tbuckley/cabot-search huggingface dataset:
A CEBPB/IL-1β/TNF-α Feedback Loop Drives Drug Resistance to Venetoclax and MDM2 Inhibitors in Monocytic Leukemia
Authors: Basil Allen, Daniel Bottomly, Thomas Köhnke, Anthony Wang, Hsin-Yun Lin, Kara Johnson, Isabel Kenna, Anastatia Streltsova, Emma Martin, Reid Chen, Lindsey Savoy, Nicola Long, Peter Ryabinin, Stephen E Kurtz, Christopher A Eide, Amy Carlos, Andy Kaempf, Tingting Liu, Cristina E. Tognon, Robert Searles, Paul D. Piehowski, Sara J.C. Gosline, Anupriya Agarwal, Bill H Chang, Michelle Barton, Brian J Druker, Shannon K. McWeeney, Ravindra Majeti, Jeffrey W. Tyner, Haijiao Zhang
Journal: Blood (2025)
Up-front Blinatumomab Improves MRD Clearance and Outcome in Adult Ph− B-lineage ALL: the GIMEMA LAL2317 Phase 2 Study
Authors: Renato Bassan, Sabina Chiaretti, Irene Della Starza, Alessandra Santoro, Orietta Spinelli, Manuela Tosi, Loredana Elia, Deborah Cardinali, Maria Stefania De Propris, Matteo Piccini, Federico Lussana, Mario Annunziata, Patrizia Chiusolo, Patrizia Zappasodi, Erika Borlenghi, Matteo Leoncin, Catello Califano, Monica Bocchia, Francesco Di Raimondo, Francesco Grimaldi, Mario Tiribelli, Anna Candoni, Albana Lico, Ernesta Audisio, Monia Lunghi, Anna Maria Mianulli, Mariangela Di Trani, Valentina Arena, Monica Messina, Alfonso Piciocchi, Paola Fazi, Alessandro Rambaldi, Robin Foà
Journal: Blood (2025)
Histo-blood group ABO system transferase plasma levels and risk of future venous thromboembolism: The HUNT Study
Authors: Asbjørn Lund Onsaker, Anna Yang Arntzen, David-Alexandre Trégouët, Therese Haugdahl Nøst, Weihong Tang, Weihua Guan, Christian Jonasson, Pierre-Emmanuel Morange, Kristian Dalsbø Hindberg, Aaron R. Folsom, Kristian Hveem, Vânia M. Morelli, John-Bjarne Hansen
Journal: Blood (2025)
Impact of sleep on postpartum health outcomes: a systematic review and meta-analysis
Authors: Zain Khan-Afridi, Stephanie-May Ruchat, Paris A T Jones, Muhammad Usman Ali, Brittany A Matenchuk, Sierra Leonard, Andrew We Jantz, Kier Vander Leek, Lauren E Maier, Laura Osachoff, Melanie J Hayman, Milena Forte, Allison Sivak, Margie H Davenport
Journal: British Journal of Sports Medicine (2025)

Objective To examine the impact of postpartum sleep interventions and postpartum sleep on maternal health outcomes. Design Systematic review with random-effects meta-analysis. Online databases were searched on 12 January 2024. Study eligibility criteria Studies of all designs (except case studies and reviews) in all languages were eligible if they contained information on the population (individuals up to 1-year post partum), sleep interventions/exposures including (type, duration, frequency, alone or in combination with other components), comparator (control or different duration, frequency or type of sleep intervention) and outcomes: mental health, cardio-metabolic, postpartum weight retention (PPWR), low back pain and pelvic girdle pain, breastfeeding and urinary incontinence. Results 60 studies (n=20 684) from 14 countries were included. ‘High’ certainty of evidence showed that sleep interventions were associated with a greater decrease in depressive symptom severity compared with no intervention (five randomised controlled trials; n=992; standardised mean difference −0.27, 95% CI −0.40 to –0.14; small effect). Sleep interventions had no impact on the odds of developing depression (‘moderate’ certainty of evidence) or anxiety or anxiety symptom severity (‘low’ certainty of evidence). Additionally, ‘low’ certainty of evidence demonstrated no effect on cardiometabolic outcomes (systolic blood pressure, diastolic blood pressure, mean arterial pressure), anthropometric measures (maternal weight, body mass index) or prevalence of exclusive breastfeeding. ‘Low’ certainty of evidence from observational studies found that high-quality sleep reduces the odds of developing anxiety and reduces the severity of depression and anxiety symptoms. ‘Low’ and ‘very low’ certainty of evidence from observational studies found that shorter sleep duration is associated with greater PPWR. Conclusions Postpartum sleep interventions reduced the severity of depression symptoms.
Gene score to quantify systemic inflammation in patients with acutely decompensated cirrhosis
Authors: Jonel Trebicka, Ferran Aguilar, Alberto Queiroz Farias, Juan-José Lozano, Cristina Sánchez-Garrido, Eva Usón-Raposo, Carlos de la Peña-Ramirez, Julia Sidorova, Anna Curto-Vilalta, Patricia Sierra-Casas, Patricia Momoyo Zitelli, Maria Papp, Gustavo Pereira, Paolo Caraceni, Luciana L Goncalves, Carlo Alessandria, Aldo Torre, Wim Laleman, Adrián Gadano, Salvatore Piano, Angelo Z Mattos, Wenyi Gu, Maximilian Joseph Brol, Robert Schierwagen, Frank Erhard Uschner, Julia Fischer, Liliana S C Mendes, Victor Vargas, Mario R Alvares-da-Silva, Raj Mookerjee, Paolo L Bittencourt, Carlos Benitez, Agustín Albillos, Cláudia Couto, Manuel Mendizabal, Rafael Bañares, Claudio L Toledo, Daniel F Mazo, Martin Janicko, Mauricio Castillo-Barradas, Pedro Martin Padilla Machaca, Pietro Gatti, Adelina Zarela-Lozano Miranda, René Malé-Velázquez, Alexander Zipprich, André Castro-Lyra, Thierry Gustot, William Bernal, Alexander L Gerbes, Rajiv Jalan, Javier Fernández, Paolo Angeli, Flair Jose Carrilho, Joan Claria, Richard Moreau, Vicente Arroyo
Journal: Gut (2025)

Background and aims Quantifying systemic inflammation (SI) in acutely decompensated cirrhosis (ADC) is of major importance because SI is a driver of the most severe forms of ADC, including acute-on-chronic liver failure (ACLF). Blood biomarkers of SI already evaluated in ADC failed to appropriately assess SI in ADC. We aimed to investigate whether gene expression related to circulating immune cells could quantify SI in ADC. Methods Standard biomarkers (white cell count, C reactive protein, cytokines) and genome-wide RNA expression (RNA-sequencing) were obtained in blood from 700 patients with ADC at the time of their hospital admission. A composite score based on standard biomarkers of SI (Chronic Liver Failure-Standard Biomarkers Composite (CLIF-SBC) score) and a gene score (CLIF-Systemic Inflammation Gene (SIG) score) composed of the 28 top differentially expressed immune cell-related genes in the comparison between high-severity and low-severity clinical phenotypes were computed. Among the 700 patients, the CLIF-SIG score was repeated once during follow-up in 375 patients, and 3 times or more in 46 patients. Results The CLIF-SIG score was more accurate in reflecting clinical severity induced by SI than the CLIF-SBC score (area under the curve 0.803 vs 0.658). A CLIF-SIG score of 0.386 (Youden Index) was the best cut-off level discriminating patients with poor outcomes from the others, in all clinical scenarios. Sequential measurement of the CLIF-SIG score showed that 78% of patients were admitted at the peak or descending part of the SI-wave. ACLF developed during hospitalisation in 80% of patients with a CLIF-SIG score &gt;0.386 on admission. Conclusions In patients with ADC, the CLIF-SIG score is an accurate estimator of SI, clinical course severity and prognosis.
Venetoclax and Decitabine vs Intensive Chemotherapy as Induction for Young Patients with Newly Diagnosed AML
Authors: Jing Lu, Shengli Xue, Ying Wang, Xuefeng He, Xiaohui Hu, Miao Miao, Yang Zhang, Zaixiang Tang, Jundan Xie, Xiaofei Yang, Mingzhu Xu, Yaoyao Shen, Feng Du, Qian Wu, Mengxing Xue, Yun Wang, Ailing Deng, Xueqing Dou, Yang Xu, Haiping Dai, Depei Wu, Suning Chen
Journal: Blood (2025)
Underwater endoscopic submucosal dissection for large non-pedunculated colorectal polyps
Authors: Roberto de Sire, Antonio Capogreco, Davide Massimi, Ludovico Alfarone, Luca Brandaleone, Vincenzo Vadalà, Francesco Minini, Spadaccini Marco, Antonio Facciorusso, Asma Alkandari, Pradeep Bhandari, Cesare Hassan, Roberta Maselli, Alessandro Repici
Journal: Gut (2025)
Serological screening for coeliac disease in an adult general population: the HUNT study
Authors: Ina Lervåg Andersen, Polina Lukina, Ole T Dyrli, Rolf Anton Klaasen, David John Warren, Nils Bolstad, Patricia Mjønes, Elin Rønne, Rasmus Iversen, Ludvig M Sollid, Knut E A Lundin, Eivind Ness-Jensen
Journal: Gut (2025)

Background A large proportion of individuals with coeliac disease (CeD) remain undiagnosed. Objective The aim of this study was to assess serological screening for CeD in the adult general population. Design The study was based on the fourth Trøndelag Health Study, a population-based study performed 2017–2019 in Nord-Trøndelag County, Norway, including 56 042 participants &gt;20 years of age (54% participation rate). Serum samples were analysed with a dual antitransglutaminase 2 (TG2) IgA and IgG assay and seropositive participants were invited to endoscopy with duodenal biopsies. A CeD diagnosis was given if mucosal damage (Marsh grade 3) was found. Results Histological evaluation of 657 seropositive participants confirmed CeD in 423. The positive predictive value (PPV) of a positive TG2 IgA was 73.3% (95% CI 69.7% to 77.0%) for biopsy-confirmed CeD. TG2 IgA ≥10 times the upper limit of normal (ULN), as used in the no-biopsy approach in children, increased the PPV to 88.1% (95% CI 84.8% to 91.4%). Primary TG2 IgG response was found in 87 participants, five of whom had biopsy-confirmed CeD. One of the participants with CeD primarily responding with TG2 IgG was IgA deficient. The PPV of a positive TG2 IgG was 5.8% (95% CI 1.9% to 12.9%) and of TG2 IgG ≥10× ULN was 9.5% (95% CI 1.2% to 30.4%) for biopsy-confirmed CeD in TG2 IgA-negative individuals. Conclusion The TG2 IgA assay showed excellent abilities as a screening tool for CeD in the adult general population. However, the diagnostic accuracy of TG2 IgG was too poor for selectively identifying individuals with CeD.
The MURANO study: final analysis and retreatment/crossover substudy results of VenR for patients with relapsed/refractory CLL
Authors: Arnon P. Kater, Rosemary Anne Harrup, Thomas J Kipps, Barbara Eichhorst, Carolyn Owen, Sarit E. Assouline, Nicole Lamanna, Tadeusz Robak, Javier de la Serna, Ulrich Jaeger, Guillaume Cartron, Marco Montillo, Clemens Mellink, Anton W. Langerak, Brenda Chyla, Relja Popovic, Yanwen Jiang, Rosemary Millen, Marcus Lefebure, Maria Thadani-Mulero, Michelle Boyer, John F Seymour
Journal: Blood (2025)

Fixed-duration venetoclax-rituximab (VenR) in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) in the phase 3 MURANO trial (NCT02005471) resulted in superior progression-free survival (PFS) and overall survival (OS) vs bendamustine-rituximab (BR). We report the final analyses of MURANO (median 7 years follow-up). Patients were randomized to VenR (venetoclax 400 mg daily for 2 years plus monthly rituximab for 6 months; n = 194) or BR (6 months; n = 195). In a substudy, patients with progressive disease (PD) received VenR as retreatment or crossover from BR. At the final data cut (3 August 2022), median PFS with VenR was 54.7 vs 17.0 months with BR. Seven-year PFS with VenR was 23.0%. Seven-year OS was 69.6% and 51.0%, respectively. Among VenR-treated patients with undetectable (u) minimal residual disease (MRD) and no PD at end of treatment (EOT) (n = 83), median PFS from EOT was 52.5 vs 18.0 months in patients with MRD at EOT (n = 35; P &amp;lt; 0.0001). Fourteen patients had enduring uMRD. Three distinct mutations in BCL2 in four patients were identified. In the substudy, 25 patients were retreated with VenR and nine patients crossed over to VenR; median PFS was 23 and 27 months, and best overall response rate was 72% and 89%, respectively. At the end of combination treatment, following retreatment or crossover, eight and six patients achieved uMRD, respectively. No new safety findings were observed. Overall, these final MURANO analyses support consideration of fixed-duration VenR therapy for patients with relapsed/refractory CLL.
Synergistic antitumor effect of combined EZH2 and DOT1L inhibition in B-cell lymphoma
Authors: Van T. M. Nguyen, Hiroe Namba, Hayley Porter, Daria Shlyueva, Ernesto Lopez, Alan Melcher, Wendy Béguelin, Ari M. Melnick, Kristian Helin
Journal: Blood (2025)

Despite the approval of several new treatments for patients with B-cell lymphoma, there is still a large unmet need. Diffuse large B-cell lymphoma (DLBCL) and Follicular lymphoma (FLs) are the two most common B-cell lymphoma subtypes, accounting for approximately 50% of all cases. EZH2 heterozygous gain-of-function somatic driver mutations are frequently found in Germinal Center B cell (GCB) DLBCLs and FLs. An EZH2 inhibitor has shown durable responses in patients with relapsed or refractory FL, however a considerable fraction of the patients did not show an objective response. To identify alternative therapeutic strategies, we performed CRISPR/Cas9 knockout screens in B-cell lymphoma cells treated with or without an EZH2 inhibitor. This led to the identification of the histone methyltransferase DOT1L as a potential therapeutic target. Specifically, we showed that an EZH2 inhibitor synergizes with a DOT1L inhibitor in a panel of B-cell lymphoma cell lines, regardless of EZH2 mutation status. Mechanistically, we demonstrated that the two inhibitors cooperatively suppress DOT1L-regulated cell cycle genes, up-regulate genes involved in interferon signaling including antigen presenting genes and ultimately drive B cell differentiation by de-repressing EZH2-regulated plasma cell signature genes. Furthermore, we demonstrated the effectiveness of this epigenetic combination strategy in a xenograft model, which resulted in significant abrogation of tumor growth. Together, our studies provide pre-clinical proof-of-concept for an epigenetic combination therapy to overcome resistance and improve durability of response for the treatment of B-cell lymphoma, warranting clinical investigation and illustrating an important convergent role of EZH2 and DOT1L in B cell lymphomagenesis.
NOTCH1 dimeric signaling is essential for T-cell leukemogenesis and leukemia maintenance
Authors: Francesco Tamiro, Costanzo Padovano, Elisabetta De Santis, Serena Di Iasio, Francesca Delia Sansico, Valentina Canistro, Mattia Colucci, Chiara Di Nunzio, Gaja Bruno, Kashish Doshi, Angela Totaro, Eric Gu, Michele Santodirocco, Andrew P. Weng, Vincenzo Giambra
Journal: Blood (2025)
Development of live biotherapeutic products: a position statement of Asia-Pacific Microbiota Consortium
Authors: Ching-Hung Tseng, Sunny Wong, Jun Yu, Yeong Yeh Lee, Jun Terauchi, Hsin-Chih Lai, Jiing-Chyuan Luo, Cheng Yen Kao, Sung-Liang Yu, Jyh-Ming Liou, Deng-Chyang Wu, Ming-Chih Hou, Ming-Shiang Wu, Jiunn-Jong Wu, Joseph J Y Sung, Emad M El-Omar, Chun-Ying Wu
Journal: Gut (2025)

Objective Live biotherapeutic products (LBPs) are biological products composed of living micro-organisms, developed to prevent, treat, or cure diseases. Examples include cultured strains of Akkermansia muciniphila and Christensenella minuta , as well as treatments using purified Firmicutes spores for recurrent Clostridioides difficile infections. There is a need for guidelines over the increasing interest in developing LBPs. A panel of microbiome experts from Asia-Pacific countries articulates their perspectives on key considerations for LBP development. Design Experts in microbiome research, microbiology, gastroenterology, internal medicine and biotherapeutics industry were invited to form a panel. During the 2023 Inauguration Conference of the Asia-Pacific Microbiota Consortium, an organised, iterative roundtable discussion was conducted to build expert consensus on critical issues surrounding the development of LBP. Results The consensus statements were organised into three main aspects: (a) rationales of LBP development, (b) preclinical studies and (c) preparation for clinical studies. The panel strongly recommended to prioritise human-derived and food-sourced strains for development, with indications based on clinical need and efficacy shown in studies. Preclinical evaluation should involve thorough screening, genotyping and phenotyping, as well as comprehensive in vitro and animal studies to assess functional mechanisms and microbiological safety. Rigorous cell banking practices and genetic monitoring are essential to ensure product consistency and safety throughout the manufacturing process. Clinical trials, including postmarketing surveillance, must be carefully designed and closely monitored, with robust safety and risk management protocols in place. Conclusions The development of LBP should be approached with a strong emphasis on microbiological evaluation, clinical relevance, scientific mechanisms and safety at every stage. These measures are essential to ensure the safety, effectiveness and long-term success of the product.
Effectiveness of reducing tendon compression in the rehabilitation of insertional Achilles tendinopathy: a randomised clinical trial
Authors: Lauren Pringels, Robbe Capelleman, Aäron Van den Abeele, Arne Burssens, Guillaume Planckaert, Evi Wezenbeek, Luc Vanden Bossche
Journal: British Journal of Sports Medicine (2025)

Objective To assess the effectiveness of low tendon compression rehabilitation (LTCR) versus high tendon compression rehabilitation (HTCR) for treating patients with insertional Achilles tendinopathy. Methods In an investigator-blinded, stratified randomised trial, 42 sport-active patients (30 males and 12 females; age 45.8±8.2 years) with chronic (&gt; 3 months) insertional Achilles tendinopathy were allocated in a 1:1 ratio to receive LTCR or HTCR. Both rehabilitation protocols consisted of a progressive 4-stage tendon-loading programme, including isometric, isotonic, energy-storage and release and sport-specific exercises. The LTCR programme was designed to control Achilles tendon compression by limiting ankle dorsiflexion during exercise, eliminating calf stretching and incorporating heel lifts. The primary outcome was the Victorian Institute of Sports Assessment-Achilles (VISA-A) score at 12 and 24 weeks, which measures tendon pain and function and was analysed on an intention-to-treat basis using a linear mixed model. Significance was accepted when p&lt;0.05. Results 20 patients were randomised to the LTCR group and 22 to the HTCR group. Improvement in VISA-A score was significantly greater for LTCR compared with HTCR after 12 weeks (LTCR=24.4; HTCR=12.2; mean between-group difference=12.9 (95% CI: 6.2 to 19.6); p&lt;0.001) and after 24 weeks (LTCR=29.0; HTCR=19.3; mean between-group difference=10.4 (95% CI: 3.7 to 17.1); p&lt;0.001). These differences exceeded the minimal clinically important difference of 10. Conclusions In sport-active patients with insertional Achilles tendinopathy, LTCR was more effective than HTCR in improving tendon pain and function at 12 and 24 weeks. Consequently, LTCR should be considered in the treatment of insertional Achilles tendinopathy. Trial registration number ClinicalTrials.gov (ID: NCT05456620 ).
CD47 as a potential predictive biomarker in colorectal cancer
Authors: Justin Stebbing, Andrea Bullock
Journal: Journal for ImmunoTherapy of Cancer (2025)

In this week’s Journal for ImmunoTherapy for Cancer, Arai and colleagues analyzed next-generation sequencing data for DNA and RNA from 14,287 patients with colorectal cancer (CRC) categorized by median CD47 expression level, and showed that CD47, a key component of innate immunity in deflecting phagocytosis, is associated with molecular subtypes of CRC, cell damage-associated molecular pattern-related genes, major oncogenic pathways, and adaptive immune checkpoint genes. Taken together, they concluded that CD47 expression is associated with activation of oncogenic pathways and an immune-engaged tumor microenvironment. Clinical outcomes data also demonstrated that high CD47 is associated with prolonged survival in patients treated with antiangiogenic and checkpoint inhibitor therapy. Biomarker studies such as this will enable broader application of immuno-oncology to patients with CRC and other malignancies.
Sustained bone marrow and imaging MRD negativity for 3 years drives discontinuation of maintenance post ASCT in myeloma
Authors: Evangelos Terpos, Panagiotis Malandrakis, Ioannis Ntanasis-Stathopoulos, Ioannis V Kostopoulos, Evangelos Eleutherakis-Papaiakovou, Nikolaos Kanellias, Vassiliki Spiliopoulou, Magdalini Migkou, Despina V Fotiou, Foteini Theodorakakou, Efstathios Kastritis, Maria Gavriatopoulou, Ourania Tsitsilonis, Meletios-Athanasios A. Dimopoulos
Journal: Blood (2025)
cMPL-Based Purification and Depletion of Human Hematopoietic Stem Cells: Implications for Pretransplant Conditioning
Authors: Daisuke Araki, So Gun Hong, Nathaniel Seth Linde, Bryan Fisk, Neelam Redekar, Christi T Salisbury-Ruf, Allen Krouse, Theresa Engels, Justin Golomb, Pradeep K Dagur, Sumith R Panicker, Yogendra Kanthi, Diogo Magnani, Zhirui Wang, Andre Larochelle
Journal: Blood (2025)
Magrolimab plus azacitidine vs physician's choice for untreated TP53-mutated acute myeloid leukemia: the ENHANCE-2 study
Authors: Joshua F. Zeidner, David A. Sallman, Christian Récher, Naval G. Daver, Anskar YH Leung, Devendra K. Hiwase, Marion Subklewe, Thomas Pabst, Pau Montesinos, Richard A Larson, Lindsay Wilde, Anoop K. Enjeti, Ichiro Kawashima, Cristina Papayannidis, Jenny O'Nions, Lisa Johnson, Mei Dong, Julie Huang, Taravat Bagheri, Gal Hacohen-Kleiman, Calvin Lee, Paresh Vyas
Journal: Blood (2025)

Patients with TP53-mutated acute myeloid leukemia (AML) have an extremely poor prognosis, necessitating new treatments. The global, randomized, phase 3 ENHANCE-2 trial evaluated the anti-CD47 monoclonal antibody magrolimab plus azacitidine (Magro/Aza) for previously untreated TP53-mutated AML. Patients determined inappropriate for intensive therapy were randomized to receive Magro/Aza or venetoclax plus azacitidine (Ven/Aza); those appropriate for intensive therapy were randomized to receive Magro/Aza or 7+3 induction chemotherapy. Primary endpoint was overall survival (OS) in the non-intensive arm. At interim analysis, non-intensive-arm OS hazard ratio (HR) between treatment groups was 1.191 (95% CI, 0.744-1.906), meeting the study's definition for futility and resulting in study termination. At final analysis, median OS was 4.4 vs 6.6 months (HR, 1.132; 95% CI, 0.783-1.637; P = .5070) in the non-intensive arm (n = 205) and 7.3 vs 11.1 months (HR, 1.434; 95% CI, 0.635-3.239; P = .3798) in the intensive arm (n = 52) between Magro/Aza and control groups, respectively. Incidences of grade ≥3 adverse events (AEs) were similar across Magro/Aza and control groups (non-intensive, n = 194: 96.9% and 95.9%; intensive, n = 50: 92.6% and 95.7%), including grade ≥3 anemia (non-intensive: 27.1% and 23.5%; intensive: 25.9% and 21.7%). Grade ≥3 infections were observed in 50.0% and 53.1% of patients in the non-intensive arm and 44.4% and 65.2% of intensive arm patients. ENHANCE-2 did not meet its primary endpoint of OS in TP53-mutated AML but provides important data informing future studies in this challenging population. This trial was registered at www.clinicaltrials.gov as #NCT04778397.