tbuckley/cabot-search huggingface dataset:
Overall Survival Analysis of the Phase III CodeBreaK 300 Study of Sotorasib Plus Panitumumab Versus Investigator's Choice in Chemorefractory <i>KRAS</i> G12C Colorectal Cancer
Authors: Filippo Pietrantonio, Lisa Salvatore, Taito Esaki, Dominik Paul Modest, David Paez Lopez-Bravo, Julien Taieb, Michalis V. Karamouzis, Erika Ruiz-Garcia, Tae Won Kim, Yasutoshi Kuboki, Fausto Meriggi, David Cunningham, Kun-Huei Yeh, Emily Chan, Joseph Chao, Qui Tran, Chiara Cremolini, Marwan Fakih
Journal: Journal of Clinical Oncology (2025)

In the phase III CodeBreaK 300 study, sotorasib 960 mg-panitumumab significantly prolonged progression-free survival (PFS) versus investigator's choice (trifluridine/tipiracil or regorafenib) in patients with KRAS G12C-mutated chemorefractory metastatic colorectal cancer (mCRC). One hundred sixty patients were randomly assigned 1:1:1 to receive sotorasib 960 mg-panitumumab (n = 53), sotorasib 240 mg-panitumumab (n = 53), or investigator's choice (n = 54; crossover permitted after primary analysis). Overall survival (OS) analysis, a key secondary end point, although not adequately powered, was prespecified at 50% maturity (after approximately 80 deaths). In this study, we report the OS, updated overall response rates (ORRs), and data for safety. After a median follow-up of 13.6 months, 24, 28, and 30 deaths occurred in the sotorasib 960 mg-panitumumab, sotorasib 240 mg-panitumumab, and investigator's choice arms, respectively; updated objective response rates (ORRs; 95% CI) were 30.2% (95% CI, 18.3 to 44.3), 7.5% (95% CI, 2.1 to 18.2), and 1.9% (95% CI, 0.0 to 9.9), respectively. Compared with investigator's choice, the hazard ratios (HRs [95% CI]) for OS were 0.70 (95% CI, 0.41 to 1.18; two-sided P = .20) with sotorasib 960 mg-panitumumab and 0.83 (95% CI, 0.49 to 1.39; two-sided P = .50) with sotorasib 240 mg-panitumumab. No new safety signals were observed. Although not statistically significant, the observed OS HR and ORR along with prior PFS and safety findings support sotorasib 960 mg-panitumumab as a standard of care in patients with chemorefractory KRAS G12C mCRC.
Erratum: Pertuzumab Retreatment for Human Epidermal Growth Factor Receptor 2–Positive Locally Advanced/Metastatic Breast Cancer (PRECIOUS Study): Final Overall Survival Analysis
Authors: Yutaka Yamamoto, Hiroji Iwata, Shigehira Saji, Masato Takahashi, Tetsuhiro Yoshinami, Takayuki Ueno, Tatsuya Toyama, Takashi Yamanaka, Toshimi Takano, Masahiro Kashiwaba, Koichiro Tsugawa, Yoshie Hasegawa, Kenji Tamura, Hiroshi Tada, Fumikata Hara, Tomomi Fujisawa, Naoki Niikura, Naruto Taira, Satoshi Morita, Masakazu Toi, Shinji Ohno, Norikazu Masuda
Journal: Journal of Clinical Oncology (2025)
Novel Postneoadjuvant Prognostic Breast Cancer Staging System
Authors: David J. Winchester, Lavisha Singh, Stephen B. Edge, Kimberly H. Allison, William E. Barlow, Veerle Bossuyt, Mariana Chavez-MacGregor, Emily F. Conant, James L. Connolly, Jennifer F. De Los Santos, Daniel F. Hayes, Nola M. Hylton, Elizabeth A. Mittendorf, Jennifer K. Plichta, Elena Provenzano, Kilian E. Salerno, Priyanka Sharma, W. Fraser Symmans, Donald Weaver, Gabriel N. Hortobagyi, David J. Winchester, Stephen B. Edge, Kimberly H. Allison, William E. Barlow, Veerle Bossuyt, Mariana Chavez-MacGregor, Emily F. Conant, James L. Connolly, Jennifer F. De Los Santos, Daniel F. Hayes, Nola M. Hylton, Elizabeth A. Mittendorf, Elena Provenzano, Kilian E. Salerno, Priyanka Sharma, W. Fraser Symmans, Donald Weaver, Gabriel N. Hortobagyi
Journal: Journal of Clinical Oncology (2025)

PURPOSE Prognostic staging after neoadjuvant chemotherapy (NACT) is not included in American Joint Commission on Cancer (AJCC) staging. This study addressed this deficiency by including responses to therapy with standardized staging variables in a validated prognostic staging system for patients treated with NACT. METHODS The National Cancer Database was queried to identify 140,605 patients treated with NACT between 2010 and 2018. Three response categories (no response, partial response, and complete response [pCR]) were created on the basis of comparison of clinical and post-NACT pathologic staging. Univariate and multivariate analyses of clinical stage, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2), and grade were analyzed for each category. Predictive models for each response category were validated using the bootstrap technique. Calibration plots compared predicted and observed 3-year survival probabilities in the training and validation data sets. RESULTS Each validated model demonstrated statistically significant survival differences in the postneoadjuvant prognostic stage assignment. Of all patients with a pCR, 94.2% were assigned to postneoadjuvant ypStage I compared with 35.5% of patients with no response. Advancing clinical stage had a progressive but small impact on overall survival (OS) with pCR (high-grade, triple-negative breast cancer [TNBC]: cStage I, 97% v cStage IIIB/IIIC, 91%; grade 2 luminal A: 97% v 91%) but was associated with a profound decrease in OS with no response for TNBC or HER2+ disease (high-grade TNBC 89% v 50%) and less profound for grade 2 luminal A disease with no response (97% v 81%). CONCLUSION We present a novel, validated prognostic staging system that predicts OS according to the response to NACT. These data will provide AJCC stage assignments for a growing proportion of patients treated with NACT.
Vision transformer based interpretable metabolic syndrome classification using retinal Images
Authors: Tae Kwan Lee, So Yeon Kim, Hyuk Jin Choi, Eun Kyung Choe, Kyung-Ah Sohn
Journal: npj Digital Medicine (2025)

Metabolic syndrome is leading to an increased risk of diabetes and cardiovascular disease. Our study developed a model using retinal image data from fundus photographs taken during comprehensive health check-ups to classify metabolic syndrome. The model achieved an AUC of 0.7752 (95% CI: 0.7719-0.7786) using retinal images, and an AUC of 0.8725 (95% CI: 0.8669-0.8781) when combining retinal images with basic clinical features. Furthermore, we propose a method to improve the interpretability of the relationship between retinal image features and metabolic syndrome by visualizing metabolic syndrome-related areas in retinal images. The results highlight the potential of retinal images in classifying metabolic syndrome.
Appendicectomy plus standard medical therapy versus standard medical therapy alone for maintenance of remission in ulcerative colitis (ACCURE): a pragmatic, open-label, international, randomised trial
Authors: Yair I Z Acherman, Naila Arebi, Elizabeth Arthurs, Willem A Bemelman, Jarmila D W van der Bilt, Henri Braat, Menno A Brink, Matthew Brookes, James P Y Brown, Steven R Brown, Christianne J Buskens, Esther C J Consten, Rachel Cooney, Rogier M P H Crolla, Richard Justin Davies, Annekatrien C T M Depla, Geert R D'Haens, Marcel G W Dijkgraaf, Glen Doherty, Peter van Duijvendijk, Marjolijn Duijvestein, Emma J Eshuis, Jonathan P Evans, Omar D Faiz, Steven Chung Ming Fong, Michael F Gerhards, Jennie Grainger, Caris E Grimes, Kelly Handley, Lianne Heuthorst, Roel Hompes, Tariq H Iqbal, Jeroen Jansen, Manjinder Kaur, Laura Magill, Rosalie C Mallant-Hent, Guido H H Mannaerts, Gordon Moran, Gary A Nicholson, Shri Pathmakanthan, Engelbertus Gerardus Johannes Maria Pierik, Thomas D Pinkney, Cyriel Y Ponsioen, Tim Raine, Ian Reilly, Saloomeh Sahami, John Paul Seenan, Tom C J Seerden, Jamshed Shabbir, Simon M Shaw, Baljit Singh, Merle Elisabeth Stellingwerf, Pieter Cornelis Frans Stokkers, Eva Visser, Malaika Sanne Vlug, Bart C Vrouenraets, Rachel West, Jimme K Wiggers, Manon E Wildenberg, Des Winter, Nuha A Yassin, Esmerij Patronella Maria van der Zanden
Journal: The Lancet. Gastroenterology & hepatology (2025)
Engineering IgG antibodies for intracellular targeting and drug delivery
Authors: Dae-Seong Kim, Seung-Eun Kim, Jeong-Seon Byeon, Hyun-Jin Lee, Ji-Won Kim, Haelyn Kim, Byeong-Ho Chae, Deok-Han Ko, Seul-Gi Lee, Sang-Rok Yoon, Juyong Lee, Jeong-Sun Kim, Yong-Sung Kim
Journal: Journal of Controlled Release (2025)
Genetic risk for open angle glaucoma subtypes is associated with specific visual field defect classes
Authors: Sayuri Sekimitsu, Kavin Selvan, Yan Zhao, Saber Kazeminasab Hashemabad, Mohammad Eslami, Mengyu Wang, Tobias Elze, Ayellet V Segrè, Joni A Tururen, Aarno Palotie, Joel Rämō, Janey L Wiggs, Louis Pasquale, Jae H Kang, Nazlee Zebardast
Journal: Ophthalmology (2025)
Delayed correct diagnoses in emerging disease outbreaks: Historical patterns and lessons for contemporary responses
Authors: Galadriel Pellejero-Sagastizábal, Casandra Bulescu, Nitin Gupta, Pikka Jokelainen, Effrossyni Gkrania-Klotsas, Aleksandra Barac, Abraham Goorhuis, Shevin T Jacob, Selidji T Agnandji, Francine Ntoumi, Marta Mora-Rillo, José Ramón Paño-Pardo, F-Xavier Lescure, Martin P Grobusch
Journal: Clinical Microbiology and Infection (2025)
Foxo1 regulates intestinal tissue–resident memory CD8 T cell biology in an anatomic compartment– and context-specific manner
Authors: Paul Hsu, Eunice J. Choi, William H. Wong, Yun Hsuan Lin, Sara A. Vandenburgh, Yi Chia Liu, Priscilla Yao, Cynthia S. Indralingam, Gene W. Yeo, Elina I. Zuniga, Ananda W. Goldrath, Wei Wang, John T. Chang
Journal: Science Immunology (2025)

Tissue-resident memory CD8 T (T RM ) cells serve as a front-line defense against microbial pathogens in barrier and mucosal tissues. Accurately predicting the roles of tissue-specific transcription factors (TFs) that regulate T RM biology remains a challenge. Here, by applying integrated transcriptomic and epigenomic analyses, we have identified an unexpected role for forkhead box O1 (Foxo1), a TF previously known to regulate circulating memory T cells, in intestinal T RM biology. Foxo1 repressed the maintenance of early small intestinal intraepithelial T RM cells in contrast with its actions in sustaining T RM cells from small intestinal lamina propria and colon and contrary to its broader role in promoting intestinal T RM cell formation. These findings highlight the emerging concept that the transcriptional regulation of T RM cells may be more complex and nuanced than previously appreciated and underscore the utility of integrated transcriptomic and epigenomic analyses in reconstructing TF-regulatory networks.
Bcl11a maintains hematopoietic stem cell function but accelerates inflammation-driven exhaustion during aging
Authors: Jing Wang, Linlin Zhang, Xinyu Cui, Xiang Xu, Rui Guo, Kairui Li, Li Zhang, Bing Xu, Cizhong Jiang, Yong Yu
Journal: Science Immunology (2025)

Preserving hematopoietic stem cell (HSC) functionality is essential for maintaining healthy blood and the immune system throughout life. HSC function declines with age; however, the underlying mechanisms are not fully understood. Using an inducible mosaic mouse model to overexpress the transcription factor Bcl11a in the hematopoietic compartment, we found that an aging-related increase in Bcl11a mitigated HSC functional decline, promoted IL-1β production in the bone marrow (BM), and accelerated HSC attrition in a non–cell-autonomous manner. Aging-related inflammation in the BM enhanced Bcl11a and Fc receptor (FcR) expression in HSCs, and FcR signaling induced HSC differentiation. This was counteracted by Bcl11a through repression of Fcer1g . Bcl11a up-regulation promoted IL-1β production in BM myeloid cells, driving inflammation and HSC deterioration. Deletion of Fcer1g , or blocking IL-1β signaling, eliminated this non–cell-autonomous effect on HSC decline. These findings demonstrate that Bcl11a plays a dual role in HSCs during aging not only by cell-intrinsically preserving HSC function but also by promoting BM inflammation and HSC dysfunction.
Psychological stress increases skin infection through the action of TGFβ to suppress immune-acting fibroblasts
Authors: Hung Chan, Fengwu Li, Tatsuya Dokoshi, Kellen J. Cavagnero, Qing Li, Yang Chen, Carlos Aguilera, Teruaki Nakatsuji, Edward Liu, Aaryan Indra, Daping Yang, Ottaviani Valentina, Tomofumi Numata, Brittany Crown, Henry Li, Kevin J. Williams, Isaac M. Chiu, Steven J. Bensinger, WanJun Chen, Richard L. Gallo
Journal: Science Immunology (2025)

Infections after psychological stress are a major health care problem. Single-cell transcriptomics and lipidomic profiling in a mouse model of stress show that dermal fibroblasts undergoing adipogenesis have defective responses to Staphylococcus aureus skin infection. Adrenalectomy or adrenergic inhibition restores the fibroblast adipogenic response to S. aureus and enables mice to effectively resist infection during stress. Increased susceptibility to S. aureus from stress is attributed to suppression of the antimicrobial peptide cathelicidin ( Camp ) because adrenaline directly inhibits Camp production by fibroblasts, and mice lacking Camp in fibroblasts do not increase infection after stress. Transforming growth factor β (TGFβ) is induced by stress and adrenergic signaling, and inhibition of TGFβ or deletion of the TGFβ receptor on fibroblasts increases Camp expression and restores protection against infection. Together, these data show that stress initiates a brain-skin axis mediated by TGFβ that impairs the immune defense function of dermal fibroblasts to produce the Camp antimicrobial peptide.
Spatiotemporal transcriptomics reveals key gene regulation for grain yield and quality in wheat
Authors: Xiaohui Li, Yiman Wan, Dongzhi Wang, Xingguo Li, Jiajie Wu, Jun Xiao, Kunming Chen, Xue Han, Yuan Chen
Journal: Genome biology (2025)

Cereal grain size and quality are critical agronomic traits in crop production. Wheat grain development is governed by intricate regulatory networks that require precise spatiotemporal coordination of gene expression to establish functional compartments in different cell types. Here, we perform a spatial transcriptomics study covering the early stages of wheat grain development, from 4 to 12 days after pollination. We classify the grain into 10 distinct cell types and identify 192 marker genes associated with them. WGCNA analysis reveals that highly expressed genes in different cell types exhibit distinct enrichment patterns, significantly influencing grain development and filling. Through co-expression and motif analyses, we identify a specific group of genes that may regulate wheat grain development, including TaABI3-B1, a transcription factor specifically expressed in the embryo and surrounding endosperm, which negatively affects embryo and grain size. This study presents a comprehensive spatiotemporal transcriptional dataset for understanding wheat grain development. Additionally, it identifies key genetic resources with potential applications for improving wheat yield.
Health Worker Burnout and Moral Injury: Drivers, Effects, and Remedies
Authors: Kevin Grumbach, Rachel Willard-Grace
Journal: Annual Review of Public Health (2025)

The prevalence of burnout among health workers is alarmingly high and worsening. Many factors across the domains of culture of wellness, efficiency of practice and work demands, and personal resilience place workers at risk for burnout. Intervention research has disproportionately studied individually focused interventions to strengthen personal resilience, demonstrating small benefit from such interventions. While coping strategies may have value, we stress the need to focus interventions on mitigating work conditions that breed burnout, such as inadequate levels of staffing, and to rigorously evaluate such interventions. A conceptual framework on burnout must include critical theory interrogating the broader economic, political, and structural forces shaping health care and the relative power of workers. The concept of moral injury may be more apt than burnout for describing the effects on workers’ well-being of accelerating health care consolidation by investor-owned organizations, government austerity policies, and the disempowered position of labor.
Health Risks and Benefits of Fluoride Exposure During Pregnancy and Infancy
Authors: Christine Till, Philippe Grandjean, E. Angeles Martinez-Mier, Howard Hu, Bruce Lanphear
Journal: Annual Review of Public Health (2025)

Health authorities have promoted community water fluoridation (CWF) to prevent dental caries for more than 75 years. However, growing evidence has raised questions about the safety of this public health intervention, particularly for young children who are at risk of excess fluoride intake. Divergent opinions about the risk–benefit ratio of CWF have ignited a global debate. The efficacy of topical fluoride in preventing dental caries is strong, whereas contemporary evidence for systemic administration of fluoride is weaker. Inequalities in access to dental care and topical fluorides introduce an additional layer of complexity. This review discusses evidence showing that fluoride ingestion is not essential for caries prevention, offers little benefit to the fetus and young infant, and can cause dental fluorosis and cognitive deficits. In an environment where fluoride is available from multiple sources, community-based administration of systemic fluoride may pose an unfavorable risk–benefit ratio for pregnant women and young children.
Long-Term Care Services and Supports Needed for Successful Aging-in-Place: A Critical Review
Authors: Katherine E.M. Miller, Chase Mulholland Green, Abigail Fassinger, Jennifer L. Wolff
Journal: Annual Review of Public Health (2025)

We summarize the state of the evidence on the long-term services and supports infrastructure to support aging-in-place. We find an extensive literature describing the importance of affordable medical and social services delivered in the home, support for family caregivers, and the role of technology for improving communication among patients, caregivers, and health care teams to support aging-in-place. We identify gaps in access to affordable services and an inadequate workforce prepared to support aging-in-place, raising concerns about meeting the future needs of our aging population. Interventions have been directed primarily at the individual level rather than at the system or policy level. Those systems-level interventions that do exist have been primarily within the health care sector: Little attention has been directed at developing holistic interventions that address multiple sectors, which reflects the lack of a cohesive public health delivery system for long-term services and supports nationally. Our findings collectively highlight the multifaceted nature of supports to enable aging-in-place and the necessity for future research to focus on drawing connections across domains of health services infrastructure.
Facing Challenges for Reducing Weight Stigma in Public Health Policy and Practice
Authors: Rebecca M. Puhl
Journal: Annual Review of Public Health (2025)

The prevalence and harms of societal weight stigma have increased attention to its presence in public health approaches and communication. Calls to action from scholars, advocates, and health professionals emphasize the need to address weight stigma as a social justice issue and eliminate harmful narratives that perpetuate weight bias and discrimination in public health messages, practices, and policies. However, debates surrounding issues of weight stigma in public health complicate, and at times impair, efforts to effectively address this problem. Different (and sometimes opposing) perspectives include views about the health risks versus stigma effects of high body weight, the use of body mass index (BMI) as a metric of health, weight-normative (i.e., weight-centric) versus weight-inclusive treatment approaches, stigmatizing language used to describe body weight, and potential challenges when framing obesity as a disease. This review summarizes the current evidence, debates, and best practices related to weight stigma in public health efforts.
Aberrant CircTMEM45A Facilitates Inflammatory Progression of Esophageal Squamous Cell Carcinoma through m5C-Mediated NLRP3 Activation
Authors: Lingjiao Meng, Haotian Wu, Jiaxiang Wu, Ping'an Ding, Jinchen He, Tongkun Li, Xiaoman Niu, Meixiang Sang, Lihua Liu
Journal: Cancer Research (2025)

Abstract The lack of diagnostic and therapeutic targets precludes effective treatment of esophageal cancer, rooted in the limited mechanistic understanding of cancer initiation and progression. Non-mutational epigenetic reprogramming, including altered 5-methylcytosine (m5C) modification and circular RNA (circRNA) expression, can drive tumorigenesis and impact cancer biology. Herein, we identified upregulation of the circRNA hsa_circ_0066658 (termed as circTMEM45A) in esophageal squamous cell carcinoma (ESCC) tissues, which was correlated with advanced clinical stages and poor survival. Functionally, elevated circTMEM45A facilitated ESCC malignant progression both in vitro and in vivo. Mechanistically, circTMEM45A interacted with the methyltransferase NSUN2 and m5C readers ALYREF and YBX1, promoting the nuclear export and stability of NLRP3 mRNA to activate the NLRP3/caspase 1/IL-1β inflammatory pathway. Additionally, circTMEM45A stabilized IL1B mRNA by binding to U2AF2 and stabilized IL1R1 mRNA by serving as a protein scaffold to enhance the IGF2BP2/HUR interaction, further activating the IL-1β/IL1R1 pro-inflammatory cascade in the tumor microenvironment. These findings reveal crosstalk between circRNA and m5C modification that drives inflammatory progression, highlighting circTMEM45A as a potential diagnostic and therapeutic target in ESCC.
Dissecting FAP+ Cell Diversity in Pancreatic Cancer Uncovers an Interferon-Response Subtype of Cancer-Associated Fibroblasts with Tumor-Restraining Properties
Authors: Joshua Cumming, Parniyan Maneshi, Mitesh Dongre, Tala Alsaed, Mohammad Javad Dehghan-Nayeri, Agnes Ling, Kristian Pietras, Cedric Patthey, Daniel Öhlund
Journal: Cancer Research (2025)

Abstract Within the stroma of pancreatic ductal adenocarcinoma (PDAC), mesenchymal cells differentiate into cancer-associated fibroblast (CAF) subtypes that differentially mediate disease progression. Defining the regulatory mechanism and diversity of CAF subtypes could identify potential therapeutic strategies to harness the tumor suppressive activities of CAFs. To address this, we utilized single-cell RNA sequencing to profile fibroblast activation protein-alpha (FAP) expressing mesenchymal cells in human PDAC. The mesenchymal subpopulations in PDAC reflected mesenchymal cell heterogeneity found in the normal developing pancreas. In addition to characterizing inflammatory CAF (iCAF) and myofibroblastic CAF (myCAF) subpopulations in detail, the analysis uncovered a previously undescribed interferon-response CAF (ifCAF) subtype. Tumor-derived signals induced specific CAF subtypes from pancreatic stellate cells (PSCs) in an organoid-based co-culture model, and time-course experiments revealed regulatory mechanisms that govern subtype formation. STING agonists promoted an ifCAF phenotype in vivo and in vitro. Importantly, induction of an ifCAF phenotype suppressed tumor cell invasiveness and induced an anti-tumor phenotype in tumor-associated neutrophils. Together, this study resolves FAP+ stromal cell heterogeneity in PDAC and identifies an ifCAF subtype that can be induced to suppress pro-tumorigenic features of PDAC.
Integrating genomic and spatial analyses to describe tuberculosis transmission: a scoping review
Authors: Yu Lan, Isabel Rancu, Melanie H Chitwood, Benjamin Sobkowiak, Kate Nyhan, Hsien-Ho Lin, Chieh-Yin Wu, Barun Mathema, Tyler S Brown, Caroline Colijn, Joshua L Warren, Ted Cohen
Journal: The Lancet Microbe (2025)
Seltoplasmid promotes ulcer healing versus placebo for treating patients with chronic limb-threatening ischemia: HOPE CLTI-2 trial
Authors: Xiao Di, Changwei Liu, Siqiao Sun, Jinbao Qin, Xueli Guo, Yikuan Chen, Xin Li, Hongkun Zhang, Ming Liu, Liu Yang, Hui Zhao, Shaoying Lu, Jingyong Huang, Yunfeng Zhang, Jun Li, Xiaolei Lin, Kai Yao, Jingdong Tang, Jian Wang, Zhanfeng Gao, Jinjun Wang, Xiaojin Huang, Songshan Xu, Yue Liu, Wei Han, Leng Ni, Wei Ye, Yuehong Zheng, Yuexin Chen, Bao Liu
Journal: Molecular Therapy (2025)