tbuckley/cabot-search huggingface dataset:
Microskin‐Inspired Injectable MSC‐Laden Hydrogels for Scarless Wound Healing with Hair Follicles
Authors: Xin Zheng, Zhaozhao Ding, Weinan Cheng, Qiang Lu, Xiangdong Kong, Xiaozhong Zhou, Guozhong Lu, David L. Kaplan
Journal: Advanced Healthcare Materials (2020)

Abstract Scarless skin regeneration with functional tissue remains a challenge for full‐thickness wounds. Here, mesenchymal stem cell (MSC)‐laden hydrogels are developed for scarless wound healing with hair follicles. Microgels composed of aligned silk nanofibers are used to load MSCs to modulate the paracrine. MSC‐laden microgels are dispersed into injectable silk nanofiber hydrogels, forming composites biomaterials containing the cells. The injectable hydrogels protect and stabilize the MSCs in the wounds. The synergistic action of silk‐based composite hydrogels and MSCs stimulated angiogenesis and M1‐M2 phenotype switching of macrophages, provides a suitable niche for functional recovery of wounds. Compared to skin defects treated with MSC‐free hydrogels, the defects treated with the MSC‐laden composite hydrogels heal faster and form scarless tissues with hair follicles. Wound healing can be further improved by adjusting the ratio of silk nanofibers and particles and the loaded MSCs, suggesting tunability of the system. To the best of current knowledge, this is the first time scarless skin regeneration with hair follicles based on silk material systems is reported. The improved wound healing capacity of the systems suggests future in vivo studies to compare to other biomaterial systems related to clinical goals in skin regeneration in the absence of scarring.
Regulatory T Cells License Macrophage Pro-Resolving Functions During Atherosclerosis Regression
Authors: Monika Sharma, Martin P. Schlegel, Milessa S. Afonso, Emily J. Brown, Karishma Rahman, Ada Weinstock, Brian E. Sansbury, Emma M. Corr, Coen van Solingen, Graeme J. Koelwyn, Lianne C. Shanley, Lauren Beckett, Daniel Peled, Juan J. Lafaille, Matthew Spite, P’ng Loke, Edward A. Fisher, Kathryn J. Moore
Journal: Circulation Research (2020)

Rationale: Regression of atherosclerosis is an important clinical goal; however, the pathways that mediate the resolution of atherosclerotic inflammation and reversal of plaques are poorly understood. Regulatory T cells (Tregs) have been shown to be atheroprotective, yet the numbers of these immunosuppressive cells decrease with disease progression, and whether they contribute to atherosclerosis regression is not known. Objective: We investigated the roles of Tregs in the resolution of atherosclerotic inflammation, tissue remodeling, and plaque contraction during atherosclerosis regression. Methods and Results: Using multiple independent mouse models of atherosclerosis regression, we demonstrate that an increase in plaque Tregs is a common signature of regressing plaques. Single-cell RNA-sequencing of plaque immune cells revealed that unlike Tregs from progressing plaques that expressed markers of natural Tregs derived from the thymus, Tregs in regressing plaques lacked Nrp1 expression, suggesting that they are induced in the periphery during lipid-lowering therapy. To test whether Tregs are required for resolution of atherosclerotic inflammation and plaque regression, Tregs were depleted using CD25 monoclonal antibody in atherosclerotic mice during apolipoprotein B antisense oligonucleotide-mediated lipid lowering. Morphometric analyses revealed that Treg depletion blocked plaque remodeling and contraction, and impaired hallmarks of inflammation resolution, including dampening of the T helper 1 response, alternative activation of macrophages, efferocytosis, and upregulation of specialized proresolving lipid mediators. Conclusions: Our data establish essential roles for Tregs in resolving atherosclerotic cardiovascular disease and provide mechanistic insight into the pathways governing plaque remodeling and regression of disease.
Single-cell RNA sequencing reveals compromised immune microenvironment in precursor stages of multiple myeloma
Authors: Oksana Zavidij, Nicholas J. Haradhvala, Tarek H. Mouhieddine, Romanos Sklavenitis-Pistofidis, Songjie Cai, Mairead Reidy, Mahshid Rahmat, Abdallah Flaifel, Benjamin Ferland, Nang K. Su, Michael P. Agius, Jihye Park, Salomon Manier, Mark Bustoros, Daisy Huynh, Marzia Capelletti, Brianna Berrios, Chia-Jen Liu, Meng Xiao He, Esteban Braggio, Rafael Fonseca, Yosef E. Maruvka, Jennifer L. Guerriero, Melissa Goldman, Eliezer M. Van Allen, Steven A. McCarroll, Jamil Azzi, Gad Getz, Irene M. Ghobrial
Journal: Nature Cancer (2020)
Abstract 14574: Association of Race With Long-term Outcomes in Patients Undergoing Popliteal and Infrapopliteal Percutaneous Peripheral Arterial Interventions
Authors: Mohammad Alasaad, Anwar Zaitoun, Hussein Othman, Susan Szpunar, Howard S Rosman, Rajendra H Mehta, Hiroshi Yamasaki
Journal: Circulation (2017)

Introduction: Blacks and patients (pts) with Infrapopliteal PAD have more comorbidities than whites and those with suprapoliteal PAD. However, the long-term outcomes of black versus white pts with ...
Loss of PYCR2 Causes Neurodegeneration by Increasing Cerebral Glycine Levels via SHMT2
Authors: Nathalie Escande-Beillard, Abigail Loh, Sahar N. Saleem, Kohei Kanata, Yui Hashimoto, Umut Altunoglu, Artina Metoska, Joanes Grandjean, Fui Mee Ng, Oz Pomp, Nithya Baburajendran, Joyner Wong, Jeffrey Hill, Emmanuel Beillard, Patrick Cozzone, Maha Zaki, Hülya Kayserili, Hiroshi Hamada, Hidetaka Shiratori, Bruno Reversade
Journal: Neuron (2020)
Loss of the Fanconi anemia–associated protein NIPA causes bone marrow failure
Authors: Stefanie Kreutmair, Miriam Erlacher, Geoffroy Andrieux, Rouzanna Istvanffy, Alina Mueller-Rudorf, Melissa Zwick, Tamina Rückert, Milena Pantic, Teresa Poggio, Khalid Shoumariyeh, Tony A. Mueller, Hiroyuki Kawaguchi, Marie Follo, Cathrin Klingeberg, Marcin Wlodarski, Irith Baumann, Dietmar Pfeifer, Michal Kulinski, Martina Rudelius, Simone Lemeer, Bernhard Kuster, Christine Dierks, Christian Peschel, Nina Cabezas-Wallscheid, Jesus Duque-Afonso, Robert Zeiser, Michael L. Cleary, Detlev Schindler, Annette Schmitt-Graeff, Melanie Boerries, Charlotte M. Niemeyer, Robert A.J. Oostendorp, Justus Duyster, Anna Lena Illert
Journal: Journal of Clinical Investigation (2020)

Inherited bone marrow failure syndromes (IBMFSs) are a heterogeneous group of disorders characterized by defective hematopoiesis, impaired stem cell function, and cancer susceptibility. Diagnosis of IBMFS presents a major challenge due to the large variety of associated phenotypes, and novel, clinically relevant biomarkers are urgently needed. Our study identified nuclear interaction partner of ALK (NIPA) as an IBMFS gene, as it is significantly downregulated in a distinct subset of myelodysplastic syndrome-type (MDS-type) refractory cytopenia in children. Mechanistically, we showed that NIPA is major player in the Fanconi anemia (FA) pathway, which binds FANCD2 and regulates its nuclear abundance, making it essential for a functional DNA repair/FA/BRCA pathway. In a knockout mouse model, Nipa deficiency led to major cell-intrinsic defects, including a premature aging phenotype, with accumulation of DNA damage in hematopoietic stem cells (HSCs). Induction of replication stress triggered a reduction in and functional decline of murine HSCs, resulting in complete bone marrow failure and death of the knockout mice with 100% penetrance. Taken together, the results of our study add NIPA to the short list of FA-associated proteins, thereby highlighting its potential as a diagnostic marker and/or possible target in diseases characterized by hematopoietic failure.
“Trans-tattoo in immersion” method for the removal of a recurrent, previously tattooed adenoma using endoscopic submucosal hydrodissection
Authors: Felipe Ramos-Zabala, Cristina Gil-Páez, Alejandra Alzina-Pérez, Sara Blasco-Algora, Jorge Vásquez-Guerrero, Rocío Cardozo-Rocabado, Luis Moreno-Almazán
Journal: Endoscopy (2020)

An obese 74-year-old man, who underwent two unsuccessful endoscopic mucosal resections of a laterally spreading lesion nongranular type in the transverse colon was referred to our hospital. The lesion had been tattooed directly with SPOT (GI Supply, Camp Hill, Pennsylvania, USA) in order to aid surgical resection ([Fig. 1]). Prior biopsies reported adenoma with high-grade dysplasia. Colorectal surgeons referred the patient for endoscopic salvage treatment.
Association between Mental Disorders and Subsequent Medical Conditions
Authors: Natalie C. Momen, Oleguer Plana-Ripoll, Esben Agerbo, Michael E. Benros, Anders D. Børglum, Maria K. Christensen, Søren Dalsgaard, Louisa Degenhardt, Peter de Jonge, Jean-Christophe P.G. Debost, Morten Fenger-Grøn, Jane M. Gunn, Kim M. Iburg, Lars V. Kessing, Ronald C. Kessler, Thomas M. Laursen, Carmen C.W. Lim, Ole Mors, Preben B. Mortensen, Katherine L. Musliner, Merete Nordentoft, Carsten B. Pedersen, Liselotte V. Petersen, Anette R. Ribe, Annelieke M. Roest, Sukanta Saha, Andrew J. Schork, Kate M. Scott, Carson Sievert, Holger J. Sørensen, Terry J. Stedman, Mogens Vestergaard, Bjarni Vilhjalmsson, Thomas Werge, Nanna Weye, Harvey A. Whiteford, Anders Prior, John J. McGrath
Journal: New England Journal of Medicine (2020)

Persons with mental disorders are at a higher risk than the general population for the subsequent development of certain medical conditions.
Vaccination Strategies and Immune Modulation of Atherosclerosis
Authors: Jan Nilsson, Göran K. Hansson
Journal: Circulation Research (2020)

Adaptive as well as innate immune responses contribute to the development of atherosclerosis. Studies performed in experimental animals have revealed that some of these immune responses are protective while others contribute to the progression of disease. These observations suggest that it may be possible to develop novel therapies for cardiovascular disease by selectively modulating such atheroprotective and proatherogenic immunity. Recent advances in cancer treatment using immune check inhibitors and CAR (chimeric antigen receptor) T-cell therapy serve as excellent examples of the possibilities of targeting the immune system to combat disease. LDL (low-density lipoprotein) that has accumulated in the artery wall is a key autoantigen in atherosclerosis, and activation of antigen-specific T helper 1–type T cells is thought to fuel plaque inflammation. Studies aiming to prove this concept by immunizing experimental animals with oxidized LDL particles unexpectedly resulted in activation of atheroprotective immunity involving regulatory T cells. This prompted several research groups to try to develop vaccines against atherosclerosis. In this review, we will discuss the experimental and clinical data supporting the possibility of developing immune-based therapies for lowering cardiovascular risk. We will also summarize ongoing clinical studies and discuss the challenges associated with developing an effective and safe atherosclerosis vaccine.
Meningeal Immunity and Its Function in Maintenance of the Central Nervous System in Health and Disease
Authors: Kalil Alves de Lima, Justin Rustenhoven, Jonathan Kipnis
Journal: Annual Review of Immunology (2020)

Neuroimmunology, albeit a relatively established discipline, has recently sparked numerous exciting findings on microglia, the resident macrophages of the central nervous system (CNS). This review addresses meningeal immunity, a less-studied aspect of neuroimmune interactions. The meninges, a triple layer of membranes—the pia mater, arachnoid mater, and dura mater—surround the CNS, encompassing the cerebrospinal fluid produced by the choroid plexus epithelium. Unlike the adjacent brain parenchyma, the meninges contain a wide repertoire of immune cells. These constitute meningeal immunity, which is primarily concerned with immune surveillance of the CNS, and—according to recent evidence—also participates in postinjury CNS recovery, chronic neurodegenerative conditions, and even higher brain function. Meningeal immunity has recently come under the spotlight owing to the characterization of meningeal lymphatic vessels draining the CNS. Here, we review the current state of our understanding of meningeal immunity and its effects on healthy and diseased brains.
Skin exposure to sunlight: a factor modulating the human gut microbiome composition
Authors: Liliane Costa Conteville, Ana Carolina P Vicente
Journal: Gut Microbes (2020)

Background: The gut microbiome has been increasingly acknowledged as playing a pivotal role in human health. Therefore, a number of studies have focused on variables that impact its microbial structure and consequent functionality. A wide range of factors, such as diet, age, sex, life stage, behavior, ethnicity, and diseases have been considered, and strong links were set out. However, some aspects regarding the microbiome determinants are still under-explored. Discussion: Recently, Bosman et al. presented evidence that skin exposure to narrowband UVB light modulated the gut microbiome of a specific human cohort. This cohort presented an increase of biodiversity, Firmicutes and Proteobacteria, and a decrease of Bacteroidetes. Based on these findings, we revisited our data on a hunter-gatherer gut microbiome (Yanomami) and identified similarities in the gut microbiome of these two cohorts. Both presented a high abundance of Proteobacteria, which had been observed as a unique feature in the Yanomami gut microbiome, and based on Bosman et al study, could be associated with their natural sunlight exposure. Conclusion: In this commentary, we would like to point out that the human lifestyle concerning sunlight exposure should be considered as one force modulating the gut microbiome, highlighting, as proposed by Bosman et al, a novel skin-gut axis which is associated with health and disease.
Dendritic Cells, the T-cell-inflamed Tumor Microenvironment, and Immunotherapy Treatment Response
Authors: Christopher S. Garris, Jason J. Luke
Journal: Clinical Cancer Research (2020)

Abstract The development of the most successful cancer immunotherapies in solid tumors, immune-checkpoint blockade, has focused on factors regulating T-cell activation. Until recently, the field has maintained a predominately T-cell centric view of immunotherapy, leaving aside the impact of innate immunity and especially myeloid cells. Dendritic cells (DC) are dominant partners of T cells, necessary for initiation of adaptive immune responses. Emerging evidence supports a broader role for DCs in tumors including the maintenance and support of effector functions during T-cell responses. This relationship is evidenced by the association of activated DCs with immune-checkpoint blockade responses and transcriptional analysis of responding tumors demonstrating the presence of type I IFN transcripts and DC relevant chemokines. T-cell-inflamed tumors preferentially respond to immunotherapies compared with non–T-cell-inflamed tumors and this model suggests a potentially modifiable spectrum of tumor microenvironmental immunity. Although host and commensal factors may limit the T-cell-inflamed phenotype, tumor cell intrinsic factors are gaining prominence as therapeutic targets. For example, tumor WNT/β-catenin signaling inhibits production of chemokine gradients and blocking DC recruitment to tumors. Conversely, mechanisms of innate immune nucleic acid sensing, normally operative during pathogen response, may enhance DC accumulation and make tumors more susceptible to cancer immunotherapy. Elucidating mechanisms whereby DCs infiltrate and become activated within tumors may provide new opportunities for therapeutic intervention. Conceptually, this would facilitate conversion of non–T-cell-inflamed to T-cell-inflamed states or overcome secondary resistance mechanisms in T-cell-inflamed tumors, expanding the proportion of patients who benefit from cancer immunotherapy.
Baseline Clearance of Infliximab Is Associated With Requirement for Colectomy in Patients With Acute Severe Ulcerative Colitis
Authors: Robert Battat, Amy Hemperly, Stephanie Truong, Natalie Whitmire, Brigid S. Boland, Parambir S. Dulai, Ariela K. Holmer, Nghia H. Nguyen, Siddharth Singh, Niels Vande Casteele, William J. Sandborn
Journal: Clinical Gastroenterology and Hepatology (2020)
Impact of COVID-19 pandemic on patients with large-vessel vasculitis in Italy: a monocentric survey
Authors: Alessandro Tomelleri, Silvia Sartorelli, Corrado Campochiaro, Elena Marina Baldissera, Lorenzo Dagna
Journal: Annals of the Rheumatic Diseases (2020)

Severe infections represent one of the major complications of immunosuppressive therapy.1 Great concern among rheumatologists has consequently raised by the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19).2 3 Italy has represented the European epicentre of this global pandemic, with more than 140 000 confirmed cases as of 11 April 2020.4 

We evaluated the impact of SARS-CoV-2 infection among patients with large-vessel vasculitis (LVV) followed up at our LVV-Clinic in Milan, Lombardy, the Italian region with the highest rate of SARS-CoV-2 infections.5 A phone survey was conducted among these patients between 2 and 10 April 2020, 6 weeks after the COVID-19 outbreak in Italy. The survey consisted of the following questions: (1) Have you been diagnosed with COVID-19? (2) Since the beginning of COVID-19 outbreak, have you experienced one of the following symptoms: sore throat, non-productive cough, fever >37.5°C, reduced smelling or tasting, flu-like symptoms? (3) Have you been in contact with a COVID-19 patient? (4) Have you regularly been taking your LVV medications? …
Can hydroxychloroquine protect patients with rheumatic diseases from COVID-19? Response to: ‘Does hydroxychloroquine prevent the transmission of COVID-19?’ by Heldwein and Calado and ‘SLE, hydroxychloroquine and no SLE patients with COVID-19: a comment’ by Joob and Wiwanitkit
Authors: Sara Monti, Carlomaurizio Montecucco
Journal: Annals of the Rheumatic Diseases (2020)

We thank Dr Heldwein and Calado1 and Dr Joob and Wiwanitkit2 for their interest and comments on our paper.3 The authors raised the hypothesis that chronic use of hydroxychloroquine (HCQ) for the currently approved indications, such as systemic lupus erythematosus (SLE), could have an impact on the rate of COVID-19 and possibly on the clinical course of the infection.

An in vitro antiviral effect of HCQ has been demonstrated on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence suggests that HCQ can interfere with the virus-receptor binding and proliferation, potentially suggesting a prophylactic and therapeutic role of the drug, together with the advantages of its immunomodulatory activity.4 5 Given the urgent need to identify an efficacious treatment to reduce mortality during the COVID-19 pandemic, HCQ has been included in a number of national protocols and guidelines to treat the infection, based on the results of preliminary clinical data. Nevertheless, the evidence supporting the use of HCQ in vivo is still based …
Adverse effects of topical timolol: Safety concerns and implications for dermatologic use
Authors: Daniel Jaeho Yoon, Ramanjot Kaur, Anthony Gallegos, Kaitlyn West, Hsinya Yang, Saul Schaefer, Catherine Tchanque-Fossuo, Sara E. Dahle, R. Rivkah Isseroff
Journal: Journal of the American Academy of Dermatology (2020)
Eosinophil responses during COVID-19 infections and coronavirus vaccination
Authors: Andrew W. Lindsley, Justin T. Schwartz, Marc E. Rothenberg
Journal: Journal of Allergy and Clinical Immunology (2020)

Eosinophils are circulating and tissue-resident leukocytes that have potent proinflammatory effects in a number of diseases. Recently, eosinophils have been shown to have various other functions, including immunoregulation and antiviral activity. Eosinophil levels vary dramatically in a number of clinical settings, especially following eosinophil-targeted therapy, which is now available to selectively deplete these cells. There are key coronavirus disease 2019 (COVID-19)-related questions concerning eosinophils whose answers affect recommended prevention and care. First, do patients with eosinophilia-associated diseases have an altered course of COVID-19? Second, do patients with eosinopenia (now intentionally induced by biological drugs) have unique COVID-19 susceptibility and/or disease course? This is a particularly relevant question because eosinopenia is associated with acute respiratory deterioration during infection with the severe acute respiratory syndrome coronavirus 2, the causative agent of COVID-19. Third, do eosinophils contribute to the lung pathology induced during COVID-19 and will they contribute to immunopotentiation potentially associated with emerging COVID-19 vaccines? Herein, we address these timely questions and project considerations during the emerging COVID-19 pandemic.
Working With Patients With Impaired Insight
Authors: Hannah E. Brown, Sydney Feinstein, David C. Henderson
Journal: JAMA Psychiatry (2020)

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