Medicine (2025)

Objectives Non-anaemic iron deficiency (IDNA) is highly prevalent in exercising females. Although iron therapy can be used to correct this issue, its impact on exercise performance is equivocal. Our aim was to assess the efficacy of intravenous iron therapy on exercise performance, fatigue, mood states, and quality of life in recreationally active IDNA females of reproductive age. Methods Twenty-six recreationally active IDNA females were randomised to either an intravenous iron treatment (IRON) group or placebo (PLA). Prior to, 4 days and 4 weeks following intervention, participants completed a variety of assessments to determine changes in exercise performance, haemoglobin mass, blood iron status and haematology, fatigue levels, mood states and quality of life. Results Intravenous iron therapy significantly improved serum ferritin, serum iron and transferrin saturation (p&lt;0.05), with a highly variable individual response. No differences were observed between groups’ peak oxygen consumption (V̇O 2Peak ), lactate threshold or haemoglobin mass. Running economy improved in IRON from baseline to 4 weeks (p&lt;0.05), which was also different to PLA at 4 weeks (p&lt;0.05). Fatigue scores improved in IRON but not PLA after 4 weeks (p&lt;0.05). Mood states and quality of life remained unchanged in both groups over the trial. Conclusion In recreationally active IDNA females, intravenous iron therapy corrects iron status and improves both exercise economy and fatigue scores after 4 weeks. Trial registration number ACTRN12620001357943.
Recommendations for use of extracorporeal shockwave therapy in sports medicine: an international modified Delphi study
Authors: Hye Chang Rhim, Mani Singh, Nicola Maffulli, Amol Saxena, Carlos Leal, Ludger Gerdesmeyer, Kristina Quirologico, John P Furia, Johannes Zwerver, Chun-De Liao, Daniel Moya, Shih-Wei Huang, David M Robinson, Johnny Jarnagin, Joseph Ruiz, Kayle E Noble-Taylor, Hazem Alkhawashki, Brice W Blatz, Joanne Borg-Stein, Lauren Borowski, Jay Bowen, Michael Chin, Robert M Conenello, Michael Fredericson, Brian W Fullem, Karin Gravare Silbernagel, Karsten Hollander, Elena J Jelsing, Paul Langer, Kenneth Mautner, Adele Meron, Robert Monaco, Rowan V Paul, Sara Raiser, James W Ratcliff, Steven Sampson, Wolfgang Schaden, Jay Spector, Wei Sun, Isaac P Syrop, Kenji Takahashi, Benedict Tan, James F Wyss, Dan Zin, Jennifer Soo Hoo, Adam S Tenforde
Journal: British Journal of Sports Medicine (2025)

While extracorporeal shockwave therapy (ESWT) may be an efficacious adjunctive treatment option for musculoskeletal injuries, current research is limited by significant heterogeneity within treatment protocols. This study aims to establish international expert consensus recommendations on ESWT terminology, parameters, procedural considerations, contraindications and side effects in the application of ESWT to sports injuries. A systematic literature search was performed on the use of ESWT for musculoskeletal and sports medicine injuries to identify potential panellists, followed by the development of a steering committee-led questionnaire. A three-stage, modified Delphi questionnaire was provided to a panel of 41 international clinical and research experts across 13 countries. Panellists had the opportunity to suggest edits to existing statements or recommend additional statements in Round 1. Consensus was defined as≥75% agreement. All 41 panellists completed Rounds 1, 2 and 3. Consensus was reached on 69/118 statements (58.5%), including recommendations on terminology and fundamental concepts, indications for use, procedural aspects for tendinopathy and bone pathologies, treatment correlations with imaging, periprocedural and postprocedural considerations, absolute and relative contraindications and potential side effects. Of the 49 statements that did not reach consensus, 17/49 (34.7%) were related to procedural aspects of bone pathology. This international panel presents recommendations on ESWT terminology, indications and treatment considerations to guide ESWT use and decision-making by sports medicine clinicians. While our panel supported the use of ESWT in the treatment of bone pathologies, certain procedural aspects of ESWT specific to these injuries did not reach consensus and require further investigation.
Microneedle-mediated hypoxic extracellular vesicle-encapsulated selenium nanoparticles delivery to treat androgenetic alopecia
Authors: Shuili Jing, Yonghao Liu, Ben Wang, Heng Zhou, Hui Zhang, Prakriti Siwakoti, Xiangyu Qu, Peng Ye, Yan He, Tushar Kumeria, Qingsong Ye
Journal: Journal of Controlled Release (2025)
Addressing systemic exclusion and gender norms to improve nutritional outcomes for adolescent girls in South Asia
Authors: Navoda Liyana Pathirana, Christina Zorbas, Seema Khadka, Hari Prasad Pokhrel, Naveen Paudyal, Nayani Dharmakeerthi, Kathryn Backholer, Vani Sethi
Journal: BMJ (2025)

Multifaceted actions are needed to better identify and challenge underlying patriarchal and socioeconomic factors affecting adolescent girls' nutrition, write <b>Navoda Liyana Pathirana and colleagues</b>
Effect of prednisone plus either adalimumab or cyclosporine on dermatological symptoms in Vogt-Koyanagi-Harada disease: systemic outcomes from a randomized trial
Authors: Zhenyu Zhong, Jiayi Wang, Weiting Liao, Junjie Xiang, Tao Cai, Peizeng Yang
Journal: Journal of the American Academy of Dermatology (2025)
AAV9-delivery of interleukin-37b gene prevents recurrent herpetic stromal keratitis via the SIGIRR pathway in mice
Authors: Jing Wu, Ye Liu, Chenchen Wang, Yurong Cai, Xiaomin Zhu, Ruining Lyu, Qiao You, Xiaoqian Liu, Qin Qin, Yajie Qian, Deyan Chen
Journal: Journal of Controlled Release (2025)
Cancer inequalities in the United Kingdom and the data used to measure them: a scoping review
Authors: Sarah Underwood, Emre Oguzman, Judith Cole, Raphael Goldacre, Nileema Patel, David Davies, Claire Friedemann-Smith, F Lucy Wright, Ben Lacey, Brian D Nicholson, Sasha Shepperd, Mark Lawler, Eva J A Morris
Journal: The Lancet Regional Health - Europe (2025)
Europe's climate leadership in an ‘America first’ era
Authors: Kim R van Daalen, Hedi K Kriit, José Chen-Xu, Jan C Semenza, Maria Nilsson, Niheer Dasandi, Slava Jankin, Anil Markandya, Josep M Antó, Joacim Rocklöv, Cathryn Tonne
Journal: The Lancet Regional Health - Europe (2025)
Targeting TRAP1-Dependent Metabolic Reprogramming to Overcome Doxorubicin Resistance in Quiescent Breast Cancer
Authors: Muhammad Zubair Saleem, Ruyi Huang, Yingying Huang, Xin Guo, Yang Liu, Miao Gao, Yinjuan Fan, Zhe-Sheng Chen, Zun-Fu Ke, Shengnan Ye, Jianhua Xu
Journal: Drug Resistance Updates (2025)

TRAP1 is involved in metabolic reprogramming and promotes drug resistance. We aimed to explore whether a novel HSP90 inhibitor, C210, overcomes doxorubicin (DOX) resistance of quiescent breast cancer cells by targeting TRAP1. Breast cancer cells were induced to quiescence by hypoxia and low glucose. The relationship of cell metabolism with HSP90 and TRAP1 was investigated by Western blotting, ECAR, OCR, mitochondrial complex activity, and proteomic analysis. The targets of C210 and their functions were analyzed by SPR and immunoprecipitation. The antitumor effect in vivo was investigated with mouse tumor model. In hypoxia and glucose deprivation, breast cancer cells exhibited elevated TRAP1 and an OXPHOS-enhanced quiescent phenotype. These cells were highly resistant to DOX but more sensitive to C210. C210 disrupted TRAP1's interaction with OXPHOS-associated client proteins, prompting proteasome-dependent degradation of these proteins, thereby reducing OCR, mitochondrial ATP production and resulting in selective elimination of the quiescent cancer cells by inducing mitochondrial apoptosis which could be reversed by exogenous ATP. Moreover, C210 targeted glycolytic, amino acid, and β-oxidation-associated proteome. C210 demonstrated promising in vivo anticancer efficacy which was particularly related to OXPHOS inhibition. C210 eliminates DOX-resistant quiescent breast cancer cells by targeting TRAP1-dependent bioenergetics.
Intranasal delivery of epigallocatechin gallate-laden platelet extracellular vesicles for mitigating retinal glaucoma
Authors: Wen-Yu Pan, Pei-Wei Weng, Shen-Han Wu, Chi-Hung Hsiao, Pei-Ru Jheng, Huynh-Ngoc-Truc Nguyen, Ching-Li Tseng, Thierry Burnou, Lekshmi Rethi, Hieu Trung Nguyen, Wei-Yung Huang, Tsung-Jen Wang, Andrew E-Y Chuang
Journal: Journal of Controlled Release (2025)
Pitavastatin and resveratrol bio-nanocomplexes against hyperhomocysteinemia-induced atherosclerosis via blocking ferroptosis-related lipid deposition
Authors: Anning Yang, Hongwen Zhang, Huiping Zhang, Nan Li, Cong Chen, Xiaoling Yang, Jue Tian, Jianmin Sun, Guizhong Li, Yue Sun, Bin Liu, Yideng Jiang
Journal: Journal of Controlled Release (2025)
Topological cues of microparticles train stem cells for tissue repair via mechanotransduction
Authors: Jiannan Mao, Yichang Xu, Wenbo Wang, Xiongwei Deng, Yujian Hui, Min Rui, Jincheng Tang, Wei Wang, Yiyang Huang, Liang Wu, Kun Xi, Yunrong Zhu, Yong Gu, Liang Chen
Journal: Bioactive Materials (2025)