tbuckley/cabot-search huggingface dataset:
Assessment of epidemiology and outcomes of adult patients with kidney-limited thrombotic microangiopathies
Authors: Valentin Maisons, Anna Duval, Laurent Mesnard, Marie Frimat, Fadi Fakhouri, Steven Grangé, Aude Servais, Claire Cartery, Laurent Fauchier, Paul Coppo, Dimitri Titeca-Beauport, Nicolas Fage, Yahsou Delmas, Anne-Hélène Quérard, Guillaume Seret, Mickaël Bobot, Moglie Le Quintrec, Simon Ville, Florent von Tokarski, Sophie Chauvet, Alain Wynckel, Manon Martins, Juliet Schurder, Christelle Barbet, Bénédicte Sautenet, Philippe Gatault, Sophie Caillard, Vincent Vuiblet, Jean-Michel Halimi
Journal: Kidney International (2024)
CLANet: A comprehensive framework for cross-batch cell line identification using brightfield images
Authors: Lei Tong, Adam Corrigan, Navin Rathna Kumar, Kerry Hallbrook, Jonathan Orme, Yinhai Wang, Huiyu Zhou
Journal: Medical Image Analysis (2024)

Cell line authentication plays a crucial role in the biomedical field, ensuring researchers work with accurately identified cells. Supervised deep learning has made remarkable strides in cell line identification by studying cell morphological features through cell imaging. However, biological batch (bio-batch) effects, a significant issue stemming from the different times at which data is generated, lead to substantial shifts in the underlying data distribution, thus complicating reliable differentiation between cell lines from distinct batch cultures. To address this challenge, we introduce CLANet, a pioneering framework for cross-batch cell line identification using brightfield images, specifically designed to tackle three distinct bio-batch effects. We propose a cell cluster-level selection method to efficiently capture cell density variations, and a self-supervised learning strategy to manage image quality variations, thus producing reliable patch representations. Additionally, we adopt multiple instance learning(MIL) for effective aggregation of instance-level features for cell line identification. Our innovative time-series segment sampling module further enhances MIL's feature-learning capabilities, mitigating biases from varying incubation times across batches. We validate CLANet using data from 32 cell lines across 93 experimental bio-batches from the AstraZeneca Global Cell Bank. Our results show that CLANet outperforms related approaches (e.g. domain adaptation, MIL), demonstrating its effectiveness in addressing bio-batch effects in cell line identification.
PDGFRα+ITGA11+ fibroblasts foster early-stage cancer lymphovascular invasion and lymphatic metastasis via ITGA11-SELE interplay
Authors: Hanhao Zheng, Mingjie An, Yuming Luo, Xiayao Diao, Wenlong Zhong, Mingrui Pang, Yan Lin, Jiancheng Chen, Yuanlong Li, Yao Kong, Yue Zhao, Yina Yin, Le Ai, Jian Huang, Changhao Chen, Tianxin Lin
Journal: Cancer Cell (2024)

Cancer-associated fibroblasts (CAFs) exhibit considerable heterogeneity in advanced cancers; however, the functional annotation and mechanism of CAFs in early-stage cancers remain elusive. Utilizing single-cell RNA sequencing and spatial transcriptomic, we identify a previously unknown PDGFRα+ITGA11+ CAF subset in early-stage bladder cancer (BCa). Multicenter clinical analysis of a 910-case cohort confirms that PDGFRα+ITGA11+ CAFs are associated with lymphovascular invasion (LVI) and poor prognosis in early-stage BCa. These CAFs facilitate LVI and lymph node (LN) metastasis in early-stage BCa, as evidenced in a PDGFRα+ITGA11+ CAFs-specific deficient mouse model. Mechanistically, PDGFRα+ITGA11+ CAFs promote lymphangiogenesis via recognizing ITGA11 surface receptor SELE on lymphatic endothelial cells to activate SRC-p-VEGFR3-MAPK pathway. Further, CHI3L1 from PDGFRα+ITGA11+ CAFs aligns the surrounding matrix to assist cancer cell intravasation, fostering early-stage BCa LVI and LN metastasis. Collectively, our study reveals the crucial role of PDGFRα+ITGA11+ CAFs in shaping metastatic landscape, informing the treatment of early-stage BCa LVI.
Mediator complex subunit 1 architects a tumorigenic Treg cell program independent of inflammation
Authors: Shuvam M. Chaudhuri, Samuel E. Weinberg, Dongmei Wang, Lenore K. Yalom, Elena Montauti, Radhika Iyer, Amy Y. Tang, Manuel A. Torres Acosta, Jian Shen, Nikita L. Mani, Shengnan Wang, Kun Liu, Weiyuan Lu, Triet M. Bui, Laura D. Manzanares, Zeinab Dehghani, Ching Man Wai, Beixue Gao, Juncheng Wei, Feng Yue, Weiguo Cui, Benjamin D. Singer, Ronen Sumagin, Yana Zhang, Deyu Fang
Journal: Cell Reports Medicine (2024)

While immunotherapy has revolutionized cancer treatment, its safety has been hampered by immunotherapy-related adverse events. Unexpectedly, we show that Mediator complex subunit 1 (MED1) is required for T regulatory (Treg) cell function specifically in the tumor microenvironment. Treg cell-specific MED1 deletion does not predispose mice to autoimmunity or excessive inflammation. In contrast, MED1 is required for Treg cell promotion of tumor growth because MED1 is required for the terminal differentiation of effector Treg cells in the tumor. Suppression of these terminally differentiated Treg cells is sufficient for eliciting antitumor immunity. Both human and murine Treg cells experience divergent paths of differentiation in tumors and matched tissues with non-malignant inflammation. Collectively, we identify a pathway promoting the differentiation of a Treg cell effector subset specific to tumors and demonstrate that suppression of a subset of Treg cells is sufficient for promoting antitumor immunity in the absence of autoimmune consequences.
AZD1222 effectiveness against severe COVID-19 in individuals with comorbidity or frailty: The RAVEN cohort study
Authors: Wilhelmine Meeraus, Mark Joy, Mario Ouwens, Kathryn S. Taylor, Sudhir Venkatesan, John Dennis, Trung N. Tran, Ashkan Dashtban, Xuejuan Fan, Robert Williams, Tamsin Morris, Lucy Carty, Debasish Kar, Uy Hoang, Michael Feher, Anna Forbes, Gavin Jamie, William Hinton, Kornelia Sanecka, Rachel Byford, Sneha N. Anand, F.D. Richard Hobbs, David A. Clifton, Andrew J. Pollard, Sylvia Taylor, Simon de Lusignan
Journal: Journal of Infection (2024)

Highlights•AZD1222 (ChAdOx1 nCoV-19) real-world vaccine effectiveness (VE) in 2021 was studied.•Over 4.5 million vaccinated individuals were assessed with ∼5 months mean follow-up.•VE was 84.1%/90.7%/85.9% for hospitalization/intensive care admission/death.•People with higher comorbidity burden or more severe frailty had lower VE.•Immunosuppressed individuals had the lowest VE from primary series vaccination.SummaryObjectivesDespite being prioritized during initial COVID-19 vaccine rollout, vulnerable individuals at high risk of severe COVID-19 (hospitalization, intensive care unit admission, or death) remain underrepresented in vaccine effectiveness (VE) studies. The RAVEN cohort study (NCT05047822) assessed AZD1222 (ChAdOx1 nCov-19) two-dose primary series VE in vulnerable populations.MethodsUsing the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub, linked to secondary care, death registration, and COVID-19 datasets in England, COVID-19 outcomes in 2021 were compared in vaccinated and unvaccinated individuals matched on age, sex, region, and multimorbidity.ResultsOver 4.5 million AZD1222 recipients were matched (mean follow-up ∼5 months); 68% were ≥50 years, 57% had high multimorbidity. Overall, high VE against severe COVID-19 was demonstrated, with lower VE observed in vulnerable populations. VE against hospitalization was higher in the lowest multimorbidity quartile (91.1%; 95% CI: 90.1, 92.0) than the highest quartile (80.4%; 79.7, 81.1), and among individuals ≥65 years, higher in the 'fit' (86.2%; 84.5, 87.6) than the frailest (71.8%; 69.3, 74.2). VE against hospitalization was lowest in immunosuppressed individuals (64.6%; 60.7, 68.1).ConclusionsBased on integrated and comprehensive UK health data, overall population-level VE with AZD1222 was high. VEs were notably lower in vulnerable groups, particularly the immunosuppressed.Graphical abstract
Antibiotic-induced intestinal microbiota depletion can attenuate the acute kidney injury to chronic kidney disease transition via NADPH oxidase 2 and trimethylamine-N-oxide inhibition
Authors: Jeonghwan Lee, Jinhaeng Lee, Kyuhong Kim, Jiwon Lee, Youngae Jung, Jin Seong Hyeon, Areum Seo, Wencheng Jin, Boram Weon, Nayeon Shin, Sejoong Kim, Chun Soo Lim, Yon Su Kim, Jung Pyo Lee, Geum-Sook Hwang, Seung Hee Yang
Journal: Kidney International (2024)

Intestinal microbiota and their metabolites affect systemic inflammation and kidney disease outcomes. Here, we investigated the key metabolites associated with the acute kidney injury (AKI)-to chronic kidney disease (CKD) transition and the effect of antibiotic-induced microbiota depletion (AIMD) on this transition. In 61 patients with AKI, 59 plasma metabolites were assessed to determine the risk of AKI-to-CKD transition. An AKI-to-CKD transition murine model was established four weeks after unilateral ischemia-reperfusion injury (IRI) to determine the effects of AIMD on the gut microbiome, metabolites, and pathological responses related to CKD transition. Human proximal tubular epithelial cells were challenged with CKD transition-related metabolites and inhibitory effects of NADPH oxidase 2 (NOX2) signals were tested. Based on clinical metabolomics, plasma trimethylamine N-oxide (TMAO) was associated with a significant increased risk for AKI-to-CKD transition [adjusted odds ratio 4.389 (95% confidence interval 1.106–17.416)]. In vivo, AIMD inhibited a unilateral IRI-induced increase in TMAO, along with a decreased in apoptosis, inflammation, and fibrosis. The expression of NOX2 and oxidative stress decreased after AIMD. In vitro, TMAO induced fibrosis with NOX2 activation and oxidative stress. NOX2 inhibition successfully attenuated apoptosis, inflammation, and fibrosis with suppression of G2/M arrest. NOX2 inhibition (in vivo) showed improvement in pathological changes with a decrease in oxidative stress without changes in TMAO levels. Thus, TMAO is a key metabolite associated with the AKI-to-CKD transition and NOX2 activation was identified as a key regulator of TMAO-related AKI-to-CKD transition both in vivo and in vitro.
Adding immunotherapy to first-line treatment of advanced and metastatic endometrial cancer
Authors: G. Bogani, B.J. Monk, M.A. Powell, S.N. Westin, B. Slomovitz, K.N. Moore, R.N. Eskander, F. Raspagliesi, M.-P. Barretina-Ginesta, N. Colombo, M.R. Mirza
Journal: Annals of Oncology (2024)
Expert consensus guidelines on management and best practices for tumor-infiltrating lymphocyte cell therapy
Authors: Allison Betof Warner, Omid Hamid, Krishna Komanduri, Rodabe Amaria, Marcus O Butler, John Haanen, Sarah Nikiforow, Igor Puzanov, Amod Sarnaik, Michael R Bishop, Adam J Schoenfeld
Journal: Journal for ImmunoTherapy of Cancer (2024)

Adoptive cell therapy with autologous, ex vivo-expanded, tumor-infiltrating lymphocytes (TILs) is being investigated for treatment of solid tumors and has shown robust responses in clinical trials. Based on the encouraging efficacy, tolerable safety profile, and advancements in a central manufacturing process, lifileucel is now the first US Food and Drug Administration (FDA)-approved TIL cell therapy product. To this end, treatment management and delivery practice guidance is needed to ensure successful integration of this modality into clinical care. This review includes clinical and toxicity management guidelines pertaining to the TIL cell therapy regimen prepared by the TIL Working Group, composed of internationally recognized hematologists and oncologists with expertize in TIL cell therapy, and relates to patient care and operational aspects. Expert consensus recommendations for patient management, including patient eligibility, screening tests, and clinical and toxicity management with TIL cell therapy, including tumor tissue procurement surgery, non-myeloablative lymphodepletion, TIL infusion, and IL-2 administration, are discussed in the context of potential standard of care TIL use. These recommendations provide practical guidelines for optimal clinical management during administration of the TIL cell therapy regimen, and recognition of subsequent management of toxicities. These guidelines are focused on multidisciplinary teams of physicians, nurses, and stakeholders involved in the care of these patients.
Multi-omics and imaging mass cytometry characterization of human kidneys to identify pathways and phenotypes associated with impaired kidney function
Authors: Evans O. Asowata, Simone Romoli, Rebecca Sargeant, Jennifer Y. Tan, Scott Hoffmann, Margaret M. Huang, Krishnaa T. Mahbubani, Fynn N. Krause, Daniel Jachimowicz, Rasmus Agren, Albert Koulman, Benjamin Jenkins, Barbara Musial, Julian L. Griffin, Magnus Soderberg, Stephanie Ling, Pernille B.L. Hansen, Kourosh Saeb-Parsy, Kevin J. Woollard
Journal: Kidney International (2024)

Despite the recent advances in our understanding of the role of lipids, metabolites and related enzymes in mediating kidney injury, there is limited integrated multi-omics data identifying potential metabolic pathways driving impaired kidney function. The limited availability of kidney biopsies from living donors with acute kidney injury has remained a major constraint. Here, we validated the use of deceased transplant donor kidneys as a good model to study acute kidney injury in humans and characterized these kidneys using imaging and multi-omics approaches. We noted consistent changes in kidney injury and inflammatory markers in donors with reduced kidney function. Neighborhood and correlation analyses of imaging mass cytometry data showed that subsets of kidney cells (proximal tubular cells and fibroblasts) are associated with the expression profile of kidney immune cells, potentially linking these cells to kidney inflammation. Integrated transcriptomic and metabolomic analysis of human kidneys showed that kidney arachidonic acid metabolism and seven other metabolic pathways were upregulated following diminished kidney function. To validate the arachidonic acid pathway in impaired kidney function we demonstrated increased levels of cytosolic phospholipase A2 protein and related lipid mediators (prostaglandin E2) in the injured kidneys. Further, inhibition of cytosolic phospholipase A2 reduced injury and inflammation in human kidney proximal tubular epithelial cells in vitro. Thus, our study identified cell types and metabolic pathways that may be critical for controlling inflammation associated with impaired kidney function in humans.
Ivermectin for COVID-19 in adults in the community (PRINCIPLE): An open, randomised, controlled, adaptive platform trial of short- and longer-term outcomes
Authors: Gail Hayward, Ly-Mee Yu, Paul Little, Oghenekome Gbinigie, Milensu Shanyinde, Victoria Harris, Jienchi Dorward, Benjamin R. Saville, Nicholas Berry, Philip H. Evans, Nicholas P.B. Thomas, Mahendra G. Patel, Duncan Richards, Oliver V. Hecke, Michelle A. Detry, Christina Saunders, Mark Fitzgerald, Jared Robinson, Charlotte Latimer-Bell, Julie Allen, Emma Ogburn, Jenna Grabey, Simon de Lusignan, FD Richard Hobbs, Christopher C. Butler
Journal: Journal of Infection (2024)
Associations of environmental factors with neurodegeneration: An exposome-wide Mendelian randomization investigation
Authors: Dun Li, Lihui Zhou, Zhi Cao, Jida Wang, Hongxi Yang, Mingqian Lyu, Yuan Zhang, Rongrong Yang, Ju Wang, Yuhong Bian, Weili Xu, Yaogang Wang
Journal: Ageing Research Reviews (2024)

Neurodegenerative diseases (NDDs) remain a global health challenge. Previous studies have reported potential links between environmental factors and NDDs, however, findings remain controversial across studies and elusive to be interpreted as evidence of robust causal associations. In this study, we comprehensively explored the causal associations of the common environmental factors with major NDDs including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), based on updated large-scale genome-wide association study data through two-sample Mendelian randomization (MR) approach. Our results indicated that, overall, 28 significant sets of exposure-outcome causal association evidence were detected, 12 of which were previously underestimated and newly identified, including average weekly beer plus cider intake, strenuous sports or other exercises, diastolic blood pressure, and body fat percentage with AD, alcohol intake frequency with PD, apolipoprotein B, systolic blood pressure, and forced expiratory volume in 1 s (FEV1) with ALS, and alcohol intake frequency, hip circumference, forced vital capacity, and FEV1 with MS. Moreover, the causal effects of several environmental factors on NDDs were found to overlap. From a triangulation perspective, our investigation provided insights into understanding the associations of environmental factors with NDDs, providing causality-oriented evidence to establish the risk profile of NDDs.
Lymphopenia is associated with broad host response aberrations in community-acquired pneumonia
Authors: Susanne E Doeleman, Tom D Y Reijnders, Sebastiaan C M Joosten, Alex R Schuurman, Tjitske S R van Engelen, Jan Verhoeff, Valentine Léopold, Xanthe Brands, Bastiaan W Haak, Jan M Prins, Maadrika M N P Kanglie, Inge A H van den Berk, Daniël R Faber, Renée A Douma, Jaap Stoker, Anno Saris, Juan J Garcia Vallejo, W Joost Wiersinga, Tom van der Poll
Journal: Journal of Infection (2024)
World Health Organization World Hand Hygiene Day, 5 May 2024. SAVE LIVES: Clean Your Hands campaign: Promoting knowledge and capacity building on infection prevention and control, including hand hygiene, among health and care workers
Authors: Kilpatrick Claire, Tartari Ermira, Deeves Miranda, Pittet Didier, Allegranzi Benedetta
Journal: Clinical Microbiology and Infection (2024)
Author correction to ‘Co-delivery of nigericin and decitabine using hexahistidine-metal nanocarriers for pyroptosis-induced immunotherapeutics’ [Acta Pharm Sin B 12 (2022) 4458–4471]
Authors: Qiang Niu, Yu Liu, Yujing Zheng, Ziwei Tang, Yuna Qian, Ruogu Qi, Jianliang Shen, Ping Zhao
Journal: Acta Pharmaceutica Sinica B (2024)

[This corrects the article DOI: 10.1016/j.apsb.2022.11.002.].
Re: Ivo I. de Vos II, Sebastiaan Remmers, Renée Hogenhout, Monique J. Roobol, ERSPC Rotterdam Study Group. Prostate Cancer Mortality Among Elderly Men After Discontinuing Organised Screening: Long-term Results from the European Randomized Study of Screening for Prostate Cancer Rotterdam. Eur Urol 2024;85:74–81
Authors: Borivoj Golijanin, Anthony Mega, Dragan Golijanin
Journal: European Urology (2024)
Combining artificial intelligence and human expertise for more accurate dermoscopic melanoma diagnosis: A 2-session retrospective reader study
Authors: Mario Giulini, Mohamad Goldust, Stephan Grabbe, Christian Ludwigs, Dominik Seliger, Priyanka Karagaiah, Hadrian Schepler, Florian Butsch, Beate Weidenthaler-Barth, Stephan Rietz
Journal: Journal of the American Academy of Dermatology (2024)
Effect of tebipenem pivoxil hydrobromide on the normal gut microbiota of a healthy adult population in Sweden: a randomised controlled trial
Authors: Tsegaye Sewunet, Mohammad Razavi, Staffan Rosenborg, Angela Camporeale, Michael Nowak, David Melnick, Leanne B Gasink, Paul B Eckburg, Ian A Critchley, Carl Erik Nord, Christian G Giske
Journal: The Lancet Microbe (2024)

Antimicrobials cause perturbations in the composition and diversity of the host microbiome. We aimed to compare gut microbiome perturbations caused by oral tebipenem pivoxil hydrobromide (a novel carbapenem) and by amoxicillin-clavulanic acid (an orally administered β-lactam-β-lactam inhibitor combination widely used in clinical practice).
Confronting the elephants in the room: reigniting momentum for universal health coverage
Authors: Katri Bertram, Bruce Aylward, Laetitia Bosio, Helen Clark, Francesca Colombo, Katie Dain, María Fernanda Espinosa, Alexis Feeney Tallman, Githinji Gitahi, Masahiko Hachiya, Arush Lal, Nupur Lalvani, Helena Legido-Quigley, Rosemary Mburu, Marjolaine Nicod, Sania Nishtar, Kumanan Rasanathan, Diah Saminarsih, Viroj Tangcharoensathien, Aquina Thulare, Robert Yates, Justin Koonin
Journal: The Lancet (2024)
Emergence of zoonotic sporotrichosis in Brazil: a genomic epidemiology study
Authors: Amanda Ribeiro dos Santos, Elizabeth Misas, Brian Min, Ngoc Le, Ujwal R Bagal, Lindsay A Parnell, D Joseph Sexton, Shawn R Lockhart, Marcia de Souza Carvalho Melhem, Juliana Possatto Fernandes Takahashi, Gabriel Manzi Oliboni, Lucas Xavier Bonfieti, Paola Cappellano, Jorge Luiz Mello Sampaio, Lisandra Siufi Araujo, Hilton L Alves Filho, James Venturini, Tom M Chiller, Anastasia P Litvintseva, Nancy A Chow
Journal: The Lancet Microbe (2024)

Zoonotic sporotrichosis is a neglected fungal disease, whereby outbreaks are primarily driven by Sporothrix brasiliensis and linked to cat-to-human transmission. To understand the emergence and spread of sporotrichosis in Brazil, the epicentre of the current epidemic in South America, we aimed to conduct whole-genome sequencing (WGS) to describe the genomic epidemiology.
Tofacitinib in Pregnancy: Assessing Pregnancy and Infant Outcomes, Cord Blood, and Breast Milk Concentrations
Authors: Katarina Mitrova, Mette Julsgaard, Patrick Augustijns, Karin Cerna, Uma Mahadevan, Dana Duricova, Raf Mols, Kristyna Zdychyncova, Michal Konecny, Philip O. Anderson, Milan Lukas
Journal: Clinical Gastroenterology and Hepatology (2024)
Secreted clusterin inhibits tumorigenesis by modulating tumor cells and macrophages in human meningioma
Authors: Chao Ke, Boya Huang, Jian Xiang, Jinlian Liang, Guangjie Wu, Minghui Qiu, Kai Cheng, Lipeng Mao, Wen Lei, Yang Hu, Xiaogen Tang, Yizhen Tian, Guobing Chen, Oscar Junhong Luo, Hongyi Zhang
Journal: Neuro-Oncology (2024)

Abstract Background Meningioma is the most common primary intracranial tumor with a high frequency of postoperative recurrence, yet the biology of the meningioma malignancy process is still obscure. Methods To identify potential therapeutic targets and tumor suppressors, we performed single-cell transcriptome analysis through meningioma malignancy, which included 18 samples spanning normal meninges, benign and high-grade in situ tumors, and lung metastases, for extensive transcriptome characterization. Tumor suppressor candidate gene and molecular mechanism were functionally validated at the animal model and cellular levels. Results Comprehensive analysis and validation in mice and clinical cohorts indicated clusterin (CLU) had suppressive function for meningioma tumorigenesis and malignancy by inducing mitochondria damage and triggering type 1 interferon pathway dependent on its secreted isoform, and the inhibition effect was enhanced by TNFα as TNFα also induced type 1 interferon pathway. Meanwhile, both intra- and extracellular CLU overexpression enhanced macrophage polarization towards M1 phenotype and TNFα production, thus promoting tumor killing and phagocytosis. Conclusions CLU might be a key brake of meningioma malignance by synchronously modulating tumor cells and their microenvironment. Our work provides comprehensive insights into meningioma malignancy and a potential therapeutic strategy.
Low Colorectal Cancer Risk After Resection of High-Risk Pedunculated Polyps
Authors: Manuel Zorzi, Jessica Battagello, Claudio Barbiellini Amidei, Giulio Antonelli, Bastianello Germanà, Flavio Valiante, Stefano Benvenuti, Alberto Tringali, Francesco Bortoluzzi, Erica Cervellin, Davide Giacomin, Tamara Meggiato, Erik Rosa Rizzotto, Diego Fregonese, Manuela Dinca, Gianluca Baldassarre, Paola Scalon, Maurizio Pantalena, Luisa Milan, Gianmarco Bulighin, Daniele Di Piramo, Maurizio Azzurro, Armando Gabbrielli, Alessandro Repici, Massimo Rugge, Cesare Hassan
Journal: Clinical Gastroenterology and Hepatology (2024)