tbuckley/cabot-search huggingface dataset:
Authors' Reply: Competing Risk Models Should Be Considered When Estimating Kidney Allograft Failure
Authors: Agathe Truchot, Marc Raynaud, Alexandre Loupy
Journal: Journal of the American Society of Nephrology (2025)

We read with interest the letter by Lindeman et al.1 regarding our recent study, "Competing and Noncompeting Risk Models for Predicting Kidney Allograft Failure."2 Using data from The Netherlands, the authors commented on the effect of competing risks on graft loss estimation. While we welcome scientific dialogue, we find their critique misaligned with our study's scope and objectives, as well as with current clinical and regulatory standards. Our study was designed with three specific aims: to evaluate the effect of the competing risk of death with a functioning graft on (1) graft loss estimation, (2) prediction model development, and (3) predictive performance. This was accomplished through an international collaboration of experts in epidemiology, biostatistics, and transplantation, using a robust methodological framework validated across diverse populations. We regret that this carefully designed and extensively validated effort is referred to as an impression of authority, as it instead reflects the rigor and deliberate strategy underpinning our study. The authors report an absolute overestimation of the cumulative incidence of graft loss of 1% for living donors and 1.6% for deceased donors at 10 years. These findings are consistent with our results, which showed a moderate absolute overestimation in this time frame (1% in the derivation cohort at 8 years). It is crucial to emphasize that our study was designed with a follow-up period of up to 8 years, in alignment with the practical realities of transplant follow-up and the needs of decision making within actionable time frames.3,4 Predictive models for graft loss evaluated by regulatory agencies, including the US Food and Drug Administration and European Medicines Agency, are not designed or qualified for horizons beyond 10 years, as the reliability and clinical utility of such extended predictions are limited by numerous factors influencing graft survival over time. The authors also indicate that our findings might not hold true for specific high-risk populations. However, we dedicated specific analyses to these scenarios, including older recipients and grafts from extended criteria donors: Our results did not show a clear benefit of a competing risk approach in these subpopulations. We clearly stated in our discussion that the optimal choice between competing and noncompeting risk approaches is context dependent, varying with specific populations, frequency of competing events, clinical questions, and research objectives—an assertion that their letter does not challenge. In conclusion, while Lindeman et al. raise methodological points, their data support rather than contradict our findings. Our work demonstrates that the choice between competing and noncompeting risk models must be guided by specific clinical and research needs within reasonable and actionable time frames.
Post-transplant Thrombotic Microangiopathy
Authors: Anuja Java, Matthew A. Sparks, David Kavanagh
Journal: Journal of the American Society of Nephrology (2025)

Abstract Thrombotic microangiopathy (TMA) is a challenging and serious complication of kidney transplantation that significantly impacts graft and patient survival, occurring in 0.8–15% of transplant recipients. TMA is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ injury due to endothelial damage and microthrombi formation in small vessels. However, clinical features can range from a renal-limited form, diagnosed only on a kidney biopsy, to full-blown systemic manifestations, which include neurological, gastrointestinal, and cardiovascular injury. TMA can arise due to genetic or acquired defects such as in complement-mediated TMA or can occur in the context of other conditions like infections, autoimmune diseases or immunosuppressive drugs, where complement activation may also play a role. Recurrent TMA after kidney transplant is almost always complement-mediated, although complement overactivation may also play a role in de novo post-transplant TMAs associated with ischemia-reperfusion injury, immunosuppressive drugs, antibody-mediated rejection, viral infections, and relapse of autoimmune diseases such as, antiphospholipid antibody syndrome. Differentiating between a complement-mediated process and one triggered by other factors is often challenging but critical to minimize allograft damage since the former is non-responsive to supportive therapy, needs long-term anti-complement therapy and has a high risk of recurrence. Given the central role of complement and impact of genetic defects on the risk of recurrence in many forms of post-transplant TMA, genetic testing for complement disorders is key for proper diagnosis and management. Given that complement activation may also play a role in a subset of TMAs associated with other conditions, prompt recognition and timely initiation of anti-complement therapy is equally important. Additionally, TMA associated with non-complement genes, often part of a broader syndromic process with distinct clinical features, has also been described. Early identification and treatment are essential to prevent graft failure and other severe complications. This review explores the pathophysiological mechanisms underlying various post-transplant TMAs.
Author Correction: Generation of a selective senolytic platform using a micelle-encapsulated Sudan Black B conjugated analog
Authors: Sophia Magkouta, Dimitris Veroutis, Angelos Papaspyropoulos, Maria Georgiou, Nikolaos Lougiakis, Natassa Pippa, Sophia Havaki, Anastasia Palaiologou, Dimitris-Foivos Thanos, Konstantinos Kambas, Nefeli Lagopati, Nikos Boukos, Nicole Pouli, Panagiotis Marakos, Athanassios Kotsinas, Dimitris Thanos, Konstantinos Evangelou, Fotios Sampaziotis, Constantin Tamvakopoulos, Stergios Pispas, Russell Petty, Nicholas Kotopoulos, Vassilis G. Gorgoulis
Journal: Nature Aging (2025)
Sugar-sweetened beverage intake, gut microbiota, circulating metabolites, and diabetes risk in Hispanic Community Health Study/Study of Latinos
Authors: Yanbo Zhang, Kai Luo, Brandilyn A Peters, Yasmin Mossavar-Rahmani, Jee-Young Moon, Yi Wang, Martha L Daviglus, Linda Van Horn, Amanda C McClain, Christina Cordero, James S Floyd, Bing Yu, Ryan W Walker, Robert D Burk, Robert C Kaplan, Qibin Qi
Journal: Cell Metabolism (2025)
Convergence of evolving artificial intelligence and machine learning techniques in precision oncology
Authors: Elena Fountzilas, Tillman Pearce, Mehmet A. Baysal, Abhijit Chakraborty, Apostolia M. Tsimberidou
Journal: npj Digital Medicine (2025)

The confluence of new technologies with artificial intelligence (AI) and machine learning (ML) analytical techniques is rapidly advancing the field of precision oncology, promising to improve diagnostic approaches and therapeutic strategies for patients with cancer. By analyzing multi-dimensional, multiomic, spatial pathology, and radiomic data, these technologies enable a deeper understanding of the intricate molecular pathways, aiding in the identification of critical nodes within the tumor's biology to optimize treatment selection. The applications of AI/ML in precision oncology are extensive and include the generation of synthetic data, e.g., digital twins, in order to provide the necessary information to design or expedite the conduct of clinical trials. Currently, many operational and technical challenges exist related to data technology, engineering, and storage; algorithm development and structures; quality and quantity of the data and the analytical pipeline; data sharing and generalizability; and the incorporation of these technologies into the current clinical workflow and reimbursement models.
Recirculating regulatory T cells mediate thymic regeneration through amphiregulin following damage
Authors: Andri L Lemarquis, Anastasia I Kousa, Kimon V Argyropoulos, Lorenz Jahn, Brianna Gipson, Jonah Pierce, Lucia Serrano-Marin, Kristen Victor, Yuzuka Kanno, Narina N Girotra, Hana Andrlova, Jennifer Tsai, Enrico Velardi, Roshan Sharma, Simon Grassmann, Olov Ekwall, Andrew B Goldstone, Jarrod A Dudakov, Susan DeWolf, Marcel R M van den Brink
Journal: Immunity (2025)

Thymic injury associated with disease or cancer treatment reduces T cell production and makes patients more vulnerable to infections and cancers. Here, we examined the role of regulatory T (Treg) cells on thymic regeneration. Treg cell frequencies increased in the thymus in various acute injury models. Depletion of Treg cells impaired thymic regeneration, impacting both the thymocyte compartment and the stromal cell compartment; adoptive transfer of Treg cells enhanced regeneration. Expansion of circulating Treg cells, as opposed to that of tissue resident or recent thymic emigrants, explained this increase, as seen using parabiotic and adoptive transfer models. Single-cell analyses of recirculating Treg cells revealed expression of various regenerative factors, including the cytokine amphiregulin. Deletion of amphiregulin in these Treg cells impaired regeneration in the injured thymus. We identified an analogous population of CD39+ICOS+ Treg cells in the human thymus. Our findings point to potential therapeutic avenues to address aging- and treatment-induced immunosuppression.
Divergent sex-specific pannexin-1 mechanisms in microglia and T cells underlie neuropathic pain
Authors: Churmy Y Fan, Brendan B McAllister, Sierra Stokes-Heck, Erika K Harding, Aliny Pereira de Vasconcelos, Laura K Mah, Lucas V Lima, Nynke J van den Hoogen, Sarah F Rosen, Boram Ham, Zizhen Zhang, Hongrui Liu, Franz J Zemp, Regula Burkhard, Markus B Geuking, Douglas J Mahoney, Gerald W Zamponi, Jeffrey S Mogil, Shalina S Ousman, Tuan Trang
Journal: Neuron (2025)
Loss of endothelial CD2AP causes sex-dependent cerebrovascular dysfunction
Authors: Milène Vandal, Adam Institoris, Louise Reveret, Ben Korin, Colin Gunn, Sotaro Hirai, Yulan Jiang, Sukyoung Lee, Jiyeon Lee, Philippe Bourassa, Ramesh C Mishra, Govind Peringod, Faye Arellano, Camille Belzil, Cyntia Tremblay, Mada Hashem, Kelsea Gorzo, Esteban Elias, Jinjing Yao, Bill Meilandt, Oded Foreman, Meron Roose-Girma, Steven Shin, Daniel Muruve, Wilten Nicola, Jakob Körbelin, Jeff F Dunn, Wayne Chen, Sang-Ki Park, Andrew P Braun, David A Bennett, Grant R J Gordon, Frédéric Calon, Andrey S Shaw, Minh Dang Nguyen
Journal: Neuron (2025)
Comprehensive Single-Cell Chromatin and Transcriptomic Profiling of Peripheral Immune Cells in Non-Segmental Vitiligo
Authors: Jesus Gay-Mimbrera, Daniel Lozano-Ojalvo, Pedro J Gómez-Arias, Irene Rivera-Ruiz, Macarena Aguilar-Luque, Carmen Mochón-Jiménez, Eloísa Andújar Pulido, Mónica Pérez-Alegre, Emma Guttman-Yassky, Juan Ruano
Journal: British Journal of Dermatology (2025)

Abstract Introduction Non-segmental vitiligo (NSV) is an autoimmune condition characterized by melanocyte loss. While skin-specific mechanisms are well-studied, systemic immune dysregulation contributing to NSV pathogenesis remains unclear. Objective This study employs a multi-omic single-cell approach to investigate circulating immune cells in NSV, integrating transcriptional and chromatin accessibility data. Methods An integrative scRNA-seq/scATAC-seq analysis was conducted on PBMCs from NSV patients (n=11) and controls (n=5), identifying transcriptional markers, cell-cell interactions, chromatin accessibility, and transcription factor (TF) dynamics. Key findings were validated in an expanded cohort (NSV, n=16; controls, n=9) using spectral flow cytometry, with additional stratification by sex, age, disease activity, severity, and duration. Results Analysis of 59,192 PBMCs identified 8,204 gene expression markers and 13,925 ATAC peaks across 25 immune cell subtypes. A broadly activated immune response was observed, characterized by cytotoxicity, antigen presentation, cell exhaustion, and stress, predominantly in monocytes, NK cells, CD8+ T cells, and dendritic cells (DCs). Multi-omic integration revealed Th1/Th17 polarization and dysfunctional regulatory T cell (Treg/mTreg) responses. Chromatin accessibility highlighted enriched TF binding sites for FOXO3, SP1, AP1, STAT1/STAT3, IRF1, and IRF4, regulating pathways linked to cytotoxicity, antigen processing, NF-κB, Toll-like receptor, and JAK-STAT signaling. Flow cytometry validated these findings, showing that disease activity and shorter duration were associated with heightened immune dysregulation. Robust TCR activation drove Th1/Th17 polarization and elevated IFN-γ and TNF-α production in CD4+ and CD8+ T cells. CLA+ skin-homing Th1/Th17-polarized CD4+ T cells, CD8+ T cells, and mTregs exhibited persistent activation, marked by basal PD1+ expression. OX40/OX40L-mediated interactions between monocytes and effector T cells amplified inflammation. Regulatory dysfunction, including reduced IL-4 and IL-13 production in mTregs, was prominent in moderate-severe and active disease. Conclusion This is the first multi-omic single-cell study in PBMCs of NSV patients, revealing systemic immune dysregulation driven by cytotoxicity, antigen presentation, exhaustion, and regulatory failure. Disease severity, activity, and evolution influence these pathways, highlighting the OX40/OX40L axis as a potential therapeutic target to mitigate immune dysregulation and relapse risk.
IRS2 as a driver of brain metastasis in colorectal cancer: a potential target for novel therapeutic strategies
Authors: Inbal Greenberg, Fayhaa Khair, Keren Merenbakh-Lamin, Ethan Sokol, Anat Klein Goldberg, Dor Simkin, Avishay Spitzer, Moshe Benhamou, Shai Bar-Shira, Michal Raz, Rachel Grossman, Eilam Yeini, Paula Ofek, Tomer Meirson, Ronit Satchi-Fainaro, Hadas Reuveni, Tami Rubinek, Ido Wolf
Journal: Neuro-Oncology (2025)

Colorectal cancer (CRC) ranks as the fourth most common cause of brain metastasis (BM), with its incidence on the rise. However, the molecular mechanisms driving the formation of these lesions from CRC remain unclear. We analyzed the FoundationOne genomic database, which includes over 35,000 CRC samples from both local and metastatic sites. The role of insulin receptor substrate 2 (IRS2) in CRC brain tropism was investigated using various in vitro (co-culture systems and 3D sphere formation assays), in vivo (intracranial and subcutaneous mouse models), and ex vivo (CRC Patient-Derived Explants (PDE)) models. The molecular and metabolic effects of IRS2 were examined through RNA sequencing and Seahorse analysis. The therapeutic potential of a combined treatment with NT219, an IRS2 inhibitor, and 5-fluorouracil (5-FU) was assessed using our CRC BM mouse model. Our research reveals a distinctive genomic profile of CRC BM and highlights the role of IRS2 in promoting CRC BM. IRS2 mediates its effect by modulating the β-catenin and oxidative phosphorylation (OXPHOS) pathways. We developed a mouse model of BM from CRC and demonstrated that treatment with the IRS2 inhibitor NT219, in combination with 5-FU, significantly suppresses BM development and prolongs survival. Our work underscores the unique role of IRS2 in facilitating CRC brain adaptation and suggests a novel therapeutic strategy for CRC patients with BM.
A 3D Self-Assembly Platform Integrating Decellularized Matrix Recapitulates In Vivo Tumor Phenotypes and Heterogeneity
Authors: Michael J. Buckenmeyer, Elizabeth A. Brooks, Madison S. Taylor, Ireolu K. Orenuga, Liping Yang, Ronald J. Holewinski, Thomas J. Meyer, Melissa Galloux, Marcial Garmendia-Cedillos, Thomas J. Pohida, Thorkell Andresson, Brad St. Croix, Matthew T. Wolf
Journal: Cancer Research (2025)

Abstract Three-dimensional (3D) in vitro cell culture models are invaluable tools for investigating the tumor microenvironment (TME). However, analyzing the impact of critical stromal elements, such as extracellular matrix (ECM), remains a challenge. Here, we developed a hydrogel-free self-assembly platform to establish ECM-rich 3D “MatriSpheres” to deconvolute cancer cell-ECM interactions. Mouse and human colorectal cancer (CRC) MatriSpheres actively incorporated microgram quantities of decellularized small intestine submucosa ECM, which proteomically-mimicked CRC tumor ECM compared to traditional formulations like Matrigel. Solubilized ECM, at sub-gelation concentrations, was organized by CRC cells into intercellular stroma-like regions within 5 days, displaying morphological similarity to CRC clinical pathology. MatriSpheres featured ECM-dependent transcriptional and cytokine profiles associated with malignancy, lipid metabolism, and immunoregulation. Model benchmarking with scRNA sequencing demonstrated that MatriSpheres enhanced correlation with in vivo tumor cells over traditional ECM-poor spheroids. This facile approach enables tumor-specific tissue morphogenesis, promoting cell-ECM communication to improve fidelity for disease modeling applications.
BNT162b2 COVID-19 vaccination elicits the expansion of CD16+CD8+ T cells endowed with Natural Killer cell features
Authors: Claudia De Pasquale, Fabiana Drommi, Alessia Calabrò, Cirino Botta, Giacomo Sidoti Migliore, Paolo Carrega, Grazia Vento, Amirhossein Gaeini, Gaetana Pezzino, José Freni, Irene Bonaccorsi, Massimo Vitale, Gilberto Filaci, Daniela Fenoglio, Raffaella Iemmo, Gregorio Costa, Riccardo Cavaliere, Guido Ferlazzo, Stefania Campana
Journal: Journal of Allergy and Clinical Immunology (2025)
In-Hospital Diabetes Management by a Diabetes Team and Insulin Titration Algorithms Based on Continuous Glucose Monitoring or Point-of-Care Glucose Testing in Patients With Type 2 Diabetes (DIATEC): A Randomized Controlled Trial
Authors: Mikkel T. Olsen, Carina K. Klarskov, Signe H. Jensen, Louise M. Rasmussen, Birgitte Lindegaard, Jonas A. Andersen, Hans Gottlieb, Suzanne Lunding, Ulrik Pedersen-Bjergaard, Katrine B. Hansen, Peter L. Kristensen
Journal: Diabetes Care (2025)

OBJECTIVE The DIATEC trial investigates the glycemic and clinical effects of inpatient continuous glucose monitoring (CGM)–guided insulin titration by diabetes teams. RESEARCH DESIGN AND METHODS This two-center trial randomized 166 non–intensive care unit patients with type 2 diabetes. Diabetes management was performed by regular staff, guided by diabetes teams using insulin titration algorithms based on either point-of-care glucose testing or CGM. The primary outcome was the difference in time in range (TIR) (3.9–10.0 mmol/L) between the two arms. Outcomes were assessed during hospitalization. RESULTS The CGM arm achieved a higher median (interquartile range [IQR]) TIR of 77.6% (24.4%) vs. 62.7% (31.5%) in the POC arm (P &amp;lt; 0.001). Median (IQR) time above range (TAR) &amp;gt;10.0 mmol/L was lower in the CGM arm at 21.1% (24.8%) vs. 36.5% (30.3%) in the POC arm (P = 0.001), and time below range (TBR) &amp;lt;3.9 mmol/L was reduced by CGM, with a relative difference to POC of 0.57 (95% CI 0.34–0.97; P = 0.042). Prolonged hypoglycemic events decreased (incidence rate ratio [IRR] 0.13; 95% CI 0.04–0.46; P = 0.001), and the mean (SD) coefficient of variation was lower in the CGM arm at 25.4% (6.3%) vs. 28.0% (8.2%) in the POC arm (P = 0.024). Mean (SD) total insulin doses were reduced in the CGM arm at 24.1 (13.9) vs. 29.3 (13.9) IU/day in the POC arm (P = 0.049). A composite of complications was lower in the CGM arm (IRR 0.76; 95% CI 0.59–0.98; P = 0.032). CONCLUSIONS In-hospital CGM increased TIR by 15 percentage points, mainly by reducing TAR. CGM also lowered TBR, glycemic variability, prolonged hypoglycemic events, insulin usage, and in-hospital complications.
Immunocompromised individuals remain at risk of COVID-19: 2023 results from the observational INFORM study
Authors: Jennifer K Quint, Sabada Dube, Lucy Carty, Renata Yokota, Samira Bell, Lance Turtle, Yi Lu, Kathryn Evans, Nahila Justo, Michelle Harley, Jurgens Peters, Carla Talarico, Richard McNulty, Ana Goios, Sylvia Taylor, Rachael A Evans
Journal: Journal of Infection (2025)
Author Correction: The NAT1–bHLH110–CER1/CER1L module regulates heat stress tolerance in rice
Authors: Hai-Ping Lu, Xue-Huan Liu, Mei-Jing Wang, Qiao-Yun Zhu, Yu-Shu Lyu, Jian-Hang Xu, Jian-Xiang Liu
Journal: Nature Genetics (2025)
Magnetic Shaftless Propeller Millirobot with Multimodal Motion for Small-Scale Fluidic Manipulation
Authors: Yaozhen Hou, Shihao Zhong, Zhiqiang Zheng, Jiabao Du, Ruhao Nie, Qing Shi, Qiang Huang, Huaping Wang
Journal: Cyborg and Bionic Systems (2025)

Magnetic miniature robots have shown great potential in biomedical applications in recent years. However, a challenge remains in which it is difficult for magnetic miniature robots to achieve balanced capabilities for multimodal locomotion and fluidic manipulation in various environments. Here, we report a magnetic shaftless propeller-like millirobot (MSPM) that possesses the capabilities of rotating-based multimodal 3-dimensional motion and cargo transportation with untethered manipulation. The MSPM utilizes the propulsion and pumping capabilities of the propeller structure to achieve fluidic manipulation. The shaftless propeller structures are designed to achieve omnidirectional locomotion through rolling, propelling, and tumbling. Additionally, the shaftless 3-blade propeller is used to perform a pumping function to achieve controllable transportation of fluids and particles. We anticipate that the MSPM holds great potential as a minimally invasive device for thrombosis treatment and targeted medicine delivery.
ODEP-based Robotic System for Manipulation and In-Flow Analysis of Primary Cells
Authors: Joanna Filippi, Paola Casti, Valentina Lacconi, Gianni Antonelli, Michele D’Orazio, Giorgia Curci, Carlo Ticconi, Rocco Rago, Massimiliano De Luca, Alessandro Pecora, Arianna Mencattini, Steven L. Neale, Luisa Campagnolo, Eugenio Martinelli
Journal: Cyborg and Bionic Systems (2025)

The presence of cellular defects of multifactorial nature can be hard to characterize accurately and early due to the complex interplay of genetic, environmental, and lifestyle factors. With this study, by bridging optically-induced dielectrophoresis (ODEP), microfluidics, live-cell imaging, and machine learning, we provide the ground for devising a robotic micromanipulation and analysis system for single-cell phenotyping. Cells under the influence of nonuniform electric fields generated via ODEP can be recorded and measured. The induced responses obtained under time-variant ODEP stimulation reflect the cells' chemical, morphological, and structural characteristics in an automated, flexible, and label-free manner. By complementing the electrokinetic fingerprint of the cell centroid motion with data on the dynamics of electro-deformation and orientation, we show that subtle differences at the single-cell level can be elucidated. Specifically, here, we demonstrate, for the first time, the ability of the combined ODEP-based robotic and automatic analysis platform to discriminate between primary endometrial stromal cells obtained from fertile patients and patients with disrupted receptivity/selectivity equilibrium. When multiple cells were considered at the patient level, the performance achieved an average accuracy of 98%. Single-cell micro-operation and analysis systems may find a more general application in the clinical diagnosis and management of patients with pathological alterations at the cellular level.