tbuckley/cabot-search huggingface dataset:
Substitution of Glutamic Acid at Position 71 of <scp>DRβ1</scp>*04:01 Induces Collagen‐Specific Tolerance Without Inducing Alloreactivity
Authors: Vibha Jha, Brian M. Freed, Elizabeth R. Sunderhaus, Jessica E. Lee, Edward B. Prage, Manjula Miglani, Edward F. Rosloniec, Jennifer L. Matsuda, Marilyne G. Coulombe, Amy S. McKee, Christina L. Roark
Journal: Arthritis & Rheumatology (2024)

Objective The DRB1 locus is strongly associated with both susceptibility and resistance to rheumatoid arthritis (RA). DRB1 alleles encoding the VKA or VRA epitope in positions 11, 71 and 74 confer the highest risk of developing RA, while the allele encoding VEA is protective. We therefore investigated the feasibility of creating antigen‐specific tolerance without inducing alloreactivity by replacing lysine with glutamic acid at position 71 in DRβ1*04:01. Materials and Methods Individual DRB1 alleles and the DRB1*04:01 K71E allele were cloned into T2 cell lines to measure binding of biotinylated peptides. Transgenic animals expressing DRB1*04:01, DRB1*01:01 or DRB1*04:01 K71E were injected with collagen to measure T cell proliferation. Skin and bone marrow transplants between DRB1*04:01 K71E and DRB1*04:01 mice were performed to determine if the single amino acid change at position 71 would be recognized as foreign. DRB1*04:01 mice transplanted with DRB1*04:01 K71E bone marrow were injected with collagen to test if resistance to collagen sensitization could be transferred. Results Replacing lysine (K) at position 71 in DRβ1*04:01 with glutamic acid (E) blocked collagen peptide binding and rendered the DRB1*04:01 K71E mice resistant to collagen sensitization. Skin and bone marrow transplants from DRB1*04:01 K71E mice were not rejected by DRB1*04:01 mice, suggesting the single E 71 difference was not recognized as allogeneic. Bone marrow from DRB1*04:01 K71E mice adoptively transferred antigen‐specific tolerance to collagen to DRB1*04:01 mice. Conclusion These studies demonstrate that editing a single amino acid in DRβ1*04:01 blocks collagen peptide binding without inducing alloreactivity and could therefore represent a gene therapy approach to induce antigen‐specific passive tolerance.
A comparative analysis of transformed indolent lymphomas and de novo diffuse large B-cell lymphoma: a population-based cohort study
Authors: John L. Vaughn, Angela Ramdhanny, Malak Munir, Sravani Rimmalapudi, Narendranath Epperla
Journal: Blood Cancer Journal (2024)

Abstract Histologic transformation (HT) of indolent non-Hodgkin lymphoma (iNHL) to diffuse large B-cell lymphoma (DLBCL) carries a poor prognosis. Using the Surveillance, Epidemiology, and End Results-17 database, we conducted a population-based study of adult patients with transformed follicular lymphoma (t-FL), marginal zone lymphoma (t-MZL), lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (t-LPL/WM), and de novo DLBCL. Primary outcome was relative survival (RS), and secondary outcomes included overall survival (OS) and lymphoma-specific survival (LSS). Outcomes were modeled using flexible parametric survival models, while multivariable modeling was used to compare RS, OS, and LSS. The incidence of HT was highest in splenic MZL (SMZL, 6.78%) and lowest in extranodal MZL (EMZL, 1.62%). Median follow-up times were similar for patients with de novo DLBCL and transformed indolent lymphomas. The 5-year RS and OS were longer in de novo DLBCL compared to all other transformed iNHL subtypes (68 versus 59%, respectively). For t-FL, early transformation (within 2 years of diagnosis, Hazard ratio [HR] = 1.34) and prior treatment (HR = 1.89) were associated with inferior survival. This association was not observed in other transformed lymphoma subtypes. This is the first comparative study to show that the outcomes of t-LPL/WM were inferior compared to de novo DLBCL and highlights the need to incorporate early experimental therapies in patients with t-FL with early transformation and receipt of prior chemotherapy.
Ocular immune‐related diseases: molecular mechanisms and therapy
Authors: Yakun Wang, Shangze Gao, Fan Cao, Hui Yang, Fengyang Lei, Shengping Hou
Journal: MedComm (2024)

Abstract Ocular immune‐related diseases, represent a spectrum of conditions driven by immune system dysregulation, include but not limit to uveitis, diabetic retinopathy, age‐related macular degeneration, Graves’ ophthalmopathy, etc. The molecular and cellular mechanisms underlying these diseases are typically dysfunctioned immune responses targeting ocular tissues, resulting in inflammation and tissue damage. Recent advances have further elucidated the pivotal role of different immune responses in the development, progression, as well as management of various ocular immune diseases. However, there is currently a relative lack of connection between the cellular mechanisms and treatments of several immune‐related ocular diseases. In this review, we discuss recent findings related to the immunopathogenesis of above‐mentioned diseases. In particular, we summarize the different types of immune cells, inflammatory mediators, and associated signaling pathways that are involved in the pathophysiology of above‐mentioned ophthalmopathies. Furthermore, we also discuss the future directions of utilizing anti‐inflammatory regime in the management of these diseases. This will facilitate a better understanding of the pathogenesis of immune‐related ocular diseases and provide new insights for future treatment approaches.
Exploring artificial intelligence-assisted diagnosis of esophageal squamous cell carcinoma: insights from a clinical trial
Authors: Bing Hu
Journal: Endoscopy (2024)

Esophageal squamous cell carcinoma (ESCC) remains a significant global health burden, with persistently high incidence and mortality rates [1]. Early detection and timely treatment are essential for improving patients outcomes, with esophagogastroduodenoscopy playing an irreplaceable role in this process [2]. The endoscopic features of superficial ESCC are however often subtle compared with the surrounding mucosa, necessitating the integration of multiple modalities, such as white-light imaging (WLI), narrow-band imaging (NBI), and iodine staining, for effective screening. The detection rate of superficial ESCC varies considerably, influenced by disparities in endoscopic equipment, as well as the skills and experience of individual endoscopists.
Risk factors and temporal associations of progression of the atopic march in children with early-onset atopic dermatitis
Authors: Una E Choi, Junwen Deng, Varsha Parthasarathy, Viviane Liao, Anjali D'Amiano, Matthew Taylor, Zachary A Bordeaux, Anusha Kambala, Hannah L Cornman, Joseph K Canner, Aaron M Drucker, Shawn G Kwatra
Journal: Journal of the American Academy of Dermatology (2024)
Adverse Events in Patients with Obstructive Sleep Apnea Undergoing Procedural Sedation in Ambulatory Settings: An Updated Systematic Review and Meta-Analysis
Authors: Felicia Ceban, Naomi Abayomi, Aparna Saripella, Jennita Ariaratnam, Glen Katsnelson, Ellene Yan, Marina Englesakis, Tong J Gan, Girish P Joshi, Frances Chung
Journal: Sleep Medicine Reviews (2024)
Semi automatic quantification of REM sleep without atonia in natural sleep environment
Authors: Daniel Possti, Shani Oz, Aaron Gerston, Danielle Wasserman, Iain Duncan, Matteo Cesari, Andrew Dagay, Riva Tauman, Anat Mirelman, Yael Hanein
Journal: npj Digital Medicine (2024)

Polysomnography, the gold standard diagnostic tool in sleep medicine, is performed in an artificial environment. This might alter sleep and may not accurately reflect typical sleep patterns. While macro-structures are sensitive to environmental effects, micro-structures remain more stable. In this study we applied semi-automated algorithms to capture REM sleep without atonia (RSWA) and sleep spindles, comparing lab and home measurements. We analyzed 107 full-night recordings from 55 subjects: 24 healthy adults, 28 Parkinson's disease patients (15 RBD), and three with isolated Rem sleep behavior disorder (RBD). Sessions were manually scored. An automatic algorithm for quantifying RSWA was developed and tested against manual scoring. RSWAi showed a 60% correlation between home and lab. RBD detection achieved 83% sensitivity, 79% specificity, and 81% balanced accuracy. The algorithm accurately quantified RSWA, enabling the detection of RBD patients. These findings could facilitate more accessible sleep testing, and provide a possible alternative for screening RBD.
Metabolic reprogramming via mitochondrial delivery for enhanced maturation of chemically induced cardiomyocyte‐like cells
Authors: Yena Nam, Yoonji Song, Seung Ju Seo, Ga Ryang Ko, Seung Hyun Lee, Eunju Cha, Su Min Kwak, Sumin Kim, Mikyung Shin, Yoonhee Jin, Jung Seung Lee
Journal: MedComm (2024)

Abstract Heart degenerative diseases pose a significant challenge due to the limited ability of native heart to restore lost cardiomyocytes. Direct cellular reprogramming technology, particularly the use of small molecules, has emerged as a promising solution to prepare functional cardiomyocyte through faster and safer processes without genetic modification. However, current methods of direct reprogramming often exhibit low conversion efficiencies and immature characteristics of the generated cardiomyocytes, limiting their use in regenerative medicine. This study proposes the use of mitochondrial delivery to metabolically reprogram chemically induced cardiomyocyte‐like cells (CiCMs), fostering enhanced maturity and functionality. Our findings show that mitochondria sourced from high‐energy‐demand organs (liver, brain, and heart) can enhance structural maturation and metabolic functions. Notably, heart‐derived mitochondria resulted in CiCMs with a higher oxygen consumption rate capacity, enhanced electrical functionality, and higher sensitivity to hypoxic condition. These results are related to metabolic changes caused by increased number and size of mitochondria and activated mitochondrial fusion after mitochondrial treatment. In conclusion, our study suggests that mitochondrial delivery into CiCMs can be an effective strategy to promote cellular maturation, potentially contributing to the advancement of regenerative medicine and disease modeling.
Inflammatory pathways and anti‐inflammatory therapies in sickle cell disease
Authors: Karina Tozatto‐Maio, Felipe A. Rós, Ricardo Weinlich, Vanderson Rocha
Journal: HemaSphere (2024)

Abstract Sickle cell disease (SCD) is a monogenic disease, resulting from a single‐point mutation, that presents a complex pathophysiology and high clinical heterogeneity. Inflammation stands as a prominent characteristic of SCD. Over the past few decades, the role of different cells and molecules in the regulation of the inflammatory process has been elucidated. In conjunction with the polymerization of hemoglobin S (HbS), intravascular hemolysis, which releases free heme, HbS, and hemoglobin‐related damage‐associated molecular patterns, initiates multiple inflammatory pathways that are not yet fully comprehended. These complex phenomena lead to a vicious cycle that perpetuates vaso‐occlusion, hemolysis, and inflammation. To date, few inflammatory biomarkers can predict disease complications; conversely, there is a plethora of therapies that reduce inflammation in SCD, although clinical outcomes vary widely. Importantly, whether the clinical heterogeneity and complications are related to the degree of inflammation is not known. This review aims to further our understanding of the roles of main immune cells, and other inflammatory factors, as potential prognostic biomarkers for predicting clinical outcomes or identifying novel treatments for SCD.
Genetic variation at 11q23.1 confers colorectal cancer risk by dysregulation of colonic tuft cell transcriptional activator<i>POU2AF2</i>
Authors: Vidya Rajasekaran, Bradley T Harris, Ruby T Osborn, Claire Smillie, Kevin Donnelly, Marion Bacou, Edward Esiri-Bloom, Li-Yin Ooi, Morven Allan, Marion Walker, Stuart Reid, Alison Meynert, Graeme Grimes, James P Blackmur, Peter G Vaughan-Shaw, Philip J Law, Ceres Fernández-Rozadilla, Ian Tomlinson, Richard S Houlston, Kevin B Myant, Farhat VN Din, Maria Timofeeva, Malcolm G Dunlop, Susan M Farrington
Journal: Gut (2024)

Background Common genetic variation at 11q23.1 is associated with colorectal cancer (CRC) risk, exerting local expression quantitative trait locus (cis-eQTL) effects on POU2AF2 , COLCA1 and POU2AF3 genes. However, complex linkage disequilibrium and correlated expression has hindered elucidation of the mechanisms by which genetic variants impart underlying CRC risk. Objective Undertake an interdisciplinary approach to understand how variation at 11q23.1 locus imparts CRC risk. Design We employ analysis of RNA sequencing, single-cell RNA sequencing, chromatin immunoprecipitation sequencing and single-cell ATAC sequencing data to identify, prioritise and characterise the genes that contribute to CRC risk. We further validate these findings using mouse models and demonstrate parallel effects in human colonic mucosa. Results We establish rs3087967 as a prime eQTL variant at 11q23.1, colocalising with CRC risk. Furthermore, rs3087967 influences expression of 21 distant genes, thereby acting as a trans-eQTL hub for a gene-set highly enriched for tuft cell markers. Epigenomic analysis implicates POU2AF2 as controlling the tuft cell-specific trans-genes, through POU2F3-correlated genomic regulation. Immunofluorescence confirms rs3087967 risk genotype (T) to be associated with a tuft cell deficit in the human colon. CRISPR-mediated deletion of the 11q23.1 risk locus genes in the mouse germline exacerbated the Apc Min/+ mouse phenotype on abrogation of Pou2af2 expression specifically. Conclusion We demonstrate that genotype at rs3087967 controls a portfolio of genes through misregulation of POU2AF2. POU2AF2 is the primary transcriptional activator of tuft cells with a tumour suppressive role in mouse models. We therefore implicate tuft cells as having a key tumour-protective role in the large bowel epithelium.
The impact of urbanization in China on influenza incidence across neighboring cities
Authors: Hao Luo, Yongbiao Cui, Wenhao Yu, Guoao Li, Qi Zhao, Mengjie Geng, Haitao Wang, Wei Ma
Journal: Journal of Infection (2024)

Although the relationship between urbanization and influenza has received increasing attention, previous studies have often examined this relationship based on single indicators, neglecting the multi-dimensions of urban development and their integrated impact on influenza incidence in neighboring cities.
A novel HIV-1 circulating recombinant form (CRF168_0107) identified from men who have sex with men in Beijing, China
Authors: Mingfeng Xiao, Jing Tang, Jia Li, Yun Lan, Xiyao Li, Li Li, Huihuang Huang, Shufang He, Hongyan Lu, Xiaoxin He, An Liu, Ruolei Xin
Journal: Journal of Infection (2024)
TIDieR-WASH: A Guideline for Reporting Implementation of Water, Sanitation, and Hygiene Interventions
Authors: Jonny Crocker, Emily Ogutu, Jedidiah S. Snyder, Antoinette Kome, Ben Tidwell, Jan Willem Rosenboom, Jesse Shapiro, Jessy Samuyachi Mahongo, Kelly T. Alexander, Michael E. Gnilo, Om Prasad Gautam, Sara Hoffman, Sovattha Neou, Matthew C. Freeman
Journal: Environmental Health Perspectives (2024)

Accurate information on context and implementation of public health interventions is necessary to replicate, adapt, and scale effective interventions and to interpret evaluations. Reporting the context and implementation of water, sanitation, and hygiene (WASH) interventions has been inconsistent and incomplete.
Dual specific STAT3/5 degraders effectively block acute myeloid leukemia and natural killer/T cell lymphoma
Authors: Daniel Pölöske, Helena Sorger, Anna Schönbichler, Elvin D. de Araujo, Heidi A. Neubauer, Anna Orlova, Sanna H. Timonen, Diaaeldin I. Abdallah, Aleksandr Ianevski, Heikki Kuusanmäki, Marta Surbek, Elisabeth Heyes, Thomas Eder, Christina Wagner, Tobias Suske, Martin L. Metzelder, Michael Bergmann, Maik Dahlhoff, Florian Grebien, Roman Fleck, Christine Pirker, Walter Berger, Emir Hadzijusufovic, Wolfgang R. Sperr, Lukas Kenner, Peter Valent, Tero Aittokallio, Marco Herling, Satu Mustjoki, Patrick T. Gunning, Richard Moriggl
Journal: HemaSphere (2024)

Abstract The transcription factors STAT3, STAT5A, and STAT5B steer hematopoiesis and immunity, but their enhanced expression and activation promote acute myeloid leukemia (AML) or natural killer/T cell lymphoma (NKCL). Current therapeutic strategies focus on blocking upstream tyrosine kinases to inhibit STAT3/5, but these kinase blockers are not selective against STAT3/5 activation and frequent resistance causes relapse, emphasizing the need for targeted drugs. We evaluated the efficacy of JPX‐0700 and JPX‐0750 as dual STAT3/5 binding inhibitors promoting protein degradation. JPX‐0700/−0750 decreased the mRNA and protein levels of STAT3/5 targets involved in cancer survival, metabolism, and cell cycle progression, exhibiting nanomolar to low micromolar efficacy. They induced cell death and growth arrest in both AML/NKCL cell lines and primary AML patient blasts. We found that both AML/NKCL cells hijack STAT3/5 signaling through either upstream activating mutations in kinases, activating mutations in STAT3, mutational loss of negative STAT regulators, or genetic gains in anti‐apoptotic, pro‐proliferative, or epigenetic‐modifying STAT3/5 targets. This emphasizes a vicious cycle for proliferation and survival through STAT3/5. Both JPX‐0700/−0750 treatment reduced leukemic cell growth in human AML or NKCL xenograft mouse models significantly, being well tolerated by mice. Synergistic cell death was induced upon combinatorial use with approved chemotherapeutics in AML/NKCL cells.
Macular Edema Ranibizumab v. Intravitreal anti-inflammatory Therapy (MERIT) Trial—24-week Outcomes of Uveitic Macular Edema Retreatment
Authors: John Gonzales, Nisha R Acharya, Elizabeth A Sugar, Alyce E Burke, Albert T Vitale, Vishali Gupta, James P Dunn, Susan L Lightman, Jennifer E Thorne, Rosa Y Kim, Steven Yeh, Michael M Altaweel, John H Kempen, Janet T Holbrook, Douglas A Jabs
Journal: Ophthalmology (2024)
Utility of AI digital pathology as an aid for pathologists scoring fibrosis in MASH
Authors: Desiree Abdurrachim, Serene Lek, Charlene Zhi Lin Ong, Chun Kit Wong, Yongqi Zhou, Aileen Wee, Gwyneth Soon, Timothy J Kendall, Michael O Idowu, Christopher Hendra, Ashmita Saigal, Radha Krishnan, Elaine Chng, Dean Tai, Gideon Ho, Thomas Forest, Annaswamy Raji, Saswata Talukdar, Chih-Liang Chin, Richard Baumgartner, Samuel S Engel, Asad Abu Bakar Ali, David E Kleiner, Arun J Sanyal
Journal: Journal of Hepatology (2024)
Sevuparin strongly reduces hepcidin expression in cells, mice, and healthy human volunteers
Authors: Michela Asperti, Andrea Denardo, Magdalena Gryzik, Kristina E. M. Persson, Göran Westerberg, John Öhd, Maura Poli
Journal: HemaSphere (2024)

Abstract Hepcidin is an essential regulator of systemic iron availability mediating both iron uptake from the diet and its release from body stores. Abnormally high hepcidin levels resulting from inflammation in chronic diseases cause iron restriction with the onset of anemia. Restoring physiological levels of hepcidin could contribute to ameliorating anemia in these patients. Heparin derivatives are known to suppress hepcidin expression acting on the BMP/SMAD pathway. The novel heparin derivative sevuparin, modified to markedly reduce its anticoagulant activity, is proposed as a promising hepcidin antagonizing strategy. Sevuparin was tested for its anti‐hepcidin properties in vitro in HepG2 cells, in vivo in mice, and in healthy volunteers. Sevuparin strongly suppressed basal, BMP6‐, and IL6‐dependent hepcidin expression in HepG2 cells in a dose‐ and time‐dependent manner, modulating the essential BMP6/SMAD cascade. These effects were evident in C57BL/6J mice after intravenous injection of a single dose of sevuparin (20 mg/kg) with a 70% reduction of hepcidin mRNA. Remarkably, similar effects were observed in healthy volunteers following single subcutaneous doses at 3, 6, and 9 mg/kg with 40%–50% suppression at 3 and 6 mg/kg and 72% at 9 mg/kg. Moreover, sevuparin was able to reduce hepcidin upregulation in a mouse model of acute inflammation induced by LPS, also showing an amelioration of the inflammatory markers. Combined with its excellent safety profile, these data suggest a role for sevuparin in treating high‐hepcidin disorders.
Prospective phase II study of allogeneic hematopoietic stem cell transplantation with targeted busulfan, fludarabine, and etoposide conditioning in pediatric acute lymphoblastic leukemia
Authors: Kyung Taek Hong, Hyun Jin Park, Bo Kyung Kim, Jung Yoon Choi, Sang Hoon Song, SeungHwan Lee, Kyung‐Sang Yu, In‐Jin Jang, Hyoung Jin Kang
Journal: HemaSphere (2024)
Beyond cancer: The potential application of CD47-based therapy in non-cancer diseases
Authors: Wei-Qing Deng, Zi-Han Ye, Zhenghai Tang, Xiao-Lei Zhang, Jin-Jian Lu
Journal: Acta Pharmaceutica Sinica B (2024)

CD47 is an immune checkpoint widely regarded as a 'don't eat me' signal. CD47-based anti-cancer therapy has received considerable attention, with a significant number of clinical trials conducted. While anti-cancer therapies based on CD47 remain a focal point of interest among researchers, it is noteworthy that an increasing number of studies have found that CD47-based therapy ameliorated the pathological status of non-cancer diseases. This review aims to provide an overview of the recent progress in comprehending the role of CD47-based therapy in non-cancer diseases, including diseases of the circulatory system, nervous system, digestive system, and so on. Furthermore, we sought to delineate the promising mechanisms of CD47-based therapy in treating non-cancer diseases. Our findings suggest that CD47-based agents may exert their effect by regulating phagocytosis, regulating T cells, dendritic cells, and neutrophils, and regulating the secretion of cytokines and chemokines. Additionally, we put forward the orientation of further research to bring to light the potential of CD47 and its binding partners as a target in non-cancer diseases.
The BMJ Appeal 2024-25: David Miliband on hospital attacks, Trump, and the International Rescue Committee in a “flammable world”
Authors: Kamran Abbasi, Mun-Keat Looi
Journal: BMJ (2024)

Former UK foreign secretary, now president of the International Rescue Committee, talks to <b>Kamran Abbasi</b> about hospital attacks in war, the US president elect, and how his parents were refugees
Interleukin-2-secreting T helper cells promote extra-follicular B cell maturation via intrinsic regulation of a B cell mTOR-AKT-Blimp-1 axis
Authors: Caterina E Faliti, Maria Mesina, Jinyong Choi, Simon Bélanger, Monique A Marshall, Christopher M Tipton, Sakeenah Hicks, Prashanti Chappa, Maria A Cardenas, Mohamed Abdel-Hakeem, Theresa C Thinnes, Christopher Cottrell, Christopher D Scharer, William R Schief, David Nemazee, Matthew C Woodruff, John M Lindner, Ignacio Sanz, Shane Crotty
Journal: Immunity (2024)
Cognate antigen engagement induces HIV-1 expression in latently infected CD4+ T cells from people on long-term antiretroviral therapy
Authors: Milica Moskovljevic, Filippo Dragoni, Nathan L Board, Fengting Wu, Jun Lai, Hao Zhang, James R White, Rebecca Hoh, Kenneth Lynn, Pablo Tebas, Karam Mounzer, Steven G Deeks, Luis J Montaner, Janet D Siliciano, Robert F Siliciano, Francesco R Simonetti
Journal: Immunity (2024)
Associations of iron deficiency with cardiac function, congestion, exercise capacity and prognosis in heart failure
Authors: Nicolò De Biase, Lavinia Del Punta, Wouter L'Hoyes, Pierpaolo Pellicori, John G.F. Cleland, Gabriele Masini, Luna Gargani, Sara Moura‐Ferreira, Sarah Hoedemakers, Valerio Di Fiore, Lieven Herbots, Jan Stassen, Alessandro Mengozzi, Silvia Armenia, Stefano Taddei, Stefano Masi, Jan Verwerft, Nicola Riccardo Pugliese
Journal: European Journal of Heart Failure (2024)