tbuckley/cabot-search huggingface dataset:
A spatiotemporal proteomic map of human adipogenesis
Authors: Felix Klingelhuber, Scott Frendo-Cumbo, Muhmmad Omar-Hmeadi, Lucas Massier, Pamela Kakimoto, Austin J. Taylor, Morgane Couchet, Sara Ribicic, Martin Wabitsch, Ana C. Messias, Arcangela Iuso, Timo D. Müller, Mikael Rydén, Niklas Mejhert, Natalie Krahmer
Journal: Nature Metabolism (2024)

White adipocytes function as major energy reservoirs in humans by storing substantial amounts of triglycerides, and their dysfunction is associated with metabolic disorders; however, the mechanisms underlying cellular specialization during adipogenesis remain unknown. Here, we generate a spatiotemporal proteomic atlas of human adipogenesis, which elucidates cellular remodelling as well as the spatial reorganization of metabolic pathways to optimize cells for lipid accumulation and highlights the coordinated regulation of protein localization and abundance during adipocyte formation. We identify compartment-specific regulation of protein levels and localization changes of metabolic enzymes to reprogramme branched-chain amino acids and one-carbon metabolism to provide building blocks and reduction equivalents. Additionally, we identify C19orf12 as a differentiation-induced adipocyte lipid droplet protein that interacts with the translocase of the outer membrane complex of lipid droplet-associated mitochondria and regulates adipocyte lipid storage by determining the capacity of mitochondria to metabolize fatty acids. Overall, our study provides a comprehensive resource for understanding human adipogenesis and for future discoveries in the field.
Quantifying possible bias in clinical and epidemiological studies with quantitative bias analysis: common approaches and limitations
Authors: Jeremy P Brown, Jacob N Hunnicutt, M Sanni Ali, Krishnan Bhaskaran, Ashley Cole, Sinead M Langan, Dorothea Nitsch, Christopher T Rentsch, Nicholas W Galwey, Kevin Wing, Ian J Douglas
Journal: BMJ (2024)

Bias in epidemiological studies can adversely affect the validity of study findings. Sensitivity analyses, known as quantitative bias analyses, are available to quantify potential residual bias arising from measurement error, confounding, and selection into the study. Effective application of these methods benefits from the input of multiple parties including clinicians, epidemiologists, and statisticians. This article provides an overview of a few common methods to facilitate both the use of these methods and critical interpretation of applications in the published literature. Examples are given to describe and illustrate methods of quantitative bias analysis. This article also outlines considerations to be made when choosing between methods and discusses the limitations of quantitative bias analysis.
Climbing fibers provide essential instructive signals for associative learning
Authors: N. Tatiana Silva, Jorge Ramírez-Buriticá, Dominique L. Pritchett, Megan R. Carey
Journal: Nature Neuroscience (2024)

Supervised learning depends on instructive signals that shape the output of neural circuits to support learned changes in behavior. Climbing fiber (CF) inputs to the cerebellar cortex represent one of the strongest candidates in the vertebrate brain for conveying neural instructive signals. However, recent studies have shown that Purkinje cell stimulation can also drive cerebellar learning and the relative importance of these two neuron types in providing instructive signals for cerebellum-dependent behaviors remains unresolved. In the present study we used cell-type-specific perturbations of various cerebellar circuit elements to systematically evaluate their contributions to delay eyeblink conditioning in mice. Our findings reveal that, although optogenetic stimulation of either CFs or Purkinje cells can drive learning under some conditions, even subtle reductions in CF signaling completely block learning to natural stimuli. We conclude that CFs and corresponding Purkinje cell complex spike events provide essential instructive signals for associative cerebellar learning.
Proteogenomic insights into early-onset endometrioid endometrial carcinoma: predictors for fertility-sparing therapy response
Authors: Zhe Hu, Zimeng Wu, Wei Liu, Yan Ning, Jingbo Liu, Wencheng Ding, Junpeng Fan, Shuyan Cai, Qinlan Li, Wenting Li, Xiaohang Yang, Yingyu Dou, Wei Wang, Wenju Peng, Funian Lu, Xucui Zhuang, Tianyu Qin, Xiaoyan Kang, Chenzhao Feng, Zhiying Xu, Qiaoying Lv, Qian Wang, Chao Wang, Xinyu Wang, Zhiqi Wang, Jianliu Wang, Jie Jiang, Beibei Wang, Gordon B. Mills, Ding Ma, Qinglei Gao, Kezhen Li, Gang Chen, Xiaojun Chen, Chaoyang Sun
Journal: Nature Genetics (2024)
Direct and selective pharmacological disruption of the YAP–TEAD interface by IAG933 inhibits Hippo-dependent and RAS–MAPK-altered cancers
Authors: Emilie A. Chapeau, Laurent Sansregret, Giorgio G. Galli, Patrick Chène, Markus Wartmann, Thanos P. Mourikis, Patricia Jaaks, Sabrina Baltschukat, Ines A. M. Barbosa, Daniel Bauer, Saskia M. Brachmann, Clara Delaunay, Claire Estadieu, Jason E. Faris, Pascal Furet, Stefanie Harlfinger, Andreas Hueber, Eloísa Jiménez Núñez, David P. Kodack, Emeline Mandon, Typhaine Martin, Yannick Mesrouze, Vincent Romanet, Clemens Scheufler, Holger Sellner, Christelle Stamm, Dario Sterker, Luca Tordella, Francesco Hofmann, Nicolas Soldermann, Tobias Schmelzle
Journal: Nature Cancer (2024)

The YAP-TEAD protein-protein interaction mediates YAP oncogenic functions downstream of the Hippo pathway. To date, available YAP-TEAD pharmacologic agents bind into the lipid pocket of TEAD, targeting the interaction indirectly via allosteric changes. However, the consequences of a direct pharmacological disruption of the interface between YAP and TEADs remain largely unexplored. Here, we present IAG933 and its analogs as potent first-in-class and selective disruptors of the YAP-TEAD protein-protein interaction with suitable properties to enter clinical trials. Pharmacologic abrogation of the interaction with all four TEAD paralogs resulted in YAP eviction from chromatin and reduced Hippo-mediated transcription and induction of cell death. In vivo, deep tumor regression was observed in Hippo-driven mesothelioma xenografts at tolerated doses in animal models as well as in Hippo-altered cancer models outside mesothelioma. Importantly this also extended to larger tumor indications, such as lung, pancreatic and colorectal cancer, in combination with RTK, KRAS-mutant selective and MAPK inhibitors, leading to more efficacious and durable responses. Clinical evaluation of IAG933 is underway.
Nanoparticles in tumor microenvironment remodeling and cancer immunotherapy
Authors: Qiang Lu, Dongquan Kou, Shenghan Lou, Milad Ashrafizadeh, Amir Reza Aref, Israel Canadas, Yu Tian, Xiaojia Niu, Yuzhuo Wang, Pedram Torabian, Lingzhi Wang, Gautam Sethi, Vinay Tergaonkar, Franklin Tay, Zhennan Yuan, Peng Han
Journal: Journal of Hematology & Oncology (2024)

Abstract Cancer immunotherapy and vaccine development have significantly improved the fight against cancers. Despite these advancements, challenges remain, particularly in the clinical delivery of immunomodulatory compounds. The tumor microenvironment (TME), comprising macrophages, fibroblasts, and immune cells, plays a crucial role in immune response modulation. Nanoparticles, engineered to reshape the TME, have shown promising results in enhancing immunotherapy by facilitating targeted delivery and immune modulation. These nanoparticles can suppress fibroblast activation, promote M1 macrophage polarization, aid dendritic cell maturation, and encourage T cell infiltration. Biomimetic nanoparticles further enhance immunotherapy by increasing the internalization of immunomodulatory agents in immune cells such as dendritic cells. Moreover, exosomes, whether naturally secreted by cells in the body or bioengineered, have been explored to regulate the TME and immune-related cells to affect cancer immunotherapy. Stimuli-responsive nanocarriers, activated by pH, redox, and light conditions, exhibit the potential to accelerate immunotherapy. The co-application of nanoparticles with immune checkpoint inhibitors is an emerging strategy to boost anti-tumor immunity. With their ability to induce long-term immunity, nanoarchitectures are promising structures in vaccine development. This review underscores the critical role of nanoparticles in overcoming current challenges and driving the advancement of cancer immunotherapy and TME modification.
Cellular metabolism regulates the differentiation and function of T-cell subsets
Authors: Sicong Ma, Yanan Ming, Jingxia Wu, Guoliang Cui
Journal: Cellular and Molecular Immunology (2024)

Abstract T cells are an important component of adaptive immunity and protect the host from infectious diseases and cancers. However, uncontrolled T cell immunity may cause autoimmune disorders. In both situations, antigen-specific T cells undergo clonal expansion upon the engagement and activation of antigens. Cellular metabolism is reprogrammed to meet the increase in bioenergetic and biosynthetic demands associated with effector T cell expansion. Metabolites not only serve as building blocks or energy sources to fuel cell growth and expansion but also regulate a broad spectrum of cellular signals that instruct the differentiation of multiple T cell subsets. The realm of immunometabolism research is undergoing swift advancements. Encapsulating all the recent progress within this concise review in not possible. Instead, our objective is to provide a succinct introduction to this swiftly progressing research, concentrating on the metabolic intricacies of three pivotal nutrient classes—lipids, glucose, and amino acids—in T cells. We shed light on recent investigations elucidating the roles of these three groups of metabolites in mediating the metabolic and immune functions of T cells. Moreover, we delve into the prospect of “editing” metabolic pathways within T cells using pharmacological or genetic approaches, with the aim of synergizing this approach with existing immunotherapies and enhancing the efficacy of antitumor and antiinfection immune responses.
Divergent local and systemic antitumor response in primary uveal melanomas
Authors: Francesca Lucibello, Ana I. Lalanne, Anne-Laure Le Gac, Abdoulaye Soumare, Setareh Aflaki, Joanna Cyrta, Lea Dubreuil, Martin Mestdagh, Marion Salou, Alexandre Houy, Christina Ekwegbara, Camille Jamet, Sophie Gardrat, Anais Le Ven, Karine Bernardeau, Nathalie Cassoux, Alexandre Matet, Denis Malaise, Gaelle Pierron, Sophie Piperno-Neumann, Marc-Henri Stern, Manuel Rodrigues, Olivier Lantz
Journal: The Journal of Experimental Medicine (2024)

Uveal melanoma (UM) is the most common cancer of the eye. The loss of chromosome 3 (M3) is associated with a high risk of metastases. M3 tumors are more infiltrated by T-lymphocytes than low-risk disomic-3 (D3) tumors, contrasting with other tumor types in which T cell infiltration correlates with better prognosis. Whether these T cells represent an antitumor response and how these T cells would be primed in the eye are both unknown. Herein, we characterized the T cells infiltrating primary UMs. CD8+ and Treg cells were more abundant in M3 than in D3 tumors. CD39+PD-1+CD8+ T cells were enriched in M3 tumors, suggesting specific responses to tumor antigen (Ag) as confirmed using HLA-A2:Melan-A tetramers. scRNAseq-VDJ analysis of T cells evidenced high numbers of proliferating CD39+PD1+CD8+ clonal expansions, suggesting in situ antitumor Ag responses. TCRseq and tumor-Ag tetramer staining characterized the recirculation pattern of the antitumor responses in M3 and D3 tumors. Thus, tumor-Ag responses occur in localized UMs, raising the question of the priming mechanisms in the absence of known lymphatic drainage.
EryDB: A Transcriptomic Profile Database for Erythropoiesis and Erythroid-related Diseases
Authors: Guangmin Zheng, Song Wu, Zhaojun Zhang, Zijuan Xin, Lijuan Zhang, Siqi Zhao, Jing Wu, Yanxia Liu, Meng Li, Xiuyan Ruan, Nan Qiao, Yiming Bao, Hongzhu Qu, Xiangdong Fang
Journal: Genomics Proteomics & Bioinformatics (2024)

Erythropoiesis is a finely regulated and complex process that involves multiple transformations from hematopoietic stem cells to mature red blood cells at hematopoietic sites from the embryonic to the adult stages. Investigations into its molecular mechanisms have generated a wealth of expression data, including bulk and single-cell RNA sequencing data. A comprehensively integrated and well-curated erythropoiesis-specific database will greatly facilitate the mining of gene expression data and enable large-scale research of erythropoiesis and erythroid-related diseases. Here, we present EryDB, an open-access and comprehensive database dedicated to the collection, integration, analysis, and visualization of transcriptomic data for erythropoiesis and erythroid-related diseases. Currently, the database includes expertly curated quality-assured data of 3803 samples and 1,187,119 single cells derived from 107 public studies of three species (Homo sapiens, Mus musculus, and Danio rerio), nine tissue types, and five diseases. EryDB provides users with the ability to not only browse the molecular features of erythropoiesis between tissues and species, but also perform computational analyses of single-cell and bulk RNA sequencing data, thus serving as a convenient platform for customized queries and analyses. EryDB v1.0 is freely accessible at https://ngdc.cncb.ac.cn/EryDB/home.
Neoadjuvant Chemotherapy With Oxaliplatin and Fluoropyrimidine Versus Upfront Surgery for Locally Advanced Colon Cancer: The Randomized, Phase III OPTICAL Trial
Authors: Huabin Hu, Jianwei Zhang, Yunfeng Li, Xiaozhong Wang, Ziqiang Wang, Hui Wang, Liang Kang, Ping Liu, Ping Lan, Xiaojian Wu, Yunhuan Zhen, Haiping Pei, Zhongcheng Huang, Hao Zhang, Wenbin Chen, Yongming Zeng, Jiajun Lai, Hongbo Wei, Xuefeng Huang, Jiansi Chen, Jigui Chen, Kaixiong Tao, Qingwen Xu, Xiang Peng, Junlin Liang, Guanfu Cai, Kefeng Ding, Zhijie Ding, Ming Hu, Wei Zhang, Bo Tang, Chuyuan Hong, Jie Cao, Zonghai Huang, Wuteng Cao, Fangqian Li, Xinhua Wang, Chao Wang, Yan Huang, Yandong Zhao, Yue Cai, Jiayu Ling, Xiaoyu Xie, Zehua Wu, Lishuo Shi, Li Ling, Hao Liu, Jianping Wang, Meijin Huang, Yanhong Deng, Yanhong Deng, Yunfeng Li, Ziqiang Wang, Xiaozhong Wang, Ruyi Zhang, Haiping Pei, Zhongcheng Huang, Hao Zhang, Wenbin Chen, Yongming Zeng, Jiajun Lai, Hongbo Wei, Xuefeng Huang, Jiansi Chen, Jigui Chen, Kaixiong Tao, Qingwen Xu, Xiang Peng, Junlin Liang, Guanfu Cai, Kefeng Ding, Zhijie Ding, Ming Hu, Wei Zhang, Bo Tang, Chuyuan Hong, Jie Cao, Zonghai Huang
Journal: Journal of Clinical Oncology (2024)

The role of neoadjuvant chemotherapy (NAC) in colon cancer remains unclear. This trial investigated whether 3 months of modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine and oxaliplatin (CAPOX) as NAC could improve outcomes in patients with locally advanced colon cancer versus upfront surgery.
Optimizing off-treatment outcome predictions: The potential of time-varying HBcrAg and the need for more research
Authors: Ying-Nan Tsai, Jia-Ling Wu, Yao-Chun Hsu
Journal: Clinical and Molecular Hepatology (2024)

commenting on our recent study published in Clinical and Molecular Hepatology 2 regarding the role of time-varying hepatitis B core-related antigen (HBcrAg) in predicting clinical relapse (CR) for chronic hepatitis B (CHB) patients who discontinued tenofovir or entecavir.We agree that nucleos(t) ide analogue (NA) cessation is generally safe with hepatitis B surface antigen (HBsAg) seroclearance, 3 which is the only treatment endpoint widely acceptable across guidelines. 4,5nfortunately, it rarely occurs during long-term NA therapy. 6reatment discontinuation without first achieving HBsAg seroclearance invariably leads to recurrence of viremia and could precipitate hepatitis flare and even life-threatening acute on chronic liver failure. 7The strategy of finite NA therapy, therefore, cannot be practiced without thorough consideration of the conceivable benefits and potential risks for an
High-Dose Isoniazid Lacks EARLY Bactericidal Activity Against Isoniazid-resistant Tuberculosis Mediated by katG Mutations: A Randomized, Phase 2 Clinical Trial
Authors: Kamunkhwala Gausi, Elisa H. Ignatius, Veronique De Jager, Caryn Upton, Soyeon Kim, Ashley McKhann, Laura Moran, Lubbe Wiesner, Florian von Groote-Bidlingmaier, Philip Marzinek, Naadira Vanker, Joseph Yvetot, Samuel Pierre, Susan L Rosenkranz, Susan Swindells, Andreas H Diacon, Eric L. Nuermberger, Paolo Denti, Kelly E Dooley
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Observational studies suggest that high-dose isoniazid may be efficacious in treating multidrug-resistant tuberculosis. However, its activity against
Integrated Microprism and Microelectrode Array for Simultaneous Electrophysiology and Two‐Photon Imaging across All Cortical Layers
Authors: Qianru Yang, Bingchen Wu, Elisa Castagnola, May Yoon Pwint, Nathaniel P. Williams, Alberto L. Vazquez, Xinyan Tracy Cui
Journal: Advanced Healthcare Materials (2024)

Cerebral neural electronics play a crucial role in neuroscience research with increasing translational applications such as brain-computer interfaces for sensory input and motor output restoration. While widely utilized for decades, the understanding of the cellular mechanisms underlying this technology remains limited. Although two-photon microscopy (TPM) has shown great promise in imaging superficial neural electrodes, its application to deep-penetrating electrodes is technically difficult. Here, a novel device integrating transparent microelectrode arrays with glass microprisms, enabling electrophysiology recording and stimulation alongside TPM imaging across all cortical layers in a vertical plane, is introduced. Tested in Thy1-GCaMP6 mice for over 4 months, the integrated device demonstrates the capability for multisite electrophysiological recording/stimulation and simultaneous TPM calcium imaging. As a proof of concept, the impact of microstimulation amplitude, frequency, and depth on neural activation patterns is investigated using the setup. With future improvements in material stability and single unit yield, this multimodal tool greatly expands integrated electrophysiology and optical imaging from the superficial brain to the entire cortical column, opening new avenues for neuroscience research and neurotechnology development.
EAACI guidelines on environmental science for allergy and asthma: The impact of short‐term exposure to outdoor air pollutants on asthma‐related outcomes and recommendations for mitigation measures
Authors: Ioana Agache, Isabella Annesi‐Maesano, Lorenzo Cecchi, Benedetta Biagioni, Kian Fan Chung, Bernard Clot, Gennaro D'Amato, Athanasios Damialis, Stefano del Giacco, Javier Dominguez‐Ortega, Carmen Galàn, Stefanie Gilles, Stephen Holgate, Mohamed Jeebhay, Stelios Kazadzis, Kari Nadeau, Nikolaos Papadopoulos, Santiago Quirce, Joaquin Sastre, Fiona Tummon, Claudia Traidl‐Hoffmann, Jolanta Walusiak‐Skorupa, Marek Jutel, Cezmi A. Akdis
Journal: Allergy (2024)

Abstract The EAACI Guidelines on the impact of short‐term exposure to outdoor pollutants on asthma‐related outcomes provide recommendations for prevention, patient care and mitigation in a framework supporting rational decisions for healthcare professionals and patients to individualize and improve asthma management and for policymakers and regulators as an evidence‐informed reference to help setting legally binding standards and goals for outdoor air quality at international, national and local levels. The Guideline was developed using the GRADE approach and evaluated outdoor pollutants referenced in the current Air Quality Guideline of the World Health Organization as single or mixed pollutants and outdoor pesticides. Short‐term exposure to all pollutants evaluated increases the risk of asthma‐related adverse outcomes, especially hospital admissions and emergency department visits (moderate certainty of evidence at specific lag days). There is limited evidence for the impact of traffic‐related air pollution and outdoor pesticides exposure as well as for the interventions to reduce emissions. Due to the quality of evidence, conditional recommendations were formulated for all pollutants and for the interventions reducing outdoor air pollution. Asthma management counselled by the current EAACI guidelines can improve asthma‐related outcomes but global measures for clean air are needed to achieve significant impact.
Sustained clinical benefit of malaria chemoprevention with sulfadoxine-pyrimethamine (SP) in pregnant women in a region with high SP resistance markers
Authors: Glória Matambisso, Nanna Brokhattingen, Sónia Maculuve, Pau Cístero, Henriques Mbeve, Anna Escoda, Gizela Bambo, Boaventura Cuna, Cardoso Melembe, Nelo Ndimande, Kevin K.A. Tetteh, Chris Drakeley, Benoit Gamain, Chetan Chitnis, Virander Chauhan, Llorenç Quintó, Eusébio Macete, Alfredo Mayor
Journal: Journal of Infection (2024)

ObjectiveThe effectiveness of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) is threatened by increasing SP resistance in Africa. We assessed the level of SP-resistance markers, and the clinical and parasitological effectiveness of IPTp-SP in southern Mozambique.MethodsP. falciparum infection, antimalarial antibodies and dhfr/dhps SP-resistance mutants were detected by quantitative polymerase chain reaction (qPCR), suspension array technology and targeted deep sequencing, respectively, among 4016 HIV negative women in Maputo province (2016-2019). Univariate and multivariate regression models were used to assess the association between taking the recommended three or more IPTp-SP doses (IPTp3+) and parasitological and clinical outcomes.Results84.3% (3385/4016) women received three or more IPTp-SP doses. The prevalence of quintuple mutants at first ANC visit was 94.2%. IPTp3+ was associated with a higher clearance rate of qPCR-detected infections from first ANC visit to delivery (adjusted odds ratio [aOR]=5.9, 95%CI: 1.5-33.3; p=0.012), lower seroprevalence at delivery of antibodies against the pregnancy-specific antigen VAR2CSADBL34 (aOR=0.72, 95%CI: 0.54-0.95; p=0.022), and lower prevalence of low birth weight deliveries (aOR: 0.61, 95% CI: 0.41-0.90; p=0.013).ConclusionA sustained parasitological effect of IPTp-SP contributes to the clinical effectiveness of IPTp3+ in areas with high prevalence of SP resistance markers.
Glycolytic activity and in vitro effect of the pyruvate kinase activator <scp>AG</scp>‐946 in red blood cells from low‐risk myelodysplastic syndromes patients: A proof‐of‐concept study
Authors: Bruno Fattizzo, Cristina Vercellati, Anna Marcello, Parija Patel, Megan Wind‐Rotolo, Loredana Pettine, Marcella Bonanomi, Daniela Gaglio, Marta Bortolotti, Claudia Leoni, Elisa Fermo, Paola Bianchi, Anna Zaninoni, Francesco Passamonti, Wilma Barcellini
Journal: American Journal of Hematology (2024)

Glycolytic activity and in vitro effect of the pyruvate kinase activator AG-946 in red blood cells from low-risk myelodysplastic syndromes patients. Data showed decreased glycolytic activity in red blood cells of 2/3 of patients with lower-risk MDS. These results highlight a potential effect of the PK activator in this setting.