tbuckley/cabot-search huggingface dataset:
Integrating personalized shape prediction, biomechanical modeling, and wearables for bone stress prediction in runners
Authors: Liangliang Xiang, Yaodong Gu, Kaili Deng, Zixiang Gao, Vickie Shim, Alan Wang, Justin Fernandez
Journal: npj Digital Medicine (2025)

Running biomechanics studies the mechanical forces experienced during running to improve performance and prevent injuries. This study presents the development of a digital twin for predicting bone stress in runners. The digital twin leverages a domain adaptation-based Long Short-Term Memory (LSTM) algorithm, informed by wearable sensor data, to dynamically simulate the structural behavior of foot bones under running conditions. Data from fifty participants, categorized as rearfoot and non-rearfoot strikers, were used to create personalized 3D foot models and finite element simulations. Two nine-axis inertial sensors captured three-axis acceleration data during running. The LSTM neural network with domain adaptation proved optimal for predicting bone stress in key foot bones-specifically the metatarsals, calcaneus, and talus-during the mid-stance and push-off phases (RMSE < 8.35 MPa). This non-invasive, cost-effective approach represents a significant advancement for precision health, contributing to the understanding and prevention of running-related fracture injuries.
New twist to a fantastical distribution: Fiji–Tonga iguanas
Authors: Jason R Ali, Uwe Fritz
Journal: Trends in Ecology & Evolution (2025)

Over-water 'rafting' accounts for much of the biota on the 'oceanic' islands. Arguably, the most spectacular example concerns the iguanas on Fiji and Tonga. Scarpetta et al. have recently provided compelling evidence for them originating in western North America, with their trans-oceanic dispersal occurring within the past 33 million years.
Modeling the HLH immune synapse uncovers critical roles for IS termination, cytokine intensity, and target cell death
Authors: Anastasia M. Frank-Kamenetskii, Hannah Klinghoffer, Jemy Anna Varghese, Vinh Dang, Jeremy Morrissette, Joseph A. Fraietta, Caroline Diorio, Janis K. Burkhardt, Scott Canna
Journal: Blood (2025)
Large B-cell lymphoma imprints a dysfunctional immune phenotype that persists years after treatment
Authors: Richard Pelzl, Giulia Benintende, Franziska Gsottberger, Julia Katharina Scholz, Matthias Ruebner, Hao Yao, Kerstin Wendland, Kai Rejeski, Heidi Altmann, Srdjan Petkovic, Lisa Mellenthin, Sabrina Kübel, Moritz Schmiedeberg, Paulina Klein, Agnese Petrera, Rebecca Baur, Sophie Eckstein, Sandra Hoepffner-Grundy, Christoph Röllig, Marion Subklewe, Hanna Huebner, Georg Schett, Andreas Mackensen, Luca Laurenti, Frederik Graw, Simon Völkl, Krystelle Nganou-Makamdop, Fabian Müller
Journal: Blood (2025)

Immunotherapy has become standard of care in the treatment of diffuse large B-cell lymphoma (DLBCL). Changes in immunophenotypes observed at first diagnosis predict therapy outcome but little is known about the resolution of these alterations in remission. Comprehensive characterization of immune changes from fresh, peripheral whole blood revealed a functionally relevant increase of myeloid-derived suppressor cells, reduced naïve T-cells, and an increase of activated and terminally differentiated T-cells before treatment which aggravated after therapy. Suggesting causal relation, injection of lymphoma in mice induced similar changes in the murine T cells. Distinct immune imprints were found in breast cancer and AML survivors. Identified alterations persisted beyond five years of ongoing complete remission and in DLBCL correlated with increased pro-inflammatory markers such as IL-6, B2M, or sCD14. The chronic inflammation was associated with functionally blunted T-cell immunity against SARS-CoV-2-specific peptides and reduced responses correlated with reduced Tn-cells. Persisting inflammation was confirmed by deep sequencing and by cytokine profiles, together pointing towards a compensatory activation of innate immunity. The persisting, lymphoma-induced immune alterations in remission may explain long-term complications, have implications for vaccine strategies, and are likely relevant for immunotherapies.
Targeting high-risk multiple myeloma genotypes with optimized anti-CD70 CAR-T cells
Authors: Corynn Kasap, Adila Izgutdina, Bonell Patiño-Escobar, Amrik Singh Kang, Nikhil Chilakapati, Naomi Akagi, Ananya Mishu Manoj, Haley Johnson, Tasfia Rashid, Juwita Werner, Abhilash Barpanda, Huimin Geng, Yu-Hsiu Tony Lin, Sham Rampersaud, Daniel Gil-Alós, Amin Sobh, Daphné Dupéré-Richer, Adolfo Aleman, Gianina Wicaksono, K.M. Kawehi Kelii, Radhika Dalal, Emilio Ramos, Anjanaa Vijayanarayanan, Kiran Lakhani, Fernando Salangsang, Paul Phojanakong, Juan Antonio Camara Serrano, ons Zakraoui, Isa Tariq, Ajai Chari, Alfred Chung, Anupama Deepa Kumar, Thomas Martin, Jeffrey Lee Wolf, Sandy Wong, Veronica Steri, Mala Shanmugam, Lawrence H Boise, Tanja Kortemme, Samir Parekh, Elliot Stieglitz, Jonathan D Licht, William Karlon, Benjamin G Barwick, Arun Wiita
Journal: Blood (2025)

Despite the success of BCMA-targeting CAR-Ts in multiple myeloma, patients with high-risk cytogenetic features still relapse most quickly and are in urgent need of additional therapeutic options. Here, we identify CD70, widely recognized as a favorable immunotherapy target in other cancers, as a specifically upregulated cell surface antigen in high-risk myeloma tumors. We use a structure-guided design to define a CD27-based anti-CD70 CAR-T design that outperforms all tested scFv-based CARs, leading to &amp;gt;80-fold improved CAR-T expansion in vivo. Epigenetic analysis via machine learning predicts key transcription factors and transcriptional networks driving CD70 upregulation in high-risk myeloma. Dual-targeting CAR-Ts against either CD70 or BCMA demonstrate a potential strategy to avoid antigen escape-mediated resistance. Together, these findings support the promise of targeting CD70 with optimized CAR-Ts in myeloma as well as future clinical translation of this approach.
A Comprehensive Genetic Study of Classical Hodgkin Lymphoma Using Circulating Tumor DNA
Authors: Maria Cristina Pirosa, Alessio Bruscaggin, Lodovico Terzi di Bergamo, Matin Salehi, Federico Jauk, Gabriela Forestieri, Simone Bocchetta, Deborah Piffaretti, Riccardo Moia, Vanessa Cristaldi, Martina di Trani, Georgia Alice Galimberti, Katia Pini, Valeria Spina, Claudia Giordano, Adalgisa Condoluci, Ilaria Romano, Salvatore Annunziata, Fabrizio Bergesio, Renzo Boldorini, Eugenio Borsatti, Pietro Bulian, Eleonora Calabretta, Stephane Chauvie, Francesco Corrado, Stefania Crisci, Marco Cuzzocrea, Rosaria De Filippi, Bernhard Gerber, Michał Kurlapski, Luigi Maria Larocca, Elisabetta Merlo, Andrea Rinaldi, Marcello Rodari, Grzegorz Romanowicz, Gian Mauro Sacchetti, Anastasios Stathis, Georg Stussi, Ilaria Zangrilli, Antonio Pinto, Luca Mazzucchelli, Valter Gattei, Jan Maciej Zaucha, Armando Santoro, Stefan Hohaus, Franco Cavalli, Alexandar Tzankov, Carmelo Carlo-Stella, Gianluca Gaidano, Luca Ceriani, Emanuele Zucca, Davide Rossi
Journal: Blood (2025)

This study analyzed the genetics of classical Hodgkin lymphoma (cHL) by using circulating tumor DNA (ctDNA). Two genetic subtypes were identified, differing in genetic instability mechanisms: one subtype (64% of cases) showed a higher mutation load and a higher fraction of mutations associated with activation-induced cytidine deaminase and microsatellite instability signatures, while the other subtype (36% of cases) exhibited chromosomal instability with more somatic copy number alterations. Whole-genome duplication was more common in cHL compared to other B-cell tumors and emerged as a prognostic biomarker for patients undergoing ABVD-based therapy. Non-coding regulatory mutations, similar to those in diffuse large B-cell lymphoma, were highly prevalent in 86% of cHL. A recurrent somatic expression quantitative trait locus (seQTL) involving the BCL6 gene was found in 30% of cases. The seQTL of BCL6 aligned with accessible chromatin and increased H3K27 acetylation in cHL, disrupted PRDM1 binding, and co-occurred with BCL6 expression in cHL cells. Weak to strong expression of BCL6 was observed in 68% of cases and BCL6 expression associated with gene repression similarly in cHL and germinal center B cells. After BCL6 degradation, the core set of genes directly bound and regulated by BCL6 was derepressed in cHL and proliferation was impaired. The number and clonality of neoantigens was associated with tumor microenvironment type and response to checkpoint blockade. Finally, ctDNA analysis was suggested as a tool to distinguish ambiguous PET/CT-positive lesions post-treatment.
Practical Guidelines for the Treatment of Gestational Trophoblastic Disease: Collaboration of the European Organisation for the Treatment of Trophoblastic Disease (EOTTD)–European Society of Gynaecologic Oncology (ESGO)–Gynecologic Cancer InterGroup (GCIG)–International Society for the Study of Trophoblastic Diseases (ISSTD)
Authors: Christianne Lok, Nienke van Trommel, Elena Ioana Braicu, Francois Planchamp, Ross Berkowitz, Michael Seckl, Inge O. Baas, Alice Bergamini, Miguel Henriques Abreu, Pierre-Adrien Bolze, Genevieve Bouchard-Fortier, Antonio Braga, Maria Stephanie Fay S. Cagayan, Antonio Casado, Min Chul Choi, John Coulter, Kevin Elias, Hind H. Elmalik, Andrea Garrett, Ehsan Ghorani, Andrea Gmur, Frederic Goffin, Francois Golfier, Neil Horowitz, Ulrika Joneborg, Baljeet Kaur, Philip Tonui Kipkirui, Jacob Korach, Xin Lu, Izildinha Maesta, Giorgia Mangili, Gloria Marquina, Jerome Massardier, Hextan Y.S. Ngan, Ray Osborne, Nelleke P.B. Ottevanger, Sinan Ozalp, Naveed Sarwar, Paradan K. Sekharan, Franziska Siegenthaler, Olesya Solheim, Lone Sunde, Fred C.G.J. Sweep, Grzegorz Szewczyk, Manuela Undurraga, Emelie Wallin, Matthew C. Winter, Eiko Yamamoto, Benoit You, Emelie Wallin, Anneke Westermann, Yang Xiang, Ignacio Zapardiel
Journal: Journal of Clinical Oncology (2025)

Gestational trophoblastic diseases (GTDs) are a group of pregnancy-related premalignant and malignant diseases with generally a favorable prognosis when treated adequately. Many different treatment protocols exist worldwide. To our knowledge, this is the first set of global consensus-based guidelines for GTD. Four international organizations (European Organisation for the Treatment of Trophoblastic Diseases, European Society of Gynecologic Oncology, Gynecologic Cancer Intergroup, and International Society for the Study of Trophoblastic Diseases) delegated 53 expert GTD clinicians from 31 countries who formulated nine consensus-based definitions and the minimum criteria required to be a GTD center. Furthermore, 18 flow diagrams were developed to diagnose, treat, and follow up all forms of primary or recurrent GTD. The definitions and flow diagrams were drafted and adapted in consecutive (online) meetings until consensus was reached followed by an external review process. Here, the final guidelines are presented together with the available supporting evidence from the literature.
Transcriptional remodeling shapes therapeutic vulnerability to necroptosis in acute lymphoblastic leukemia
Authors: Anna Saorin, Anna Dehler, Bartimée Galvan, Fabio Daniel Steffen, Marine Ray, Dong Lu, Xin Yu, James Kim, Aneta Drakul, Samanta Kisele, Jin Wang, Jean-Pierre Bourquin, Beat Bornhauser
Journal: Blood (2025)

Insufficient eradication of cancer cells and survival of drug tolerant clones are major relapse driving forces. Underlying molecular mechanisms comprise activated pro-survival and anti-apoptotic signaling leading to insufficient apoptosis and drug resistance. The identification of programmed cell death pathways alternative to apoptosis opens up for possibilities to antagonize apoptosis escape routes. We have earlier shown that acute lymphoblastic leukemia (ALL) harbours a distinct propensity to undergo cell death by RIPK1-dependent necroptosis, activated by small molecule second mitochondria-derived activators of caspase (SMAC) mimetics. Despite demonstrated safety and tolerability of SMAC mimetics in clinical trials, their efficacy as single agent appears still limited, highlighting the need for combinatorial treatments. Here, we investigate so far unexplored regulatory mechanisms of necroptosis and identify targets for interference to augment the necroptotic anti-leukemia response. Ex vivo drug response profiling in a model of the bone marrow microenvironment reveals powerful synergy of necroptosis induction with histone deacetylase inhibition. Subsequent transcriptome analysis and functional in vivo CRISPR screening identify gene regulatory circuitries through the master transcription regulators SP1, p300 and HDAC2 to drive necroptosis. While deletion of SP1 or p300 confers resistance to necroptosis, loss of HDAC2 sensitizes to RIPK1-dependent cell death by SMAC mimetics. Consequently, our data inform strong in vivo anti-leukemic activity of combinatorial necroptosis induction and HDAC inhibition in patient-derived human leukemia models. Thus, transcriptional dependency of necroptosis activation is a key regulatory mechanism that identifies novel targets for interference, pointing out a strategy to exploit alternative non-apoptotic cell death pathways to eradicate resistant disease.
A Multi-Omics Approach Reveals Novel Regulators of Plasma Factor V Levels: highlight on CLEC4M as a Clearance Receptor
Authors: Gaëlle Munsch, Adarsh Mohapatra, Astrid van Hylckama Vlieg, Marcus E Kleber, Angel Martinez-Perez, Ngoc-Quynh Le, Kristian Dalsbø Hindberg, Philip J Dusart, Marine Germain, Florian Thibord, Jean-François Deleuze, Graciela E Delgado, Louisa Goumidi, Pierre Suchon, Noémie Saut, Juan Carlos Souto, Lynn Butler, Jose Manuel Soria, John-Bjarne Hansen, Winfried März, Frits R Rosendaal, Elisabetta Castoldi, Franck Peiretti, Maria Sabater-Lleal, David-Alexandre Tregouet, Pierre-Emmanuel Morange
Journal: Blood (2025)
Shear-Dependent Platelet Aggregation by ChAdOx1 nCoV-19 Vaccine: A Novel Biophysical Mechanism for Arterial Thrombosis
Authors: Yiyao Catherine Chen, Naveen Eugene Louis Richard Louis, Angela Huang, Allan Sun, Alexander Dupuy, Laura Moldovan, Tiana Pelaia, Jianfang Ren, Taylor S Cohen, Sarah Gilbert, Huyen A Tran, Karlheinz Peter, James D McFadyen, Lining Arnold Ju
Journal: Blood (2025)

Rare thrombotic events associated with ChAdOx1 nCoV-19 (ChAdOx1) vaccination have raised concerns; however, the underlying mechanisms remain elusive. Here we report a novel biophysical mechanism by which ChAdOx1 directly interacts with platelets under arterial shear conditions, potentially contributing to post-vaccination arterial thrombosis. Using microfluidic post assays, we demonstrate that ChAdOx1 induces shear-dependent platelet aggregation, distinct from conventional von Willebrand factor-mediated adhesion. This interaction is mediated by platelet integrin αIIbβ3 and requires biomechanical activation, explaining the absence of significant binding under static conditions. Molecular dynamics simulations and docking studies reveal preferential binding of ChAdOx1's penton RGD motif to the activated conformation of αIIbβ3. Inhibiting integrin αIIbβ3 completely abolishes ChAdOx1-induced platelet aggregation, whereas blocking GPIb has minimal effect, confirming a mechanism that bypasses the conventional GPIb-dependent platelet adhesion pathway. Mutagenesis of the RGD motif to AAA eliminates platelet binding, verifying the specificity of this interaction. These findings provide a potential explanation for the association between ChAdOx1 vaccination and arterial thrombotic events, distinct from vaccine-induced immune thrombotic thrombocytopenia (VITT). Our results highlight the importance of considering biomechanical factors in vaccine-related thrombotic complications and suggest that shear-dependent integrin activation may be another determinant in the pathogenesis of these rare adverse events.
Efficacy of targeting high mean arterial pressure for older patients with septic shock (OPTPRESS): a multicentre, pragmatic, open-label, randomised controlled trial
Authors: Akira Endo, Kazuma Yamakawa, Takashi Tagami, Yutaka Umemura, Takeshi Wada, Ryo Yamamoto, Hiroki Nagasawa, Wataru Takayama, Masayuki Yagi, Kyosuke Takahashi, Mitsuaki Kojima, Chihiro Narita, Satoshi Kazuma, Jiro Takahashi, Atsushi Shiraishi, Masaki Todani, Masaki Nakane, Toshihiko Nagata, Shohei Tanaka, Yuta Yokokawa, Kunihiko Takahashi, Haruka Ishikita, Ryo Hisamune, Junichi Sasaki, Ken-Ichi Muramatsu, Hiroyuki Sonobe, Kazunobu Minami, Hiromasa Hoshi, Yasuhiro Otomo
Journal: Intensive Care Medicine (2025)

We examined the effect of a high-target mean arterial pressure (MAP) on septic shock in a previously underrepresented region. A multicentre, pragmatic, open-label, randomised controlled trial was conducted in 29 hospitals in Japan, where the prevalence of chronic hypertension among older individuals is 66.9%. Patients who were diagnosed with septic shock, aged ≥ 65 years, and admitted to an intensive care unit were randomised 1:1 to the high (target MAP = 80-85 mmHg) or control (target MAP = 65-70 mmHg) groups from 1 July 2021 to 12 December 2023. The target MAP was maintained for 72 h or until vasopressors were no longer required. The primary outcome was the 90-day all-cause mortality. Secondary outcomes included organ support-free days and adverse events. The trial was terminated early on the basis of the interim analysis results, suggesting the harm of the high-target strategy. Of the 518 patients, 258 were in the high-target group, and 260 were in the control group. By 90 days after randomisation, 101 patients (39.3%) in the high-target group and 74 (28.6%) in the control group had died from any cause (risk difference = 10.7; 95% confidence interval, 2.6-18.9). Renal replacement therapy-free days at 28 days were shorter in the high-target group. No clinical benefits for any outcome were observed in any subpopulation, including those with known chronic hypertension. Among older patients with septic shock, high-target MAP significantly increased mortality compared with standard care. UMIN Clinical Trials Registry; UMIN000041775; 13 September 2020.
Heterogeneity of IKZF1 genomic alterations and risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia
Authors: Ruth W Wang'ondu, Emily Ashcraft, Ti-Cheng Chang, Kathryn G Roberts, Samuel W Brady, Yiping Fan, William Evans, Mary V Relling, Kristine R Crews, Jun Yang, Wenjian Yang, Stanley Pounds, Gang Wu, Meenakshi Devidas, Kelly Maloney, Leonard Mattano, Reuven J Schore, Anne Angiolillo, Eric Larsen, Wanda Salzer, Michael J Burke, Mignon L Loh, Sima Jeha, Ching-Hon Pui, Hiroto Inaba, Cheng Cheng, Charles G Mullighan
Journal: Leukemia (2025)
Refining histopathological growth pattern-based risk group discrimination in nodular lymphocyte-predominant Hodgkin lymphoma: an analysis from the German Hodgkin Study Group
Authors: Dennis A Eichenauer, Aylin Basaran, Ina Bühnen, Michael Fuchs, Bastian von Tresckow, Andreas Rosenwald, Martin-Leo Hansmann, Heinz-Wolfram Bernd, Peter Borchmann, Wolfram Klapper, Sylvia Hartmann
Journal: Leukemia (2025)

Abstract Histopathological growth patterns (GP) in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) have previously been divided into GP AB (typical) vs CDEF (variant). However, it is unclear whether this division is optimal. We thus investigated alternative GP grouping approaches (GP ABC vs DEF; GP ABCF vs DE). Overall, 583 NLPHL patients who had first-line treatment within GHSG trials were included in the analysis. Median age was 39 years; 74% of patients were male; 76% presented with early-stage and 24% with advanced-stage disease. The 5-year and 10-year progression-free survival (PFS) estimates for all patients were 85.9% and 76.6%; overall survival (OS) estimates were 95.8% and 94.5%. Significant PFS and OS differences were detected for the comparison GP ABCF vs DE with worse outcomes for the GP DE group (HR: 1.7; 95%-CI: 1.1–2.7; HR: 2.5; 95%-CI: 1.1–5.7). No PFS and OS differences were observed for the comparisons GP AB vs CDEF and GP ABC vs DEF. Median time to death was shorter and death more often due to NLPHL in the GP DE (13 months; 66.7%) than in the GP ABCF (31 months; 5.6%) group. Hence, the division of GP into GP ABCF vs DE allows an optimized GP-based risk group discrimination in NLPHL.
Acute myeloid leukemia stem cells remodel the bone marrow niche via TGF-β-activated Alcam+ bone lining cells, creating a self-sustaining environment
Authors: Ngan Thi Kim Nguyen, Hisayuki Yao, Kentaro Hosokawa, Yuki Esaki, Ryosuke Yuta, Shunichi Adachi, Fumio Arai
Journal: Leukemia (2025)
NeuroD1 induces microglial apoptosis and cannot induce microglia-to-neuron cross-lineage reprogramming
Authors: Yanxia Rao, Siling Du, Baozhi Yang, Yuqing Wang, Yuxin Li, Ruofan Li, Tian Zhou, Xiangjuan Du, Yang He, Yafei Wang, Xin Zhou, Ti-Fei Yuan, Ying Mao, Bo Peng
Journal: Neuron (2025)
Protein-Restricted Diets and Their Impact on Metabolic Health and Aging
Authors: Sora Q. Kim, Redin A. Spann, Cristal M. Hill, Claire E. Berryman, Hans-Rudolf Berthoud, David H. McDougal, Yanlin He, Heike Münzberg, Sangho Yu, Christopher D. Morrison
Journal: Annual Review of Nutrition (2025)

Recent improvements in human longevity have highlighted the challenge of maintaining health throughout extended lifespans. This review examines how organisms regulate nutrient intake and metabolism, focusing on dietary protein's unique role in health and longevity. While caloric restriction enhances longevity, adherence to a low-calorie diet is challenging. Protein restriction represents an alternate nutritional intervention that improves longevity and health in model organisms and may be easier to translate to humans. However, its impacts are complex, and its mechanisms are poorly understood. The beneficial effects of protein restriction on metabolism and longevity may come at a cost to lean mass and physical resilience. Conversely, while public health recommendations often emphasize high protein intake, human epidemiological data and work on model organisms suggest that excessive protein consumption correlates with increased mortality. Understanding this paradox is crucial for developing evidence-based protein intake recommendations that balance longevity with physical performance.
Involvement of <scp>IL</scp>‐13‐Induced Dysregulation of <scp>BDNF</scp>‐<scp>NTRK2</scp> Pathway in Symptoms of Eosinophilic Esophagitis
Authors: Kasumi Osonoi, Akinari Sawada, Yuki Maekawa, Mari Yamaguchi, Shingo Yamada, Kazuhiro Matsuyama, Mark Rochman, Marc E. Rothenberg, Xiaobo Han, Naoki Matsuda, Ikuro Suzuki, Fumio Tanaka, Yasuhiro Fujiwara, Tetsuo Shoda
Journal: Allergy (2025)