tbuckley/cabot-search huggingface dataset:
A dynamic regulome of shoot-apical-meristem-related homeobox transcription factors modulates plant architecture in maize
Authors: Zi Luo, Leiming Wu, Xinxin Miao, Shuang Zhang, Ningning Wei, Shiya Zhao, Xiaoyang Shang, Hongyan Hu, Jiquan Xue, Tifu Zhang, Fang Yang, Shutu Xu, Lin Li
Journal: Genome biology (2024)
Colesevelam for lenalidomide associated diarrhea in patients with multiple myeloma
Authors: Malin Hultcrantz, Hani Hassoun, Neha Korde, Kylee MacLachlan, Sham Mailankody, Dhwani Patel, Urvi A Shah, Carlyn Rose Tan, David J Chung, Oscar B Lahoud, Heather J Landau, Michael Scordo, Gunjan L Shah, Sergio A Giralt, Matthew J Pianko, Miranda Burge, Kelly Barnett, Meghan Salcedo, Julia Caple, Linh Tran, Jenna Blaslov, Tala Shekarkhand, Selena Hamid, David Nemirovsky, Andriy Derkach, Oluwatobi Arisa, Cody J Peer, William D Figg, Saad Z Usmani, Ola Landgren, Alexander M Lesokhin
Journal: Blood Cancer Journal (2024)
Bioinspired Asymmetric‐Adhesion Janus Hydrogel Patch Regulating by Zwitterionic Polymers for Wet Tissues Adhesion and Postoperative Adhesion Prevention
Authors: Shuangyang Li, Lingyuan Liu, Fengtao Qiao, Jinzhu Ma, Hui Miao, Shangdong Gao, Yongqiang Ma, Xinghui Yu, Siyuan Liu, Haicheng Yuan, Anjie Dong
Journal: Advanced Healthcare Materials (2024)

Abstract Asymmetrically adhesive hydrogel patch with robust wet tissue adhesion simultaneously anti‐postoperative adhesion is essential for clinical applications in internal soft‐tissue repair and postoperative anti‐adhesion. Herein, inspired by the lubricative role of serosa and the underwater adhesion mechanism of mussels, an asymmetrically adhesive hydrogel Janus patch is developed with adhesion layer (AL) and anti‐adhesion layer (anti‐AL) through an in situ step‐by‐step polymerization process in the mold. The AL exhibits excellent adhesion to internal soft‐tissues. In contrast, the anti‐AL demonstrated ultralow fouling property against protein and fibroblasts, which hinders the early and advanced stages of development of the adhesion. Moreover, the Janus patch simultaneously promotes tissue regeneration via ROS clearance capability of catechol moieties in the AL. Results from in vivo experiments with rabbits and rats demonstrate that the AL strongly adheres to traumatized tissue, while the anti‐AL surface demonstrate efficacy in preventing of post‐abdominal surgery adhesions in contrast to clinical patches. Considering the advantages in terms of therapeutic efficacy and off the shelf, the Janus patch developed in this work presents a promise for preventing postoperative adhesions and promoting regeneration of internal tissue defects.
Spatial colocalization and combined survival benefit of natural killer and CD8 T cells despite profound MHC class I loss in non-small cell lung cancer
Authors: Remziye E Wessel, Nardin Ageeb, Joseph M Obeid, Ileana S Mauldin, Kate A Goundry, Gabriel F Hanson, Mahdin Hossain, Chad Lehman, Ryan D Gentzler, Nolan A Wages, Craig L Slingluff, Timothy N J Bullock, Sepideh Dolatshahi, Michael G Brown
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Major histocompatibility complex class I (MHC-I) loss is frequent in non-small cell lung cancer (NSCLC) rendering tumor cells resistant to T cell lysis. NK cells kill MHC-I-deficient tumor cells, and although previous work indicated their presence at NSCLC margins, they were functionally impaired. Within, we evaluated whether NK cell and CD8 T cell infiltration and activation vary with MHC-I expression. Methods We used single-stain immunohistochemistry (IHC) and Kaplan-Meier analysis to test the effect of NK cell and CD8 T cell infiltration on overall and disease-free survival. To delineate immune covariates of MHC-I-disparate lung cancers, we used multiplexed immunofluorescence (mIF) imaging followed by multivariate statistical modeling. To identify differences in infiltration and intercellular communication between IFNγ-activated and non-activated lymphocytes, we developed a computational pipeline to enumerate single-cell neighborhoods from mIF images followed by multivariate discriminant analysis. Results Spatial quantitation of tumor cell MHC-I expression revealed intratumoral and intertumoral heterogeneity, which was associated with the local lymphocyte landscape. IHC analysis revealed that high CD56 + cell numbers in patient tumors were positively associated with disease-free survival (HR=0.58, p=0.064) and overall survival (OS) (HR=0.496, p=0.041). The OS association strengthened with high counts of both CD56 + and CD8 + cells (HR=0.199, p&lt;1×10 −3 ). mIF imaging and multivariate discriminant analysis revealed enrichment of both CD3 + CD8 + T cells and CD3 – CD56 + NK cells in MHC-I-bearing tumors (p&lt;0.05). To infer associations of functional cell states and local cell–cell communication, we analyzed spatial single-cell neighborhood profiles to delineate the cellular environments of IFNγ +/– NK cells and T cells. We discovered that both IFNγ + NK and CD8 T cells were more frequently associated with other IFNγ + lymphocytes in comparison to IFNγ – NK cells and CD8 T cells (p&lt;1×10 –30 ). Moreover, IFNγ + lymphocytes were most often found clustered near MHC-I + tumor cells. Conclusions Tumor-infiltrating NK cells and CD8 T cells jointly affected control of NSCLC tumor progression. Coassociation of NK and CD8 T cells was most evident in MHC-I-bearing tumors, especially in the presence of IFNγ. Frequent colocalization of IFNγ + NK cells with other IFNγ + lymphocytes in near-neighbor analysis suggests NSCLC lymphocyte activation is coordinately regulated.
The effects of age and frailty on the risks of end-stage renal disease, death, and severe infection in older adults with antineutrophil cytoplasmic antibody-associated vasculitis: a retrospective cohort study
Authors: Sebastian E Sattui, Bohang Jiang, Xiaoqing Fu, Claire Cook, Shruthi Srivatsan, Zachary K Williams, Guy Katz, Yuqing Zhang, Zachary S Wallace
Journal: The Lancet Rheumatology (2024)
Stereotactic body radiotherapy with sequential tislelizumab and chemotherapy as neoadjuvant therapy in patients with resectable non-small-cell lung cancer in China (SACTION01): a single-arm, single-centre, phase 2 trial
Authors: Ze-Rui Zhao, Shi-Liang Liu, Ting Zhou, Gang Chen, Hao Long, Xiao-Dong Su, Xu Zhang, Jian-Hua Fu, Peng Lin, Lan-Jun Zhang, Tie-Hua Rong, Jia-Di Wu, Zhi-Chao Li, Hui-Lin Su, Ji-Yang Chen, Yun-Peng Yang, Yong-Bin Lin, Mian Xi, Hong Yang
Journal: The Lancet Respiratory Medicine (2024)
Immunosuppressive agents or intravenous immunoglobulin in addition to glucocorticoids in the treatment of Susac syndrome: a French national cohort study
Authors: Alexandra Kachaner, Arthur Mageau, Tiphaine Goulenok, Chrystelle François, Nicole Delory, Marie-Paule Chauveheid, Cedric Louenan, Serge Doan, Caroline Halimi, Isabelle Klein, Thomas Papo, Karim Sacré
Journal: The Lancet Rheumatology (2024)
Temporary adaptations to sexual behaviour during the mpox outbreak in 23 countries in Europe and the Americas: findings from a retrospective cross-sectional online survey
Authors: Mateo Prochazka, Pietro Vinti, Ana Hoxha, Andy Seale, Antons Mozalevskis, Rosamund Lewis, Ruben Mayorga Sagastume, Martha Scherzer, Leilia Dore, Meg Doherty
Journal: The Lancet Infectious Diseases (2024)
Human hypofunctional<i>NCF1</i>variants promote pulmonary fibrosis in the bleomycin-induced mouse model and patients with systemic sclerosis via expansion of SPP1<sup>+</sup>monocytes-derived macrophages
Authors: Xinran Yuan, Xiaodong Qin, Kenji Takemoto, Jian Zhao, Matthew Sanderson, Xue Xu, Yu Zhang, Kristi L Helke, Bethany Jacobs Wolf, Joel M Guthridge, Judith A James, Xiaodong Zhou, Shervin Assassi, Carol Feghali-Bostwick, Dandan Wang, Lingyun Sun, Betty P Tsao
Journal: Annals of the Rheumatic Diseases (2024)

We assessed the role of a systemic lupus erythematosus causal hypofunctional variant, neutrophil cytosolic factor 1 (NCF1)-p.Arg90His (p.R90H) substitution, in systemic sclerosis (SSc). Association of NCF1-H90 with SSc was performed in case-control cohorts, bleomycin (BLM)-treated Ncf1-R90 C57BL/6 wildtype and Ncf1-H90 knock-in (KI) littermates. Peripheral blood mononuclear cell (PBMC) subsets were analysed by cytometry by time-of-flight. The NCF1-H90 allele is associated with risk for diffuse cutaneous SSc (dcSSc) in Chinese and European Americans, and lung fibrosis in Chinese patients with SSc (OR=2.09, p=7.96E-10). Low copy number of NCF1 associated with lung fibrosis in European Americans (OR=4.33, p=2.60E-2). BLM-treated KI mice demonstrated increased pulmonary fibrosis, exhibiting activated type I interferon signature, elevated Spp1, Ccl2, Arg1, Timp1 and Il6 expression, enriched macrophage scores in lung tissues. In a longitudinal observation cohort, homozygous H90 patients with SSc at baseline had increased anti-nuclear antibody titres, anti-topoisomerase antibody seropositivity and anti-centromere antibody seronegativity, increased incidence of lung fibrosis and Gender-Age-lung Physiology index, elevated modified Rodnan Skin Score (mRSS) and elevated plasma osteopontin (OPN, SPP1), CCL2, ARG1, TIMP-1 and IL-6. These H90 patients with SSc sustained elevated mRSS during follow-up years with decreased survival. The 0, 1 and 2 copies of H90 carriage in SSc PBMCs exhibited dose-dependent increases in profibrotic CD14+CD68+CD11b+Tim3+monocytes. Elevated OPN, CCL2 and ARG1 in CD68+CD11b+monocyte-derived macrophages from H90 patients were decreased after co-culturing with anti-CCL2 antibody. Low NCF1 activity increases the risk for the development of dcSSc and lung fibrosis via expanding profibrotic SPP1+MoMs in a CCL2-dependent manner, contributing to the severity of lung fibrosis in both BLM-treated mice and patients with SSc.
Is a 1-year course of methotrexate in patients with arthralgia at-risk for rheumatoid arthritis cost-effective? A cost-effectiveness analysis of the randomised, placebo-controlled TREAT EARLIER trial
Authors: Elise van Mulligen, Sterre S Bour, Lucas M A Goossens, Pascal Hendrik Pieter de Jong, Maureen Rutten-van Mölken, Annette van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2024)

Rheumatoid arthritis (RA) has a considerable disease burden with life-long physical limitations, reduced work productivity and high societal costs. Trials on arthralgia at-risk for RA are therefore conducted, aiming to intercept evolving RA and reduce the disease burden. A 1-year course of methotrexate in patients with clinically suspect arthralgia (CSA) caused sustained improvements in subclinical joint inflammation and physical impairments. Since the cost-effectiveness of treatment in CSA has never been investigated, we investigated whether methotrexate is cost-effective. Cost-effectiveness was assessed using the TREAT EARLIER trial. 236 patients with CSA with subclinical joint inflammation were randomised to 1-year treatment with methotrexate, or placebo, and followed for 2 years. Cost-effectiveness was analysed by computing costs and effects. For costs, both a societal perspective (healthcare-productivity and work-productivity costs) and a healthcare perspective (healthcare costs only) were used. For effects, quality adjusted life years (QALYs) were used. Treatment increased QALYs by 0.041 (95% CI -0.050 to 0.091), and reduced costs with €-4809 (95% CI -12 382 to 2726) over the course of 2 years using a societal perspective, with a probability of 88.1% that treatment was cost-effective. From a healthcare perspective, the cost-difference between treatment and placebo was estimated at €-418 (95% CI -1198 to 225). A fixed treatment course in individuals with arthralgia at-risk for RA and MRI-detected subclinical joint inflammation resulted in better work productivity, lower healthcare costs and improved quality of life over the course of 2 years; with the largest gain in productivity costs. This is the first evidence that methotrexate treatment aiming at secondary prevention in arthralgia at-risk for RA is cost-effective.
Exploring recent advances in drugs severe cutaneous adverse reactions immunopathology
Authors: Romane Cadot, Perrine Gery, Vanina Lenief, Jean‐François Nicolas, Marc Vocanson, Marie Tauber
Journal: Allergy (2024)

Abstract Severe cutaneous adverse reactions to drugs (SCARs) are rare but life‐threatening delayed allergies. While they primarily affect the skin, they can also affect internal organs. Accordingly, they present with diverse clinical symptoms that vary not only between SCARs subtypes but also among patients. Despite the availability of topical and systemic treatments, these only address the symptoms and not the cause. To develop more effective therapies, it is necessary to elucidate the complexity of the pathophysiology of SCARs in relation to their severity. In line with the new type IV hypersensitivity reactions nomenclature proposed by the European Academy of Allergy and Clinical Immunology (EAACI), this review highlights the current insights into the intricate immune mechanisms engaged, the interplay between the culprit drug and genetic predisposition in drug presentation mechanisms, but also how external factors, such as viruses, are implicated in SCARs. Their relevance to the development of targeted medicine is also discussed.
m<sup>6</sup>A RNA methylation controls salivary gland epithelial cell function and has a protective role in Sjögren’s disease
Authors: Frederic Truffinet, Alejandro Arco-Hierves, Hosnia Shalabi, Juliette Pascaud, Paul Mazet, Elodie Rivière, Sacha E Silva-Saffar, Lucilla Fabbri, Sophie Leboucher, Laetitia Besse, Cedric Messaoudi, Aurore Attina, Alexandre David, Stephan Vagner, Gaetane Nocturne, Xavier Mariette, Rami Bechara
Journal: Annals of the Rheumatic Diseases (2024)

Objectives The RNA epitranscriptomic modification known as N6 -methyladenosine (m 6 A) represents a novel mechanism of gene regulation that is poorly understood in human autoimmune diseases. Our research explores the role of this RNA m 6 A modification in salivary gland epithelial cells (SGEC) and its impact on the pathogenesis of Sjögren’s disease (SjD). Methods SGECs from SjD patients and controls were analysed for m 6 A writers METTL3 and METTL14 expression using RNA-seq, quantitative PCR and immunohistochemistry. Functional assays assessed the impact of METTL3 knockdown or pharmacological inhibition on proinflammatory gene expression and immune cell interactions (using transwell and coculture systems). Mechanistic studies examined METTL3-mediated m 6 A modifications in double-stranded RNA (dsRNA) formation through immunofluorescence. Unsupervised clustering identified patterns of interferon activation in salivary glands and their correlation with m 6 A writers. Results METTL3 and METTL14 were elevated in SGEC from SjD patients in comparison to controls. Paradoxically, inhibiting METTL3 increased proinflammatory gene expression, enhancing SGEC’s ability to attract immune cells and activate B cells. Conversely, inhibiting the eraser FTO had the opposite effect. METTL3-mediated m 6 A modifications prevented dsRNA formation and IFN signalling activation. SGEC from SjD showed insufficient METTL3 upregulation compared with controls in response to inflammatory triggers, indicating a limited capacity to regulate the inflammatory response. SjD patients with elevated disease activity and higher interferon signature exhibit reduced METTL3 expression. Conclusions Impairment of m 6 A modifications in SGEC in response to inflammatory triggers favour the formation of dsRNA, potentially amplifying the interferon loop and contributing to SjD pathogenesis.
Assessing the performance of AI chatbots in answering patients’ common questions about low back pain
Authors: Simone P S Scaff, Felipe J J Reis, Giovanni E Ferreira, Maria Fernanda Jacob, Bruno T Saragiotto
Journal: Annals of the Rheumatic Diseases (2024)

The aim of this study was to assess the accuracy and readability of the answers generated by large language model (LLM)-chatbots to common patient questions about low back pain (LBP). This cross-sectional study analysed responses to 30 LBP-related questions, covering self-management, risk factors and treatment. The questions were developed by experienced clinicians and researchers and were piloted with a group of consumer representatives with lived experience of LBP. The inquiries were inputted in prompt form into ChatGPT 3.5, Bing, Bard (Gemini) and ChatGPT 4.0. Responses were evaluated in relation to their accuracy, readability and presence of disclaimers about health advice. The accuracy was assessed by comparing the recommendations generated with the main guidelines for LBP. The responses were analysed by two independent reviewers and classified as accurate, inaccurate or unclear. Readability was measured with the Flesch Reading Ease Score (FRES). Out of 120 responses yielding 1069 recommendations, 55.8% were accurate, 42.1% inaccurate and 1.9% unclear. Treatment and self-management domains showed the highest accuracy while risk factors had the most inaccuracies. Overall, LLM-chatbots provided answers that were 'reasonably difficult' to read, with a mean (SD) FRES score of 50.94 (3.06). Disclaimer about health advice was present around 70%-100% of the responses produced. The use of LLM-chatbots as tools for patient education and counselling in LBP shows promising but variable results. These chatbots generally provide moderately accurate recommendations. However, the accuracy may vary depending on the topic of each question. The reliability level of the answers was inadequate, potentially affecting the patient's ability to comprehend the information.
Lupus and inflammatory bowel disease share a common set of microbiome features distinct from other autoimmune disorders
Authors: Hao Zhou, Diana Balint, Qiaojuan Shi, Tim Vartanian, Martin A Kriegel, Ilana Brito
Journal: Annals of the Rheumatic Diseases (2024)

This study aims to elucidate the microbial signatures associated with autoimmune diseases, particularly systemic lupus erythematosus (SLE) and inflammatory bowel disease (IBD), compared with colorectal cancer (CRC), to identify unique biomarkers and shared microbial mechanisms that could inform specific treatment protocols. We analysed metagenomic datasets from patient cohorts with six autoimmune conditions-SLE, IBD, multiple sclerosis, myasthenia gravis, Graves' disease and ankylosing spondylitis-contrasting these with CRC metagenomes to delineate disease-specific microbial profiles. The study focused on identifying predictive biomarkers from species profiles and functional genes, integrating protein-protein interaction analyses to explore effector-like proteins and their targets in key signalling pathways. Distinct microbial signatures were identified across autoimmune disorders, with notable overlaps between SLE and IBD, suggesting shared microbial underpinnings. Significant predictive biomarkers highlighted the diverse microbial influences across these conditions. Protein-protein interaction analyses revealed interactions targeting glucocorticoid signalling, antigen presentation and interleukin-12 signalling pathways, offering insights into possible common disease mechanisms. Experimental validation confirmed interactions between the host protein glucocorticoid receptor (NR3C1) and specific gut bacteria-derived proteins, which may have therapeutic implications for inflammatory disorders like SLE and IBD. Our findings underscore the gut microbiome's critical role in autoimmune diseases, offering insights into shared and distinct microbial signatures. The study highlights the potential importance of microbial biomarkers in understanding disease mechanisms and guiding treatment strategies, paving the way for novel therapeutic approaches based on microbial profiles. NCT02394964.
Antimicrobial resistance: a concise update
Authors: Charlotte S Ho, Carlos T H Wong, Thet Tun Aung, Rajamani Lakshminarayanan, Jodhbir S Mehta, Saaeha Rauz, Alan McNally, Balint Kintses, Sharon J Peacock, Cesar de la Fuente-Nunez, Robert E W Hancock, Darren S J Ting
Journal: The Lancet Microbe (2024)
Intravenous versus oral iron for anaemia among pregnant women in Nigeria (IVON): an open-label, randomised controlled trial
Authors: Bosede B Afolabi, Ochuwa A Babah, Titilope A Adeyemo, Mobolanle Balogun, Aduragbemi Banke-Thomas, Ajibola I Abioye, Opeyemi R Akinajo, Hadiza S Galadanci, Rachel A Quao, Hameed Adelabu, Nadia A Sam-Agudu, Victoria O Adaramoye, Abdulazeez Abubakar, Bolanle Banigbe, Gbenga Olorunfemi, Lenka Beňová, Elin C Larsson, Kristi S Annerstedt, Claudia Hanson, Jim Thornton
Journal: The Lancet Global Health (2024)
Evaluating national infection prevention and control minimum requirements: evidence from global cross-sectional surveys, 2017–22
Authors: Ermira Tartari, Sara Tomczyk, Anthony Twyman, Ana Paula Coutinho Rehse, Mohamed Gomaa, Maha Talaat, Aparna Singh Shah, Howard Sobel, Joao Paulo Toledo, Benedetta Allegranzi
Journal: The Lancet Global Health (2024)
Combined interventions for the testing and treatment of HIV and schistosomiasis among fishermen in Malawi: a three-arm, cluster-randomised trial
Authors: Augustine T Choko, Kathryn L Dovel, Sekeleghe Kayuni, Donaldson F Conserve, Anthony Buttterworth, Amaya L Bustinduy, J Russell Stothard, Wala Kamchedzera, Madalo Mukoka-Thindwa, James Jafali, Peter MacPherson, Katherine Fielding, Nicola Desmond, Elizabeth L Corbett
Journal: The Lancet Global Health (2024)
Delivery effectiveness of and adherence to intermittent preventive treatment for malaria in pregnancy with dihydroartemisinin–piperaquine with or without targeted information transfer or sulfadoxine–pyrimethamine in western Kenya: a three-armed, pragmatic, open-label, cluster-randomised trial
Authors: Hellen C Barsosio, Jayne Webster, Frederick Omiti, Alloys K'Oloo, Isdorah A Odero, Michael A Ojuok, Dawn Odiwa, Benson Omondi, Elizabeth Okello, James Dodd, Miriam Taegtmeyer, Feiko O Ter Kuile, Maia Lesosky, Simon Kariuki, Jenny Hill
Journal: The Lancet Global Health (2024)
Assessing the effect of health system resources on HIV and tuberculosis programmes in Malawi: a modelling study
Authors: Tara D Mangal, Sakshi Mohan, Timothy Colbourn, Joseph H Collins, Mathew Graham, Andreas Jahn, Eva Janoušková, Ines Li Lin, Robert Manning Smith, Emmanuel Mnjowe, Margherita Molaro, Tisungane E Mwenyenkulu, Dominic Nkhoma, Bingling She, Asif Tamuri, Paul Revill, Andrew N Phillips, Joseph Mfutso-Bengo, Timothy B Hallett
Journal: The Lancet Global Health (2024)
Population attributable fractions for risk factors for dementia in seven Latin American countries: an analysis using cross-sectional survey data
Authors: Regina Silva Paradela, Ismael Calandri, Natalia Pozo Castro, Emanuel Garat, Carolina Delgado, Lucia Crivelli, Kristine Yaffe, Cleusa P Ferri, Naaheed Mukadam, Gill Livingston, Claudia Kimie Suemoto
Journal: The Lancet Global Health (2024)
Will Transformers change gastrointestinal endoscopic image analysis? A comparative analysis between CNNs and Transformers, in terms of performance, robustness and generalization
Authors: Carolus H J Kusters, Tim J M Jaspers, Tim G W Boers, Martijn R Jong, Jelmer B Jukema, Kiki N Fockens, Albert J de Groof, Jacques J Bergman, Fons van der Sommen, Peter H N De With
Journal: Medical Image Analysis (2024)
FTO-mediated DSP m6A demethylation promotes an aggressive subtype of growth hormone-secreting pituitary neuroendocrine tumors
Authors: Yunzhi Zou, Xiaoqiong Bao, Depei Li, Zhen Ye, Rong Xiang, Yuanzhong Yang, Zhe Zhu, Ziming Chen, Lingxing Zeng, Chunling Xue, Hongzhe Zhao, Boyuan Yao, Qilin Zhang, Zeming Yan, Zekun Deng, Jintong Cheng, Guanghao Yue, Wanming Hu, Jixiang Zhao, Ruihong Bai, Zhenhua Zhang, Aiqun Liu, Jialiang Zhang, Zhixiang Zuo, Xiaobing Jiang
Journal: Molecular Cancer (2024)
Urinary bladder transplantation in humans — current status and future perspectives
Authors: Michał C Czarnogórski, Krzysztof Koper, Piotr Petrasz, Malte W Vetterlein, Marta Pokrywczyńska, Kajetan Juszczak, Tomasz Drewa, Jan Adamowicz
Journal: Nature Reviews Urology (2024)