tbuckley/cabot-search huggingface dataset:
Efficacy and safety of nivolumab plus ipilimumab in patients with metastatic variant histology (non-clear cell) renal cell carcinoma
Authors: Mohammad Jad Moussa, Jaanki Khandelwal, Nathaniel R Wilson, Kiran L Malikayil, Devaki Shilpa Surasi, Tharakeswara K Bathala, Yiyun Lin, Priya Rao, Pheroze Tamboli, Kanishka Sircar, Helen Ajufo, Khaled M Elsayes, Amishi Shah, Andrew C Johns, Sangeeta Goswami, Elshad Hasanov, Eric Jonasch, Pavlos Msaouel, Matthew T Campbell, Omar Alhalabi, Nizar M Tannir
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Nivolumab plus ipilimumab (nivo/ipi) is a standard of care first-line (1 L) therapy for patients with metastatic clear-cell renal cell carcinoma (ccRCC), but its role in patients with metastatic, non-ccRCC has not been fully defined. We report a single-institution experience with nivo/ipi in non-ccRCC. Methods Between November 2017 and February 2024, 55 patients with metastatic non-ccRCC received nivo/ipi at MD Anderson Cancer Center. The tumor response was assessed by blinded radiologists using RECIST v1.1. The overall response rate (ORR), progression-free survival (PFS), PFS milestone, duration of response (DoR), and overall survival (OS) were determined. Next-generation sequencing (NGS) was performed on available tumor specimens. Results Twenty-five (45.5%) patients had papillary histology (pRCC), 12 (21.8%) patients had chromophobe (chRCC), and 18 (32.7%) patients had unclassified RCC (uRCC). Fifty-two (94.5%) patients received nivo/ipi in 1 L. Sarcomatoid features (SF) were found in 20 (36.4%) cases. ORR was 48% (12/25) in pRCC, 25% (3/12) in chRCC (all 3 cases had SF), 27.8% (5/18) in uRCC, and 55% (11/20) across histologies with SF. The median PFS was 10.6 months (95% CI: 2.8 to 22.8) in pRCC, 3.6 months (95% CI: 0.9 – NE) in chRCC, and 3 months (95% CI: 2.1 to 7) in uRCC; 6-month milestone PFS was 56% (95% CI: 36.3 to 75.7), 41.7% (95% CI: 22 to 61.3), and 38.9% (95% CI: 21.7 to 56.1) in pRCC, chRCC, and uRCC, respectively. The median DoR for the entire cohort was 8.5 months (95% CI: 8 – NE). The median OS was 36.7 months (95% CI: 11.5 to 54.8) in pRCC, 25.7 months (95% CI: 0.9 – NE) in chRCC, and 11.1 months (95% CI: 6.5 – NE) in uRCC. Ten (18.2%) patients discontinued treatment due to treatment-related adverse events (AEs). Grade 3/4 immune-mediated AEs were noted in 17 (30.9%) patients. We performed NGS on 26 cases: TP53 (42%), PTEN (23%), and TERT (23%) alterations were most frequently found, with TERT and TP53 mutations enriched in pRCC and chRCC, respectively. Conclusion Nivo/ipi produced favorable outcomes in patients with pRCC supporting its use as 1 L therapy. Responses in patients with chRCC were noted exclusively with SF. Despite achieving an ORR of 27.8% with nivo/ipi, patients with uRCC had short PFS and inferior OS.
CD56<sup>bright</sup>cytokine-induced memory-like NK cells and NK-cell engagers synergize against non-small cell lung cancer cancer-stem cells
Authors: Maria L Guevara Lopez, Ann Gebo, Monica Parodi, Stefano Persano, Josephine Maus-Conn, Maria Cristina Mingari, Fabrizio Loiacono, Paola Orecchia, Simona Sivori, Claudia Cantoni, Marco Gentili, Federica Facchinetti, Riccardo Ferracini, Daniel A Vallera, Martin Felices, Giulia Bertolini, Marco Pravetoni, Luca Roz, Massimo Vitale
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Due to their enhanced responsiveness and persistence, cytokine-induced memory-like (CIML)-natural killer (NK) cells have emerged as new immunotherapeutic tools against malignancies. However, their effects on tumor-cell spread and metastases in solid tumors remain poorly investigated. Moreover, a clear identification of the most effective CIML-NK subsets, especially in controlling cancer stem cells (CSC), is still lacking. Methods We performed combined phenotypical and functional analyses of CIML-NK cell subsets, either selected by flow-cytometry gating, or generated from sorted CD56 bright /CD56 dim NK cells. By co-culture experiments, we analyzed the effect of CIML-NK cells on non-small cell lung cancer (NSCLC) cell spheroids, or patient-derived xenografts (PDX), assessing changes in their CSC content, tumorigenicity, and/or tumor disseminating capability in vivo. CIML-NK cells were also infused in PDX-bearing mice to validate their effect on the CSC dissemination from the PDX to the lungs. Finally, we generated and functionally analyzed CIML-NK cells from patients with stages I/III NSCLC (n=6). Results We show that CIML-NK cells exert antitumor activity mostly through their CD56 bright cell subset, which greatly expands during CIML differentiation. Compared with NK cells conventionally activated with interleukin-2, CIML-NK cells express lower levels of check-point receptors, TIGIT and TIM3, and higher effector functions against NSCLC cells from PDX, and against in vitro-generated tumor spheroids. Remarkably, CIML-NK cells also significantly reduce the CSC-containing CD133 + cell subpopulation within spheroids and PDX, and limit tumor cell tumorigenicity and ability to disseminate CSCs from primary tumors to distant sites. Sorting experiments on CIML or tumor cell subsets reveal that CD56 bright cells drive most of this anti-CSC activity, and suggest that such functional advantage could be related to increased expression of LFA-1 and ICAM-1 on CD56 bright cells and CSCs, respectively. We also show that the tri-specific killer cell engager (TriKE) 1615133 significantly enhances CIML-NK cell activity against CSCs. Finally, we demonstrate that CIML-NK cells, capable of killing autologous tumor cells and responding to the 1615133 TriKE, could be induced from patients with NSCLC. Conclusions Our study discloses for the first time the therapeutic potential of CIML-NK cells in controlling CSCs and metastatic spread, highlighting the role of the CD56 bright subset expansion and 1615133 TriKE for optimizing CIML-NK-based therapies against metastatic tumors.
ICRS-FIFA-Aspetar consensus on the management of knee cartilage injuries in football players: part 1 – appropriateness of surgery in different clinical scenarios using the RAND/UCLA appropriateness method
Authors: Elizaveta Kon, Emmanuel Papakostas, Luca Andriolo, Andreas Serner, Andrew Massey, Peter Verdonk, Peter Angele, Claudia Arias, Camila Cohen Kaleka, Ramon Cugat, Pieter D'Hooghe, Francesco Della Villa, Cristiano Eirale, Christoph Erggelet, João Espregueira-Mendes, Christian Fink, Celeste Geertsema, Liesel Geertsema, Cassandra A Lee, Bert Mandelbaum, Norimasa Nakamura, David A Parker, Kristof Sas, Bertrand Sonnery-Cottet, Willem van der Merwe, Andy Williams, Stefano Zaffagnini, Bashir Ahmed Zikria, Giuseppe Filardo
Journal: British Journal of Sports Medicine (2025)

Knee cartilage lesions are frequent in football players, but evidence for surgical treatment is lacking. The aim of this International Cartilage Regeneration &amp; Joint Preservation Society, Fédération Internationale de Football Association, and Aspetar (ICRS-FIFA-Aspetar) consensus was to develop specific expert-based, patient-specific practical recommendations on the appropriateness of non-surgical or surgical treatments for symptomatic knee cartilage lesions in competitive football players. The RAND/UCLA appropriateness method was used, and 17 voting experts provided recommendations on the appropriateness of surgical treatment in 96 different clinical scenarios defined on 6 variables: cartilage injury onset, lesion location, defect size, bone involvement, player symptom level and preference towards higher priority of a quick return to play or long-term results. Surgical treatment of a cartilage lesion was considered appropriate in 32% of the scenarios, in 21% inappropriate, while in 47% of the scenarios, the appropriateness was considered uncertain. The parameters with the highest appropriateness for the surgical treatment of a cartilage lesion in a football player were the inability to play (75.0% of appropriate scenarios), a lesion sized 2 cm 2 or bigger (47.9% of appropriate scenarios) and the preference of the player for long-term results (41.7% of appropriate scenarios). In this ICRS-FIFA-Aspetar expert consensus, surgical treatment for cartilage injuries in competitive football players was considered appropriate only in one-third of the clinical scenarios, and the choice was mainly driven by the level of symptoms. Surgical preference was also influenced by larger lesions, lesions of the condyles and trochlea with subchondral bone involvement and player’s preference towards long-term results.
Increasing child vaccination coverage can reduce influenza cases across age groups: An agent-based modeling study
Authors: Katherine V. Williams, Mary G. Krauland, Mary P. Nowalk, Lee H. Harrison, John V. Williams, Mark S. Roberts, Richard K. Zimmerman
Journal: Journal of Infection (2025)

Highlights•Influenza vaccinations in children has declined since the COVID-19 pandemic•Children have high influenza attacks rate and are a key source of influenza spread•New in the 2025-26 season, caregivers will be able to administer influenza vaccine•Caregiver administration is an opportunity to increase child vaccination coverage•Increased child vaccination coverage can reduce all age influenza burdenAbstractObjectivesAvailability of caregiver-administered nasal spray live attenuated influenza vaccine (LAIV) raises the potential for increased influenza vaccine uptake. Direct and indirect benefits (decreased influenza cases and hospitalizations) of increased uptake among school-age children may be realized across the age spectrum. We used an agent-based model to determine the extent to which increased vaccination of children might affect overall influenza epidemiology.MethodsThe Framework for Reproducing Epidemiological Dynamics (FRED) uses a population based on the US census and accounts for individual characteristics to estimate the effect of changes in parameters including vaccine uptake, on outcomes. We modeled increases in vaccine uptake among school-age children 5-17 years old on influenza cases and hospitalizations by age group.ResultsIncreasing vaccination rates in school-aged children by 5%-15% decreased their symptomatic influenza cases by 3.2%-10.9%, and among all age groups by 3.3%-11.6%, corresponding to an estimated annual reduction in cases of 522,867-1,810,170 among school-age children and of 1,394,687-4,945,952 overall. Annual U.S. hospitalizations could decrease by as much as 49,977, with the greatest impact (23,258) in those ages 65 years and over.ConclusionsThe opportunity to increase vaccination coverage in school-age children using LAIV can have a positive impact across all ages.Graphical abstract
Association of Historical Redlining With Gestational Diabetes Mellitus: The Mediating Role of BMI and Area Deprivation Index
Authors: Wajeeha Umer, Yi Sun, Anqi Jiao, Karen D. Lincoln, Mengyi Li, Chantal C. Avila, Vicki Y. Chiu, Jeff M. Slezak, David A. Sacks, John Molitor, Tarik Benmarhnia, Jiu-Chiuan Chen, Darios Getahun, Jun Wu
Journal: Diabetes Care (2025)

OBJECTIVE We investigated the association between historic redlining and risk of gestational diabetes mellitus (GDM), and whether this relationship is mediated by maternal obesity and area-level deprivation. RESEARCH DESIGN AND METHODS This retrospective study included 86,834 singleton pregnancies from Kaiser Permanente Southern California’s health records (2008–2018). Redlining was assessed using digitized Home Owners’ Loan Corporation (HOLC) maps, with patients’ residential addresses geocoded and assigned HOLC grades (A, B, C, or D) based on their geographic location within HOLC-graded zones. For GDM case patients, exposure was assigned based on address at diagnosis date; for noncase patients, it was assigned based on address during the 24th to 28th gestational week. Health records were combined with area deprivation index (ADI) from 2011 to 2015 census data. Mixed-effect logistic regression models assessed associations between redlining and GDM, with mediation by BMI and ADI evaluated using inverse odds ratio weighting. Models were adjusted for maternal age, education, race and ethnicity, neighborhood-level income, and smoking status. RESULTS Among the 10,134 (11.67%) GDM case patients, we found increased risk of GDM in B (“still desirable,” adjusted odds ratio [aOR] 1.20, 95% CI 0.99–1.44), C-graded (“definitely declining,” aOR 1.22, 95% CI 1.02–1.47), and D-graded (“hazardous,” i.e., redlined, aOR 1.30, 95% CI 1.08–1.57) neighborhoods compared with the “best”-graded zone. Prepregnancy BMI and ADI mediated 44.2% and 64.5% of the increased GDM risk among mothers in redlined areas. CONCLUSIONS Historic redlining is associated with an increased risk of GDM, mediated by maternal obesity and neighborhood deprivation. Future research is needed to explore the complex pathways linking redlining to pregnancy outcomes.
LA-peptide Hydrogel—Regulation of macrophage and fibroblast fates and their crosstalk via attenuating TGF-β to promote scarless wound healing
Authors: Zichao Li, Leyang Zhang, Yang Wang, Yifu Zhu, Haomiao Shen, Juzheng Yuan, Xiao Li, Zhou Yu, Baoqiang Song
Journal: Bioactive Materials (2025)
Articulating the JACC Journals' Direction in Times of Global Change
Authors: Harlan M. Krumholz, Biykem Bozkurt, Y. Chandrashekhar, Bonnie Ky, Douglas L. Mann, David J. Moliterno, Kalyanam Shivkumar, Candice K. Silversides, Gilbert H.L. Tang, Jian’an Wang
Journal: JACC CardioOncology (2025)
Articulating the JACC Journals' Direction in Times of Global Change
Authors: Harlan M. Krumholz, Biykem Bozkurt, Y. Chandrashekhar, Bonnie Ky, Douglas L. Mann, David J. Moliterno, Kalyanam Shivkumar, Candice K. Silversides, Gilbert H.L. Tang, Jian’an Wang
Journal: JACC. Cardiovascular imaging (2025)
Articulating the JACC Journals' Direction in Times of Global Change
Authors: Harlan M. Krumholz, Biykem Bozkurt, Y. Chandrashekhar, Bonnie Ky, Douglas L. Mann, David J. Moliterno, Kalyanam Shivkumar, Candice K. Silversides, Gilbert H.L. Tang, Jian’an Wang
Journal: Journal of the American College of Cardiology (2025)
Supporting the bereaved child in the adult ICU: a narrative review
Authors: Annelies Rowland, Carole Boulanger, Louise Dalton
Journal: Intensive Care Medicine (2025)

Childhood bereavement is a significant issue globally, affecting millions of children each year, with incidence rates significantly increasing following the COVID-19 pandemic. The loss of an important adult, particularly in the ICU environment, can lead to lasting psychological and behavioural challenges for children. While family-centred practices in the ICU have advanced, the unique bereavement needs of grieving children in the family remain insufficiently addressed. Both families and healthcare professionals (HCPs) often feel unprepared and uncomfortable engaging in honest, supportive conversations with children about bereavement, further complicating children's grief processing. This narrative review examines the pivotal role ICU HCPs can play in facilitating child-centred bereavement support, focusing on promoting honest communication, supportive visitation practices, creating a child-friendly and humanised ICU environment, and encouraging child involvement during end-of-life care. It recommends prioritising research on the lived experiences of bereaved children, caregivers, and ICU HCPs to inform targeted interventions addressing children's developmental and psychological needs during ICU bereavement. The review also advocates for specialised training to equip ICU staff with the necessary skills to support grieving children and families. Developing comprehensive, child-centred ICU bereavement guidelines will provide evidence-based frameworks that recognise children as integral family members during end-of-life care while advocating for the participation of children in meaningful rituals will empower families to make informed decisions about their involvement. Together, these recommendations aim to create a more compassionate, inclusive, and supportive bereavement experience in ICU settings, prioritising the unique needs of children and promoting healthy emotional adjustment after losing an important adult.
Toward Improving Initial Therapy of Acute Graft Versus Host Disease
Authors: Ansh Krishnachandra Mehta, John Koreth
Journal: American Journal of Hematology (2025)

ABSTRACT Acute graft versus host disease (aGVHD) is a major complication of hematopoietic stem cell transplantation; it results from donor‐derived immune response against host tissues and typically involves the liver, skin and the GI tract. The incidence of acute GVHD is declining due to the advances in HLA typing, reduced intensity conditioning and GVHD prophylaxis. However, corticosteroids remain the mainstay frontline treatment of aGVHD for many decades and as the number of allogeneic transplants continues to increase, there remains a large unmet need to improve frontline treatment for aGVHD. In this review, we outline risk factors, epidemiology and pathogenesis of aGVHD. We discuss the evolving risk stratification, beginning from the initial Gluckesberg system to more recent biomarker‐based strategies. We summarize the completed trials that underpin current frontline management and outline future directions.
Acute Myeloid Leukemia: 2025 Update on Diagnosis, Risk‐Stratification, and Management
Authors: Shai Shimony, Maximilian Stahl, Richard M. Stone
Journal: American Journal of Hematology (2025)

ABSTRACT Disease Overview Acute myeloid leukemia (AML) is a bone marrow stem cell cancer that is often fatal despite available treatments. Diagnosis, risk assessment, monitoring, and therapeutic management of AML have changed dramatically in the last decade due to increased pathophysiologic understanding, improved assessment technology, and the addition of at least 12 approved therapies. Diagnosis The diagnosis is based on the presence of immature leukemia cells in the blood, and/or bone marrow or less often in extra‐medullary tissues. New biological insights have been integrated into recent classification systems. Risk Assessment The European Leukemia Network has published risk classification algorithms for both intensively and non‐intensively treated patients based on cytogenetic and on molecular findings. Prognostic factors may differ based on the therapeutic approach. Monitoring Our increasing ability to quantify lower levels of measurable residual disease (MRD) potentially allows better response assessment, as well as dynamic monitoring of disease status. The incorporation of MRD findings into therapeutic decision‐making is rapidly evolving. Risk Adapted Therapy The availability of 12 newly approved agents has been welcomed; however, optimal strategies incorporating newer agents into therapeutic algorithms are debated. The overarching approach integrates patient and caregiver goals of care, comorbidities, and disease characteristics.
The global burden of human metapneumovirus-associated acute respiratory infections in older adults: a systematic review and meta-analysis
Authors: Durga Kulkarni, Bingbing Cong, Mamata Jyothish Kumar Ranjini, Geetika Balchandani, Shuting Chen, Jingyi Liang, Lina González Gordon, Ajoke Sobanjo-ter Meulen, Xin Wang, You Li, Richard Osei-Yeboah, Kate Templeton, Harish Nair
Journal: The Lancet Healthy Longevity (2025)
Correction: Position paper on the physiology and nomenclature of dual circulation during venoarterial ECMO in adults
Authors: Jenelle Badulak, Darryl Abrams, Andrew M. Luks, Bishoy Zakhary, Steven A. Conrad, Robert Bartlett, Graeme MacLaren, Leen Vercaemst, Roberto Lorusso, Lars Mikael Broman, Cara Agerstrand, Susanna Price, Alain Combes, Giles Peek, Eddy Fan, Kiran Shekar, John Fraser, Daniel Brodie
Journal: Intensive Care Medicine (2025)
High-throughput multiplexed serology via the mass-spectrometric analysis of isotopically barcoded beads
Authors: Alexandros P. Drainas, David R. McIlwain, Alec Dallas, Theresa Chu, Antonio Delgado-González, Maya Baron, Maria Angulo-Ibáñez, Angelica Trejo, Yunhao Bai, John W. Hickey, Guolan Lu, Scott Lu, Jesus Pineda-Ramirez, Khamal Anglin, Eugene T. Richardson, John C. Prostko, Edwin Frias, Venice Servellita, Noah Brazer, Charles Y. Chiu, Michael J. Peluso, Jeffrey N. Martin, Oliver F. Wirz, Tho D. Pham, Scott D. Boyd, J. Daniel Kelly, Julien Sage, Garry P. Nolan, Xavier Rovira-Clavé
Journal: Nature Biomedical Engineering (2025)
Systems neuroimmunology: current bottlenecks, research priorities and future directions
Authors: Harini Iyer, Christophe Benoist, Staci D. Bilbo, Lisa M. Boulanger, Michael D. Burton, Brian P. Daniels, Aleksandra Deczkowska, Martin F. Flajnik, Mélanie G. Gareau, Peter M. Grace, Javier E. Irazoqui, Susanna Rosi, Irene Salinas, Anne Schaefer, Caroline L. Sokol, Dionna W. Williams, Robyn S. Klein
Journal: Nature Immunology (2025)
A gut-on-a-chip incorporating human faecal samples and peristalsis predicts responses to immune checkpoint inhibitors for melanoma
Authors: Mattia Ballerini, Serena Galiè, Punit Tyagi, Carlotta Catozzi, Hariam Raji, Amir Nabinejad, Angeli D. G. Macandog, Alessandro Cordiale, Bianca Ionela Slivinschi, Karol K. Kugiejko, Martina Freisa, Paola Occhetta, Jennifer A. Wargo, Pier F. Ferrucci, Emilia Cocorocchio, Nicola Segata, Andrea Vignati, Andrey Morgun, Michela Deleidi, Teresa Manzo, Marco Rasponi, Luigi Nezi
Journal: Nature Biomedical Engineering (2025)

Patient responses to immune checkpoint inhibitors can be influenced by the gastrointestinal microbiome. Mouse models can be used to study microbiome–host crosstalk, yet their utility is constrained by substantial anatomical, functional, immunological and microbial differences between mice and humans. Here we show that a gut-on-a-chip system mimicking the architecture and functionality of the human intestine by including faecal microbiome and peristaltic-like movements recapitulates microbiome–host interactions and predicts responses to immune checkpoint inhibitors in patients with melanoma. The system is composed of a vascular channel seeded with human microvascular endothelial cells and an intestinal channel with intestinal organoids derived from human induced pluripotent stem cells, with the two channels separated by a collagen matrix. By incorporating faecal samples from patients with melanoma into the intestinal channel and by performing multiomic analyses, we uncovered epithelium-specific biomarkers and microbial factors that correlate with clinical outcomes in patients with melanoma and that the microbiome of non-responders has a reduced ability to buffer cellular stress and self-renew. The gut-on-a-chip model may help identify prognostic biomarkers and therapeutic targets. A gut-on-a-chip incorporating peristaltic-like movements and faecal samples from patients with melanoma recapitulates microbiome–host interactions and predicts the responses of the patients to immune checkpoint inhibitors.