tbuckley/cabot-search huggingface dataset:
Multimodal transcriptomics reveal neurogenic aging trajectories and age-related regional inflammation in the dentate gyrus
Authors: Yicheng Wu, Vladyslav I. Korobeynyk, Margherita Zamboni, Felix Waern, John Darby Cole, Sarah Mundt, Melanie Greter, Jonas Frisén, Enric Llorens-Bobadilla, Sebastian Jessberger
Journal: Nature Neuroscience (2025)

Abstract The mammalian dentate gyrus (DG) is involved in certain forms of learning and memory, and DG dysfunction has been implicated in age-related diseases. Although neurogenic potential is maintained throughout life in the DG as neural stem cells (NSCs) continue to generate new neurons, neurogenesis decreases with advancing age, with implications for age-related cognitive decline and disease. In this study, we used single-cell RNA sequencing to characterize transcriptomic signatures of neurogenic cells and their surrounding DG niche, identifying molecular changes associated with neurogenic aging from the activation of quiescent NSCs to the maturation of fate-committed progeny. By integrating spatial transcriptomics data, we identified the regional invasion of inflammatory cells into the hippocampus with age and show here that early-onset neuroinflammation decreases neurogenic activity. Our data reveal the lifelong molecular dynamics of NSCs and their surrounding neurogenic DG niche with age and provide a powerful resource to understand age-related molecular alterations in the aging hippocampus.
The epitranscriptional factor PCIF1 orchestrates CD8+ T cell ferroptosis and activation to control antitumor immunity
Authors: Bolin Xiang, Meiling Zhang, Kai Li, Zijian Zhang, Yutong Liu, Minling Gao, Xiyong Wang, Xiangling Xiao, Yishuang Sun, Chuan He, Jie Shi, Hongzeng Fan, Xixin Xing, Gaoshan Xu, Yingmeng Yao, Gang Chen, Haichuan Zhu, Chengqi Yi, Jinfang Zhang
Journal: Nature Immunology (2025)
Neoadjuvant chemoradiation with or without PD-1 blockade in locally advanced rectal cancer: a randomized phase 2 trial
Authors: Yingchi Yang, Kai Pang, Guole Lin, Xinzhi Liu, Jiale Gao, Jiaolin Zhou, Lai Xu, Zhidong Gao, Yingchao Wu, Ang Li, Jiagang Han, Guoju Wu, Xin Wang, Fei Li, Yingjiang Ye, Jie Zhang, Guangyong Chen, Hao Wang, Yuanyuan Kong, Aiwen Wu, Yi Xiao, Hongwei Yao, Zhongtao Zhang
Journal: Nature Medicine (2025)
Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial
Authors: Juanita Lopez, Thomas Powles, Fadi Braiteh, Lillian L. Siu, Patricia LoRusso, Claire F. Friedman, Ani S. Balmanoukian, Michael Gordon, Jeffrey Yachnin, Sylvie Rottey, Ioannis Karydis, George A. Fisher, Marcus Schmidt, Martin Schuler, Ryan J. Sullivan, Howard A. Burris, Vladimir Galvao, Brian S. Henick, Luc Dirix, Dirk Jaeger, Patrick A. Ott, Kit Man Wong, Guy Jerusalem, Aglaia Schiza, Lawrence Fong, Neeltje Steeghs, Rom S. Leidner, Achim Rittmeyer, Scott A. Laurie, Eelke Gort, Raid Aljumaily, Ignacio Melero, Rachel L. Sabado, Ina Rhee, Michael R. Mancuso, Lars Muller, Gregg D. Fine, Mahesh Yadav, Leesun Kim, Vincent J. P. Leveque, Alberto Robert, Martine Darwish, Ting Qi, Jiawen Zhu, Jingbin Zhang, Patrick Twomey, Gautham K. Rao, Donald W. Low, Chris Petry, Amy A. Lo, Jill M. Schartner, Lélia Delamarre, Ira Mellman, Martin Löwer, Felicitas Müller, Evelyna Derhovanessian, Andrea Cortini, Luisa Manning, Daniel Maurus, Sebastian Brachtendorf, Verena Lörks, Tana Omokoko, Eva Godehardt, Dirk Becker, Christine Hawner, Christine Wallrapp, Christian Albrecht, Christoph Kröner, Arbel D. Tadmor, Jan Diekmann, Mathias Vormehr, Anette Jork, Anna Paruzynski, Maren Lang, Jonathon Blake, Oliver Hennig, Andreas N. Kuhn, Ugur Sahin, Özlem Türeci, D. Ross Camidge
Journal: Nature Medicine (2025)
Ferric carboxymaltose for anemia in late pregnancy: a randomized controlled trial
Authors: Sant-Rayn Pasricha, Ernest Moya, Ricardo Ataíde, Glory Mzembe, Rebecca Harding, Martin N. Mwangi, Truwah Zinenani, Khic-Houy Prang, Justina Kaunda, Owen P. L. Mtambo, Maclean Vokhiwa, Gomezgani Mhango, Elisabeth Mamani-Mategula, Katherine Fielding, Ayşe Demir, Naomi Von Dinklage, Hans Verhoef, Alistair RD McLean, Lucinda Manda-Taylor, Sabine Braat, Kamija S. Phiri
Journal: Nature Medicine (2025)

Abstract Over 46% of African pregnant women are anemic. Oral iron is recommended but often suboptimal, particularly late in pregnancy. Intravenous ferric carboxymaltose (FCM) could treat anemia in women in the third trimester in sub-Saharan Africa. In an open-label, individually randomized trial in antenatal clinics in southern Malawi, we randomized 590 women at 27–35 weeks of gestation with capillary hemoglobin &lt;10.0 g dl −1 to FCM (20 mg kg −1 up to 1,000 mg, once at enrollment) or standard of care (60 mg elemental iron, twice daily for 90 days). Participants and their infants were followed to 4 weeks postpartum. Primary outcomes were maternal anemia at 36 weeks’ gestation or delivery (whichever occurred first) and neonatal birthweight. At the primary timepoint, 126 of 270 (46.7%) of women in the FCM group were anemic, compared to 170 of 271 (67.3%) women in the standard-of-care group (PR, 0.74 (95% CI 0.64, 0.87); P = 0.0002). There was no difference between groups in birthweight (mean difference 10.9 g (−65.7, 87.5 g); P = 0.78). No serious infusion-related reactions occurred, and there were no differences in adverse events between groups. In Malawian women in late pregnancy, FCM effectively and safely reduced anemia before childbirth. Australia New Zealand Clinical Trial registration: ANZCTR12621001239853
Typical development of synaptic and neuronal properties can proceed without microglia in the cortex and thalamus
Authors: Mary O’Keeffe, Sam A. Booker, Darren Walsh, Mosi Li, Chloe Henley, Laura Simões de Oliveira, Mingshan Liu, Xingran Wang, Maria Banqueri, Katherine Ridley, Kosala N. Dissanayake, Cristina Martinez-Gonzalez, Kirsty J. Craigie, Deepali Vasoya, Tom Leah, Xin He, David A. Hume, Ian Duguid, Matthew F. Nolan, Jing Qiu, David J. A. Wyllie, Owen R. Dando, Alfredo Gonzalez-Sulser, Jian Gan, Clare Pridans, Peter C. Kind, Giles E. Hardingham
Journal: Nature Neuroscience (2025)
Glecirasib in KRASG12C-mutated nonsmall-cell lung cancer: a phase 2b trial
Authors: Yuankai Shi, Jian Fang, Ligang Xing, Yu Yao, Jian Zhang, Lian Liu, Yongsheng Wang, Changlu Hu, Jianping Xiong, Zhihua Liu, Runxiang Yang, Zhen Wang, Enfeng Zhao, Mengzhao Wang, Yanqiu Zhao, Kejing Tang, Zhihua Li, Zhengbo Song, Yongsheng Li, Wu Zhuang, Bo Jin, Ying Cheng, Yanping Hu, Yanhong Gu, Lin Wu, Rui Ma, Qitao Yu, Yan Yu, Jun Zhao, Hui Zhao, Dongqing Lv, Yanhong Shang, Puyuan Xing, Jin Zhou, Xingya Li, Zhe Liu, Zhaoxia Dai, Guohao Xia, Xueqin Chen, Yi Ba, Chunmei Bai, Qingshan Li, Guangyu An, Weiguo Hu, Yinxiang Wang, Andrea Wang-Gillam, Yuli Ding, Qiao Li, Zhiyue Rao
Journal: Nature Medicine (2025)
Selumetinib in adults with NF1 and inoperable plexiform neurofibroma: a phase 2 trial
Authors: Andrea M. Gross, Geraldine O’Sullivan Coyne, Eva Dombi, Cecilia Tibery, William G. Herrick, Staci Martin, Steven P. Angus, Jack F. Shern, Steven D. Rhodes, Jared C. Foster, Larry V. Rubinstein, Andrea Baldwin, Christopher Davis, Shelley A. H. Dixon, Margaret Fagan, Mary Jane Ong, Pamela L. Wolters, Mary Anne Tamula, Olivia Reid, Hari Sankaran, Fang Fang, Jeevan Prasaad Govindharajulu, Alice T. Browne, Rosandra N. Kaplan, Kara Heisey, Thomas J. On, Xiaoling Xuei, Xiyuan Zhang, Barry C. Johnson, Ralph E. Parchment, D. Wade Clapp, Apurva K. Srivastava, James H. Doroshow, Alice P. Chen, Brigitte C. Widemann
Journal: Nature Medicine (2025)
Personalized Heart Digital Twins Detect Substrate Abnormalities in Scar-Dependent Ventricular Tachycardia
Authors: Michael C. Waight, Adityo Prakosa, Anthony C. Li, Nick Bunce, Anna Marciniak, Natalia A. Trayanova, Magdi M. Saba
Journal: Circulation (2025)

BACKGROUND: Current outcomes from catheter ablation for scar-dependent ventricular tachycardia (VT) are limited by high recurrence rates and long procedure durations. Personalized heart digital twin technology presents a noninvasive method of predicting critical substrate in VT, and its integration into clinical VT ablation offers a promising solution. The accuracy of the predictions of digital twins to detect invasive substrate abnormalities is unknown. We present the first prospective analysis of digital twin technology in predicting critical substrate abnormalities in VT. METHODS: Heart digital twin models were created from 18 patients with scar-dependent VT undergoing catheter ablation. Contrast-enhanced cardiac magnetic resonance images were used to reconstruct finite-element meshes, onto which regional electrophysiological properties were applied. Rapid-pacing protocols were used to induce VTs and to define the VT circuits. Predicted optimum ablation sites to terminate all VTs in the models were identified. Invasive substrate mapping was performed, and the digital twins were merged with the electroanatomical map. Electrogram abnormalities and regions of conduction slowing were compared between digital twin–predicted sites and nonpredicted areas. RESULTS: Electrogram abnormalities were significantly more frequent in digital twin–predicted sites compared with nonpredicted sites (468/1029 [45.5%] versus 519/1611 [32.2%]; P &lt;0.001). Electrogram duration was longer at predicted sites compared with nonpredicted sites (82.0±25.9 milliseconds versus 69.7±22.3 milliseconds; P &lt;0.001). Digital twins correctly identified 21 of 26 (80.8%) deceleration zones seen on isochronal late activation mapping. CONCLUSIONS: Digital twin–predicted sites display a higher prevalence of abnormal and prolonged electrograms compared with nonpredicted sites and accurately identify regions of conduction slowing. Digital twin technology may help improve substrate-based VT ablation. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04632394.
High SAFE scores predict hepatocellular carcinoma in viral and non-viral hepatitis and metabolic dysfunction associated steatotic liver disease
Authors: Tung-Hung Su, Sheng-Shun Yang, Mei-Hsuan Lee, Wei-Yu Kao, Shang-Chin Huang, Fen-Fang Chen, Francis SK Poon, Lung-Wen Tsai, Yi-Ting Chen, Che Lin, Weichung Wang, W Ray Kim, Jia-Horng Kao
Journal: Clinical and Molecular Hepatology (2025)

Background/Aims:There are no hepatocellular carcinoma (HCC) surveillance recommendations for non-viral chronic liver diseases (CLD), such as metabolic dysfunction associated steatotic liver disease (MASLD).We explored the Steatosis-Associated Fibrosis Estimator (SAFE) score to predict HCC in MASLD and other CLD etiologies. Methods:Patients with various CLDs were included from medical centers in Taiwan.The SAFE score, consisting of age, BMI, diabetes, and laboratory data, was calculated at baseline, and patients were traced for new development of HCC.The predictability of the SAFE score for HCC was analyzed using the subdistribution hazard model with adjustments for competing risks. Results:Among 12,963 CLD patients with a median follow-up of 4 years, 258 developed HCC.The SAFE score classifies 1, 3, and 5-year HCC risk regardless of CLD etiologies.High (≥100) and intermediate (0-100) SAFE scores increased 11 and 2 folds HCC risks compared to low (<0) SAFE scores.Combining two lower risk tiers (SAFE < 100), a high SAFE score (≥100) was associated with a 7.5-fold risk of HCC (adjusted sub-distributional hazard ratio [aSHR]: 7.54, 95% confidence interval (CI): 5.38-10.60).A high SAFE score increased the risks of HCC in subgroups of viral hepatitis, non-viral hepatitis (aSHR: 11.10, 95%CI: 3.97-31.30)and MASLD (aSHR: 4.23, 95%CI: 1.43-12.50).A hospital cohort (n=8,103) and a community MASLD cohort (n=120,166) validated the high SAFE score (≥100) for HCC risk prediction. Conclusions:The SAFE score stratifies high risks for HCC in CLD patients regardless of etiologies and helps to select at-risk candidates for HCC surveillance.
PDPN+ cancer‐associated fibroblasts enhance gastric cancer angiogenesis via AKT/NF‐κB activation and the CCL2‐ACKR1 axis
Authors: Zhenxiong Zhao, Hui Sun, Yingxue Liu, Yanqiu Zhang, Xin Wang, Xu Wang, Cong Tan, Shujuan Ni, Weiwei Weng, Meng Zhang, Lei Wang, Dan Huang, Wenchao Gu, Jinjia Chang, Weiqi Sheng, Mi‐die Xu
Journal: MedComm (2025)

Abstract Cancer‐associated fibroblasts (CAFs) are intrinsic components of the tumor microenvironment that promote cancer progression and metastasis. Through an unbiased integrated analysis of gastric tumor grade and stage, we identified a subset of proangiogenic CAFs characterized by high podoplanin (PDPN) expression, which are significantly enriched in metastatic lesions and secrete chemokine (CC‐motif) ligand 2 (CCL2). Mechanistically, PDPN(+) CAFs enhance angiogenesis by activating the AKT/NF‐κB signaling pathway. The canonical NF‐κB signaling protein P65 binds to the promoter region of CCL2, inducing its expression. Additionally, we found that CCL2 interacts with its nonclassical receptor ACKR1 (expressed on endothelial cells) to exert its proangiogenic effects. Furthermore, the disruption of CCL2‐ACKR1 communication via a CCL2 neutralizing antibody or the inhibition of AKT signaling transduction using AKT inhibitors effectively suppressed tumor growth. Together, this study elucidates the mechanism by which PDPN(+) CAFs promote angiogenesis, providing a deeper understanding of the molecular processes underlying CAF‐mediated angiogenesis and suggesting potential therapeutic targets for gastric cancer treatment.
Predatory journals: what can we do to protect their prey?
Authors: Christine Laine, Dianne Babski, Vivienne C Bachelet, Till W Bärnighausen, Christopher Baethge, Kirsten Bibbins-Domingo, Frank Frizelle, Laragh Gollogy, Sabine Kleinert, Elizabeth Loder, João Monteiro, Eric J Rubin, Peush Sahni, Christina C Wee, Jin-Hong Yoo, Lilia Zakhama
Journal: The Lancet (2025)
Assessing the Risk for Falls in Older Adults After Initiating Gabapentin Versus Duloxetine
Authors: Alexander Chaitoff, Rishi J. Desai, Niteesh K. Choudhry, Katharina T. Jungo, Nancy Haff, Julie C. Lauffenburger
Journal: Annals of Internal Medicine (2025)

The evidence informing the harms of gabapentin use are at risk of bias from comparing users with nonusers.
Adaptive Significance of Non-coding RNAs: Insights from Cancer Biology
Authors: John F McDonald
Journal: Molecular Biology and Evolution (2025)

Abstract The molecular basis of adaptive evolution and cancer progression are both complex processes that share many striking similarities. The potential adaptive significance of environmentally-induced epigenetic changes is currently an area of great interest in both evolutionary and cancer biology. In the field of cancer biology intense effort has been focused on the contribution of stress-induced non-coding RNAs (ncRNAs) in the activation of epigenetic changes associated with elevated mutation rates and the acquisition of environmentally adaptive traits. Examples of this process are presented and combined with more recent findings demonstrating that stress-induced ncRNAs are transferable from somatic to germline cells leading to cross-generational inheritance of acquired adaptive traits. The fact that ncRNAs have been implicated in the transient adaptive response of various plants and animals to environmental stress is consistent with findings in cancer biology. Based on these collective observations, a general model as well as specific and testable hypotheses are proposed on how transient ncRNA-mediated adaptive responses may facilitate the transition to long-term biological adaptation in both cancer and evolution.
Post-switching discontinuation of biosimilars in psoriasis: registry analyses fall short in addressing real-world biases
Authors: Luis Puig
Journal: British Journal of Dermatology (2025)

Journal Article Accepted manuscript Post-switching discontinuation of biosimilars in psoriasis: registry analyses fall short in addressing real-world biases Get access Luis Puig Luis Puig Department of Dermatology, Hospital de la Santa Creu I Sant Pau. Universitat Autònoma de Barcelona. Barcelona, Catalonia, Spain Correspondence author: Email:[email protected] https://orcid.org/0000-0001-6083-0952 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljaf003, https://doi.org/10.1093/bjd/ljaf003 Published: 07 January 2025 Article history Received: 27 December 2024 Revision received: 28 December 2024 Accepted: 03 January 2025 Published: 07 January 2025
Faithful interpretation of protein structures through weighted persistent homology improves evolutionary distance estimation
Authors: Léa Bou Dagher, Dominique Madern, Philippe Malbos, Céline Brochier-Armanet
Journal: Molecular Biology and Evolution (2025)

Phylogenetic inference is mainly based on sequence analysis and requires reliable alignments. This can be challenging, especially when sequences are highly divergent. In this context, the use of three-dimensional protein structures is a promising alternative. In a recent study, we introduced an original topological data analysis method based on persistent homology to estimate the evolutionary distances from structures. The method was successfully tested on 518 protein families representing 22,940 predicted structures. However, as anticipated, the reliability of the estimated evolutionary distances was impacted by the quality of the predicted structures and the presence of indels in the proteins. This paper introduces a new topological descriptor, called bio-topological marker (BTM), which provides a more faithful description of the structures, as well as a topological analysis for estimating evolutionary distances from BTMs and a weight-filtering method adapted to protein structures. These new developments significantly improve the estimation of evolutionary distances and phylogenies inferred from structures.
Disappointing long-term efficacy of secukinumab in patients with hidradenitis suppurativa: the need for defining long-term outcomes and evaluating treatment combinations
Authors: Thomas Bettuzzi, Chloé Grolleau
Journal: British Journal of Dermatology (2025)

Journal Article Accepted manuscript Disappointing long-term efficacy of secukinumab in patients with hidradenitis suppurativa: the need for defining long-term outcomes and evaluating treatment combinations Get access Thomas Bettuzzi, Thomas Bettuzzi Service de dermatologie, Hôpital Henri Mondor, AP-HP, EpiDermE, Université Paris Est Créteil Val de Marne, Créteil, France Correspondence: Dr Thomas Bettuzzi, Email:[email protected] https://orcid.org/0000-0001-7303-5552 Search for other works by this author on: Oxford Academic Google Scholar Chloé Grolleau Chloé Grolleau Service de dermatologie, Hôpital Saint Louis, AP-HP, Université Paris Cité, Paris, France https://orcid.org/0000-0002-8393-7442 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljaf011, https://doi.org/10.1093/bjd/ljaf011 Published: 07 January 2025 Article history Received: 02 January 2025 Accepted: 03 January 2025 Published: 07 January 2025
Squamous cell carcinoma arising from lichen planus
Authors: Jiang-Wei Cheng, Jiu-Hong Li
Journal: British Journal of Dermatology (2025)

We describe a middle-aged female patient who presented with a 1-year history of a thick-crusted plaque on an erythematous base of the left heel. Twenty years earlier, the patient was diagnosed with lichen planus and received treatment, leaving residual erythema on the heel. Over the past year, she noticed a progressive enlargement and desquamation of the erythema with a newly formed brown-yellow, hyperkeratotic and thick-crusted plaque in the centre, which was recalcitrant to empirical topical glucocorticoids, antibiotics and antifungals. Based on the clinical and typical histological findings, a diagnosis of squamous cell carcinoma arising from lichen planus was made.
Cardiovascular Safety and Fracture Prevention Effectiveness of Denosumab Versus Oral Bisphosphonates in Patients Receiving Dialysis
Authors: Soichiro Masuda, Toshiki Fukasawa, Shuichi Matsuda, Koji Kawakami
Journal: Annals of Internal Medicine (2025)

Dialysis patients have high rates of fracture morbidity, but evidence on optimal management strategies for osteoporosis is scarce. To determine the risk for cardiovascular events and fracture prevention effects with denosumab compared with oral bisphosphonates in dialysis-dependent patients. An observational study that attempts to emulate a target trial. A Japanese administrative claims database (April 2014 to October 2022). Adults aged 50 years or older who have initiated denosumab or oral bisphosphonates for osteoporosis in dialysis-dependent patients. The safety outcome was major adverse cardiac events (MACE). The effectiveness outcome was a composite of all fractures. Follow-up was 3 years. A total of 1032 patients were identified (658 denosumab users and 374 oral bisphosphonate users). Overall average age was 74.5 years, and 62.9% were women. The weighted 3-year risk difference for MACE was 8.2% (95% CI, -0.2% to 16.7%), with a weighted 3-year risk ratio of 1.36 (CI, 0.99 to 1.87). The weighted 3-year risk difference for composite fractures was -5.3% (CI, -11.3% to -0.6%), and the weighted 3-year risk ratio was 0.55 (CI, 0.28 to 0.93). Lack of clinical data on kidney or osteoporosis disease severity and cardiovascular or other metabolic risk with residual confounding. Safety outcomes did not include kidney end points. It was estimated that, compared with oral bisphosphonates, denosumab lowered the risk for fractures by 45% and increased the risk for MACE by 36%. The estimates, however, are imprecise and need to be confirmed in future studies. None.
In insulin-naive T2D, weekly efsitora was noninferior to daily degludec for reducing HbA<sub>1c</sub> at 52 wk
Authors: Felipe Larios, Michael R. Gionfriddo, Victor M. Montori
Journal: Annals of Internal Medicine (2025)

GIM/FP/GP: [Formula: see text] Endocrinology: [Formula: see text].
Predatory Journals: What Can We Do to Protect Their Prey?
Authors: Christine Laine, Dianne Babski, Vivienne C. Bachelet, Till W. Bärnighausen, Christopher Baethge, Kirsten Bibbins-Domingo, Frank Frizelle, Laragh Gollogy, Sabine Kleinert, Elizabeth Loder, João Monteiro, Eric J. Rubin, Peush Sahni, Christina C. Wee, Jin-Hong Yoo, Lilia Zakhama
Journal: Annals of Internal Medicine (2025)
Efficacy and Safety of Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss Among Adults Without Diabetes
Authors: Areesha Moiz, Kristian B. Filion, Helia Toutounchi, Michael A. Tsoukas, Oriana H.Y. Yu, Tricia M. Peters, Mark J. Eisenberg
Journal: Annals of Internal Medicine (2025)

Recent randomized controlled trials (RCTs) have investigated glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual or triple co-agonists for weight loss among adults with overweight or obesity and without diabetes.
Predatory Journals — What Can We Do to Protect Their Prey?
Authors: Christine Laine, Dianne Babski, Vivienne C Bachelet, Till W Bärnighausen, Christopher Baethge, Kirsten Bibbins-Domingo, Frank Frizelle, Laragh Gollogly, Sabine Kleinert, Elizabeth Loder, João Monteiro, Eric J Rubin, Peush Sahni, Christina C Wee, Jin-Hong Yoo, Lilia Zakhama
Journal: New England Journal of Medicine (2025)