tbuckley/cabot-search huggingface dataset:
Redifferentiation therapy in unresectable or metastatic radioactive iodine refractory thyroid cancer: an International Thyroid Oncology Group statement
Authors: Sophie Leboulleux, Laura Boucai, Naifa Busaidy, Cosimo Durante, James A Fagin, Sasan Fazeli, Andrew G Gianoukakis, Bryan R Haugen, Hyunseok Kang, Bhavana Konda, Theodore W Laetsch, Laura Locati, Mabel Ryder, Christine Spitzweg, Francis P Worden, Lori Wirth, Alan Ho
Journal: The Lancet Diabetes & Endocrinology (2025)

In patients with follicular cell-derived thyroid cancer that have distant metastases and no iodine uptake, redifferentiation-ie, the restoration of tumoural 131I uptake with systemic therapy-is now possible. The use of mitogen-activated protein kinase (MAPK) inhibitors for a short period of time before the administration of high activity 131I shows promising results with iodine uptake restoration and tumour response. Redifferentiation has been used in patients with BRAF-mutated and RAS-mutated tumours in prospective trials and in the case of patients with RET or NTRK fusions. The iodine uptake restoration ranges from 33% to 95%, and tumour response rates from 11% to 80%. There is substantial variability between trials with regards to inclusion criteria, duration of redifferentiation drug therapy, activity of radioactive iodine, and use of dosimetry. Randomised studies are missing to clearly establish the effectiveness and applicability of redifferentiation. Thus, long-term studies are needed to establish the most effective redifferentiation protocols. The objectives of this Review are to: (1) provide a comprehensive review of the available results from prospective trials and case reports, including results regarding the restoration of radioiodine uptake and treatment efficacy (morphological and biological); (2) describe the differences in redifferentiation trial design between studies and discuss their potential impact on treatment efficacy; (3) describe the implications and limitations of dosimetry; and (4) outline the key questions to be addressed in future redifferentiation trials.
Collection of the digital data from the neurological examination
Authors: Bruno Kusznir Vitturi, Patrik Theodor Nerdal, Walter Maetzler
Journal: npj Digital Medicine (2025)

This review presents the status quo of how far the digitalization of elements of the neurological examination has progressed. Our focus was on studies that assessed the examination conducted in person, rather than through telemedicine platforms. Five hundred and twenty studies were included in this systematic review. The digital tools covered ten elements of the neurological examination: gait (173, 33%), motor system (149, 29%), eyes (85, 16%), cognitive functions (53, 10%), sensory system (47, 9%), balance (35, 7%), other movements (24, 5%), other cranial nerves (24, 5%), coordination (10, 2%), and autonomic nervous system (9, 2%). Most of the tools were portable (442, 85%), and in 215 studies (41%) the devices were wearable. The cost of the digital tools used was described and discussed in 167 (32%) studies. Most devices (61%) had a low complexity, and half required high additional analytic effort.
Lymphatic chain gradients regulate the magnitude and heterogeneity of T cell responses to vaccination
Authors: Michael T. Conlon, Jessica Y. Huang, Michael Y. Gerner
Journal: The Journal of Experimental Medicine (2025)

Upon activation, T cells proliferate and differentiate into diverse populations, including highly differentiated effector and memory precursor subsets. Initial diversification is influenced by signals sensed during T cell priming within lymphoid tissues. However, the rules governing how cellular heterogeneity is spatially encoded in vivo remain unclear. Here, we show that immunization establishes concentration gradients of antigens and inflammation across interconnected chains of draining lymph nodes (IC-LNs). While T cells are activated at all sites, individual IC-LNs elicit divergent responses: proximal IC-LNs favor the generation of effector cells, whereas distal IC-LNs promote formation of central memory precursor cells. Although both proximal and distal sites contribute to anamnestic responses, T cells from proximal IC-LNs preferentially provide early effector responses at inflamed tissues. Conversely, T cells from distal IC-LNs demonstrate an enhanced capacity to generate long-lasting responses to chronic antigens in cancer settings, including after checkpoint blockade therapy. Therefore, formation of spatial gradients across lymphatic chains following vaccination regulates the magnitude, heterogeneity, and longevity of T cell responses.
Targeting Intracellular Innate RNA-Sensing Systems Overcomes Resistance to CAR T Cell Therapy in Solid Tumors
Authors: Nardine Soliman, Tatiana Nedelko, Giada Mandracci, Stefan Enssle, Vincent Grass, Julius C. Fischer, Florian Bassermann, Hendrik Poeck, Sebastian Kobold, Nadia El Khawanky, Simon Heidegger
Journal: Cancer Research (2025)

Despite the remarkable success of CAR T cells in certain hematological malignancies, only modest responses have been achieved in solid tumors. Defective cell death pathways have recently been suggested as a tumor-intrinsic form of resistance to CAR T cell treatment. Here, we showed that insufficient activity of the innate RNA-sensing receptor system, RIG I/MAVS, leads to tumor cell-inherent resistance to CAR T cell attack. Active RIG-I/MAVS signaling in tumor cells primed intrinsic mitochondrial apoptosis pathways and expression of cell death receptors, which funneled into CAR T cell-triggered cell death. CAR T cell reliance on tumor-intrinsic RIG-I signaling was observed in various murine and human cancer types, independent of the CAR construct used, and the dependence was most pronounced under conditions with low target antigen expression or low effector/target ratios. RIG-I-induced pro-apoptotic priming of CAR T cell susceptibility involved auto-/paracrine type I IFN signaling loops and could spread to bystander tumor cells. Strong tumor-intrinsic RIG I/MAVS signaling imprinted an activated cytolytic phenotype on tumor-interacting CAR T cells. Agonist-mediated targeting of the RIG-I pathway in the tumor microenvironment rendered murine melanoma susceptible to CAR T cell therapy in vivo with enhanced infiltration of active CAR T cells. Together, this data identifies insufficient RIG-I/MAVS activity and associated impaired cell death signaling in malignant cells as a resistance mechanism to CAR T cells. Targeting tumor-intrinsic RIG-I is a potential strategy to sensitize solid tumors to CAR T cell treatment.
Alcohol-induced disruption of hepatic m6A modification exacerbates alcohol-associated steatohepatitis by impairing liver immune microenvironment homeostasis
Authors: Jinghao Yao, Pei Liu, Xinkun Teng, Dejie Kong, Biwei Han, Chengying Cui, Mingwei Yin, Xinze Yan, Ang Zhao, Yingquan Ye, Haiyuan Shen, Miaomiao Wu, Juan Wang, Qianying Cheng, Xiaoli Wei, Yushun Wang, Quan Yuan, Yang Li, Hua Wang
Journal: Hepatology (2025)

Alcohol-associated steatohepatitis (ASH), a severe form of alcohol-associated liver disease (ALD), is characterized by pronounced steatosis and immune cells infiltration. As an inflammatory disease, ASH still lacks effective immunotherapies, and the mechanisms underlying alcohol-induced immune imbalance in the liver microenvironment remain elusive. RNA modifications are known to maintain hepatic homeostasis during physiological and pathological processes. This study aimed to investigate the alteration of RNA modification in ASH and its specific roles in regulating immune homeostasis. In this study, we found that the levels of RNA N6-methyladenosine (m6A) modification and its key writer, METTL3, are markedly reduced in mice livers during ASH. Notably, hepatocyte-specific Mettl3 knockout exacerbated ASH by enhancing steatosis and neutrophil infiltration, whereas hepatocyte-specific Mettl3 overexpression alleviated these effects. Mechanistically, ethanol promotes METTL3 degradation via E3-ubiquitin-ligase STUB1-mediated ubiquitination and disrupts the protective interaction between HSP70 and METTL3, impairing hepatic m6A modification. Furthermore, the expression of ATF3 was upregulated via m6A-dependent mechanism. Importantly, hepatocyte-specific Atf3 overexpression abolished METTL3-mediated amelioration of ASH, whereas hepatocyte-specific Atf3 knockdown attenuated Metl3 knockout-induced exacerbation of ASH in vivo. Consistently, high hepatic ATF3 expression is associated with an inflammatory liver microenvironment in ALD patients. Collectively, our results demonstrate that alcohol consumption disrupts the homeostasis of hepatic immune microenvironment in ASH through impairment of METTL3-dependent m6A RNA modification. Targeting METTL3 to preserve its enzymatic activity and stability could represent a novel therapeutic avenue for ASH intervention.
Integration of Germline and Somatic Variation Improves Chronic Lymphocytic Leukemia Risk Stratification
Authors: Aubrey K. Hubbard, Derek W. Brown, Jie Liu, Irenaeus C. Chan, Weiyin Zhou, Giulio Genovese, Alexander DePaulis, Sruthi Srinivasan, Shu-Hong Lin, Batel Blechter, Ian D. Buller, Qinglin Zeng, Yin Cao, Wen-Yi Huang, Neal D. Freedman, Haoyu Zhang, Diptavo Dutta, Stephen J. Chanock, Kelly L. Bolton, Mitchell J. Machiela
Journal: Cancer Research (2025)

Both acquired mutations and germline genetic variation are known risk factors for chronic lymphocytic leukemia (CLL). Joint characterization of germline, acquired, and clinical risk has the potential to improve CLL risk prediction. Here, we investigated whether inclusion of a CLL-associated polygenic score (PGS) and two common types of clonal hematopoiesis (CH), autosomal mosaic chromosomal alterations (mCAs) and CH of indeterminate potential (CHIP), could improve CLL risk stratification in 436,784 participants in the UK Biobank and a replication set of 35,382 participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Individual mCAs on chromosomes 11, 12, 23, 14, and 22, as well as CHIP mutations in known lymphoid driver genes, were strongly associated with CLL risk. Integrative models that included sex, age, smoking status, blood cell traits, genetic similarity, CLL PGS, autosomal mCAs, and CHIP had the greatest discriminative ability with predictive utility waning five years after measurement of CH. Sensitivity analyses removing individuals with abnormal blood cell counts and CH commonly observed in CLL showed persistent increased discriminative ability. Evaluating cumulative absolute risk, the CLL PGS and CH had improved ability to stratify CLL cases into higher risk categories and controls into lower risk categories. Overall, this analysis details the enhanced ability to identify individuals at high risk of CLL when integrating germline and somatic data derived from peripheral blood.
FABP4-tastic Pancreatic Stellate Cells Coddle KITL to Uphold Inherent Microenvironmental Tumor Suppression
Authors: Aleksandr Dolskii, Edna Cukierman
Journal: Cancer Discovery (2025)

Oñate and colleagues demonstrate that KITL expression in pancreatic stellate cells is crucial for maintaining the inherent tumor-suppressive function of the pancreatic microenvironment, and its loss enables pancreatic cancer development. This pivotal discovery not only reinforces the century-old hypothesis of natural microenvironmental tumor suppression but also highlights a promising therapeutic avenue whereby restoring KITL expression could reestablish the tumor-suppressive functions of pancreas-resident fibroblastic cells. See related article by Oñate et al., p. 913.
Large-Scale Characterization of Orthotopic Cell Line-Derived Xenografts Identifies TGF-β Signaling as a Key Regulator of Breast Cancer Morphology and Aggressiveness
Authors: Catrin Lutz, Xue Chao, Bim de Klein, Jinhyuk Bhin, Madelon Badoux, Timo Eijkman, Apostolos P. Nikolakopoulos, Stefan J. Hutten, Natalie Proost, Bjørn Siteur, Marieke van de Ven, Ji-Ying Song, Jacco van Rheenen, Jessica Morgner, Stefan Prekovic, Jos Jonkers
Journal: Cancer Research (2025)

Breast cancer (BC) is a heterogeneous disease with diverse morphological and molecular subtypes. Preclinical models that recapitulate the heterogeneity of human BC are needed to advance our fundamental understanding of what makes BC an aggressive disease. To study mechanisms underlying BC progression, we generated orthotopic cell line-derived xenograft (CDX) models from 20 different human BC cell lines using both mammary intraductal (MIND) injections and fat-pad transplantations (FPT). The resulting MIND-CDX and FPT-CDX models covered the full spectrum of disease progression, from in situ disease to metastatic growth. Pathological analysis revealed two distinct tumor growth morphologies, flat vs. nodular, and transcriptomics analysis identified the TGF-β pathway as a potential regulator of these two phenotypes in primary BC. Indeed, knockout of SMAD4 converted nodular-growing tumors to a more confined disease, while constitutively active TGFBR1 renders lesions more aggressive. This research not only offers insights into the factors driving BC morphology and aggressiveness but also establishes a comprehensive and valuable resource of well-characterized orthotopic CDX models for BC research.
Multi-task Deep Learning Based on Longitudinal CT Images Facilitates Prediction of Lymph Node Metastasis and Survival in Chemotherapy-Treated Gastric Cancer
Authors: Bingjiang Qiu, Yunlin Zheng, Shunli Liu, Ruirui Song, Lei Wu, Cheng Lu, Xianqi Yang, Wei Wang, Zaiyi Liu, Yanfen Cui
Journal: Cancer Research (2025)

Accurate preoperative assessment of lymph node metastasis (LNM) and overall survival (OS) status is essential for patients with locally advanced gastric cancer (LAGC) receiving neoadjuvant chemotherapy (NAC), providing timely guidance for clinical decision-making. However, current approaches to evaluate LNM and OS have limited accuracy. In this study, we used longitudinal CT images from 1,021 LAGC patients to develop and validate a multi-task deep learning model named co-attention tri-oriented spatial Mamba (CTSMamba) to simultaneously predict LNM and OS. CTSMamba was trained and validated on 398 patients, and the performance was further validated on 623 patients at two additional centers. Notably, CTSMamba exhibited significantly more robust performance than a clinical model in predicting LNM across all of the cohorts. Additionally, integrating CTSMamba survival scores with clinical predictors further improved personalized OS prediction. These results support the potential of CTSMamba to accurately predict LNM and OS from longitudinal images, potentially providing clinicians with a tool to inform individualized treatment approaches and optimized prognostic strategies.
Microenvironment-responsive living hydrogel containing engineered probiotic for treatment of massive bone defects
Authors: Haoyu Fang, Yanyi Wang, Li Li, Xiaotong Qin, Daoyu Zhu, Pei Liu, Qianhao Yang, Youshui Gao, Zhongmin Shi, Xin Ma, Chao Zhong, Yixuan Chen
Journal: Bioactive Materials (2025)
Understanding (and counteracting) the appeal of transgressive leaders
Authors: Gerben A van Kleef
Journal: Trends in Cognitive Sciences (2025)

Transgressive leaders enjoy growing popularity. Synthesizing recent evidence, I propose that (i) such leaders are appealing not despite their transgressive behavior, but because of it, and (ii) this appeal hinges on perceived benefits emanating from their transgressions. This analysis points to new strategies for curtailing transgressive leaders.
Predicting Survival Outcomes in Patients with Hepatocellular Carcinoma Receiving Lenvatinib by Using the Up7-ALBI Score
Authors: Chien-Hung Lu, Wei-Yu Kao, Chih-Horng Wu, Wei-Yi Ting, Chia-Hsun Lu, Kai-I Chuang, Cheng-Fu Ni, Yao-Yu Hsieh, Ming-Shun Wu, Chien-Wei Su, San‑Chi Chen
Journal: Liver Cancer (2025)

Introduction: Lenvatinib effectively manages unresectable hepatocellular carcinoma (HCC). Current prognostic models do not integrate tumor burden with liver function. By combining the Up-to-7 criteria and the albumin–bilirubin (ALBI) grade, we developed the Up7-ALBI score, a novel scoring system for predicting survival outcomes in patients with unresectable HCC receiving lenvatinib. Methods: This multicenter, retrospective study analyzed 205 patients with unresectable HCC. Tumor burden and liver function were assessed using the Up-to-7 criteria and the ALBI grade, respectively. Cox proportional-hazards models evaluated their impact on survival. The Up7-ALBI score was developed to categorize patients into distinct prognostic groups. Its prognostic value was validated in a cohort of HCC patients receiving immunotherapy. Results: The overall response rate (assessed as per the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria) was 13.2%. This rate was significantly higher for patients without metastases (18.6%) and those with a radiologic tumor burden within the Up-to-7 criteria (22.7%). The median progression-free survival and OS were 7.3 and 12.2 months, respectively. Exceeding the Up-to-7 criteria (hazard ratio [HR]: 1.61; 95% confidence interval [CI]: 1.00–2.57) and an ALBI grade of 2 or 3 (HR: 1.62; 95% CI: 1.06–2.47) emerged as independent risk factors of OS. A novel Up7-ALBI score stratified patients into low-, intermediate-, and high-risk groups for survival (30.8 vs. 14.4 vs. 9.3 months; p &amp;lt; 0.01). A validation cohort of 58 HCC patients with immunotherapy showed the consistent prognostic value of Up7-ALBI score. The Akaike information criterion value of the Cox proportional-hazards model for BCLC stage, ALBI grade, and Up7-ALBI score was 1203, 1174, and 1170, respectively. Conclusion: The Up7-ALBI score, incorporating tumor burden and liver function, effectively stratified survival outcomes in HCC patients treated with lenvatinib. Further validation in larger cohorts and across different systemic therapies is required to confirm its broad clinical applicability.
Human Organoids as an Emerging Tool for Genome Screenings
Authors: Francesco Andreatta, Delilah Hendriks, Benedetta Artegiani
Journal: Annual Review of Biomedical Engineering (2025)

Over the last decade, a plethora of organoid models have been generated to recapitulate aspects of human development, disease, tissue homeostasis, and repair. Organoids representing multiple tissues have emerged and are typically categorized based on their origin. Tissue-derived organoids are established directly from tissue-resident stem/progenitor cells of either adult or fetal origin. Starting from pluripotent stem cells (PSCs), PSC-derived organoids instead recapitulate the developmental trajectory of a given organ. Gene editing technologies, particularly the CRISPR-Cas toolbox, have greatly facilitated gene manipulation experiments with considerable ease and scalability, revolutionizing organoid-based human biology research. Here, we review the recent adaptation of CRISPR-based screenings in organoids. We examine the strategies adopted to perform CRISPR screenings in organoids, discuss different screening scopes and readouts, and highlight organoid-specific challenges. We then discuss individual organoid-based genome screening studies that have uncovered novel genes involved in a variety of biological processes. We close by providing an outlook on how widespread adaptation of CRISPR screenings across the organoid field may be achieved, to ultimately leverage our understanding of human biology.
Microfabricated Organ-Specific Models of Tumor Microenvironments
Authors: Jeong Min Oh, Yongkuk Park, Jungwoo Lee, Keyue Shen
Journal: Annual Review of Biomedical Engineering (2025)

Despite the advances in detection, diagnosis, and treatments, cancer remains a lethal disease, claiming the lives of more than 600,000 people in the United States alone in 2024. To accelerate the development of new therapeutic strategies with improved responses, significant efforts have been made to develop microfabricated in vitro models of tumor microenvironments (TMEs) that address the limitations of animal-based cancer models. These models incorporate several advanced tissue engineering techniques to better reflect the organ- and patient-specific TMEs. Additionally, microfabricated models integrated with next-generation single-cell omics technologies provide unprecedented insights into patient's cellular and molecular heterogeneity and complexity. This review provides an overview of the recent understanding of cancer development and outlines the key TME elements that can be captured in microfabricated models to enhance their physiological relevance. We highlight the recent advances in microfabricated cancer models that reflect the unique characteristics of their organs of origin or sites of dissemination.
Physics-Inspired Generative Models in Medical Imaging
Authors: Dennis Hein, Afshin Bozorgpour, Dorit Merhof, Ge Wang
Journal: Annual Review of Biomedical Engineering (2025)

Physics-inspired generative models (GMs), in particular diffusion models and Poisson flow models, enhance Bayesian methods and promise great utility in medical imaging. This review examines the transformative role of such generative methods. First, a variety of physics-inspired GMs, including denoising diffusion probabilistic models, score-based diffusion models, and Poisson flow generative models (including PFGM++), are revisited, with an emphasis on their accuracy, robustness and acceleration. Then, major applications of physics-inspired GMs in medical imaging are presented, comprising image reconstruction, image generation, and image analysis. Finally, future research directions are brainstormed, including unification of physics-inspired GMs, integration with vision-language models, and potential novel applications of GMs. Since the development of generative methods has been rapid, it is hoped that this review will give peers and learners a timely snapshot of this new family of physics-driven GMs and help capitalize their enormous potential for medical imaging.
A Hundred Ways to Encode Sound Signals for Cochlear Implants
Authors: Dietmar M. Wohlbauer, Norbert Dillier
Journal: Annual Review of Biomedical Engineering (2025)

Cochlear implants are the most successful neural prostheses used to restore hearing in severe-to-profound hearing-impaired individuals. The field of cochlear implant coding investigates interdisciplinary approaches to translate acoustic signals into electrical pulses transmitted at the electrode-neuron interface, ranging from signal preprocessing algorithms, enhancement, and feature extraction methodologies to electric signal generation. In the last five decades, numerous coding strategies have been proposed clinically and experimentally. Initially developed to restore speech perception, increasing computational possibilities now allow coding of more complex signals, and new techniques to optimize the transmission of electrical signals are constantly gaining attention. This review provides insights into the history of multichannel coding and presents an extensive list of implemented strategies. The article briefly addresses each method and considers promising future directions of neural prostheses and possible signal processing, with the ultimate goal of providing a current big picture of the large field of cochlear implant coding.