tbuckley/cabot-search huggingface dataset:
ASTCT and USCLC Clinical Practice Recommendations for Allogeneic Stem Cell Transplant in Mycosis Fungoides and Sézary Syndrome
Authors: Amrita Goyal, Daniel O'Leary, Bouthaina Dabaja, Wen-Kai Weng, Jasmine Zain, Corey Cutler, Joan Guitart, Youn H Kim, Larisa J Geskin, Richard T Hoppe, Lynn D Wilson, Anne W Beaven, Steve Horwitz, Pamela B Allen, Stefan K Barta, Kimberly Bohjanen, Jonathan E Brammer, Joi B Carter, Nneka Comfere, Jennifer A DeSimone, Kathryn Dusenbery, Madeleine Duvic, Auris Huen, Deepa Jagadeesh, Chris R Kelsey, Michael S Khodadoust, Mary Jo Lechowicz, Neha Mehta-Shah, Alison J Moskowitz, Elise A Olsen, Christina Poh, Barbara Pro, Christiane Querfeld, Craig Sauter, Lubomir Sokol, Olayemi Sokumbi, Ryan A Wilcox, John A Zic, Alejandro Gru, Mehdi Hamadani, Francine Foss
Journal: Journal of the American Academy of Dermatology (2025)
Human Extracellular Matrix‐Like Collagen‐Based Hydrogels for Soft Tissue Regeneration and Mandibular Retrognathia Treatment
Authors: E. Xiao, Peng Wang, Kaikai Zheng, Huanyu Zhong, Hui Zhou, Qiushi Liu, Xiaojing Liu, Pengju Fan, Jincheng Yao, Qiang Wei
Journal: Advanced Healthcare Materials (2025)

Abstract Skin aging, trauma, and congenital diseases lead to tissue defects and functional loss. Effective regeneration remains challenging due to limited material bioactivity and inadequate consideration of mechanical cues. This study develops a hydrogel integrating human extracellular matrix‐like collagen (hCol) derived from induced human adipose mesenchymal stem cells (hASCs) with hyaluronic acid (HA) and polyethylene glycol diamine (PEGDA), engineered to achieve a modulus (≈1 kPa) representative of subcutaneous soft tissue. The hCol, produced at scale, provides essential biochemical signals, which, in conjunction with the hydrogel mechanical properties, synergistically modulate immune responses, cellular differentiation, and anti‐aging processes. Both animal experiments and clinical trials validate the regenerative efficacy of the hydrogels. Clinical regeneration therapy for mandibular retrognathia shows rapid and sustained improvements, with repair efficacy rates of 95.2% at 3 months and 76.2% at 6 months. These findings underscore the hydrogel's ability to reshape the soft tissue microenvironment, supporting immediate tissue repair and sustained regeneration, while offering a promising platform for future biomaterial development in soft tissue engineering.
Ectopic gene conversion causing quantitative trait variation
Authors: Marina Pfalz, SeÏf-Eddine Naadja, Jacqui Anne Shykoff, Juergen Kroymann
Journal: Molecular Biology and Evolution (2025)

Abstract Why is there so much non-neutral genetic variation segregating in natural populations? We dissect function and evolution of a near-cryptic quantitative trait locus (QTL) for defense metabolites in Arabidopsis using the CRISPR/Cas9 system and nucleotide polymorphism patterns. The QTL is explained by genetic variation in a family of four tightly linked indole-glucosinolate O-methyltransferase genes. Some of this variation appears to be maintained by balancing selection, some appears to be generated by non-reciprocal transfer of sequence, also known as ectopic gene conversion (EGC), between functionally diverged gene copies. Here we elucidate how EGC, as an inevitable consequence of gene duplication, could be a general mechanism for generating genetic variation for fitness traits.
EULAR/PReS endorsed recommendations for the management of familial Mediterranean fever (FMF): 2024 update
Authors: Seza Ozen, Erdal Sağ, Teresa Oton, Ahmet Gül, Cristiana Sieiro Santos, Deniz Bayraktar, Fabian Nikolai Proft, Helen J Lachmann, Jasmin Kuemmerle Deschner, Marco Gattorno, Nuray Aktay Ayaz, Ömer Karadağ, Sezin Yüce, Shaye Kivity, Sophie Georgin-Lavialle, Tamara Sarkisian, Tilmann Kallinich, Véronique Hentgen, Yeliz Prior, Yosef Uziel, Ziv Yardeni, Loreto Carmona
Journal: Annals of the Rheumatic Diseases (2025)

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease despite being a rare disease for many rheumatologists. These evidence-based recommendations update the ones issued in 2016 to account for the recent developments in the field and aim to guide rheumatologists and other health professionals in the treatment and follow-up of patients with FMF. A multidisciplinary panel was assembled, including rheumatologists, internists, paediatricians, a nephrologist, an occupational therapist, a physiotherapist, 2 methodologists, and 2 patient representatives, all from the Eastern Mediterranean area and Europe. Several systematic reviews were performed on the pharmacological treatment of FMF and its complications. The previous recommendations were revised considering the updated evidence, and the new levels of evidence were incorporated. The agreement with the recommendations was obtained through a Delphi survey. The final set comprises 4 overarching principles and 12 recommendations, each presented with its degree of agreement (0-10), level of evidence, and rationale. The degree of agreement was greater than 9/10 in all instances, and the level of evidence improved in most updated statements. Improving adherence is emphasised as an important aspect in several statements. These new recommendations include a priority set, quality indicators, and other suggested implementation strategies. This article presents a set of widely accepted recommendations for treating and monitoring FMF, supported by the best available evidence and expert opinion. These recommendations are valuable for guiding physicians in caring for patients with FMF.
The mitochondrial unfolded protein response inhibits pluripotency acquisition and mesenchymal-to-epithelial transition in somatic cell reprogramming
Authors: Zhongfu Ying, Yanmin Xin, Zihuang Liu, Tianxin Tan, Yile Huang, Yingzhe Ding, Xuejun Hong, Qiuzhi Li, Chong Li, Jingyi Guo, Gaoshen Liu, Qi Meng, Shihe Zhou, Wenxin Li, Yao Yao, Ge Xiang, Linpeng Li, Yi Wu, Yang Liu, Miaohui Mu, Zifeng Ruan, Wenxi Liang, Junwei Wang, Yaofeng Wang, Baojian Liao, Yang Liu, Wuming Wang, Gang Lu, Dajiang Qin, Duanqing Pei, Wai-Yee Chan, Xingguo Liu
Journal: Nature Metabolism (2025)
Autologous T cell therapy for PRAME+ advanced solid tumors in HLA-A*02+ patients: a phase 1 trial
Authors: Martin Wermke, Dejka M Araurjo, Manik Chatterjee, Apostolia M Tsimberidou, Tobias A W Holderried, Amir A Jazaeri, Ran Reshef, Carsten Bokemeyer, Winfried Alsdorf, Katrin Wetzko, Peter Brossart, Katrin Aslan, Linus Backert, Sebastian Bunk, Jens Fritsche, Swapna Gulde, Silvana Hengler, Norbert Hilf, Mohammad B Hossain, Jens Hukelmann, Mamta Kalra, Delfi Krishna, M Alper Kursunel, Dominik Maurer, Andrea Mayer-Mokler, Regina Mendrzyk, Ali Mohamed, Karine Pozo, Arun Satelli, Marilena Letizia, Heiko Schuster, Oliver Schoor, Claudia Wagner, Hans-Georg Rammensee, Carsten Reinhardt, Harpreet Singh-Jasuja, Steffen Walter, Toni Weinschenk, Jason J Luke, Cedrik M Britten
Journal: Nature Medicine (2025)

In contrast to chimeric antigen receptor T cells, T cell receptor (TCR)-engineered T cells can target intracellular tumor-associated antigens crucial for treating solid tumors. However, most trials published so far show limited clinical activity. Here we report interim data from a first-in-human, multicenter, open-label, 3 + 3 dose-escalation/de-escalation phase 1 trial studying IMA203, an autologous preferentially expressed antigen in melanoma (PRAME)-directed TCR T cell therapy in HLA-A*02+ patients with PRAME+ recurrent and/or refractory solid tumors, including melanoma and sarcoma. Primary objectives include the evaluation of safety and tolerability and the determination of the maximum tolerated dose (MTD) and/or recommended dose for extension. Secondary objectives include the evaluation of IMA203 TCR-engineered T cell persistence in peripheral blood, tumor response as well as duration of response. A total of 27 patients were enrolled in the phase 1a dose escalation and 13 patients in the phase 1b dose extension. IMA203 T cells were safe, and the MTD was not reached. Of the 41 patients receiving treatment (that is, who started lymphodepletion), severe cytokine release syndrome was observed in 4.9% (2/41), and severe neurotoxicity did not occur. In the 40 patients treated with IMA203, an overall response rate consisting of patients with unconfirmed or confirmed response (u/cORR) of 52.5% (21/40) and a cORR of 28.9% (11/38) was observed with a median duration of response of 4.4 months (range, 2.4-23.0, 95% confidence interval: 2.6-not reached) across multiple indications. Rapid T cell engraftment and long-term persistence of IMA203 T cells were observed. IMA203 T cells trafficked to all organs, and confirmed responses were more frequent in patients with higher dose. T cell exhaustion was not observed in the periphery; deep responses were enriched at higher PRAME expression; and higher T cell infiltration resulted in longer progression-free survival. Overall, IMA203 showed promising anti-tumor activity in multiple solid tumors, including refractory melanoma. ClinicalTrials.gov identifier: NCT03686124 .
Plasma phospho-tau217 for Alzheimer’s disease diagnosis in primary and secondary care using a fully automated platform
Authors: Sebastian Palmqvist, Noëlle Warmenhoven, Federica Anastasi, Andrea Pilotto, Shorena Janelidze, Pontus Tideman, Erik Stomrud, Niklas Mattsson-Carlgren, Ruben Smith, Rik Ossenkoppele, Kübra Tan, Anna Dittrich, Ingmar Skoog, Henrik Zetterberg, Virginia Quaresima, Chiara Tolassi, Kina Höglund, Duilio Brugnoni, Albert Puig-Pijoan, Aida Fernández-Lebrero, José Contador, Alessandro Padovani, Mark Monane, Philip B Verghese, Joel B Braunstein, Silke Kern, Kaj Blennow, Nicholas J Ashton, Marc Suárez-Calvet, Oskar Hansson
Journal: Nature Medicine (2025)

Abstract Global implementation of blood tests for Alzheimer’s disease (AD) would be facilitated by easily scalable, cost-effective and accurate tests. In the present study, we evaluated plasma phospho-tau217 (p-tau217) using predefined biomarker cutoffs. The study included 1,767 participants with cognitive symptoms from 4 independent secondary care cohorts in Malmö (Sweden, n = 337), Gothenburg (Sweden, n = 165), Barcelona (Spain, n = 487) and Brescia (Italy, n = 230), and a primary care cohort in Sweden ( n = 548). Plasma p-tau217 was primarily measured using the fully automated, commercially available, Lumipulse immunoassay. The primary outcome was AD pathology defined as abnormal cerebrospinal fluid Aβ42:p-tau181. Plasma p-tau217 detected AD pathology with areas under the receiver operating characteristic curves of 0.93–0.96. In secondary care, the accuracies were 89–91%, the positive predictive values 89–95% and the negative predictive values 77–90%. In primary care, the accuracy was 85%, the positive predictive values 82% and the negative predictive values 88%. Accuracy was lower in participants aged ≥80 years (83%), but was unaffected by chronic kidney disease, diabetes, sex, APOE genotype or cognitive stage. Using a two-cutoff approach, accuracies increased to 92–94% in secondary and primary care, excluding 12–17% with intermediate results. Using the plasma p-tau217:Aβ42 ratio did not improve accuracy but reduced intermediate test results (≤10%). Compared with a high-performing mass-spectrometry-based assay for percentage p-tau217, accuracies were comparable in secondary care. However, percentage p-tau217 had higher accuracy in primary care and was unaffected by age. In conclusion, this fully automated p-tau217 test demonstrates high accuracy for identifying AD pathology. A two-cutoff approach might be necessary to optimize performance across diverse settings and subpopulations.
Site-directed multivalent conjugation of antibodies to ubiquitinated payloads
Authors: Angela F El Hebieshy, Zacharias Wijfjes, Camille M Le Gall, Jim Middelburg, Kim E de Roode, Felix L Fennemann, Marjolein Sluijter, Thorbald van Hall, Douwe J Dijkstra, Leendert A Trouw, Floris J van Dalen, Andrea Rodgers Furones, Johan M S van der Schoot, Ian Derksen, Hans de Haard, Bas van der Woning, Cami M P Talavera Ormeño, Bjorn R van Doodewaerd, Carl G Figdor, Gerbrand J van der Heden van Noort, Paul W H I Parren, Sandra Heskamp, Huib Ovaa, Martijn Verdoes, Ferenc A Scheeren
Journal: Nature Biomedical Engineering (2025)

Antibody conjugates are the foundation of a wide range of diagnostic and therapeutic applications. Although many antibody-conjugation techniques are robust and efficient, obtaining homogeneous multimeric conjugation products remains challenging. Here we report a modular and versatile technique for the site-directed multivalent conjugation of antibodies via the small-protein ubiquitin. Specifically, multiple ubiquitin fusions with antibodies, antibody fragments, nanobodies, peptides or small molecules such as fluorescent dyes can be conjugated to antibodies and nanobodies within 30 min. The technique, which we named 'ubi-tagging', allowed us to efficiently generate a bispecific T-cell engager as well as nanobodies conjugated to dendritic-cell-targeted antigens that led to potent T-cell responses. Using both recombinant ubi-tagged proteins and synthetic ubiquitin derivatives allows for the iterative, site-directed and multivalent conjugation of antibodies and nanobodies to a plethora of molecular moieties.
Regorafenib plus avelumab in advanced gastroenteropancreatic neuroendocrine neoplasms: a phase 2 trial and correlative analysis
Authors: Sophie Cousin, Jean-Philippe Guégan, Lola Jade Palmieri, Jean Philippe Metges, Simon Pernot, Carine A Bellera, Eric Assenat, Iphigenie Korakis, Philippe Alexandre Cassier, Antoine Hollebecque, Coralie Cantarel, Michèle Kind, Isabelle Soubeyran, Harry Sokol, Lucile Vanhersecke, Alban Bessede, Antoine Italiano
Journal: Nature Cancer (2025)
Genomic census of invasive nontyphoidal Salmonella infections reveals global and local human-to-human transmission
Authors: Haiyang Zhou, Chenghao Jia, Ping Shen, Chenghu Huang, Lin Teng, Beibei Wu, Zining Wang, Haoqiu Wang, Yonghong Xiao, Stephen Baker, François-Xavier Weill, Yan Li, Min Yue
Journal: Nature Medicine (2025)
CD40L stimulates tumor-infiltrating B-cells and improves ex vivo TIL expansion
Authors: Renata Ariza Marques Rossetti, Leticia Tordesillas, Matthew S Beatty, Junior Cianne, Elena Martinez Planes, Dongliang Du, Sebastian Snedal, Chao Wang, Bradford A Perez, Anders Berglund, Yian Ann Chen, Amod Sarnaik, James J Mulé, Benjamin Creelan, Shari Pilon-Thomas, Daniel Abate-Daga
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Adoptive transfer of tumor-infiltrating lymphocytes (TIL) is now a Food and Drug Administration (FDA)-approved treatment for melanoma. While this is a major milestone, there is room for improvement to increase clinical response rates and to further optimize the manufacturing of TIL products. In this study, we characterized the association of tumor-infiltrating B-cells (TIL-B) and tertiary lymphoid structures (TLSs) with clinical response to TIL therapy and tested whether the presence of B-cells in the tumor can be leveraged to optimize TIL manufacture. Methods Tumor sections from TIL responders (R, n=9) and non-responders (NR, n=11) were analyzed by RNA sequencing, and immune cell content was estimated in silico. To study the association between B-cells and TIL expansion, we quantified B-cell subsets and TIL phenotype by flow cytometry. CD40L-induced effects on melanoma-infiltrating B-cells were analyzed by flow cytometry and scRNA-sequencing. Results Tumors from TIL clinical responders had greater abundance of class-switched B-cells (p=0.007) and a greater TLS score (p=0.03) than those of NRs. In addition, greater abundance of B-cells (p≤0.05) and switched memory B-cells (CD27 + IgD−, p≤0.05) in the tumors were associated with greater TIL expansion. Stimulation of TIL-B through addition of CD40L during TIL ex vivo culture improved their expansion success rate from 33% to 67% (p=0.03). Similarly, the addition of CD40L to non-small cell lung cancer (NSCLC) TIL cultures shortened the manufacturing period by 1 week. Moreover, CD40L-enhanced TIL showed more stem-like T-cells (CD39 − CD69 − , p≤0.05) and an enrichment of neoantigen-reactive T-cell clones in NSCLC TIL. Gene expression analysis showed that CD40L induced gene expression changes in TIL-B after 48 hours in culture (126 differentially expressed genes (DEGs)), with minimal to no changes observed in other immune cell types (including 12 DEG in macrophages, 10 DEG in dendritic cells, and none in monocytes). B-cell DEGs included upregulated co-stimulatory ligands (CD83, CD58), chemokines (CCL22, CCL17), among others. CD40L-induced upregulation of CD58 by melanoma infiltrating B-cells was associated with successful TIL expansion. Conclusions Our results show that CD40L-stimulated B-cells can be leveraged to enhance the quality and quantity of TIL. Clinical trial NCT05681780 is currently testing this concept applied to NSCLC TIL.
Multi-cohort analysis reveals colorectal cancer tumor location-associated fecal microbiota and their clinical impact
Authors: Yufeng Lin, Harry Cheuk-Hay Lau, Chuanfa Liu, Xiao Ding, Yang Sun, Jiamei Rong, Xiang Zhang, Luyao Wang, Kai Yuan, Yinglei Miao, William Ka-Kei Wu, Sunny Hei Wong, Joseph Jao-Yiu Sung, Jun Yu
Journal: Cell Host & Microbe (2025)

Microbial alterations in different tumor locations of colorectal cancer (CRC) remain unclear. Here, 1,375 fecal metagenomes from six in-house and published datasets were analyzed, including 128 right-sided CRC (rCRC), 168 left-sided CRC (lCRC), 250 rectal cancer (RC), and 829 controls. Firmicutes progressively increase from rCRC, lCRC, to RC, in contrast to the gradual decrease of Bacteroidetes. Tumor location-associated fecal microbes are identified, including Veillonella parvula for rCRC, Streptococcus angionosus for lCRC, and Peptostreptococcus anaerobius for RC, while Fusobacterium nucleatum is enriched in all tumor locations. Tumor location-associated bacteria correlate with patient survival. Clinically, we establish a microbial biomarker panel for each tumor location that accurately diagnoses rCRC (area under the receiver operating characteristic curve [AUC] = 91.59%), lCRC (AUC = 91.69%), or RC (AUC = 90.53%) from controls. Tumor location-specific biomarkers also have higher diagnostic accuracy (AUC = 91.38%) than location-non-specific biomarkers (AUC = 82.92%). Overall, we characterize fecal microbes associated with different CRC tumor locations, highlighting that tumor location should be considered in non-invasive diagnosis.
Single-neuron projectome reveals organization of somatosensory ascending pathways in the mouse brain
Authors: Wen-Qun Ding, Wei Song, Xiaoxue Shi, Zhao Feng, Xu Chen, Taorong Xie, Yuan Liu, Jiandong Zhou, Yu Chen, Jun-Kai Lin, Qiu-Miao Wang, Hua Zhou, Tong-Yu Liang, Tao Jiang, Biyu Ren, Haishan Yao, Yun-Qing Li, Henry C Evrard, Mu-Ming Poo, Hui Li, Xiangning Li, Hui Gong, Andrew J Todd, Anan Li, Xiaofei Wang, Juan Deng, Yan-Gang Sun
Journal: Neuron (2025)
Standard Dermatoscope Images vs an Autonomous Total Body Photography and Dermoscopic Imaging Device
Authors: Pau Rosés-Gibert, Cristina Heras, Narcis Ricart, Enric Campmol, Núria Ferrera, Susana Puig, J. Malvehy
Journal: JAMA Dermatology (2025)

Importance Recent advancements in autonomous medical devices for skin imaging offer the potential to improve the efficiency and quality of total body photography (TBP) and dermatoscopic documentation, which are essential in treating patients with skin cancer, especially those with high-risk melanoma with atypical mole syndrome. Objective To compare the image quality and time efficiency of an autonomous TBP and dermoscopic device for TBP and dermoscopic imaging with traditional manual digital dermoscopic techniques. Design, Setting, and Participants A prospective cohort study was conducted from March 1, 2023, to October 30, 2023, comparing image quality and time efficiency between an autonomous TBP and dermoscopic device and manual dermoscopic documentation across 316 patients with atypical mole syndrome at 2 dermatology clinics in Spain. All analyses took place in June 2024. Main Outcomes and Measures The primary outcome was the acceptability of the images, assessed by 2 independent dermatologists. Secondary outcomes included diagnostic agreement between the 2 methods and time efficiency for image acquisition. Results Overall, mean (SD) age of patients was 47.13 (3.31) years. The number of male patients was 105 (33%), while the number of female patients was 211 (66%). The autonomous TBP and dermoscopic device produced dermoscopic images with a mean (SD) quality score of 9.84 (0.72), compared with 9.44 (0.85) for manual digital dermoscopy, with no significant differences by body site or lesion type. Diagnostic classification agreement between the 2 methods was 91.60%, with most discrepancies related to small benign lesions. The mean (SD) imaging time for the autonomous device was 570 (169) seconds, compared with 606 (286) seconds for the manual method. Conclusions and Relevance This cohort study found that the autonomous TBP and dermoscopic device produced images of comparable quality to standard dermoscopic techniques while operating with greater time efficiency. These findings suggest that the device may contribute to clinical workflow optimization in dermatology by supporting TBP and dermoscopic imaging.
Sociodemographic Characteristics of Infants Receiving Nirsevimab
Authors: Salomé Boutin, Marion Bertrand, Jérémie F. Cohen, Mahmoud Zureik, Martin Chalumeau, Marie-Joëlle Jabagi
Journal: JAMA Network Open (2025)

This cohort study investigates inequalities by sociodemographic group in the receipt of nirsevimab immunization by infants in France from 2023 to 2024.
Self-Administered Etripamil and Emergency Department Visits in Supraventricular Tachycardia
Authors: Sean D. Pokorney, A. John Camm, Paul Dorian, James E. Ip, Bruce S. Stambler, David B. Bharucha, Jonathan P. Piccini
Journal: JAMA Cardiology (2025)

This secondary analysis of a randomized clinical trial describes the use of emergency care after self-administration of etripamil by patients experiencing paroxysmal supraventricular tachycardia episodes at home.
Epitope Spreading in Immune Checkpoint Inhibitor–Associated Bullous Pemphigoid
Authors: Hiroshi Koga, Masahiro Tsutsumi, Kwesi Teye, Toshihiro Shirahama, Norito Ishii, Koichi Azuma, Takekuni Nakama
Journal: JAMA Dermatology (2025)

This case report describes a patient with immune checkpoint inhibitor–associated bullous pemphigoid and preexisting anti-BP180–C-terminus antibodies.