tbuckley/cabot-search huggingface dataset:
Evaluating the Effects of Neburon Exposure on Ovarian Folliculogenesis Using Zebrafish and Mouse Granulosa Cell Line
Authors: Chen Tang, Ying Zhang, Fucong Zhang, Yiwen Sun, Yue Zhu, Fanzheng Xue, Zhenhong Wang, You Wu, Jinpeng Ruan, Yiming Yue, Chunyan Yang, Wei Ge, Chengyong He, Zhenghong Zuo
Journal: Environmental Health Perspectives (2025)

Ovarian folliculogenesis is crucial for female reproduction. This can be disrupted by various factors, including pollutants with aryl hydrocarbon receptor (AHR) agonistic activity, but the underlying mechanisms remain unclear. Using the herbicide neburon, a moderate AHR agonist among current pesticides, we investigated its effects on ovarian folliculogenesis in zebrafish through life-cycle exposure at environmentally relevant concentrations to elucidate the associated mechanisms. Wild-type (WT) and three different genotypes of female zebrafish (amh+/-;bmpr2a+/+, amh+/+;bmpr2a+/-, amh+/-;bmpr2a+/-) were exposed to neburon for 150 days. Neburon and its metabolites in fish were quantified using LC-MS/MS. Ovarian pathology was assessed by H&E and TUNEL staining. The differentially expressed pathways were identified by transcriptome analysis, followed by validation using RT-qPCR, WB, IHC, and ELISA. Finally, AHR antagonist, ChIP-RT-qPCR, and other methods were used to further elucidate the mechanism in mouse granulosa cell line (KK1). After neburon exposure, only four metabolites of neburon were detected but not itself, and all these metabolites had AHR agonistic activity, indicating the persistent toxicity of neburon. Neburon exposure altered follicle-stage distribution and poorer oocyte quality in WT zebrafish. Further experiments found that neburon exposure induced greater secretion of anti-Mullerian hormone (Amh), greater expression of genes in the Amh/Bmpr2a pathway, accelerated follicular development, and lower expression of insulin-like growth factors, which was associated with oocyte atresia. Notably, amh+/-;bmpr2a+/- zebrafish showed a rescued phenotype with regard to these neburon-associated outcomes. Moreover, AHR exhibited specific binding to the Amh promoter in KK1 cells, and neburon treatment enhanced their interaction. In zebrafish, AMH was identified as a critical target for reproductive disorders following neburon exposure. Despite the short half-lives of currently used pesticides, their metabolites might still have significant toxicological risks. This study provides a novel insight into how one AHR agonistic pollutant affects female zebrafish reproduction. https://doi.org/10.1289/EHP15372.
Efficacy and safety of azacitidine for VEXAS syndrome: a large-scale retrospective study from the FRENVEX group
Authors: Vincent Jachiet, Olivier Kosmider, Maxime Beydon, Jerome Hadjadj, Lin-Pierre Zhao, Vincent Grobost, Valentin Lacombe, Guillaume Le Guenno, Yann Nguyen, Jean Benoit Arlet, Jeremie Dion, Mael Heiblig, Alice Garnier, Maxime Samson, Achille Aouba, Sylvain Thepot, Sophie Dimicoli-Salazar, Fabien Dutasta, Benoit Faucher, Estibaliz Lazaro, Veronique Morel, Antoine Neel, Roderau Outh, Holy Bezanahary, Julien Rossignol, Anne-Sophie Alary, Audrey Bidet, Pauline Blateau, Anne Bouvier, Guilaine Boursier, Matthieu Decamp, Benjamin Lebecque, Yannick Le Bris, Pierre Sujobert, Alice Marceau-Renaut, Cedric Pastoret, David Rizzo, Nathalie Boiret-Dupré, Lara Boucher, Stéphanie Dulucq, Franck Genevieve, Cassandra Jadeau, Pierre Lemaire, Romain Vazquez, Jean Baptiste Rieu, Olivier Fain, Sophie Anne Georgin-Lavialle, Lucie Rigolot, Lise Larcher, Pierre Hirsch, Benjamin Terrier, Pierre Fenaux, Arsène M Mékinian, Thibault Comont
Journal: Blood (2025)
Platelet NLRP6 protects from microvascular thrombosis in sepsis
Authors: Huimin Jiang, Shuang Chen, Xiang Gui, Yingying Li, Yueyue Sun, Hui Zhu, Yue Dai, Jie Zhang, Xiaoqian Li, Wen Ju, Zhenyu Li, Lingyu Zeng, Kailin Xu, Jianlin Qiao
Journal: Blood (2025)
Social odor as a source of learning in human infants
Authors: Antonia Düfeld, Robin Nehler, Emma Peplies, Sarah Jessen
Journal: Trends in Cognitive Sciences (2025)

Maternal odor has recently emerged as an important but ill-understood factor in sociocognitive learning in early human development. We propose that social odor plays its unique role in the first year of life through dissociable affective and perceptual mechanisms. These mechanisms yield distinct predictions for future studies of social odor.
Synchrony and subjective experience: the neural correlates of the stream of consciousness
Authors: Matthew D Lieberman
Journal: Trends in Cognitive Sciences (2025)

Human subjectivity, our first-person conscious experience of the world, is among the deepest scientific mysteries. This opinion article lays out an approach to examining the neural correlates of subjectivity as it unfolds over time. Subjective experience is inherently idiosyncratic, arising from effortless interpretations that feel like perceived facts (p-interpretations), and integrative, with past and expected future moments influencing the current experience. Differential synchrony effects (i.e., neural synchrony that differs between groups) suggest that parts of gestalt cortex (inferior parietal lobule and posterior temporal cortex) and posterior medial cortex track p-interpretations. Differential synchrony may result from each person's preexisting idiosyncratic non-sensory representations (e.g., expectations, memories, motivations) being integrated with sensory inputs to yield unique meaning-infused immediate experiences across the stream of consciousness.
Defective neutrophil clearance in JAK2V617F myeloproliferative neoplasms drives myelofibrosis via immune checkpoint CD24
Authors: Eman Khatib-Massalha, Christian Andrea Di Buduo, Agathe L Chédeville, Ya-Hsuan Ho, Yexuan Zhu, Elodie Grockowiak, Yuki Date, Lam Tan Khuat, Zijian Fang, Jose Quesada-Salas, Eva Carrillo Félez, Matteo Migliavacca, Isabel Montero, José Antonio Pérez-Simón, Alessandra Balduini, Simón Méndez-Ferrer
Journal: Blood (2025)

Myeloproliferative neoplasms (MPNs) are hematopoietic stem cell-driven malignancies marked by excessive myelopoiesis and high risk of myelofibrosis, which remains therapeutically challenging. Senescent neutrophils home daily to the bone marrow (BM) to be cleared by macrophages. This avoids their accumulation, which can increase the risk of chronic inflammation or oncogenesis. Neutrophils carrying the most common oncogenic MPN driver (JAK2V617F) are protected from apoptosis, which may prolong their lifespan and enhance their pro-inflammatory activity. On the other hand, abnormal interactions of neutrophils with megakaryocytes ("emperipolesis") have been associated with BM fibrosis in disparate hematological disorders, including MPN and grey platelet syndrome; however, the underlying pathophysiology remains unclear. We investigated neutrophil homeostasis and cellular interactions in MPN. We found that senescent neutrophils evade homeostatic clearance and accumulate in JAK2V617F MPN, but not in MPN caused by the second most prevalent mutations affecting Calreticulin (CALR) gene. This is explained by GM-CSF-JAK2-STAT5-dependent upregulation of the "don't-eat-me" signal CD24 in neutrophils. Mechanistically, JAK2V617F CD24hi neutrophils evade efferocytosis, invade megakaryocytes and increase active TGF-b. Collectively, JAK2V617F neutrophil-megakaryocyte interactions promote platelet production in a humanized bioreactor and myelofibrosis in mouse models. Notably, chronic antibody blockade or genetic loss of CD24 restores clearance of senescent neutrophils, reduces emperipolesis and active TGF-b. Consequently, CD24 blockade improves thrombocytosis and prevents myelofibrosis in MPN mice. Taken together, these findings reveals defective neutrophil clearance as a cause of pathogenic microenvironmental interactions of inflammatory neutrophils with megakaryocytes, associated with myelofibrosis in MPN. Our study postulate CD24 as a candidate innate immune checkpoint in MPN.
How do we avoid over-treating skin cancer in people with severe frailty and limited life expectancy?
Authors: James B Powell, Jugdeep K Dhesi, Catherine A Harwood, Emily J McGrath, Zoe C Venables, Ser-Ling Chua, Stephen G Keohane, Raj Mallipeddi, Jerry R Marsden, Rubeta N Matin, Ashish Sharma, M Firouz Mohd Mustapa, Ser-Ling Chua, Andrew J Birnie, Cristina Bordea, Jonathan Botting, Peter G Budny, Seau T Cheung, Clare Connop, David A R de Berker, Olivia M Dolan, Louise Fearfield, Kate Fife, Girish Gupta, Catherine A Harwood, Susannah Hoey, Stephen G Keohane, John T Lear, Raj Mallipeddi, Jerry R Marsden, Rubeta N Matin, Emily J McGrath, Colin A Morton, Richard J Motley, Carrie Newlands, Jodie Newman, Agata Rembielak, Ashish Sharma, Neil Shroff, Neil M Steven, Lesley S Exton, Soha Seddk Tawfik, M Firouz Mohd Mustapa
Journal: British Journal of Dermatology (2025)

The British Association of Dermatologists and British Geriatrics Society recommend routine screening for frailty for all patients aged ≥65 years being considered for surgical management of skin cancer using a validated tool such as the Rockwood Clinical Frailty Scale (CFS).
Genomic instability, DNA damage response and telomere homeostasis in pancreatic cancer
Authors: Saba Selvi, Carmen Macías Real, Manuel Gentiluomo, Katerina Balounova, Klara Vokacova, Andrea Cumova, Beatrice Mohlenikova-Duchonova, Cosmeri Rizzato, Erika Halasova, Ludmila Vodickova, Bozena Smolkova, Kari Hemminki, Daniele Campa, Pavel Vodicka
Journal: Seminars in Cancer Biology (2025)
Sensitivity to immune checkpoint inhibitors in BRAF/MEK inhibitor refractory melanoma
Authors: Riyaben P Patel, Lydia Rui Jia Lim, Reem Saleh, Darius Schenk, Michael K Lee, Emily Lelliott, Aparna D Rao, Shaghayegh Arabi, Lorey Smith, Anna S Trigos, Nicole Haynes, Grant A McArthur, Karen E Sheppard
Journal: Journal for ImmunoTherapy of Cancer (2025)

Resistance to BRAF and MEK inhibitors (BRAFi/MEKi) in metastatic melanoma frequently results in cross-resistance to immune checkpoint inhibitors (ICI), limiting effective treatment options. However, a subset of BRAFi/MEKi-resistant patients remains responsive to second-line ICI, suggesting heterogeneous underlying resistance mechanisms. This study aimed to explore the tumor immune microenvironment in BRAFi/MEKi-resistant melanoma to uncover factors influencing sensitivity to second-line ICI therapy. To investigate mechanisms underlying resistance and responsiveness to second-line ICIs, BRAFi/MEKi-resistant melanoma mouse models were used. Flow cytometry was employed to analyze immune cell populations within the tumor microenvironment, focusing on changes in CD8+T effector cells and other key immune subsets. RNA sequencing was performed to profile transcriptomic changes in resistant tumors, providing insights into the signaling pathways associated with resistance. Clinical samples from BRAFi/MEKi-resistant patients were further evaluated for correlations between immune profiles and key signaling pathways to support findings from the preclinical models. Using BRAFi/MEKi-resistant melanoma mouse models, we observed distinct alterations in the tumor-immune microenvironment. Tumors exhibiting resistance showed a significant increase in CD8+T effector cells following BRAFi/MEKi treatment, suggesting an immune-stimulatory response. Mechanistic analysis identified the activation of the EGFR-STAT signaling pathway as a key driver of intrinsic resistance in these models. Notably, these tumors retained sensitivity to second-line ICI therapy, contrasting with NRAS-driven BRAFi/MEKi-resistant tumors, which demonstrated cross-resistance to ICIs. Supporting these findings, clinical samples from BRAFi/MEKi-resistant patients revealed a correlation between elevated EGFR activation and higher immune scores, indicating potential sensitivity to ICI therapy in this subset of patients. EGFR overexpression emerges as a potential predictive biomarker for responsiveness to second-line ICIs in BRAFi/MEKi-resistant melanoma. These findings underscore the need for stratified therapeutic approaches and highlight EGFR as a target for improving outcomes in ICI therapy.
Patient-Specific In Vivo Gene Editing to Treat a Rare Genetic Disease
Authors: Kiran Musunuru, Sarah A. Grandinette, Xiao Wang, Taylor R. Hudson, Kevin Briseno, Anne Marie Berry, Julia L. Hacker, Alvin Hsu, Rachel A. Silverstein, Logan T. Hille, Aysel N. Ogul, Nancy A. Robinson-Garvin, Juliana C. Small, Sarah McCague, Samantha M. Burke, Christina M. Wright, Sarah Bick, Venkata Indurthi, Shweta Sharma, Michael Jepperson, Christopher A. Vakulskas, Michael Collingwood, Katie Keogh, Ashley Jacobi, Morgan Sturgeon, Christian Brommel, Ellen Schmaljohn, Gavin Kurgan, Thomas Osborne, He Zhang, Kyle Kinney, Garrett Rettig, Christopher J. Barbosa, Sean C. Semple, Ying K. Tam, Cathleen Lutz, Lindsey A. George, Benjamin P. Kleinstiver, David R. Liu, Kim Ng, Sadik H. Kassim, Petros Giannikopoulos, Mohamad-Gabriel Alameh, Fyodor D. Urnov, Rebecca C. Ahrens-Nicklas
Journal: New England Journal of Medicine (2025)

Base editors can correct disease-causing genetic variants. After a neonate had received a diagnosis of severe carbamoyl-phosphate synthetase 1 deficiency, a disease with an estimated 50% mortality in early infancy, we immediately began to develop a customized lipid nanoparticle-delivered base-editing therapy. After regulatory approval had been obtained for the therapy, the patient received two infusions at approximately 7 and 8 months of age. In the 7 weeks after the initial infusion, the patient was able to receive an increased amount of dietary protein and a reduced dose of a nitrogen-scavenger medication to half the starting dose, without unacceptable adverse events and despite viral illnesses. No serious adverse events occurred. Longer follow-up is warranted to assess safety and efficacy. (Funded by the National Institutes of Health and others.).
ECM1 protects against liver steatosis through PCBP1-mediated iron homeostasis
Authors: Danyan Zhang, Ayiguzhali Abulitipu, Pengcheng Pang, Lei Bai, Lian Liu, Shaliyan Tuerxunmaimaiti, Wen Chen, Shuangfeng Chen, Houkun Lv, Yadong Fu, Qizhen Du, Fuquan Jin, Chunyan Yi, Yangmin Hao, Liyan Ma, Jinsong Li, Zhiyang Ling, Yaguang Zhang, Liang Zhao, Weiguo Fan, Guoli Du, Bing Sun
Journal: Hepatology (2025)

Background and Aims: Extracellular matrix protein 1 (ECM1) is known to inhibit transforming growth factor β (TGF-β) signalling and hepatic stellate cells (HSCs) activation, thereby attenuating liver fibrosis. RNA-seq profiling of livers from wild-type (WT) and Ecm1-deficient mice revealed different enrichments in metabolic changes in fatty acid synthesis and inflammatory pathways, suggesting a regulatory role for ECM1 in liver steatosis. Here, we studied the role of ECM1 in metabolic dysfunction-associated steatotic liver disease (MASLD) pathogenesis and underlying mechanisms. Approach and Results: Hepatic ECM1 expression was evaluated and found to be significantly reduced in liver samples from patients with metabolic dysfunction-associated steatohepatitis (MASH), and in four established MASH mouse models (HFD, MCD, HFHC, and ob/ob -/- ). Although overexpression of ECM1 effectively blocked hepatic insulin resistance, steatosis, and inflammation, ECM1 ablation exacerbated diet-induced MASH progression. Mechanistically, ECM1 interacted with the K-Homology 3 (KH3) domain of poly rC binding protein 1 (PCBP1) to suppress iron overload, mitigating lipid peroxidation and consequently impeding metabolic dysfunction-associated steatohepatitis (MASH) advancement under metabolic stress. Re-expression of ECM1 and PCBP1 ameliorated liver disease progression. Conclusion: Our study reveals that ECM1 is a critical regulator in MASH, modulating lipid peroxidation by maintaining PCBP1-mediated intracellular iron homeostasis. Targeting ECM1 to restore PCBP1-dependent iron homeostasis may offer a novel therapeutic avenue for MASH.
Genetic variants predisposing to increased risk of kidney stone disease
Authors: Catherine E Lovegrove, Michelle Goldsworthy, Jeremy Haley, Diane Smelser, Caroline Gorvin, Fadil M Hannan, Anubha Mahajan, Mohnish Suri, Omid Sadeghi-Alavijeh, Shabbir H Moochhala, Daniel P Gale, David Carey, Michael V Holmes, Dominic Furniss, Rajesh V Thakker, Sarah A Howles
Journal: Journal of Clinical Investigation (2025)

Kidney stone disease (KSD) affects ~10% of adults, is heritable, and associated with mineral metabolic abnormalities. Genetic variants and pathways increasing KSD risk via calcium and phosphate homeostasis were ascertained using genome-wide association analyses, region-specific Mendelian randomization (MR), and genetic colocalization. Utility of pathway modulation was estimated via drug-target MR, and effects of variants on calcium-sensing receptor (CaSR)-signaling characterized. Seventy-nine independent KSD-associated genetic signals at 71 loci were identified. MR identified three loci affecting KSD risk via increased serum calcium or decreased serum phosphate concentrations (odds ratios for genomic regions=4.30, 11.42, and 13.83 per 1 standard deviation alteration; p<5.6x10-10). Colocalization analyses defined putative, non-coding KSD-causing variants estimated to account for 11-19% of KSD cases in proximity to diacylglycerol kinase delta (DGKD), a CaSR-signalling partner; solute carrier family 34 member 1 (SLC34A1), a renal sodium-phosphate transporter; and cytochrome P450 family 24 subfamily A member 1 (CYP24A1), which degrades 1,25-dihydroxyvitamin D. Drug- target MR indicated that reducing serum calcium by 0.08mmol/L via CASR, DGKD, or CYP24A1, or increasing serum phosphate by 0.16mmol/L via SLC34A1 may reduce KSD relative risk by up to 90%. Furthermore, reduced DGKδ expression and KSD-associated DGKD missense variants impaired CaSR-signal transduction in vitro, which was ameliorated by cinacalcet, a positive CaSR-allosteric modulator. DGKD-, SLC34A1-, and CYP24A1-associated variants linked to reduced CaSR-signal transduction, increased urinary phosphate excretion, and impaired 1,25-dihydroxyvitamin D inactivation, respectively, are common causes of KSD. Genotyping patients with KSD may facilitate personalised KSD-risk stratification and targeted pharmacomodulation of associated pathways to prevent KSD.
Chemical discovery of a novel MD2/ADAM17 dual-target inhibitor as a potential therapeutic candidate for saturated fatty acid-induced myocardial inflammatory injury
Authors: Xiao-Dan Zhang, Yun-Shan Zhong, Hao Yan, Le-Hao Jin, Jing Chen, Zhong-Xi Chen, Zhe-Yan Zhang, Yun-Jie Zhao, Jian-Chang Qian
Journal: Metabolism (2025)
Development of the Food Systems–related Greenhouse Gas Emissions Factor Database using the Korea National Health and Nutrition Examination Survey (2016-2018)
Authors: Jee Yeon Hong, Mi Kyung Kim
Journal: Environmental Health Perspectives (2025)

The increase in the frequency and scale of climate-related disasters is closely linked to greenhouse gas emissions (GHGEs) from food systems. Due to a lack of a comprehensive emission database that covers entire food systems, data on per-capita dietary GHGEs are limited. We created the Food Systems-related GHGE Factor Database (FS-GHGEF-D) to cover an entire food system and estimate per-capita GHGEs for Korea. We include GHGE factors for 3,894 food items derived from 24-hour-recall data of the seventh Korea National Health and Nutrition Examination Survey (2016-2018). We extracted these factors from 920 articles, excluding studies that focused only on specific GHG types or single system boundaries, and used a Monte Carlo Markov chain simulation to assess uncertainty of estimates. The FS-GHGEF-D covered 96.6% of food items. A total of 265 food items, primarily alcoholic and non-alcoholic beverages, were characterized by high degrees of uncertainty. However, removing these foods did not significantly alter the average GHGE factor across all food groups or affect coverage significantly, with the exception of the beverage category (both alcoholic and non-alcoholic). The average daily diet-related GHGEs per capita in Korea, as calculated using FS-GHGEF-D, was 5.08 kgCO2eq. Among food groups, meats contributed the most to the total variation in dietary GHGEs in the Korea population (75.7%). Men generally emitted more GHGEs than did women, with men in their 30s being the highest emitters. This study highlights the utility of a full-system GHGE database that addresses prior limitations in global estimates. Korean dietary patterns exceed climate-compatible thresholds, with substantial variation by demographic groups. These findings support the need for equity-focused strategies and integration of environmental considerations into national dietary guidelines for sustainable and climate-resilient food systems. https://doi.org/10.1289/EHP15534.
GDBIG: A Pioneering Birth Cohort Genomic Platform Facilitating Intergenerational Genetic Research
Authors: Shujia Huang, Chengrui Wang, Mingxi Huang, Jinhua Lu, Jian-Rong He, Shanshan Lin, Siyang Liu, Huimin Xia, Xiu Qiu
Journal: Genomics Proteomics & Bioinformatics (2025)

Abstract High-quality genome databases derived from large-scale, family-based birth cohorts are vital resources for investigating the genetic determinants of early-life traits and the impact of early-life environments on the health of both parents and offspring. Here, we established the genomic platform of the Born in Guangzhou Cohort Study (BIGCS), named the Genome Database of BIGCS (GDBIG), which represents the first birth cohort-based genomic database in China and is designed to facilitate intergenerational genetic research. Based on the phase I results of the BIGCS, GDBIG includes low-coverage (∼ 6.63×) whole genome sequencing (WGS) data and extensive pregnancy phenotypes from 4053 Chinese participants. These participants are from 30 of China’s 34 administrative divisions, encompassing Han and 12 minority ethnic groups. Currently, GDBIG provides a range of services, including allele frequency queries for 56.23 million variants across two generations, a genotype imputation server featuring a high-quality family-based reference panel, and a genome-wide association study (GWAS) meta-analysis interface for various maternal and infant phenotypes. The GDBIG database addresses the lack of Asian birth cohort-based genomic resources and provides a valuable platform for conducting genetic analysis, accessible online or via application programming interfaces (API) at http://gdbig.bigcs.com.cn/.
Disparities in Early Lecanemab Uptake Among US Medicare Beneficiaries
Authors: Frank F. Zhou, Utibe R. Essien, Jeffrey M. Souza, Catherine A. Sarkisian, Cheryl L. Damberg, Bruce E. Landon, John N. Mafi
Journal: JAMA Network Open (2025)

This cross-sectional study examines lecanemeb update among Medicare fee-for-service beneficiaries with Alzheimer disease or mild cognitive impairment and evaluates whether there are disparities among potentially eligible patients.