tbuckley/cabot-search huggingface dataset:
Novel Less Toxic, Lymphoid Tissue‐Targeted Lipid Nanoparticles Containing a Vitamin B5‐Derived Ionizable Lipid for mRNA Vaccine Delivery (Adv. Healthcare Mater. 7/2025)
Authors: Soyeon Yoo, Muhammad Faisal, Seo‐Hyeon Bae, Kounghwa Youn, Hyo‐Jung Park, Sung Pil Kwon, Il Kwon Hwang, Jisun Lee, Hyeong Jun Kim, Jae‐Hwan Nam, Gyochang Keum, Eun‐Kyoung Bang
Journal: Advanced Healthcare Materials (2025)
TLR Agonist Nano Immune Therapy Clears Peritoneal and Systemic Ovarian Cancer (Adv. Healthcare Mater. 7/2025)
Authors: Ben Marwedel, Henning De May, Lauren Anderson, Lorél Y. Medina, Ellie Kennedy, Erica Flores, John O'Rourke, Marian Olewine, Irina Lagutina, Lillian Fitzpatrick, Fred Shultz, Donna F. Kusewitt, Eric Bartee, Sarah Adams, Achraf Noureddine, Rita E. Serda
Journal: Advanced Healthcare Materials (2025)
Lipid Nanoparticle‐Mediated CRISPR‐Cas13a Delivery for the Control of Bacterial Infection (Adv. Healthcare Mater. 7/2025)
Authors: Bookun Kim, Hwi Won Seo, Kyuri Lee, Dongeun Yong, Yoon Kyung Park, Yujin Lee, Solip Lee, Do‐Wan Kim, Dajeong Kim, Choong‐Min Ryu
Journal: Advanced Healthcare Materials (2025)
White matter connections of human ventral temporal cortex are organized by cytoarchitecture, eccentricity and category-selectivity from birth
Authors: Emily Kubota, Xiaoqian Yan, Sarah Tung, Bella Fascendini, Christina Tyagi, Sophie Duhameau, Danya Ortiz, Mareike Grotheer, Vaidehi S. Natu, Boris Keil, Kalanit Grill-Spector
Journal: Nature Human Behaviour (2025)
Engineered bacteria for near-infrared light-inducible expression of cancer therapeutics
Authors: Longliang Qiao, Lingxue Niu, Zhihao Wang, Zhenqiang Deng, Dai Di, Xiaoding Ma, Yang Zhou, Deqiang Kong, Qilin Wang, Jianli Yin, Lingli Jin, Jing Sun, Bo Feng, Weiqiang Lu, Fengfeng Cai, Ningzi Guan, Haifeng Ye
Journal: Nature Cancer (2025)
Cross-ancestry and sex-stratified genome-wide association analyses of amygdala and subnucleus volumes
Authors: Yuan Ji, Nana Liu, Yunjun Yang, Meiyun Wang, Jingliang Cheng, Wenzhen Zhu, Shijun Qiu, Zuojun Geng, Guangbin Cui, Yongqiang Yu, Weihua Liao, Hui Zhang, Bo Gao, Xiaojun Xu, Tong Han, Zhenwei Yao, Quan Zhang, Wen Qin, Feng Liu, Meng Liang, Sijia Wang, Qiang Xu, Jiayuan Xu, Jilian Fu, Peng Zhang, Wei Li, Dapeng Shi, Caihong Wang, Su Lui, Zhihan Yan, Feng Chen, Jing Zhang, Wen Shen, Yanwei Miao, Dawei Wang, Jia-Hong Gao, Xiaochu Zhang, Kai Xu, Xi-Nian Zuo, Longjiang Zhang, Zhaoxiang Ye, Mulin Jun Li, Junfang Xian, Bing Zhang, Chunshui Yu
Journal: Nature Genetics (2025)
Molecular residual disease analysis of adjuvant osimertinib in resected EGFR-mutated stage IB–IIIA non-small-cell lung cancer
Authors: Roy S. Herbst, Thomas John, Christian Grohé, Jonathan W. Goldman, Terufumi Kato, Konstantin Laktionov, Laura Bonanno, Marcello Tiseo, Margarita Majem, Manuel Dómine, Myung-Ju Ahn, Dariusz M. Kowalski, Maurice Pérol, Virote Sriuranpong, Mustafa Özgüroğlu, Preetida Bhetariya, Aleksandra Markovets, Yuri Rukazenkov, Caitlin Muldoon, Jacqulyne Robichaux, Ryan Hartmaier, Masahiro Tsuboi, Yi-Long Wu
Journal: Nature Medicine (2025)

Osimertinib—a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor—is recommended as adjuvant therapy for resected stage IB–IIIA epidermal growth factor receptor-mutated non-small-cell lung cancer, based on significant disease-free survival (DFS) and overall survival improvement shown in the previously reported phase 3 ADAURA trial. A trend toward an increased DFS event rate after completion of 3 years adjuvant treatment in ADAURA suggests that some patients may benefit from longer adjuvant osimertinib treatment. We therefore explored whether tumor-informed, circulating tumor DNA-based, molecular residual disease (MRD) could predict recurrence in an exploratory post hoc analysis of 220 patients (n = 112 osimertinib; n = 108 placebo) from ADAURA. MRD preceded imaging DFS events in this study by a median of 4.7 (95% confidence interval, 2.2–5.6) months. DFS and MRD event-free rate at 36 months was 86% versus 36% for patients in the osimertinib versus placebo groups (hazard ratio, 0.23 (95% confidence interval, 0.15–0.36)). In the osimertinib group, DFS or MRD events were detected in 28 (25%) patients; most events occurred following osimertinib cessation (19 of 28, 68%) and within 12 months of stopping osimertinib (11 of 19, 58%). At 24 months after osimertinib, the DFS and MRD event-free rate was 66%. In this study, MRD preceded DFS events in most patients across both arms. DFS and MRD event-free status was maintained for most patients during adjuvant osimertinib treatment and posttreatment follow-up, with most MRD or DFS events occurring after osimertinib treatment discontinuation or completion. MRD detection could potentially identify patients who may benefit from longer adjuvant osimertinib, although this requires clinical confirmation. ClinicalTrials.gov identifier: NCT02511106 . Exploratory post hoc analysis of molecular residual disease from the ADAURA trial of adjuvant osimertinib in patients with resected EGFR-mutated stage IB–IIIA non-small-cell lung cancer shows that molecular residual disease detection predicts disease recurrence with long-term adjuvant osimertinib treatment.
A Gremlin 1-expressing splenic niche cell population restrains chronic myeloid leukemia by antagonizing the BMP pathway
Authors: Jinming Wang, Penghui Xu, Zhongzhong Ji, Chaping Cheng, Yiyun Liu, Genyu Du, Shilei Zhang, Juju Miao, Deng Wang, Ruoyang Chen, Dawei Li, Kai Zhang, Huifang Zhao, Yujiao Sun, Xinyu Chen, Na Jing, Kaiyuan Liu, Yuman He, Xialian Xi, Yingchao Zhang, Nan Wang, Longmei Xu, Jufang Yao, Xiaomei Gao, Jianhua Zhou, Songqing Fan, Xiaorui Wang, Shuxian Dong, Fangli Chen, Jian Hou, Ming Zhang, Wei-Qiang Gao, Lijing Shen, Pengcheng Zhang, Helen He Zhu
Journal: Nature Cancer (2025)
Absence of care among community-dwelling older adults with dementia and functional limitations
Authors: Zhuoer Lin, Yuting Qian, Thomas M. Gill, Xiaohui Hou, Heather Allore, Shanquan Chen, Xi Chen
Journal: Nature Aging (2025)

Assistance with daily activities is crucial for persons living with dementia and functional limitations, yet many face substantial challenges in accessing adequate care and support. Using harmonized longitudinal survey data (2012–2018) from the United States, England, 18 European countries, Israel and China, we found that at least one-fifth of persons with dementia and functional limitations received no personal assistance for basic activities of daily living or instrumental activities of daily living, regardless of regional development level. Care gaps were widespread across both basic activities of daily living or instrumental activities of daily living limitations, as well as for informal and formal care. Disparities were evident, with less educated people more likely to lack formal care, whereas those living alone often lacked informal support, resulting in the absence of any care. Alarmingly, care availability showed no improvement over time. Our findings underscore the urgent need for policies to address inequities and ensure critical access to care services for this vulnerable population worldwide. Using data from the United States, England, Europe, Israel and China, Lin, Qian et al. identify that at least one-fifth of persons with dementia and functional limitations received no care for daily activities, with care deficits persisting globally over time.
Odronextamab monotherapy in patients with relapsed/refractory diffuse large B cell lymphoma: primary efficacy and safety analysis in phase 2 ELM-2 trial
Authors: Won Seog Kim, Tae Min Kim, Seok-Goo Cho, Isidro Jarque, Elżbieta Iskierka-Jażdżewska, Li Mei Poon, H. Miles Prince, Huilai Zhang, Junning Cao, Mingzhi Zhang, Benoît Tessoulin, Sung Yong Oh, Francesca Lim, Cecilia Carpio, Tran-Der Tan, Sabarish Ayyappan, Antonio Gutierrez, Jingxian Cai, Melanie Ufkin, Saleem Shariff, Jurriaan Brouwer-Visser, Aafia Chaudhry, Hesham Mohamed, Srikanth Ambati, Jan Walewski, Hannah Rose, Geoffrey Chong, Vinod Ganju, Michael Chu, Mary-Margaret Keating, Yuqin Song, Jun Zhu, Xiaoyan Ke, Shuhua Yi, Huilai Zhang, Qingyuan Zhang, Liqun Zou, Mingzhi Zhang, Dengju Li, Wenbin Qian, Ou Bai, Li Gao, Jie Jin, Caixia Li, Huiqiang Huang, Zheng Wei, Youhua Chen, Pengcheng He, Gandhi Laurent Damaj, Kamal Bouabdballah, Emmanuel Bachy, Corinne Haioun, Franck Morschhauser, Sylvain Choquet, Vincent Delwail, Catherine Thieblemont, Johannes Duell, Thomas Weber, Paul Graf La Rosee, Holger Hebart, Enrico Capochiani, Vittorio Zilioli, Francesca Rossi, Stefano Luminari, Pier Luigi Zinzani, Laura Bagnato, Gianluca Gaidano, Marco Brociner, Cristina Skert, Monica Tani, Roberta Battistini, Leonardo Flenghi, Ryusuke Yamamoto, Kunihiro Tsukasaki, Kenichi Ishizawa, Tomomi Tobai, Toshiki Uchida, Yosuke Minami, Nobuhiko Yamauchi, Junichiro Yuda, Masahiro Takeuchi, Hirokazu Nagai, Youko Suehiro, Yoshiaki Ogawa, Junya Kuroda, Tatsuro Jo, Hirohisa Nakamae, Isao Yoshida, Michal Taszner, Ewa Lech-Maranda, Wanda Knopinska-Posluszny, Tomasz Wrobel, Tadeusz Robak, Wen Son Hsieh, Shin Yeu Ong, Hyeon-Seok Eom, Yeung-Chul Mun, Young Rok Do, Jin Seok Kim, Byung Soo Kim, Jae-Cheol Jo, Ana Jimenez-Ubieto, Rafael Andreu, Alejandro Martin, Agustin Penedo Coello, Raul Cordoba, Aranzazu Alonso, Laura Magnano, Eva Gonzalez-Barca, Sara Miqueleiz, Tsai Yun Chen, Su Peng Yeh, Shang-Ju Wu, Ming-Chung Wang, David Cunningham, Andrea Kuhnl, David Tucker, David Lewis, Nagah Elmusharaf, John Allan, Thomas Jandl, Sami Ibrahimi, Deepa Jagadeesh, Lori Leslie, Parameswaran Venugopal, Jon Arnason, Jose C. Villasboas, Rakhee Vaidya, Don Stevens, Farrukh Awan, Andreas Klein, Umar Farooq
Journal: Nature Cancer (2025)
The time is now: accounting for time-of-day effects to improve reproducibility and translation of metabolism research
Authors: Shaunak Deota, Julie S. Pendergast, Ullas Kolthur-Seetharam, Karyn A. Esser, Frédéric Gachon, Gad Asher, Charna Dibner, Salvador Aznar Benitah, Carolina Escobar, Deborah M. Muoio, Eric Erquan Zhang, Gökhan S. Hotamışlıgil, Joseph Bass, Joseph S. Takahashi, Joshua D. Rabinowitz, Katja A. Lamia, Rafael de Cabo, Shingo Kajimura, Valter D. Longo, Ying Xu, Mitchell A. Lazar, Eric Verdin, Juleen R. Zierath, Johan Auwerx, Daniel J. Drucker, Satchidananda Panda
Journal: Nature Metabolism (2025)
Design of sensitive monospecific and bispecific synthetic chimeric T cell receptors for cancer therapy
Authors: Sylvain Simon, Grace Bugos, Rachel Prins, Anusha Rajan, Arulmozhi Palani, Kersten Heyer, Andrew Stevens, Longhui Zeng, Kirsten A. Thompson, Pinar A. Atilla, Jason P. Price, Mitchell G. Kluesner, Carla A. Jaeger-Ruckstuhl, Tamer B. Shabaneh, James M. Olson, Xiaolei Su, Stanley R. Riddell
Journal: Nature Cancer (2025)

The adoptive transfer of T cells expressing chimeric antigen receptors (CARs) is effective in B cell malignancies. However, the persistence of cancer cells with low levels or complete absence of the target antigen, thereby evading detection by CAR T cells, leads to relapse. These evasion mechanisms highlight the need for receptors with enhanced sensitivity and multispecificity. We introduce a synthetic chimeric T cell receptor (ChTCR) that confers superior antigen sensitivity compared with CARS and previous hybrid TCR designs and is readily adapted for bispecific targeting. ChTCRs replicate the structure of natural TCRs, form classical immune synapses and demonstrate TCR-like signaling. T cells expressing bispecific ChTCRs (Bi-ChTCRs) are more effective than bispecific CAR T cells in eradicating tumors with heterogeneous antigen expression in vivo in female mice. The Bi-ChTCR architecture is resilient and can be designed to target pairs of B cell and multiple myeloma antigens. These findings provide a widely applicable strategy to combat tumor heterogeneity and prevent relapse. Simon, Bugos and colleagues report the design and characterization of monospecific and bispecific synthetic chimeric T cell receptors, conferring increased antigen sensitivity and antitumor activity in B cell malignancies and multiple myeloma models.
The Farm Animal Genotype–Tissue Expression (FarmGTEx) Project
Authors: Lingzhao Fang, Jinyan Teng, Qing Lin, Zhonghao Bai, Shuli Liu, Dailu Guan, Bingjie Li, Yahui Gao, Yali Hou, Mian Gong, Zhangyuan Pan, Ying Yu, Emily L. Clark, Jacqueline Smith, Konrad Rawlik, Ruidong Xiang, Amanda J. Chamberlain, Michael E. Goddard, Mathew Littlejohn, Greger Larson, David E. MacHugh, John F. O’Grady, Peter Sørensen, Goutam Sahana, Mogens Sandø Lund, Zhihua Jiang, Xiangchun Pan, Wentao Gong, Haihan Zhang, Xi He, Yuebo Zhang, Ning Gao, Jun He, Guoqiang Yi, Yuwen Liu, Zhonglin Tang, Pengju Zhao, Yang Zhou, Liangliang Fu, Xiao Wang, Dan Hao, Lei Liu, Siqian Chen, Robert S. Young, Xia Shen, Charley Xia, Hao Cheng, Li Ma, John B. Cole, Ransom L. Baldwin, Cong-jun Li, Curtis P. Van Tassell, Benjamin D. Rosen, Nayan Bhowmik, Joan Lunney, Wansheng Liu, Leluo Guan, Xin Zhao, Eveline M. Ibeagha-Awemu, Yonglun Luo, Lin Lin, Oriol Canela-Xandri, Martijn F. L. Derks, Richard P. M. A. Crooijmans, Marta Gòdia, Ole Madsen, Martien A. M. Groenen, James E. Koltes, Christopher K. Tuggle, Fiona M. McCarthy, Dominique Rocha, Elisabetta Giuffra, Marcel Amills, Alex Clop, Maria Ballester, Gwenola Tosser-Klopp, Jing Li, Chao Fang, Ming Fang, Qishan Wang, Zhuocheng Hou, Qin Wang, Fuping Zhao, Lin Jiang, Guiping Zhao, Zhengkui Zhou, Rong Zhou, Hehe Liu, Juan Deng, Long Jin, Mingzhou Li, Delin Mo, Xiaohong Liu, Yaosheng Chen, Xiaolong Yuan, Jiaqi Li, Shuhong Zhao, Yi Zhang, Xiangdong Ding, Dongxiao Sun, Hui-Zeng Sun, Cong Li, Yu Wang, Yu Jiang, Dongdong Wu, Wenwen Wang, Xinzhong Fan, Qin Zhang, Kui Li, Hao Zhang, Ning Yang, Xiaoxiang Hu, Wen Huang, Jiuzhou Song, Yang Wu, Jian Yang, Weiwei Wu, Claudia Kasper, Xinfeng Liu, Xiaofei Yu, Leilei Cui, Xiang Zhou, Seyoung Kim, Wei Li, Hae Kyung Im, Edward S. Buckler, Bing Ren, Michael C. Schatz, Jingyi Jessica Li, Abraham A. Palmer, Laurent Frantz, Huaijun Zhou, Zhe Zhang, George E. Liu, Curtis P. Van Tassell
Journal: Nature Genetics (2025)
A telomere-to-telomere genome assembly of cotton provides insights into centromere evolution and short-season adaptation
Authors: Guanjing Hu, Zhenyu Wang, Zunzhe Tian, Kai Wang, Gaoxiang Ji, Xingxing Wang, Xianliang Zhang, Zhaoen Yang, Xuan Liu, Ruoyu Niu, De Zhu, Yuzhi Zhang, Lian Duan, Xueyuan Ma, Xianpeng Xiong, Jiali Kong, Xianjia Zhao, Ya Zhang, Junjie Zhao, Shoupu He, Corrinne E. Grover, Junji Su, Keyun Feng, Guangrun Yu, Jinlei Han, Xinshan Zang, Zhiqiang Wu, Weihua Pan, Jonathan F. Wendel, Xiongfeng Ma
Journal: Nature Genetics (2025)
Genomic analysis of 1,325 Camellia accessions sheds light on agronomic and metabolic traits for tea plant improvement
Authors: Weilong Kong, Xiangrui Kong, Zhongqiang Xia, Xiaofeng Li, Fang Wang, Ruiyang Shan, Zhihui Chen, Xiaomei You, Yuanyan Zhao, Yanping Hu, Shiqin Zheng, Sitong Zhong, Shengcheng Zhang, Yanbing Zhang, Kaixing Fang, Yinghao Wang, Hui Liu, Yazhen Zhang, Xinlei Li, Hualing Wu, Guo-Bo Chen, Xingtan Zhang, Changsong Chen
Journal: Nature Genetics (2025)

The tea plant stands as a globally cherished nonalcoholic beverage crop, but the genetic underpinnings of important agronomic and metabolomic traits remain largely unexplored. Here we de novo deep resequenced 802 tea plants and their relative accessions globally. By integrating public Camellia accessions, we constructed a comprehensive genome-wide genetic variation map and annotated deleterious mutations for 1,325 accessions. Population genetic analyses provided insights into genetic divergence from its relatives, different evolutionary bottlenecks, interspecific introgression and conservation of wild relatives. Our findings suggest the pivotal role of southwest China as the origin of tea plants, revealing the genetic diversity and domestication status of ancient tea plants. Genome-wide association studies herein identified thousands of substantial associations with leaf shape and metabolite traits, pinpointing candidate genes for crucial agronomic and flavor traits. This study illuminates the tea plant's evolution and provides references for tea plant design breeding. This study provides a de novo resequencing of 802 Camellia accessions and a genome-wide variation map. Genome-wide association study (GWAS) and metabolite GWAS identify genes responsible for crucial agronomic and flavor traits.
Human colitis-associated colorectal carcinoma progression is accompanied by dysbiosis with enriched pathobionts
Authors: Amr H. Masaadeh, Mohamed Eletrebi, Bishal Parajuli, Nicola De Jager, Dustin E. Bosch
Journal: Gut Microbes (2025)

Dysbiosis and pathobionts contribute to inflammation and the risk of colitis-associated carcinoma (CAC) in animal models, but their roles in humans with this uncommon disease are unknown. We identified microbiome differences in human CAC compared with longstanding inflammatory bowel disease (IBD) and sporadic colorectal carcinoma (CRC). Twenty-four CAC resections were matched with CRC and IBD controls. Methods included histopathology, 16S rDNA metagenomics, and pathobiont-specific qPCR. Beta diversity differed by diagnosis (PERMANOVA p = 0.007). The distinguishing taxa included Akkermansia enriched in CRC, and Bacteroides spp. enriched in IBD. The non-neoplastic mucosae presented distinct beta diversity (p = 0.005), but the CAC/CRC tumor microbiomes were similar (p = 0.7). Within metastases and margins, Enterobacteriaceae were enriched in CAC, and Bacteroidales in CRC. Pathobiont-specific qPCR confirmed a greater frequency of pks+ E. coli and enterotoxigenic Bacteroides fragilis in CAC than IBD. High alpha diversity was associated with active inflammation, advanced cancer stage, and shorter overall survival (log-rank p = 0.008). Mucosal microbiomes distinguish CAC from longstanding IBD, implicating pathobionts as markers for disease progression. Integrating our findings with prior animal model research, pathobionts promote carcinogenesis in IBD patients through genotoxicity and host cell signaling.
Waldenström Macroglobulinemia: 2025 Update on Diagnosis, Risk Stratification, and Management
Authors: Morie A. Gertz
Journal: American Journal of Hematology (2025)

ABSTRACT Disease Overview Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and rarely hyperviscosity. Diagnosis The presence of IgM monoclonal protein associated with ≥ 10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. The L265P mutation in MYD88 is detectable in more than 90% of patients and is found in most IgM MGUS patients. MYD88 is not required for the diagnosis. Risk Stratification Age, albumin, hemoglobin level, platelet count, β 2 microglobulin, Lactate dehydrogenase (LDH), and monoclonal IgM concentrations are characteristics that are predictive of outcomes. Risk‐Adapted Therapy Not all patients who fulfill WM criteria require therapy; these patients can be observed until symptoms develop. Rituximab‐monotherapy is inferior to combination regimens. Recommended first‐line therapy can be chemoimmunotherapy or a covalent Bruton tyrosine kinase inhibitor. The preferred Mayo Clinic induction is either rituximab and bendamustine (without rituximab maintenance) or zanubrutinib. Management of Refractory Disease Bortezomib, cyclophosphamide, fludarabine, thalidomide, everolimus, pirtobrutinib, carfilzomib, lenalidomide, bendamustine, and venetoclax have all been shown to have activity in relapsed WM. Given WM's natural history, the reduction of therapy toxicity is an important part of treatment selection. Most patients succumb to causes unrelated to macroglobulinemia.
Biofunctionalization of ADA‐GEL Hydrogels Based on the Degree of Cross‐Linking and Polymer Concentration Improves Angiogenesis
Authors: Stefanie Heltmann‐Meyer, Rainer Detsch, Jonas Hazur, Lasse Kling, Sabrina Pechmann, Rajkumar Reddy Kolan, Justus Osterloh, Aldo R. Boccaccini, Silke Christiansen, Carol I. Geppert, Andreas Arkudas, Raymund E. Horch, Dominik Steiner
Journal: Advanced Healthcare Materials (2025)

Abstract The creation of bioartificial tissues is a promising option for the reconstruction of large‐volume defects. The vascularization of tissue engineering constructs, as well as the material properties of the carrier matrix, are important factors for successful clinical application. In this regard, hydrogels are promising biomaterials, providing an extracellular matrix‐like milieu that enables the possibility of cell transplantation and de novo tissue formation. Furthermore, biofunctionalization allows for a certain fine‐tuning of angiogenic properties. This study aims to investigate vascularization and tissue formation of highly cross‐linked alginate dialdehyde (ADA) and gelatin (GEL). This highly cross‐linked network is created using a dural cross‐linking mechanism combining ionic (Ca 2+ ions) and enzymatic (human transglutaminase (hTG)) cross‐linking, resulting in reduced swelling and moderate degradation rates. Vascularization of the ADA‐GEL‐hTG constructs is induced surgically using arteriovenous (AV) loops. Biocompatibility, tissue formation, and vascularization are analyzed by histology and X‐ray microscopy. After only 2 weeks, vascularization of the ADA‐GEL‐hTG constructs is already present. After 4 weeks, both de novo tissue formation and vascularization of the ADA‐GEL‐hTG matrix increase. In conclusion, ADA‐GEL‐hTG‐based hydrogels are shown to be promising scaffold materials for tissue engineering applications.
Exploring and mitigating shortcomings in single-cell differential expression analysis with a new statistical paradigm
Authors: Chih-Hsuan Wu, Xiang Zhou, Mengjie Chen
Journal: Genome biology (2025)

Differential expression analysis is pivotal in single-cell transcriptomics for unraveling cell-type–specific responses to stimuli. While numerous methods are available to identify differentially expressed genes in single-cell data, recent evaluations of both single-cell–specific methods and methods adapted from bulk studies have revealed significant shortcomings in performance. In this paper, we dissect the four major challenges in single-cell differential expression analysis: excessive zeros, normalization, donor effects, and cumulative biases. These "curses" underscore the limitations and conceptual pitfalls in existing workflows. To address the limitations of current single-cell differential expression analysis methods, we propose GLIMES, a statistical framework that leverages UMI counts and zero proportions within a generalized Poisson/Binomial mixed-effects model to account for batch effects and within-sample variation. We rigorously benchmarked GLIMES against six existing differential expression methods using three case studies and simulations across different experimental scenarios, including comparisons across cell types, tissue regions, and cell states. Our results demonstrate that GLIMES is more adaptable to diverse experimental designs in single-cell studies and effectively mitigates key shortcomings of current approaches, particularly those related to normalization procedures. By preserving biologically meaningful signals, GLIMES offers improved performance in detecting differentially expressed genes. By using absolute RNA expression rather than relative abundance, GLIMES improves sensitivity, reduces false discoveries, and enhances biological interpretability. This paradigm shift challenges existing workflows and highlights the need for careful consideration of normalization strategies, ultimately paving the way for more accurate and robust single-cell transcriptomic analyses.