Article
Biochemistry & Molecular Biology
Apparao B. Kummarapurugu, Shuo Zheng, Jonathan Ma, Shobha Ghosh, Adam Hawkridge, Judith A. Voynow
Summary: Neutrophil extracellular traps (NE) increase cystic fibrosis (CF) airway inflammation. This study found that NE triggers the release of macrophage extracellular traps (METs), thereby enhancing NE-induced CF airway inflammation.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Article
Cell Biology
Hidehito Kimura, Akiko Mii, Jun Shoji, Yusuke Arakawa, Akira Shimizu
Summary: This study investigated the relationship between infiltrating citrullinated histone H3 (H3Cit)-positive neutrophils and disease specificity and activity in various glomerulonephritides. The presence of H3Cit+ neutrophils was found to be a potential marker for disease activity in antineutrophil cytoplasmic antibody-associated vasculitis (AAV).
Article
Hematology
Henry Ng, Sebastian Havervall, Axel Rosell, Katherina Aguilera, Kristel Parv, Fien A. von Meijenfeldt, Ton Lisman, Nigel Mackman, Charlotte Thalin, Mia Phillipson
Summary: Elevated levels of NET markers in patients with moderate to severe COVID-19 were found to be associated with disease severity, respiratory support requirement, and short-term mortality. These markers declined to healthy individual levels four months post-infection. The study suggests a potential role of NETs in COVID-19 disease progression and as targets for novel therapeutic interventions.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Immunology
Giulia Franzoni, Samanta Mecocci, Chiara Grazia De Ciucis, Lorena Mura, Filippo Dell'Anno, Susanna Zinellu, Floriana Fruscione, Livia De Paolis, Tania Carta, Antonio G. Anfossi, Silvia Dei Guidici, Elisabetta Chiaradia, Luisa Pascucci, Annalisa Oggiano, Katia Cappelli, Elisabetta Razzuoli
Summary: This study investigated the immunomodulatory effects of goat milk extracellular vesicles (EVs) on untreated and classically activated porcine monocyte-derived macrophages. The results showed that these particles were efficiently internalized by macrophages and high doses upregulated MHC I and MHC II DR on untreated macrophages, while low doses enhanced the gene expression of IL10, EBI3, and IFNB. High doses also upregulated several pro-inflammatory cytokines. Overall, these findings support the clinical application of these molecules in polarizing macrophages towards an M1-like phenotype.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Hematology
M. Christella L. G. D. Thomassen, Bryan R. C. Bouwens, Kanin Wichapong, Dennis P. Suylen, Freek G. Bouwman, Tilman M. Hackeng, Rory R. Koenen
Summary: This study found that PAD4 inactivates TFPI by citrullination of its arginines, and this process is time- and concentration-dependent. Furthermore, inducers of PAD4 blocked the citrullination of TFPI. This process may play a crucial role in the increased thrombosis risk associated with inflammation.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Immunology
Abby D. Ivey, B. Matthew Fagan, Pranav Murthy, Michael T. Lotze, Herbert J. Zeh, Lori A. Hazlehurst, Werner J. Geldenhuys, Brian A. Boone
Summary: Chloroquine (CQ) and hydroxychloroquine (HCQ) inhibit NET formation by directly inhibiting PAD4. These drugs may reduce NET formation through blockade of autophagy or inhibition of PAD4.
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2023)
Article
Clinical Neurology
Kenji Shimada, Izumi Yamaguchi, Manabu Ishihara, Takeshi Miyamoto, Shu Sogabe, Kazuhisa Miyake, Yoshiteru Tada, Keiko T. Kitazato, Yasuhisa Kanematsu, Yasushi Takagi
Summary: The study found evidence of intravascular expression of neutrophil extracellular traps (NETs) in all cerebral arteriovenous malformation (cAVM) samples, suggesting a potential association with vascular inflammation in cAVMs. The samples also showed migration of Iba-I-positive cells and expression of inflammatory markers in the endothelium and intravascular neutrophils. These results provide insight into the role of NETs in the pathobiology of cAVMs.
WORLD NEUROSURGERY
(2021)
Article
Biochemistry & Molecular Biology
Lorenna Rocha Reis, Douglas Ricardo Souza Junior, Rebeka Tomasin, Alexandre Bruni-Cardoso, Paolo Di Mascio, Graziella Eliza Ronsein
Summary: Neutrophil extracellular traps (NETs) are released by activated neutrophils through a process called NETosis. This study investigated the early events in ionomycin-triggered NETosis and found that profound biochemical changes occur in and around the nucleus of neutrophils before NET release. These changes involve cytoskeleton reorganization, nuclear redistribution of actin-remodeling related proteins, and citrullination of actin-ligand and nuclear structural proteins. Additionally, ionomycin-stimulated neutrophils lose their characteristic polymorphic nucleus and secrete proteins related to immune response.
Article
Cell Biology
Yin Li, Qinyi Jiang, Xiaohua Zhou, Mengyuan Wu, Jian Chen, Hao Liu, Siming Dai, Ziyang Zheng, Xuan Zhao, Chenxi Zhang, Zhuoying Shi, Haitao Zhang, Jinyu Gu, Zhenfei Huang, Guoyong Yin, Shujie Zhao
Summary: This study investigated the predictive value of neutrophil extracellular traps (NETs) in postoperative deep venous thrombosis (DVT) formation and developed a predictive model based on clinical admission information. The results showed that higher body mass index (BMI), neutrophil levels, D-dimer, and citrullinated histone H3 (CitH3) were independent risk factors for postoperative DVT. The study provides new insights for the prediction and prevention of DVT in patients with lumbar fractures.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Gastroenterology & Hepatology
Gabriele Dragoni, Gert De Hertogh, Severine Vermeire
Summary: Citrullination, mediated by PAD enzymes, is implicated in various diseases from cancer to autoimmune disorders. Research is accumulating on its role in IBD and fibrosis complications. Further study is needed to determine therapeutic targets for this process.
INFLAMMATORY BOWEL DISEASES
(2021)
Article
Immunology
Renato G. S. Chirivi, Jos W. G. van Rosmalen, Maarten van der Linden, Maximilien Euler, Gonny Schmets, Galina Bogatkevich, Konstantinos Kambas, Jonas Hahn, Quinte Braster, Oliver Soehnlein, Markus H. Hoffmann, Helmuth H. G. van Es, Jos M. H. Raats
Summary: The study demonstrated that therapeutic anti-citrullinated protein antibody can inhibit NET release, reduce tissue damage, and potentially serve as a drug candidate for NET-mediated inflammatory diseases.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Review
Gastroenterology & Hepatology
Gabriele Dragoni, Gert De Hertogh, Severine Vermeire
Summary: Citrullination is a posttranslational modification of proteins that has been linked to various autoimmune disorders, particularly in inflammatory and fibrotic contexts. Further research is needed to investigate the role of citrullination in the gut and its potential therapeutic targeting.
INFLAMMATORY BOWEL DISEASES
(2021)
Article
Medical Laboratory Technology
Lei Liu, Wenjie Zhang, Yu Su, Yuying Chen, Xiangyu Cao, Jun Wu
Summary: This study investigated the role of NETs in thrombosis in patients with traumatic fractures and found that H3Cit and cfDNA can assist in the diagnosis of DVT in these patients. The study suggests that NET biomarkers may be used to predict the risk of thrombosis in such patients.
CLINICA CHIMICA ACTA
(2021)
Article
Medical Laboratory Technology
Wolf Eilenberg, Branislav Zagrapan, Sonja Bleichert, Nahla Ibrahim, Viktoria Knobl, Annika Brandau, Luca Martelanz, Marie-Therese Grasl, Hubert Hayden, Paimann Nawrozi, Renata Rajic, Charlotte Hausler, Alexandros Potolidis, Nawa Schirwani, Andreas Scheuba, Johannes Klopf, Peter Teubenbacher, Markus P. Weigl, Patrick Kirchweger, Dietrich Beitzke, Alexander Stiglbauer-Tscholakoff, Adelheid Panzenbock, Irene Lang, Lisa-Marie Mauracher, Lena Hell, Ingrid Pabinger, Marc A. Bailey, D. Julian A. Scott, Lars Maegdefessel, Albert Busch, Ihor Huk, Christoph Neumayer, Christine Brostjan
Summary: Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of abdominal aortic aneurysms (AAAs). This study found that the NET component citrullinated histone H3 (citH3) may serve as a promising biomarker for AAA, with increased levels in AAA patients compared to healthy controls. CitH3 could also predict AAA growth over 6 months and dropped significantly after surgical aneurysm repair, indicating its potential as a therapeutic target.
TRANSLATIONAL RESEARCH
(2021)
Article
Fisheries
Xiaojing Lv, Chunli Jiao, Yuying Chen, Lizhu Chen, Xuan Li, Xiangquan Liu, Dinglong Yang, Jianmin Zhao
Summary: In this study, a novel histone H2A (RpH2A) was identified in clam Ruditapes philippinarum and found to play a crucial role in immune responses by functioning as antimicrobial peptides.
FISH & SHELLFISH IMMUNOLOGY
(2022)
Article
Physics, Multidisciplinary
Debashis Ghosh
Summary: In this article, an approach to interpreting SDR techniques using information theory is developed, leading to a less assumption-lean understanding of what SDR methods do and allowing for connections to results in the information theory literature.
Article
Mathematical & Computational Biology
Debashis Ghosh, Michael S. Sabel
Summary: This study introduces a weighting approach using convex optimization to transfer information and develop prediction-guided analyses by incorporating information from external risk calculators to local datasets. It also utilizes tree structures to describe 'calculator-guided observations' and sheds light on the potential transferability of external calculators to local datasets.
STATISTICS IN BIOSCIENCES
(2022)
Article
Computer Science, Interdisciplinary Applications
Youngjoo Cho, Xiang Zhan, Debashis Ghosh
Summary: In clinical trials, individuals in different subgroups may have different treatment effects, highlighting the importance of considering individual differences in treatment benefit. This study introduces the concept of predictive directions and validates its utility through simulation studies and real data analysis.
COMPUTATIONAL STATISTICS & DATA ANALYSIS
(2022)
Article
Multidisciplinary Sciences
Matthew D. Galbraith, Kohl T. Kinning, Kelly D. Sullivan, Paula Araya, Keith P. Smith, Ross E. Granrath, Jessica R. Shaw, Ryan Baxter, Kimberly R. Jordan, Seth Russell, Monika Dzieciatkowska, Julie A. Reisz, Fabia Gamboni, Francesca Cendali, Tusharkanti Ghosh, Kejun Guo, Cara C. Wilson, Mario L. Santiago, Andrew A. Monte, Tellen D. Bennett, Kirk C. Hansen, Elena W. Y. Hsieh, Angelo D'Alessandro, Joaquin M. Espinosa
Summary: The impacts of IFN signaling on COVID-19 pathology are diverse, with both protective and harmful effects. Different types of IFNs are associated with specific biosignatures and have unique metabolic signatures. They also show differential relationships with clinical markers of prognosis and disease severity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemical Research Methods
Souvik Seal, Debashis Ghosh
Summary: This study presents a new method for analyzing the interaction of proteins or markers in the tumor microenvironment of cancer patients, finding co-expression to be associated with disease risk and survival, and demonstrating the robustness of the method.
Article
Chemistry, Analytical
Cameron Severn, Krithika Suresh, Carsten Gorg, Yoon Seong Choi, Rajan Jain, Debashis Ghosh
Summary: Machine learning models have shown remarkable accuracy in predicting clinical factors from medical imaging, but their lack of interpretability has been a concern. Explainable machine learning methods, such as Shapley values, can help explain the behavior of these models and identify important predictors. Incorporating these methods into medical software can increase trust in machine learning predictions and assist physicians in making important decisions. This article presents a novel pipeline for explainable medical imaging using radiomics data and Shapley values, and demonstrates its application in predicting a genetic mutation from MRI data.
Article
Mathematical & Computational Biology
Kevin P. Josey, Fan Yang, Debashis Ghosh, Sridharan Raghavan
Summary: Proper evaluations of internal and external validity are important in clinical research studies. Randomized clinical trials can address internal validity but may lack external validity. Large prospective observational studies may have external validity but are susceptible to threats to internal validity. Methods that address confounding and enhance transportability of study results across populations are crucial for valid causal inference.
STATISTICS IN MEDICINE
(2022)
Article
Biochemical Research Methods
Thao Vu, Julia Wrobel, Benjamin G. Bitler, Erin L. Schenk, Kimberly R. Jordan, Debashis Ghosh
Summary: Investigating spatial patterns and interactions of cells in the tumor microenvironment (TME) provides useful insights into cancer development and progression. In this work, we proposed a novel approach which combined established spatial summary functions with functional data analysis to flexibly model the cell-cell interactions with overall survival at different inter-cell distances, in conjunction with other clinical predictors such as age, disease stage. By applying the proposed framework to multiplex immunohistochemistry (mIHC) data of patients with non-small cell lung cancer (NSCLC), we studied the nonlinear impact of spatial interactions between tumor and stromal cells on overall survival. The applicability of our proposed method is further validated using a publicly available multiplexed ion beam imaging (MIBI) triple-negative breast cancer (TNBC) dataset.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Rheumatology
Jennifer A. Seifert, Elizabeth A. Bemis, Kristina Ramsden, Cassidy Lowell, Kristen Polinski, Marie Feser, Chelsie Fleischer, M. Kristen Demoruelle, Jane Buckner, Peter K. Gregersen, Richard M. Keating, Ted R. Mikuls, James R. O'Dell, Michael H. Weisman, Kevin D. Deane, Jill M. Norris, Allen C. Steere, V. Michael Holers
Summary: This study evaluated anti-Pcopri antibody responses in individuals with rheumatoid arthritis (RA) and found that RA patients had higher levels of anti-Pcopri antibodies, especially in early-stage RA. Participants with RA who were positive for RA-related autoantibodies also showed higher levels of anti-Pcopri antibodies. These findings suggest a potential etiologic role for Pcopri in the development and pathogenesis of RA.
ARTHRITIS & RHEUMATOLOGY
(2023)
Article
Multidisciplinary Sciences
Yonghua Zhuang, Fuyong Xing, Debashis Ghosh, Brian D. D. Hobbs, Craig P. P. Hersh, Farnoush Banaei-Kashani, Russell P. P. Bowler, Katerina Kechris
Summary: Network approaches have been used to study the complex mechanisms of diseases like COPD. However, integrating protein-protein interaction (PPI) network information with omics data for disease prediction is still limited. This study uses a deep learning method called ConvGNN to integrate COPD-associated PPI, proteomics, and transcriptomics data and improve the accuracy of COPD classification. The updated COPD-associated network developed using AhGlasso algorithm further enhances prediction accuracy. Gene Ontology enrichment analysis identifies important gene/proteins and signaling pathways for COPD classifications.
Article
Medicine, General & Internal
Eric W. Prince, Debashis Ghosh, Carsten Gorg, Todd C. Hankinson
Summary: Diagnosis of ACP mainly relies on invasive pathological examination, although clinical experts can distinguish it from MRI with an accuracy of 86%. Deep learning classification provides a potential non-invasive diagnostic solution, but its implementation is limited due to the lack of predictive uncertainty representation.
Article
Endocrinology & Metabolism
Randi K. Johnson, Amanda J. Ireton, Patrick M. Carry, Lauren A. Vanderlinden, Fran Dong, Alex Romero, David R. Johnson, Debashis Ghosh, Fan Yang, Brigitte Frohnert, Ivana V. Yang, Katerina Kechris, Marian Rewers, Jill M. Norris
Summary: This study examined the association between T1D family history and T1D risk mediated by methylation near the DLGAP2 gene. The results showed a significant interaction between T1D family history and methylation at DLGAP2 region CpGs on T1D risk. The increased risk of T1D for children with affected mothers compared to those with no family history was mediated through differences in methylation at two CpGs in the DLGAP2 region, while DNA methylation changes did not explain the increased risk for children with an affected father or sibling. Additionally, DNA methylation in the DLGAP2 region was associated with gene expression of nearby protein-coding genes.
PEDIATRIC DIABETES
(2023)
Article
Genetics & Heredity
Souvik Seal, Benjamin G. Bitler, Debashis Ghosh
Summary: This article introduces a non-parametric method called SMASH for detecting spatially variable genes in high-throughput spatial transcriptomics studies. Compared with other methods, SMASH has superior statistical power and robustness, and can be applied to datasets from different platforms, helping to uncover the structural and functional characteristics of tissues.
Article
Statistics & Probability
Youngjoo Cho, Paul L. Auer, Debashis Ghosh
Summary: Mendelian Randomization is a popular method used in genomic studies to estimate causal effects. This paper focuses on IV selection and introduces nonparametric variable selection approaches, comparing linear and nonlinear instrumental variable selection methods. Simulation studies demonstrate the good performance of the proposed methods, which are also applied to the UKBiobank data for Mendelian Randomization.
SANKHYA-SERIES B-APPLIED AND INTERDISCIPLINARY STATISTICS
(2023)
Article
Rheumatology
Chelsie L. Fleischer, Elizabeth A. Bemis, Marie L. Feser, Vasilisa A. Kormendi, Alvina Zhang, Katherine Ketcham, Sharon D. White, Christopher C. Striebich, Kevin D. Deane, Mark Harrison
Summary: This study examined the factors influencing the decisions of individuals with ACPA positivity to participate in a prevention trial for rheumatoid arthritis (RA). The results showed that participants were more concerned about personal risk and benefits, while non-participants were more concerned about medication side effects and lack of personal or family experience with RA. Participants also had a higher proportion of first-degree relatives with RA. Further exploration is needed to understand these differences and inform prevention strategies.
ACR OPEN RHEUMATOLOGY
(2022)
Article
Immunology
Shane Kelly, Katherine J. L. Jackson, Timothy J. Peters, Dan Suan, Christopher C. Goodnow
Summary: This study successfully identified and characterized PR3-specific B cells from the peripheral blood of patients with PR3 autoantibodies. These cells exhibited specific immunological features, suggesting that PR3 self-reactivity may occur early in B-cell development.
JOURNAL OF AUTOIMMUNITY
(2024)
Article
Immunology
Ana Merino-Vico, Jan Piet van Hamburg, Paul Tuijnenburg, Giulia Frazzei, Aram Al-Soudi, Carlo G. Bonasia, Boy Helder, Abraham Rutgers, Wayel H. Abdulahad, Coen A. Stegeman, Jan-Stephan Sanders, Laura Bergamaschi, Paul A. Lyons, Theo Bijma, Laura van Keep, Kirsten Wesenhagen, Aldo Jongejan, Henric Olsson, Niek de Vries, Taco W. Kuijpers, Peter Heeringa, Sander W. Tas
Summary: B lineage cells play a critical role in ANCA-associated vasculitis (AAV), and the transcription factor NF-kappa B may be a potential therapeutic target for AAV and other autoimmune diseases with prominent B cell involvement.
JOURNAL OF AUTOIMMUNITY
(2024)
Article
Immunology
Christopher Nelke, Thomas Muentefering, Derya Cengiz, Lukas Theissen, Vera Dobelmann, Christina B. Schroeter, Helena Block, Corinna Preu, Alexander P. E. Michels, Stefanie Lichtenberg, Marc Pawlitzki, Steffen Pfeuffer, Niklas Huntemann, Alexander Zarbock, Thorben Briese, Christoph Kittl, Carsten Dittmayer, Thomas Budde, Ingrid E. Lundberg, Werner Stenzel, Sven G. Meuth, Tobias Ruck
Summary: K2P2.1 plays a regulatory role in the autoimmune response of idiopathic inflammatory myopathies (IIMs), by regulating inflammatory cell response, adhesion, and transmigration in both endothelial and skeletal muscle cells. Inhibiting K2P2.1 enhances the inflammatory response, while activating K2P2.1 improves the disease course.
JOURNAL OF AUTOIMMUNITY
(2024)
Article
Immunology
Xuan Zhang, Jun Xia, Ying Jiang, David S. Pisetsky, Josef S. Smolen, Rong Mu, Shengming Dai, Michael E. Weinblatt, Tore K. Kvien, Juan Li, Thomas Doerner, Yu Zhang, Liwei Lu, Chengde Yang, Pingting Yang, Yuan Zhang, Chenchen Xu, Zhan Zhao, Peter E. Lipsky
Summary: The study suggests that TwHF may be as effective as MTX in treating active RA, and combination therapy may be more effective than monotherapy.
JOURNAL OF AUTOIMMUNITY
(2024)
Article
Immunology
Maya F. Amjadi, Maxwell H. Parker, Ryan R. Adyniec, Zihao Zheng, Alex M. Robbins, S. Janna Bashar, Michael F. Denny, Sara S. Mccoy, Irene M. Ong, Miriam A. Shelef
Summary: Rheumatoid factors (RFs) are polyreactive antibodies that can bind disease-specific epitopes. Recent studies have found that RFs in COVID-19 can bind novel IgG epitopes, which provides new insights into the mechanism of RFs.
JOURNAL OF AUTOIMMUNITY
(2024)
Article
Immunology
Johanne Liberatore, Yann Nguyen, Jerome Hadjadj, Pascal Cohen, Luc Mouthon, Xavier Puechal, Loic Guillevin, Benjamin Terrier
Summary: B-cell depletion induced by rituximab (RTX) in ANCA-associated vasculitis (AAV) can lead to decreased gammaglobulin levels, which is associated with an increased risk of relapse and severe infections. Older age, low gammaglobulin levels, and receiving pulses of methylprednisolone at induction therapy are risk factors for gammaglobulin decline.
JOURNAL OF AUTOIMMUNITY
(2024)