tbuckley/cabot-search huggingface dataset:
Author Correction: Single-cell guided prenatal derivation of primary fetal epithelial organoids from human amniotic and tracheal fluids
Authors: Mattia Francesco Maria Gerli, Giuseppe Calà, Max Arran Beesley, Beatrice Sina, Lucinda Tullie, Kylin Yunyan Sun, Francesco Panariello, Federica Michielin, Joseph R. Davidson, Francesca Maria Russo, Brendan C. Jones, Dani Do Hyang Lee, Savvas Savvidis, Theodoros Xenakis, Ian C. Simcock, Anna A. Straatman-Iwanowska, Robert A. Hirst, Anna L. David, Christopher O’Callaghan, Alessandro Olivo, Simon Eaton, Stavros P. Loukogeorgakis, Davide Cacchiarelli, Jan Deprest, Vivian S. W. Li, Giovanni Giuseppe Giobbe, Paolo De Coppi
Journal: Nature Medicine (2025)
An immunosenescent <scp>CD8</scp>+ T cell subset in patients with axial Spondyloarthritis and Psoriatic Arthritis links spontaneous motility to telomere shortening and dysfunction
Authors: Giorgia Paldino, Valentina Tedeschi, Valentina Proganò, Erica Salvati, Valerio Licursi, Eleonora Vertecchi, Alexandru L. Bivolaru, Emanuele Molteni, Rossana Scrivo, Mattia Congia, Alberto Cauli, Rosalba Caccavale, Marino Paroli, Martina Kunkl, Loretta Tuosto, Rosa Sorrentino, Maria Teresa Fiorillo
Journal: Arthritis & Rheumatology (2025)

Objective A pathogenetic role of CD8+ T lymphocytes in radiographic axial spondyloarthritis (r‐axSpA) and other spondyloarthritis (SpA) is sustained by genome‐wide association studies (GWAS) and by the expansion of public T cell clonotypes in the target tissues. This study investigates the migration of CD8+ T cells, along with their phenotype and functions in patients with r‐axSpA and psoriatic arthritis (PsA). Methods Peripheral blood CD8+ and CD4+ T cells were isolated from r‐axSpA (n= 128), PsA (n= 60) and rheumatoid arthritis (RA, n= 74) patients and healthy donors (HD, n= 79). Transwell migration assay was performed in the presence of different chemokines. CD8+ T cell immunoprofiling and effector functions were assessed by multiparametric flow cytometry. Transcriptome signature was evaluated by RNA‐seq analysis whereas telomere length and dysfunction were measured by RT‐PCR and IF‐fluorescence in situ hybridization (FISH), respectively. Results A significantly higher number of CD8+ T cells migrating in the absence of chemokine stimuli was found in patients with SpA compared to HD and RA patients. This subset, producing cytotoxic (granzyme B, perforin, granulysin) and proinflammatory molecules (TNFα), was significantly enriched in terminally differentiated (CCR7‐CD45RA+) and senescent (CD28‐CD57+) cells having a gene expression profile characterized by cytolytic signature and natural killer (NK) markers. Remarkably, these spontaneously migrating CD8+ T cells showed DNA damage response (DDR) activation, telomere shortening and dysfunction. Conclusion These data describe a terminally differentiated CD8+ T cell subset with a senescent and cytotoxic/proinflammatory profile and an intrinsic invasive potential enriched in SpA patients that represents a possible player in disease pathogenesis.
Neoadjuvant nivolumab and chemotherapy in early estrogen receptor-positive breast cancer: a randomized phase 3 trial
Authors: Sherene Loi, Roberto Salgado, Giuseppe Curigliano, Roberto Iván Romero Díaz, Suzette Delaloge, Carlos Ignacio Rojas García, Marleen Kok, Cristina Saura, Nadia Harbeck, Elizabeth A. Mittendorf, Denise A. Yardley, Alberto Suárez Zaizar, Facundo Rufino Caminos, Andrei Ungureanu, Joaquin G. Reinoso-Toledo, Valentina Guarneri, Daniel Egle, Felipe Ades, Misena Pacius, Aparna Chhibber, Rajalakshmi Chandra, Raheel Nathani, Thomas Spires, Jenny Qun Wu, Lajos Pusztai, Heather McArthur
Journal: Nature Medicine (2025)

Patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) primary breast cancer (BC) have low pathological complete response (pCR) rates with neoadjuvant chemotherapy. A subset of ER+/HER2- BC contains dense lymphocytic infiltration. We hypothesized that addition of an anti-programmed death 1 agent may increase pCR rates in this BC subtype. We conducted a randomized, multicenter, double-blind phase 3 trial to investigate the benefit of adding nivolumab to neoadjuvant chemotherapy in patients with newly diagnosed, high-risk, grade 3 or 2 (ER 1 to ≤10%) ER+/HER2- primary BC. In total, 510 patients were randomized to receive anthracycline and taxane-based chemotherapy with either intravenous nivolumab or placebo. The primary endpoint of pCR was significantly higher in the nivolumab arm compared with placebo (24.5% versus 13.8%; P = 0.0021), with greater benefit observed in patients with programmed death ligand 1-positive tumors (VENTANA SP142 ≥1%: 44.3% versus 20.2% respectively). There were no new safety signals identified. Of the five deaths that occurred in the nivolumab arm, two were related to study drug toxicity; no deaths occurred in the placebo arm. Adding nivolumab to neoadjuvant chemotherapy significantly increased pCR rates in high-risk, early-stage ER+/HER2- BC, particularly among patients with higher stromal tumor-infiltrating lymphocyte levels or programmed death ligand 1 expression, suggesting a new treatment paradigm that emphasizes the role of immunotherapy and T cell immunosurveillance in luminal disease. Clinical trials.gov identifier: NCT04109066.
Non-Canonical TERT Activity Initiates Osteogenesis in Calcific Aortic Valve Disease
Authors: Rolando A. Cuevas, Luis Hortells, Claire C. Chu, Ryan Wong, Alex Crane, Camille Boufford, Cailyn Regan, William J. Moorhead III, Michael J. Bashline, Aneesha Parwal, Angelina M. Parise, Parya Behzadi, Mark J. Brown, Aditi Gurkar, Dennis Bruemmer, John Sembrat, Ibrahim Sultan, Thomas G. Gleason, Marie Billaud, Cynthia St. Hilaire
Journal: Circulation Research (2025)

BACKGROUND: Calcific aortic valve disease is the pathological remodeling of valve leaflets. The initial steps in valve leaflet osteogenic reprogramming are not fully understood. As TERT (telomerase reverse transcriptase) overexpression primes mesenchymal stem cells to differentiate into osteoblasts, we investigated whether TERT contributes to the osteogenic reprogramming of valve interstitial cells. METHODS: Human control and calcific aortic valve disease aortic valve leaflets and patient-specific human aortic valve interstitial cells were used in in vivo and in vitro calcification assays. Loss of function experiments in human aortic valve interstitial cells and cells isolated from Tert −/− and Terc −/− mice were used for mechanistic studies. Calcification was assessed in Tert +/+ and Tert −/− mice ex vivo and in vivo. In silico modeling, proximity ligation, and coimmunoprecipitation assays defined novel TERT interacting partners. Chromatin immunoprecipitation and cleavage under targets and tagmentation sequencing defined protein-DNA interactions. RESULTS: TERT protein was highly expressed in calcified valve leaflets without changes in telomere length, DNA damage, or senescence markers, and these features were retained in isolated primary human aortic valve interstitial cells. TERT expression increased with osteogenic or inflammatory stimuli, and knockdown or genetic deletion of TERT prevented calcification in vitro and in vivo. Mechanistically, TERT was upregulated via NF-κB and required to initiate osteogenic reprogramming, independent of its canonical reverse transcriptase activity and the long noncoding RNA TERC . TERT exerts noncanonical osteogenic functions via binding with STAT5 (signal transducer and activator of transcription 5). Depletion or inhibition of STAT5 prevented calcification. STAT5 was found to bind the promoter region of RUNX2 (runt-related transcription factor 2), the master regulator of osteogenic reprogramming. Finally, we demonstrate that TERT and STAT5 are upregulated and colocalized in calcific aortic valve disease tissue compared with control tissue. CONCLUSIONS: TERT’s noncanonical activity is required to initiate calcification. TERT is upregulated via inflammatory signaling pathways and partners with STAT5 to bind the RUNX2 gene promoter. These data identify a novel mechanism and potential therapeutic target to decrease vascular calcification.
Pembrolizumab and chemotherapy in high-risk, early-stage, ER+/HER2− breast cancer: a randomized phase 3 trial
Authors: Fatima Cardoso, Joyce O’Shaughnessy, Zhenzhen Liu, Heather McArthur, Peter Schmid, Javier Cortes, Nadia Harbeck, Melinda L. Telli, David W. Cescon, Peter A. Fasching, Zhimin Shao, Delphine Loirat, Yeon Hee Park, Manuel Gonzalez Fernandez, Gábor Rubovszky, Laura Spring, Seock-Ah Im, Rina Hui, Toshimi Takano, Fabrice André, Hiroyuki Yasojima, Yu Ding, Liyi Jia, Vassiliki Karantza, Konstantinos Tryfonidis, Aditya Bardia
Journal: Nature Medicine (2025)

Abstract Addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab improved outcomes in patients with high-risk, early-stage, triple-negative breast cancer. However, whether the addition of neoadjuvant pembrolizumab to chemotherapy would improve outcomes in high-risk, early-stage, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER + /HER2 − ) breast cancer remains unclear. We conducted a double-blind, placebo-controlled phase 3 study (KEYNOTE-756) in which patients with previously untreated ER + /HER2 − grade 3 high-risk invasive breast cancer (T1c-2 (≥2 cm), cN1–2 or T3–4, cN0–2) were randomly assigned (1:1) to neoadjuvant pembrolizumab 200 mg or placebo Q3W given with paclitaxel QW for 12 weeks, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide Q2W or Q3W. After surgery (with/without adjuvant radiation therapy), patients received adjuvant pembrolizumab or placebo for nine cycles plus adjuvant endocrine therapy. Dual primary endpoints were pathological complete response and event-free survival in the intention-to-treat population. In total, 635 patients were assigned to the pembrolizumab−chemotherapy arm and 643 to the placebo−chemotherapy arm. At the study’s prespecified first interim analysis, the pathological complete response rate was 24.3% (95% confidence interval (CI), 21.0–27.8%) in the pembrolizumab−chemotherapy arm and 15.6% (95% CI, 12.8–18.6%) in the placebo−chemotherapy arm (estimated treatment difference, 8.5 percentage points; 95% CI, 4.2–12.8; P = 0.00005). Event-free survival was not mature in this analysis. During the neoadjuvant phase, treatment-related adverse events of grade ≥3 were reported in 52.5% and 46.4% of patients in the pembrolizumab−chemotherapy and placebo−chemotherapy arms, respectively. In summary, the addition of pembrolizumab to neoadjuvant chemotherapy significantly improved the pathological complete response rate in patients with high-risk, early-stage ER + /HER2 − breast cancer. Safety was consistent with the known profiles of each study treatment. Follow-up continues for event-free survival. ClinicalTrials.gov identifier: NCT03725059 .
Cholesterol mobilization regulates dendritic cell maturation and the immunogenic response to cancer
Authors: Meriem Belabed, Matthew D. Park, Cédric M. Blouin, Sreekumar Balan, Chang Y. Moon, Grace Freed, Miguel Quijada-Álamo, Ante Peros, Raphaël Mattiuz, Amanda M. Reid, Nader Yatim, Jesse Boumelha, Camillia S. Azimi, Nelson M. LaMarche, Leanna Troncoso, Angelo Amabile, Jessica Le Berichel, Steven T. Chen, C. Matthias Wilk, Brian D. Brown, Kristen J. Radford, Sourav Ghosh, Carla V. Rothlin, Laurent Yvan-Charvet, Thomas U. Marron, Daniel J. Puleston, Elvin Wagenblast, Nina Bhardwaj, Christophe Lamaze, Miriam Merad
Journal: Nature Immunology (2025)
Comparing <i>Campylobacter jejuni</i> to three other enteric pathogens in OligoMM <sup>12</sup> mice reveals pathogen-specific host and microbiota responses
Authors: Mathias K.-M. Herzog, Audrey Peters, Nizar Shayya, Monica Cazzaniga, Kardokh Kaka Bra, Trisha Arora, Manja Barthel, Ersin Gül, Luca Maurer, Patrick Kiefer, Philipp Christen, Katharina Endhardt, Julia A. Vorholt, Gad Frankel, Markus M. Heimesaat, Stefan Bereswill, Cormac G. M. Gahan, Marcus J. Claesson, Xavier Domingo-Almenara, Wolf-Dietrich Hardt
Journal: Gut Microbes (2025)

Campylobacter jejuni, non-typhoidal Salmonella spp., Listeria monocytogenes and enteropathogenic/enterohemorrhagic Escherichia coli (EPEC/EHEC) are leading causes of food-borne illness worldwide. Citrobacter rodentium has been used to model EPEC and EHEC infection in mice. The gut microbiome is well-known to affect gut colonization and host responses to many food-borne pathogens. Recent progress has established gnotobiotic mice as valuable models to study how microbiota affect the enteric infections by S. Typhimurium, C. rodentium and L. monocytogenes. However, for C. jejuni, we are still lacking a suitable gnotobiotic mouse model. Moreover, the limited comparability of data across laboratories is often negatively affected by variations between different research facilities or murine microbiotas. In this study, we applied the standardized gnotobiotic OligoMM12 microbiota mouse model and compared the infections in the same facility. We provide evidence of robust colonization and significant pathological changes in OligoMM12 mice following infection with these pathogens. Moreover, we offer insights into pathogen-specific host responses and metabolite signatures, highlighting the advantages of a standardized mouse model for direct comparisons of factors influencing the pathogenesis of major food-borne pathogens. Notably, we reveal for the first time that C. jejuni stably colonizes OligoMM12 mice, triggering inflammation. Additionally, our comparative approach successfully identifies pathogen-specific responses, including the detection of genes uniquely associated with C. jejuni infection in humans. These findings underscore the potential of the OligoMM12 model as a versatile tool for advancing our understanding of food-borne pathogen interactions.
KDIGO 2025 clinical practice guideline for the evaluation, management, and treatment of autosomal dominant polycystic kidney disease (ADPKD): executive summary
Authors: Vicente E Torres, Curie Ahn, Thijs R M Barten, Godela Brosnahan, Melissa A Cadnapaphornchai, Arlene B Chapman, Emilie Cornec-Le Gall, Joost P H Drenth, Ron T Gansevoort, Peter C Harris, Tess Harris, Shigeo Horie, Max C Liebau, Michele Liew, Andrew J Mallett, Changlin Mei, Djalila Mekahli, Dwight Odland, Albert C M Ong, Luiz F Onuchic, York P-C Pei, Ronald D Perrone, Gopala K Rangan, Brian Rayner, Roser Torra, Ethan M Balk, Craig E Gordon, Amy Earley, Reem A Mustafa, Olivier Devuyst
Journal: Kidney International (2025)
Corrigendum to “KDIGO 2024 Clinical Practice Guideline for the Management of Antineutrophil Cytoplasmic Antibody (ANCA)–Associated Vasculitis.” Kidney International 2024;105(3S):S71–S116
Authors: Jürgen Floege, David R.W. Jayne, Jan-Stephan F. Sanders, Vladimír Tesar, Brad H. Rovin
Journal: Kidney International (2025)
KDIGO 2025 Clinical Practice Guideline for the Evaluation, Management, and Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Authors: Olivier Devuyst, Curie Ahn, Thijs R.M. Barten, Godela Brosnahan, Melissa A. Cadnapaphornchai, Arlene B. Chapman, Emilie Cornec-Le Gall, Joost P.H. Drenth, Ron T. Gansevoort, Peter C. Harris, Tess Harris, Shigeo Horie, Max C. Liebau, Michele Liew, Andrew J. Mallett, Changlin Mei, Djalila Mekahli, Dwight Odland, Albert C.M. Ong, Luiz F. Onuchic, York P-C Pei, Ronald D. Perrone, Gopala K. Rangan, Brian Rayner, Roser Torra, Reem Mustafa, Vicente E. Torres
Journal: Kidney International (2025)
Global dissemination of Klebsiella pneumoniae in surface waters: genomic insights into drug resistance, virulence, and clinical relevance
Authors: Damian Rolbiecki, Edyta Kiedrzyńska, Małgorzata Czatzkowska, Marcin Kiedrzyński, Ewa Korzeniewska, Monika Harnisz
Journal: Drug Resistance Updates (2025)
Vitronectin regulates lung tissue remodeling and emphysema in chronic obstructive pulmonary disease
Authors: Gang Liu, Alan C Hsu, Silke Geirnaert, Christine Cong, Prema M Nair, Sj Shen, Jacqueline E Marshall, Tatt Jhong Haw, Michael Fricker, Ashleigh M Philp, Nicole G Hansbro, Stelios Pavlidis, Yike Guo, Janette K Burgess, Leandro Castellano, Antonio Ieni, Gaetano Caramori, Brain G G Oliver, K Fan Chung, Ian M Adcock, Darryl A Knight, Francesca Polverino, Ken Bracke, Peter A Wark, Philip M Hansbro
Journal: Molecular Therapy (2025)
Association of nucleoside reverse transcriptase inhibitors with adverse perinatal outcomes in pregnant women living with HIV: systematic review and meta-analysis
Authors: Imogen Cowdell, Katharina Beck, Molly Hey, Clara Portwood, Harriet Sexton, Mary Kumarendran, Zoe Brandon, Shona Kirtley, Joris Hemelaar
Journal: Clinical Microbiology and Infection (2025)
A call to action: The need to update population descriptors in dermatology research studies with the use of an inclusive skin classification system
Authors: Valerie M Harvey, Stafford G Brown, Cheryl M Burgess, Angel S Byrd, Caryn B C Cobb, Seemal R Desai, Candrice R Heath, Tarannum Jaleel, Amy J McMichael, Yvette Miller-Monthrope, Hema Sundaram, Junko Takeshita, Susan C Taylor, Jonathan S Weiss, Jane Yoo, Valerie D Callender
Journal: Journal of the American Academy of Dermatology (2025)
Anaerobic Probiotics-in situ Se nanoradiosensitizers Selectively Anchor to Tumor with Immuno-regulations for Robust Cancer Radio-immunotherapy
Authors: Yangyang Yu, Ying Wang, Jin Zhang, Qingyue Bu, Dan Jiang, Yalin Jiang, Ligeng Xu, Zhenyu Ju, Tianfeng Chen
Journal: Biomaterials (2025)
Concussion and depressive symptoms in high school students: impact of physical activity and substance use
Authors: Mathew J Wingerson, Patrick Carry, Rebekah Mannix, Timothy Meier, Katherine L Smulligan, Julie C Wilson, David R Howell
Journal: British Journal of Sports Medicine (2025)

Objective To investigate the association between concussion history and depressive symptoms after adjusting for physical activity, substance use, and illicit drug use. Methods We analysed data from the Adolescent Behaviour and Experiences Survey, a nationally representative survey of adolescents in the USA. Our independent variables were history of concussion in the 12 months preceding survey completion; self-reported weekly physical activity (days per week with &gt;60 min of physical activity, 0–7 scale); substance use over the past 30 days (yes vs no) and illicit drug use throughout lifetime (yes vs no). Our dependent variable was participant-reported sadness/hopelessness over the past 12 months (yes vs no). Results Among 7499 adolescents (9th–12th grade, 50.4% female), reporting one or more concussions over the past year was not associated with the odds of depressive symptoms (OR: 1.13, 95% CI: 0.93 to 1.37, p=0.21). Each additional day of physical activity per week was associated with a lower odds of depressive symptoms (OR: 0.91; 95% CI: 0.89 to 0.94; p&lt;0.0001). Illicit drug use (OR ever vs never: 2.48; 95% CI: 1.96 to 3.13; p&lt;0.0001) and substance use (OR yes vs no: 2.77; 95% CI: 2.34 to 3.29; p&lt;0.001) were associated with a higher odds of depressive symptoms. Conclusions Adjusting for physical activity, substance use and illicit drug use, concussion was not significantly associated with depressive symptoms. This novel discovery informs clinicians as they counsel adolescents with concussion; future research should examine physical activity and avoidance of substance/illicit drug use as postinjury recommendations in an effort to lower the risk of depressive symptoms.
Art of TIL immunotherapy: SITC’s perspective on demystifying a complex treatment
Authors: Simon Turcotte, Marco Donia, Brian Gastman, Michal Besser, Robert Brown, George Coukos, Benjamin Creelan, John Mullinax, Vernon K Sondak, James C Yang, Maartje W Rohaan, Inge Marie Svane, Michael T Lotze, John B A G Haanen, Stephanie L Goff
Journal: Journal for ImmunoTherapy of Cancer (2025)

In a first for solid cancers, cellular immunotherapy has entered standard of care in the treatment of patients with metastatic melanoma. The infusion of autologous tumor-infiltrating T lymphocytes (TIL) is capable of mediating durable tumor regression and is now Food and Drug Administration-approved for patients with disease refractory to immune checkpoint inhibitors. Since the advent of chimeric antigen receptor (CAR) T cells for patients with hematological malignancies, a growing network of centers capable of delivering effector T cell products to patients has developed. Administration of TIL can be layered onto that institutional framework, but there are many complex and unique aspects to TIL immunotherapy. The highly multidisciplinary clinical expertise and coordination required to successfully and safely deliver TIL to patients began within the National Cancer Institute Surgery Branch and have been subsequently adopted worldwide. The general steps, most of which require hospital inpatient resources, include a surgical procedure to harvest sufficient tumor for TIL manufacturing, admission for non-myeloablative lymphodepleting chemotherapy followed by TIL, and intravenous interleukin-2 (IL-2, aldesleukin). Here, we provide the principles, practice, and required resources underlying the efficient and safe delivery of TIL immunotherapy derived from the clinical expertise of high-volume centers around the world. This article enhances published clinical practice guidelines by providing underlying clinical rationale and data-driven examples to demystify TIL immunotherapy in order to facilitate uptake and improve patient access to this promising treatment modality in clinical and research settings.
Efficacy of anti‐PD1 therapy in extranodal NK/T cell lymphoma: A matched cohort analysis from the LYSA
Authors: Amira Marouf, Sammara Chaubard, Raphaël Liévin, Jean‐Marie Michot, Nicolas Molinari, Julien Rossignol, Doriane Cavalieri, Camille Golfier, Olivier Allangba, Laure Philippe, Benoît Tessoulin, Adrien Chauchet, Bénédicte Deau, Lucie Oberic, Jacques Vargaftig, Aline Moignet, Aline Clavert, Rémy Dulery, Gabriel Brisou, Stéphanie Tardy, Virginie Fataccioli, Roch Houot, René O. Casasnovas, Catherine Thieblemont, Hervé Ghesquières, Sylvain Carras, Steven Le Gouill, Guillaume Cartron, Vincent Ribrag, Morgane Cheminant, Ambroise Marçais, Felipe Suarez, Aurélien Marabelle, Olivier Tournilhac, Gandhi Damaj, Philippe Gaulard, Laurence De Leval, François Lemonnier, Emmanuel Bachy, Sylvie Chevret, Olivier Hermine, Lucile Couronné, Arnaud Jaccard
Journal: HemaSphere (2025)