tbuckley/cabot-search huggingface dataset:
LNPs-mediated VEGF-C mRNA Delivery Promotes Heart Repair and Attenuates Inflammation by Stimulating Lymphangiogenesis Post-myocardial Infarction
Authors: Haonan Zhang, Huaiyu Jiang, Weichang Xie, Bei Qian, Qiang Long, Zhaoxi Qi, Shixing Huang, Yiming Zhong, Yecen Zhang, Lan Chang, Junjie Zhang, Qiang Zhao, Xinming Wang, Xiaofeng Ye
Journal: Biomaterials (2025)
Safety and tolerability of low-dose oral minoxidil in patients aged 65 or older. A multicenter study of 321 patients.
Authors: Juan Jimenez-Cauhe, María González-Ramos, Adrian Imbernon-Moya, Valentina Balaguera-Orjuela, Angela Hermosa-Gelbard, Cristina Pindado-Ortega, Diego Buendia-Castaño, Rocio Gil-Redondo, David Saceda-Corralo, Sergio Vaño-Galvan
Journal: Journal of the American Academy of Dermatology (2025)
The exposome and pancreatic cancer, lifestyle and environmental risk factors for PDAC
Authors: Giulia Peduzzi, Livia Archibugi, Riccardo Farinella, Ruggero Ponz de Leon Pisani, Ludmila Vodickova, Pavel Vodicka, Bledar Kraja, Juan Sainz, David Bars-Cortina, Neil Daniel, Roberto Silvestri, Pinar Uysal-Onganer, Stefano Landi, Joanna Dulińska-Litewka, Annalisa Comandatore, Daniele Campa, David J Hughes, Cosmeri Rizzato
Journal: Seminars in Cancer Biology (2025)
Metagenomic profiling of hospital wastewater: A comprehensive national scale analysis of antimicrobial resistance genes and opportunistic pathogens
Authors: Reshma Silvester, William B Perry, Gordon Webster, Laura Rushton, Amy Baldwin, Daniel A Pass, Neil Andrew Byrnes, Kata Farkas, Margaret Heginbothom, Noel Craine, Gareth Cross, Peter Kille, Barbara Kasprzyk-Hordern, Andrew J Weightman, Davey L Jones
Journal: Journal of Infection (2025)
Vulvar basosquamous carcinoma: Insights from Surveillance, Epidemiology, and End Results Database Analysis (2000-2021)
Authors: Trang M Nguyen, Tung S Tran, Duc V Le, Jamie N Bakkum-Gamez, Clark C Otley, Julia S Lehman, Giang Huong Nguyen
Journal: Journal of the American Academy of Dermatology (2025)
Reflectance confocal microscopy terminology for non-melanocytic skin lesions: A Delphi consensus of experts
Authors: Cristian Navarrete-Dechent, Caterina Longo, Konstantinos Liopyris, Marco Ardigo, Verena Ahlgrimm-Siess, Phillipe Bahadoran, Cristina Carrera, Juliana Casagrande Tavoloni Braga, Chih-Shan J Chen, Lilia Correa, Nathalie de Carvahlo, John Durkin, Francesca Farnetani, Jane M Grant-Kels, Melissa Gill, Salvador Gonzalez, Daniela Hartmann, Rainer Hoffman-Wellenhof, Albert Huho, Joanna Ludzik, Josep Malvehy, Ashfaq A Marghoob, Elvira Moscarella, Margaret Oliviero, Susana Puig, Harold Rabinovitz, Babar Rao, Gisele G Rezze, Anthony M Rossi, Gene Rubinstein, Cristel Ruini, Elke Sattler, H Peter Soyer, Rodrigo Schwartz, Steven Thng, Martina Ulrich, Alexander Witkowski, Stephen W Dusza, Pascale Guitera, Giovanni Pellacani, Alon Scope, Manu Jain
Journal: Journal of the American Academy of Dermatology (2025)
From injury to recovery: investigating wound healing in a 3D tissue-engineered cornea equivalent
Authors: Nicola Knetzger, Ann-Katrin Regensburger, Annika Goy, Hong Han, Johanna Theuersbacher, Ioana-Sandra Tarau, Carla Cleve, Lukas Königer, Tamara Finger, Sabina Eibichova, Malik Salman Haider, Thomas Schwarz, Jan Hansmann, Jost Hillenkamp, Daniel Kampik, Christian Lotz
Journal: Biomaterials (2025)
Systemic Inactivation of TREX1 Induces Selective Inflammation of the Tumor Microenvironment and Invigorated T Cell-Mediated Tumor Control
Authors: Emilija Marinkovic, Minyi Chen, Nadja Schubert, Elif Dogan Dar, Tanja Poth, Janet Y. Leung, Jack Lohre, Jennifer M. Sahni, Christine Tun, Pavithra Rajeswaran, Tanja Mehlo-Jensen, Olivia Perng, C. Mark Hill, Pallavur Sivakumar, Michael J. Barnes, Rohit Malik, Rayk Behrendt, Axel Roers
Journal: Cancer Research (2025)

Abstract Therapeutic innate immune stimulation within the tumor microenvironment can potentiate endogenous antitumor T cell immunity. Strategies for controlled activation of cGAS/STING signaling are currently under intense investigation. DNase 3’-repair exonuclease 1 (TREX1) is essential for cellular DNA disposal, which prevents autoimmunity ensuing from cGAS/STING activation by endogenous DNA. TREX1-deficient tumor cells elicit enhanced protective immunity in syngeneic models. Here, we showed that induced inactivation of the Trex1 gene in host (non-cancer) cells yields improved type I IFN- and T cell-dependent control of established TREX1-competent tumors. Host TREX1 deficiency was well tolerated and triggered selective immune cell infiltration into tumors but not into other tissues. Induced systemic loss of TREX1 in tumor-bearing mice resulted in enhanced intra-tumoral T cell proliferation and massive increase in numbers of effector and effector-like ‘exhausted’ cells, enabling complete rejection in combination with checkpoint inhibition. To conclude, systemic TREX1 inhibition is a promising approach to boost anti-tumor immunity and to overcome immune evasion mediated by cancer cell-intrinsic cGAS/STING inactivation.
The Genetic Footprint of Tobacco Smoking: Unraveling the Mutational Signatures in Head and Neck Cancer
Authors: Kaito Mimura, Kenichi Yoshida
Journal: Cancer Research (2025)

Abstract Tobacco smoking and alcohol consumption are among the most significant, yet preventable, behavioral risk factors for cancer. In a recent paper in Nature Genetics, Torrens and colleagues performed whole-genome sequencing of 265 head and neck cancer (HNC) samples collected from eight countries across Europe and South America. They investigated the mechanisms underlying HNC development using mutational signature analysis and driver mutation analysis, complemented by regression analysis with epidemiological data. While the analyses confirmed the established roles of tobacco smoking and alcohol consumption as the primary causes of HNC, key findings included the synergistic effect of tobacco smoke and alcohol consumption, and that alcohol-induced mutational burden was significantly higher when combined with tobacco smoking. Additionally, the difference in smoking habits between countries was identified as a direct contributor to regional differences in HNC incidence. Furthermore, a novel smoking-related mutational signature SBS_I was discovered, awaiting further investigation into the underlying mutational process. This genomics-driven work by Torrens and colleagues evokes further research interest regarding the precise mechanisms of tumor initiation and promotion, and in the field of public health measures. In the end, Torrens and colleagues conclude with a call for anti-smoking measures, emphasizing the need to combat this major cancer risk factor.
Modeling the PAX5P80R Mutation Reveals HIF2α Activation as a Common Feature and Therapeutic Target in B-Cell Acute Lymphoblastic Leukemia
Authors: Manon Bayet, Vincent Fregona, Mathieu Bouttier, Clémence Rouzier, Jérémy Bigot, Laura Jamrog, Sylvie Hebrard, Naïs Prade, Stéphanie Lagarde, Christine Didier, Stéphanie Gachet, Marie Passet, Laetitia Largeaud, Marlène Pasquet, Ahmed Amine Khamlichi, Emmanuelle Clappier, Eric Delabesse, Cyril Broccardo, Bastien Gerby
Journal: Cancer Research (2025)

Abstract The transcription factor PAX5 is a major target of genetic alterations in human B-cell precursor acute lymphoblastic leukemia (B-ALL). Among the alterations, the P80R mutation affecting the DNA-binding domain represents the most frequent PAX5 point mutation in B-ALL. In contrast to other somatic PAX5 mutations, PAX5P80R defines a distinct B-ALL subtype characterized by a unique transcriptional program. Here, we aimed to develop a model to elucidate the mechanism by which PAX5P80R perturbs normal B-cell differentiation and the oncogenic relays involved in PAX5P80R-driven malignant progression. A retroviral complementation approach of Pax5-deficient murine fetal liver cells demonstrated at the functional and molecular levels that PAX5P80R failed to rescue definitive B-cell commitment but maintained the repression of T-cell development. Moreover, PAX5P80R eventually led to clonal B-ALL transformation after transplantation through the acquisition of secondary mutations in genes involved in the JAK/STAT and RAS/MAPK pathways. Finally, transcriptomic analyses combined with pharmacological investigation revealed ectopic activation of HIF2α as a common feature of B-ALL and identified acriflavine as a potent drug against B-ALL. Hence, this study provides a strategy to model the multistep process of B-ALL and sheds light on the biological mechanism by which the PAX5P80R mutation leads to leukemia.
Assessing the Performance of the PREDICT Breast Version 3.0 Prognostic Tool in Patients With Breast Cancer in the United States
Authors: Yi-Wen Hsiao, Gordon C. Wishart, Paul D.P. Pharoah, Pei-Chen Peng
Journal: Journal of the National Comprehensive Cancer Network (2025)

Background: PREDICT Breast version 3 (v3) is the latest updated prognostication tool, developed using data from approximately 35,000 women diagnosed with breast cancer between 2000 and 2018 in the United Kingdom. Although an earlier version of PREDICT was tested in the United States, the performance of the latest version remains unknown. This study aims to validate PREDICT Breast v3 using newly released SEER outcome data for patients with breast cancer in the United States and to address potential health disparities. Methods: A total of 615,865 female patients diagnosed with primary breast cancer between 2000 and 2018 and followed for at least 10 years were selected from the SEER database. Predicted and observed 10- and 15-year breast cancer–specific survival outcomes were compared for the overall cohort, stratified by estrogen receptor (ER) status and predefined subgroups. Discriminatory accuracy was evaluated using the area under the receiver operating characteristic curve (AUC). Results: PREDICT Breast v3 demonstrated good calibration and discrimination for long-term breast cancer–specific survival. It provided accurate mortality estimates (within ±10% absolute error) across the US population for 10-year (−10% in ER-positive and 2% in ER-negative breast cancer) and 15-year (4% in ER-positive and 3% in ER-negative breast cancer) all-cause mortality, for both ER statuses. The model also showed good performance for 10- and 15-year all-cause mortality across the US population, with AUC values of 0.769 and 0.794 for ER-positive breast cancer as well as AUC of 0.738 and 0.746 for ER-negative breast cancer, respectively, indicating good discriminatory ability. However, recalibration is needed for specific groups, including non-Hispanic Asian and non-Hispanic Black patients with ER-negative disease. Conclusions: PREDICT v3 accurately predicts 10- and 15-year breast cancer–specific survival in contemporary US patients with breast cancer. Future efforts should focus addressing disparities observed in predictive tools to promote equitable care.
Financial Toxicity in Cancer Clinical Trials: An Issue in Need of Clarity and Solutions
Authors: Elizabeth K.S. Barksdale, Wendy Selig, Willyanne DeCormier Plosky, Erin Miller, Keri McDonough, Chelsea Backler, Elizabeth George, Mark E. Fleury, Marc J. Taylor, Diana E. Pankevich, Jim Murphy, Kristin Hermann, Leigh Ann Davis, Gissoo DeCotiis, Cecile Gonzalez-Cerimele, Colleen Cook, Sandra Shaw, Luke Gelinas, Dana L. Dornsife, Barbara E. Bierer, David E. Gerber
Journal: Journal of Clinical Oncology (2025)
Randomized Phase II Study of Nab-Paclitaxel and Gemcitabine With or Without Tocilizumab as First-Line Treatment in Advanced Pancreatic Cancer: Survival and Cachexia
Authors: Inna M. Chen, Julia S. Johansen, Susann Theile, Libbie M. Silverman, Katherine R. Pelz, Kasper Madsen, Olav Dajani, Kevin Z.M. Lim, Torben Lorentzen, Omnia Gaafer, Leonidas G. Koniaris, Anna C. Ferreira, Brian Neelon, Denis C. Guttridge, Michael C. Ostrowski, Teresa A. Zimmers, Dorte Nielsen
Journal: Journal of Clinical Oncology (2025)

PURPOSE This randomized phase-II trial (ClinicalTrials.gov identifier: NCT02767557 ) compared efficacy of gemcitabine/nab-paclitaxel (Gem/Nab) with or without the anti–interleukin-6 (IL-6) receptor antibody tocilizumab (Toc) for advanced pancreatic cancer (PC). METHODS A safety cohort received Gem 1,000 mg/m 2 and Nab 125 mg/m 2 on days 1, 8, and 15, and Toc 8 mg/kg on day 1 for each 28-day cycle. Participants with modified Glasgow prognostic scores of 1 or 2 were randomly assigned 1:1 to receive Gem/Nab/Toc or Gem/Nab. The primary end point was the overall survival (OS) rate at 6 months (OS6). Secondary end points were progression-free survival (PFS), overall response rate (ORR), and safety. Exploratory end points were cachexia, quality of life, and biomarkers, including the cachexia-promoting protein, growth differentiation factor 15 (GDF15). RESULTS Overall, 147 patients were treated, including six safety cohort participants. The median follow-up period was 8.1 months (IQR, 4.2-13.9). OS6 was 68.6% (95% CI, 56.3 to 78.1) for the Gem/Nab/Toc group and 62.0% (49.6-72.1) for the Gem/Nab group ( P = .409). OS for Gem/Nab/Toc versus Gem/Nab improved at 18 months (27.1% v 7.0%, P = .001). No differences in median OS, PFS, or ORR were observed. Incidence of grade-3+ treatment-related adverse events (TrAEs) was 88.1% for Gem/Nab/Toc and 63.4% for Gem/Nab ( P &lt; .001). Gem/Nab/Toc decreased muscle loss versus Gem/Nab, with median change +0.1013% versus –3.430% ( P = .0012) at 2 months and +0.7044 versus –3.353% ( P = .036) at 4 months. Incidence of muscle loss was 43.48% on Gem/Nab/Toc versus 73.52% on Gem/Nab at 2 months ( P = .0045) and 41.82% versus 68.75% ( P = .0062) at 4 months. GDF15 was not changed by Gem/Nab or Gem/Nab/Toc. CONCLUSION Although the primary end point was not met and TrAEs were increased by Toc, increased survival at 18 months and reduced muscle wasting support an anticachexia effect of IL-6 blockade independent of GDF15. Further studies could leverage these findings for precision anticachexia therapy.
Effects of cooking with liquefied petroleum gas or biomass fuels on neurodevelopmental outcomes in pre-school aged children living in Puno, Peru
Authors: Carolyn J Reuland, Laura Nicolaou, Maureen M Black, Mingling Yang, Ryan McCord, Milagros Alvarado, Fiorella Arana, Paola S Sanchez, Kendra N Williams, Shakir Hossen, Marilú Chiang, Stella M Hartinger, William Checkley
Journal: Environmental Health Perspectives (2025)

Burning biomass fuels for cooking is a widespread environmental exposure that may adversely affect child health. We conducted an 18-month randomized field trial comparing a liquefied petroleum gas (LPG) stove, continuous fuel delivery and behavioral messaging intervention starting in pregnancy through infancy with usual cooking practices using biomass fuels in Puno, Peru. A total of 800 pregnant women were enrolled. The intervention successfully lowered personal exposures to fine particulate matter (PM2.5) during pregnancy and infancy. We sought to evaluate the effects of the intervention on neurodevelopment among pre-school aged offspring. We conducted a longitudinal follow-up study in a subset of Peruvian children born during the trial and assessed neurodevelopment between 24 and 36 months of age. Trained staff measured neurodevelopment using the Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III). The Bayley-III neurodevelopmental assessment test yields separate cognition, language, and motor scores. We measured personal exposures to PM2.5 three times during pregnancy and three times in infancy. We conducted modified intention-to-treat analyses of the intervention on Bayley-III scores, and exposure-response analyses between pre-natal and post-natal PM2.5 exposures and Bayley-III scores. A total of 301 children (mean age 29.0 ± 3.5 months; 47.8% girls; and 54.8% in intervention) were visited. Mean cognitive, language and motor scores were 90.8 ± 11.0, 89.0 ± 10.8, and 95.3 ± 12.9, respectively. On intention-to-treat, the adjusted differences between intervention and control arms were -1.9 (98.3% CI -4.9 to 1.2), -2.9 (-6.0 to 0.1), and -1.4 (-5.0 to 2.3) for the composite cognitive, language, and motor scores, respectively. We did not identify associations between PM2.5 exposures during the 18-month intervention and any of the Bayley-III scores, or when the personal exposures to PM2.5 were separated as either prenatal or post-natal. The LPG intervention did not improve neurodevelopment in Peruvian children. We also did not find an association between prenatal or post-natal PM2.5 exposures and neurodevelopment. https://doi.org/10.1289/EHP15500.
Mitigating Bias in Machine Learning Models with Ethics-Based Initiatives: The Case of Sepsis
Authors: John D. Banja, Yao Xie, Jeffrey R. Smith, Shaheen Rana, Andre L. Holder
Journal: The American Journal of Bioethics (2025)

This paper discusses ethics-based strategies for mitigating bias in machine learning models used to predict sepsis onset. The first part discusses how various kinds of bias and their potential synergies can reduce predictive accuracy, especially as those biases derive from social determinants of health (SDOHs) and from the design and construction of the predictive model. The second part of the essay discusses how certain ethically-based strategies might mitigate the potential for disparate or unfair treatment produced by these models, not only as they might apply to sepsis but to any syndrome that witnesses the impact of adverse SDOHs on socioeconomically disadvantaged or marginalized populations.
Living myocardial slices: walking the path towards standardization
Authors: Jort S A van der Geest, Teun P de Boer, Cesare M Terracciano, Thomas Thum, Andreas Dendorfer, Pieter A Doevendans, Linda W van Laake, Joost P G Sluijter, Vasco Sampaio-Pinto
Journal: Cardiovascular Research (2025)

Abstract Cardiovascular disease remains a persistent global health burden, underscoring the necessity for effective therapeutic strategies. Despite significant advances, the ability to mechanistically study human disease and predict clinical outcomes remains limited, especially in complex diseases such as heart failure. This limitation is evident through the continuous high attrition rates in drug development pipelines. To address these challenges and contribute to improved pre-clinical studies, there is a need for platforms that more accurately recapitulate the human heart. This need increased the interest in living myocardial slices (LMS) – thin sections of the heart of approximately 100-400 μm. LMS retain the native multicellular architecture of the heart and enable extended ex vivo culture. However, as their utilization grows, so does variability in preparation methodologies and readouts. This review provides an overview of differences in sample selection, interspecies variations, intra-cardiac differences, and potential confounding factors. Additionally, we examine culture methods, addressing electrical and mechanical stimulation differences, and medium compositions. Our review concludes by highlighting the current limitations of LMS research and offer guidelines for standardization and future applications. The ultimate aim of this review is to serve as a resource for researchers working with LMS and for those entering this field. By presenting the landscape of methodological considerations, we aim to facilitate informed decision-making in study design and execution. We advocate for accurate reporting of methodologies to promote reproducibility and comparability across studies, advancing LMS research and strengthening its role as a valuable addition to the current drug development toolbox and basic cardiovascular research.
A neural signature of touch aversion and interpersonal problems in Borderline Personality Disorder
Authors: Jella Voelter, Danilo Postin, Ilona Croy, René Hurlemann, Dirk Scheele
Journal: Psychotherapy and Psychosomatics (2025)

Introduction: Patients with borderline personality disorder (BPD) suffer from severe social impairments and interpersonal problems. Social touch can provide comfort and facilitate the maintenance of social bonds, and preliminary evidence indicates a negative evaluation of social touch in patients with BPD. However, the neural mechanisms underlying aberrant touch processing in BPD and its role for social impairments are still unclear. Methods: We recruited 55 BPD patients and 31 healthy controls and used functional magnetic resonance imaging to probe neural responses to slow (i.e. C-tactile (CT)-optimal; affective) and fast (i.e. CT-suboptimal; discriminative) touch before and after four weeks of a residential dialectical behavior therapy (DBT) program. In addition to assessing BPD symptoms and interpersonal problems, we evaluated touch allowance maps and the attitude towards social touch. Results: BPD patients showed a comprehensive negative bias towards social touch before the DBT, evident in a significantly more negative attitude towards and reduced comfort zones of social touch compared to healthy controls. Activation in the posterior insular cortex in response to CT-optimal touch was significantly reduced and correlated with the severity of interpersonal problems in BPD patients. Despite significant improvements in overall BPD symptom load, dysfunctional social touch processing persisted after four weeks of DBT, indicating trait-like disturbances in BPD. Conclusions: An impaired insula-mediated integration of affective and sensory components of touch may constitute a clinically relevant biological signature of the complex interpersonal problems in BPD.
Phase II study of venetoclax added to bendamustine and obinutuzumab in patients with high-risk follicular lymphoma as front-line therapy: PrE0403
Authors: Craig A Portell, Opeyemi A Jegede, Nina Wagner-Johnston, Grzegorz S Nowakowski, Christopher Fletcher, Jonathon B Cohen, Andrew M Evens, Lori J Rosenstein, Jeffrey W Craig, Nishitha Reddy, Brad S Kahl
Journal: Blood Cancer Journal (2025)

Over-expression of BCL-2 defines follicular lymphoma (FL). Venetoclax (VEN), a selective BCL-2 inhibitor, has previously been evaluated with bendamustine-based chemoimmunotherapy. VEN was given continuously, resulting in promising efficacy but unacceptable toxicity. The Phase II PrE0403 study was designed to evaluate intermittent dosing of VEN (10 days per cycle) combined with obinutuzumab and bendamustine (VEN-OB) in untreated FL subjects with high-risk features defined as a FLIPI-1 score of ≥3 and/or high tumor burden by GELF criteria. A total of 56 subjects were planned to be accrued with a goal of having 51 subjects eligible to improve the historical 50% CR rate to 65% with an 85% power and 15% type I error rate. Immunohistochemistry (IHC) expression of 3 antiapoptotic proteins (BCL-xL, MCL-1, and BCL-2) was performed and correlated with clinical outcomes. All 56 subjects were eligible and treated. CR rate was 41/56 (73.2%) and ORR was 52/56 (92.5%) meeting the primary endpoint. 2-year estimated PFS was 87.5% (90% CI: 75.3,93.9%) and 2-year estimated OS was 94.6% (90% CI: 86.7, 97.9%). However, the incidence of treatment-related adverse events ≥ grade 3 was 83.9% and serious adverse events were seen in 57.1%. After induction, atypical infections, including Grade 5 events, occurred. Anti-apoptotic protein expression by IHC was not correlated with clinical outcomes. Thus, while meeting the primary efficacy end point, VEN-OB is considered overly toxic in high-risk FL.
Acquired semi-squamatization during chemotherapy suggests differentiation as a therapeutic strategy for bladder cancer
Authors: Manli Wang, Xuelan Chen, Ping Tan, Yiyun Wang, Xiangyu Pan, Tianhai Lin, Yong Jiang, Bo Wang, Huan Xu, Yuying Wang, Yucen Yang, Jian Wang, Lei Zhao, Jiapeng Zhang, Ailing Zhong, Yiman Peng, Jiajia Du, Qi Zhang, Jianan Zheng, Jingyao Chen, Siqi Dai, Feifei Na, Zhenghao Lu, Jiaming Liu, Xiaonan Zheng, Lu Yang, Peng Zhang, Ping Han, Qiyong Gong, Qian Zhong, Kai Xiao, Hanshuo Yang, Hongxin Deng, Yinglan Zhao, Hubing Shi, Jianghong Man, Maling Gou, Chengjian Zhao, Lunzhi Dai, Zhihong Xue, Lu Chen, Yuan Wang, Musheng Zeng, Canhua Huang, Qiang Wei, Yuquan Wei, Yu Liu, Chong Chen
Journal: Cancer Cell (2025)