tbuckley/cabot-search huggingface dataset:
The emergence of circulating activated autoreactive desmoglein 3-specific follicular regulatory T cells is associated with long-term efficacy of rituximab in patients with pemphigus vulgaris
Authors: Vivien Hébert, Julien Novarino, Maud Maho-Vaillant, Corine Perals, Sébastien Calbo, Marie-Laure Golinski, Fanny Martinez, Pascal Joly, Nicolas Fazilleau
Journal: British Journal of Dermatology (2024)

Abstract Background Pemphigus vulgaris (PV) is characterized by autoantibodies targeting keratinocyte adhesion proteins desmoglein (Dsg) 1 and 3, and by the human leukocyte antigen (HLA) predisposition allele HLA-DRB1*0402. Treatment using rituximab (RTX) combined with short-term corticosteroids (CS) allows disease control and long-lasting remission. Objectives The principal aim of this study was to evaluate the impact of RTX on the circulating subpopulations of Dsg3-specific T lymphocytes that specifically regulate B-cell responses: follicular helper T (Tfh) and follicular regulatory T (Tfr) lymphocytes. Methods Using the HLA-DRB1*0402 tetramer loaded with the Dsg3 immunodominant peptide, we used flow cytometry to analyse the frequency, polarization and activation status of blood Dsg3-specific follicular T-cell populations at baseline, month (M) 6 and long-term follow-up (M60–90) from patients with PV. Results At baseline, we observed a predominance of Tfh1* and Tfh17 subsets and an underrepresentation of the Tfh2 subset among autoreactive Dsg3-specific Tfh cells compared with nonautoreactive Tfh cells. RTX treatment induced a decrease of autoreactive Tfh cells with no effect on their polarization during follow-up. In parallel, we observed the emergence of a Dsg3-specific Tfr subpopulation with a significant overexpression of the surface activation markers PD1, ICOS and CD25 that was not observed at the surface of autoreactive Tfh and nonautoreactive Tfr cells of the same patients with PV. In contrast, very few Dsg3-specific Tfr cells were observed in patients with PV who were treated with CS alone. Conclusions Here we show that the emergence of circulating autoreactive Dsg3-specific Tfr cells is associated with the long-term efficacy of RTX in patients with PV. Graphical Abstract
Leukotriene receptor antagonists as add-on therapy to antihistamines for urticaria: a systematic review and meta-analysis of randomized clinical trials
Authors: Daniel G Rayner, Ming Liu, Alexandro W L Chu, Xiajing Chu, Gordon H Guyatt, Paul Oykhman, Daniel J Cao, Joseph Moellman, Moshe Ben-Shoshan, Diane R Baker, Susan Waserman, David Lang, Javed Sheikh, Sameer K Mathur, Lisa A Beck, David A Khan, Eric T Oliver, Rachel N Asiniwasis, Emily F Cole, Kathryn E Wheeler, Lauren Runyon, Jeffrey Chan, Kathryn P Trayes, Sanaz Eftekhari, Donna D Gardner, Tonya Winders, Sarbjit S Saini, Jonathan A Bernstein, Derek K Chu
Journal: Journal of Allergy and Clinical Immunology (2024)
Tumor‐Associated Myeloid Cells Selective Delivery of a Therapeutic Tumor Nano‐Vaccine for Overcoming Immune Barriers for Effective and Long‐Term Cancer Immunotherapy
Authors: Chufan Wang, Jinglian Zhao, Yufei Duan, Liping Lin, Qiang Zhang, Haiping Zheng, Wenjun Shan, Xiumin Wang, Lei Ren
Journal: Advanced Healthcare Materials (2024)

Abstract Therapeutic cancer vaccines have the potential to induce regression of established tumors, eradicate microscopic residual lesions, and prevent metastasis and recurrence, but their efficacy is limited by the low antigenicity of soluble antigens and the immunosuppressive tumor‐associated macrophages (TAMs) that promote tumor growth. In this study, a novel strategy is reported for overcoming these defenses: a dual‐targeting nano‐vaccine (NV) based on hepatitis B core antigen (HBcAg) derived virus‐like particles (VLPs), N‐M2T‐gp100 HBc NV, equipped with both SIGNR + dendritic cells (DCs)/TAMs‐targeting ability and high‐density display of tumor‐associated antigen (TAA). N‐M2T‐gp100 HBc NVs‐based immunotherapy has demonstrated an optimal interaction between tumor‐associated antigens (TAAs) and the immune composition of the tumor microenvironment. In a melanoma model, N‐M2T‐gp100 HBc VLPs significantly reducing in situ and abscopal tumor growth, and provide long‐term immune protection. This remarkable anti‐tumor effect is achieved by efficiently boosting of T cells and repolarizing of M2‐like TAMs. This work opens exciting avenues for the development of personalized tumor vaccines targeting not just melanoma but potentially a broad range of cancer types based on functionalized VLPs.
NGS-based stratification refines the risk stratification in T-ALL and identifies a Very High-Risk subgroup of patients
Authors: Mathieu Simonin, Loic Vasseur, Etienne Lengliné, Ludovic Lhermitte, Aurelie Cabannes-Hamy, Marie Balsat, Aline Schmidt, Marie-Emilie Dourthe, Aurore Touzart, Carlos Graux, Nathalie Grardel, Jean-Michel Cayuela, Isabelle Arnoux, Virginie Gandemer, Françoise Rigal-Huguet, Stéphane Ducassou, Veronique Lheritier, Yves Chalandon, Norbert Ifrah, Herve Dombret, Elizabeth A. Macintyre, Arnaud Petit, Philippe Rousselot, Jerome Lambert, André Baruchel, Nicolas Boissel, Vahid Asnafi
Journal: Blood (2024)
Foxo1 is an iron-responsive transcriptional factor regulating systemic iron homeostasis
Authors: Teng Xu, Xu Zhang, Wenting Zhao, Jiaxin Shi, Sitong Wan, Yan Zhang, Yanling Hao, Mingyue Sun, Jingjing He, Li Jiang, Hao Wang, Hong Gao, Junjie Luo, Yongting Luo, Peng An
Journal: Blood (2024)
Asciminib is a novel inhibitor of ABL1 and ABL2 gene fusions in ALL but requires the ABL SH3 domain for efficacy
Authors: Laura N. Eadie, Elias Lagonik, Elyse C. Page, Caitlin E. Schutz, Susan L. Heatley, Barbara J. McClure, Michelle O. Forgione, David T. Yeung, Timothy P. Hughes, Deborah L. White
Journal: Blood (2024)
Updated cutaneous T-cell lymphoma TNMB staging criteria fail to identify Sézary syndrome patients with low blood burden
Authors: Lauren P. Chrisman, Payton Fors Trimark, Yanzhen Pang, David Randall Pease, Maria Estela Martinez-Escala, William Q. Nguyen, Rony Fernandez, Teresa L. Griffin, Lindsey Ayanruoh, Madeline J. Hooper, Xiaolong A. Zhou, Lucy Fu, Kristy L. Wolniak, Joan Guitart
Journal: Blood (2024)
Upfront resection versus no resection of the primary tumor in patients with synchronous metastatic colorectal cancer: the randomized phase III CAIRO4 study conducted by the Dutch Colorectal Cancer Group and the Danish Colorectal Cancer Group
Authors: D.E.W. van der Kruijssen, S.G. Elias, P.M. van de Ven, K.L. van Rooijen, J.’t Lam-Boer, L. Mol, C.J.A. Punt, D.W. Sommeijer, P.J. Tanis, J.D. Nielsen, M.K. Yilmaz, J.M.G.H. van Riel, D.K. Wasowiz-Kemps, O.J.L. Loosveld, G.P. van der Schelling, J.W.B. de Groot, H.L. van Westreenen, H.L. Jakobsen, A.L. Fromm, P. Hamberg, M. Verseveld, C. Jaensch, G.I. Liposits, P. van Duijvendijk, J. Oulad Hadj, J.A.B. van der Hoeven, M. Trajkovic, J.H.W. de Wilt, M. Koopman, Jeroen Vincent, Johannes A. Wegdam, Brigitte C.M. Haberkorn, Erwin van der Harst, Mathijs P. Hendriks, W.H. Hermien Schreurs, Huib A. Cense, Ron C. Rietbroek, Marie-José de Gier, Edwin A. van Breugel, Aad I. de Vos, Rebecca P.M. Brosens, P.G. Doornebosch, Felix E. de Jongh, Wouter J. Vles, Marien O. den Boer, Jeroen W.A. Leijtens, A.J. Hans Gelderblom, Koen C.M.J. Peeters, Bart C. Kuenen, Bareld B. Pultrum, Joyce M. van Dodewaard-de Jong, Esther C.J. Consten, A.J. Yes van de Wouw, J.L.M. Konsten, R. Hoekstra, Martijn F. Lutke Holzik, Allert H. Vos, M.J. van Hoogstraten, Nis H. Schlesinger, Geert-Jan Creemers, Ignace H.J.T. de Hingh, Monica L. Kjær, Lone N. Petersen, Michael Seiersen, Rahim Altaf, Hester van Cruijsen, Daniël A. Hess, Lobke L. van Leeuwen-Snoeks, Apollo Pronk, Coen I.M. Baeten, Wendy M. van der Deure, Koop Bosscha, Heidi Schut, W.K.G. Leclercq, L.H.J. Simkens, Koen Reijnders, Kees van Arkel, W.M.U. Helma van Grevenstein, Anthony W.H. van de Ven, Ronald J.C.L.M. Vuylsteke, Philomeen Kuijer, Sandra D. Bakker, Hauwy Goei, Helgi H. Helgason, Gijs J.D. van Acker, Mehmet Temizkan, Marc W.A. van Tilburg, Michael F. Gerhards, E.D. Kerver, Elske Gootjes, Peter Nieboer, Wim A. Bleeker, G.R. Bleeker
Journal: Annals of Oncology (2024)

Upfront primary tumor resection (PTR) has been associated with longer overall survival (OS) in patients with synchronous unresectable metastatic colorectal cancer (mCRC) in retrospective analyses. The aim of the CAIRO4 study was to investigate whether the addition of upfront PTR to systemic therapy resulted in a survival benefit in patients with synchronous mCRC without severe symptoms of their primary tumor.
Magnetically Guided Adeno‐Associated Virus Delivery for the Spatially Targeted Transduction of Retina in Eyes
Authors: Seungkuk Ahn, Oliver Siontas, Janis Koester, Jacek Krol, Sascha Fauser, Daniel J. Müller
Journal: Advanced Healthcare Materials (2024)

Abstract Adeno‐associated viruses (AAVs) are intensively explored for gene therapies in general and have found promising applications for treating retina diseases. However, controlling the specificity (tropism) and delivery of AAVs to selected layers, cell types, and areas of the retina is a major challenge to further develop retinal gene therapies. Magnetic nanoparticles (MNPs) provide effective delivery platforms to magnetically guide therapeutics to target cells. Yet, how MNPs can deliver AAVs to transfect particular retina layers and cells remains elusive. Here, it is demonstrated that MNPs can be used to transport different AAVs through the retina and to modulate the selective transduction of specific retinal layers or photoreceptor cells in ex vivo porcine explants and whole eyes. Thereby, transduction is triggered by bringing the viruses in close proximity to the target cell layer and by controlling their interaction time. It is shown that this magnetically guided approach to transport AAVs to selected areas and layers of the retina does not require the cell‐specific optimization of the AAV tropism. It is anticipated that the new approach to control the delivery of AAVs and to selectively transduce cellular systems can be applied to many other tissues or organs to selectively deliver genes of interest.
Radiopaque FeMnN-Mo composite drawn filled tubing wires for braided absorbable neurovascular devices
Authors: Adam J Griebel, Petra Maier, Henry Summers, Benjamin Clausius, Isabella Kanasty, Weilue He, Nicholas Peterson, Carolyn Czerniak, Alexander A Oliver, David F Kallmes, Ramanathan Kadirvel, Jeremy E Schaffer, Roger J Guillory
Journal: Bioactive Materials (2024)
Hidden Links Between Skin Microbiome and Skin Imaging Phenome
Authors: Mingyue Cheng, Hong Zhou, Haobo Zhang, Xinchao Zhang, Shuting Zhang, Hong Bai, Yugo Zha, Dan Luo, Dan Chen, Siyuan Chen, Kang Ning, Wei Liu
Journal: Genomics Proteomics & Bioinformatics (2024)

Abstract Despite the skin microbiome has been linked to skin health and diseases, its role in modulating human skin appearance remains understudied. Using a total of 1244 face imaging phenomes and 246 cheek metagenomes, we first established three skin age indices by machine learning including skin phenotype age (SPA), skin microbiota age (SMA), and skin integration age (SIA) as surrogates of phenotypic aging, microbial aging, and their combination, respectively. Moreover, we found that besides aging and gender as intrinsic factors, skin microbiome might also play a role in shaping skin imaging phenotypes (SIPs). Skin taxonomic and functional α diversity was positively linked to melanin, pore, pigment, and ultraviolet spot levels, but negatively linked to sebum, lightening, and porphyrins levels. Furthermore, certain species were correlated with specific SIPs, such as sebum and lightening levels negatively correlated with Corynebacterium matruchotii, Staphylococcus capitis, and Streptococcus sanguinis. Notably, we demonstrated skin microbial potential in predicting SIPs, among which the lightening level presented the least error of 1.8%. Lastly, we provided a reservoir of potential mechanisms through which skin microbiome adjusted the SIPs, including the modulation of pore, wrinkle, and sebum levels by cobalamin and heme synthesis pathways, predominantly driven by Cutibacterium acnes. This pioneering study unveils the paradigm for the hidden links between skin microbiome and skin imaging phenome, providing novel insights into how skin microbiome shapes skin appearance and its healthy aging.
Scm6A: A Fast and Low-cost Method for Quantifying m6A Modifications at the Single-cell Level
Authors: Yueqi Li, Jingyi Li, Wenxing Li, Shuaiyi Liang, Wudi Wei, Jiemei Chu, Jingzhen Lai, Yao Lin, Hubin Chen, Jinming Su, Xiaopeng Hu, Gang Wang, Jun Meng, Junjun Jiang, Li Ye, Sanqi An
Journal: Genomics Proteomics & Bioinformatics (2024)

It is widely accepted that N6-methyladenosine (m6A) exhibits significant intercellular specificity, which poses challenges for its detection using existing m6A quantitative methods. In this study, we introduced Single-cell m6A Analysis (Scm6A), a machine learning-based approach for single-cell m6A quantification. Scm6A leverages input features derived from the expression levels of m6A trans regulators and cis sequence features, and offers remarkable prediction efficiency and reliability. To further validate the robustness and precision of Scm6A, we applied a winscore-based m6A calculation method to conduct N6-methyladenosine sequencing (m6A-seq) analysis on CD4+ and CD8+ T-cells isolated through magnetic-activated cell sorting (MACS). Subsequently, we employed Scm6A for analysis on the same samples. Notably, the m6A levels calculated by Scm6A exhibited a significant positive correlation with m6A quantified through m6A-seq in different cells isolated by MACS, providing compelling evidence for Scm6A's reliability. Additionally, we performed single-cell level m6A analysis on lung cancer tissues as well as blood samples from the coronavirus disease 2019 (COVID-19) patients, and demonstrated the landscape and regulatory mechanisms of m6A in different T-cell subtypes from these diseases. In summary, our work has yielded a novel, dependable, and accurate method for single-cell m6A detection. We are confident that Scm6A have broad applications in the realm of m6A-related research.
Immune responses associated with mpox viral clearance in men with and without HIV in Spain: a multisite, observational, prospective cohort study
Authors: Igor Moraes-Cardoso, Susana Benet, Julieta Carabelli, Daniel Perez-Zsolt, Adrià Mendoza, Angel Rivero, Andrea Alemany, Vicente Descalzo, Yovaninna Alarcón-Soto, Alba Grifoni, Alessandro Sette, José Moltó, Aurélien Marc, Michael Marks, Oriol Mitjà, Christian Brander, Roger Paredes, Nuria Izquierdo-Useros, Jorge Carrillo, Clara Suñer, Alex Olvera, Beatriz Mothe
Journal: The Lancet Microbe (2024)
Human γδ T cells in diverse tissues exhibit site-specific maturation dynamics across the life span
Authors: Joshua I. Gray, Daniel P. Caron, Steven B. Wells, Rebecca Guyer, Peter Szabo, Daniel Rainbow, Can Ergen, Ksenia Rybkina, Marissa C. Bradley, Rei Matsumoto, Kalpana Pethe, Masaru Kubota, Sarah Teichmann, Joanne Jones, Nir Yosef, Mark Atkinson, Maigan Brusko, Todd M. Brusko, Thomas J. Connors, Peter A. Sims, Donna L. Farber
Journal: Science Immunology (2024)

During ontogeny, γδ T cells emerge from the thymus and directly seed peripheral tissues for in situ immunity. However, their functional role in humans has largely been defined from blood. Here, we analyzed the phenotype, transcriptome, function, and repertoire of human γδ T cells in blood and mucosal and lymphoid tissues from 176 donors across the life span, revealing distinct profiles in children compared with adults. In early life, clonally diverse Vδ1 subsets predominate across blood and tissues, comprising naïve and differentiated effector and tissue repair functions, whereas cytolytic Vδ2 subsets populate blood, spleen, and lungs. With age, Vδ1 and Vδ2 subsets exhibit clonal expansions and elevated cytolytic signatures, which are disseminated across sites. In adults, Vδ2 cells predominate in blood, whereas Vδ1 cells are enriched across tissues and express residency profiles. Thus, antigenic exposures over childhood drive the functional evolution and tissue compartmentalization of γδ T cells, leading to age-dependent roles in immunity.
Plasma membrane abundance dictates phagocytic capacity and functional cross-talk in myeloid cells
Authors: Benjamin Y. Winer, Alexander H. Settle, Alexandrina M. Yakimov, Carlos Jeronimo, Tomi Lazarov, Murray Tipping, Michelle Saoi, Anjelique Sawh, Anna-Liisa L. Sepp, Michael Galiano, Justin S. A. Perry, Yung Yu Wong, Frederic Geissmann, Justin Cross, Ting Zhou, Lance C. Kam, H. Amalia Pasolli, Tobias Hohl, Jason G. Cyster, Orion D. Weiner, Morgan Huse
Journal: Science Immunology (2024)

Professional phagocytes like neutrophils and macrophages tightly control what they consume, how much they consume, and when they move after cargo uptake. We show that plasma membrane abundance is a key arbiter of these cellular behaviors. Neutrophils and macrophages lacking the G protein subunit Gβ
Lymphatic vessel transit seeds cytotoxic resident memory T cells in skin draining lymph nodes
Authors: Taylor A. Heim, Austin C. Schultz, Ines Delclaux, Vanessa Cristaldi, Madeline J. Churchill, Katherine S. Ventre, Amanda W. Lund
Journal: Science Immunology (2024)

Lymphatic transport shapes the homeostatic immune repertoire of lymph nodes (LNs). LN-resident memory T cells (T RMs ) play an important role in site-specific immune memory, yet how LN T RMs form de novo after viral infection remains unclear. Here, we tracked the anatomical distribution of antiviral CD8 + T cells as they seeded skin and LN T RMs using a model of vaccinia virus–induced skin infection. LN T RMs localized to the draining LNs (dLNs) of infected skin, and their formation depended on the lymphatic egress of effector CD8 + T cells from the skin, already poised for residence. Effector CD8 + T cell transit through skin was required to populate LN T RMs in dLNs, a process reinforced by antigen encounter in skin. Furthermore, LN T RMs were protective against viral rechallenge in the absence of circulating memory T cells. These data suggest that a subset of tissue-infiltrating CD8 + T cells egress from tissues during viral clearance and establish a layer of regional protection in the dLN basin.
Antibody responses to respiratory syncytial virus: A population-based cross-sectional serological study in southern China, 2021
Authors: Qianli Wang, Nuolan Liu, Yan Wang, Tracy J. Ruckwardt, Meng Xu, Jianan Wu, Juanjuan Zhang, Xiaofeng Tong, Jiaxin Zhou, Jiqun Lin, Yuxia Liang, Juan Yang, Lan Yi, Helen Y. Chu, Hongjie Yu
Journal: Clinical Microbiology and Infection (2024)

ObjectivesWith remarkable progress in the field of RSV prophylaxis, it is critical to understand population immunity against RSV. We aim to describe the RSV pre-F immunoglobin G (IgG) antibodies across all age groups in southern China and evaluate the risk factors associated with lower antibody levels.MethodsWe conducted a community-based cross-sectional sero-epidemiological study in Anhua County, Hunan Province, southern China, from July to November 2021. Serum samples were tested for IgG antibodies against the RSV prefusion F (pre-F) protein using an enzyme-linked immunosorbent assay. We estimated the geometric mean titres (GMTs) and seropositivity rates across all age groups. Generalized linear models (GLMs) were built to identify factors associated with antibody levels.ResultsA total of 890 participants aged 4 months to >89 years were enrolled. The lowest RSV pre-F IgG GMTs were observed in infants and toddlers aged 4 months to <2 years (3.0, 95% confidence interval [CI]: 2.6-3.5). With increasing age, RSV pre-F IgG GMT increased to 4.3 (95% CI: 4.1-4.4) between the ages of 2 and <5 years and then stabilized at high levels throughout life. All the children had serological evidence of RSV infection by the age of 5 years. Age was associated with RSV pre-F antibody levels in children, with an estimated 1.8-fold (95% CI: 1.1-2.9) increase in titre per year before 5 years of age, while it was not significantly associated with antibody levels in adults aged >60 years.ConclusionsOur findings could provide a comprehensive understanding of the gaps in RSV immunity at the population level and inform the prioritization of immunization platforms.
The Development of Cannabinoids as Therapeutic Agents in the United States
Authors: Conor H. Murray, Brenda M. Gannon, Peter J. Winsauer, Ziva D. Cooper, Marcus S. Delatte
Journal: Pharmacological Reviews (2024)

Cannabis is one of the oldest and widely used substances in the world. Cannabinoids within the cannabis plant, known as phytocannabinoids, mediate cannabis9 effects through interactions with the body9s endogenous cannabinoid system. This endogenous system, the endocannabinoid system, has important roles in physical and mental health. These roles point to the potential to develop cannabinoids as therapeutic agents, while underscoring the risks related to interfering with the endogenous system during non-medical use. This scoping narrative review synthesizes the current evidence for both the therapeutic and adverse effects of the major (i.e., Δ9-tetrahydrocannabinol and cannabidiol) and lesser studied minor phytocannabinoids, from nonclinical to clinical research. We pay particular attention to the areas where evidence is well-established, including analgesic effects after acute exposures and neurocognitive risks after acute and chronic use. In addition, drug development considerations for cannabinoids as therapeutic agents within the United States are reviewed. The proposed clinical study design considerations encourage methodological standards for greater scientific rigor and reproducibility, ultimately, to extend our knowledge of the risks and benefits of cannabinoids for patients and providers. <b>Significance Statement</b> This work provides a review of prior research related to phytocannabinoids, including therapeutic potential and known risks in the context of drug development within the United States. We also provide study design considerations for future cannabinoid drug development.
European multi-center study to establish MIC and zone diameter epidemiological cut-off (ECOFF) values for Bacillus anthracis
Authors: Flavia Dematheis, Viviana Manzulli, Gregor Grass, Erika Matuschek, Daniela Jacob, Falk Melzer, Mandy Elschner, Agnieszka Kedrak-Jablonska, Sylwia Budniak, Marcella Mori, Tiziano Fancello, Roland Grunow, Gunnar Kahlmeter, Domenico Galante, Sabine Zange
Journal: Clinical Microbiology and Infection (2024)

Bacillus anthracis clinical breakpoints, representing a systematic approach to guide clinicians in selecting the most appropriate antimicrobial treatments, are not part of the guidance from the European Committee on Antimicrobial Susceptibility Testing (EUCAST). This is because defined distributions of MIC values and of epidemiological cut-off values (ECOFFs) have been lacking. In this study, a Europe-wide network of laboratories in collaboration with EUCAST, aimed at establishing standardized antimicrobial susceptibility testing methods, wild-type MIC distributions, and ECOFFs for ten therapeutically relevant antimicrobials.
Publisher Correction: METLIN-CCS Lipid Database: An authentic standards resource for lipid classification and identification
Authors: Erin S. Baker, Winnie Uritboonthai, Aries Aisporna, Corey Hoang, Heino M. Heyman, Lisa Connell, Damien Olivier-Jimenez, Martin Giera, Gary Siuzdak
Journal: Nature Metabolism (2024)