tbuckley/cabot-search huggingface dataset:
MicroRNA-21–Dependent Macrophage-to-Fibroblast Signaling Determines the Cardiac Response to Pressure Overload
Authors: Deepak Ramanujam, Anna Patricia Schön, Christina Beck, Paula Vaccarello, Giulia Felician, Anne Dueck, Dena Esfandyari, Gunter Meister, Thomas Meitinger, Christian Schulz, Stefan Engelhardt
Journal: Circulation (2021)

Cardiac macrophages (cMPs) are increasingly recognized as important regulators of myocardial homeostasis and disease, yet the role of noncoding RNA in these cells is largely unknown. Small RNA sequencing of the entire miRNomes of the major cardiac cell fractions revealed microRNA-21 (miR-21) as the single highest expressed microRNA in cMPs, both in health and disease (25% and 43% of all microRNA reads, respectively). MiR-21 has been previously reported as a key microRNA driving tissue fibrosis. Here, we aimed to determine the function of macrophage miR-21 on myocardial homeostasis and disease-associated remodeling.Macrophage-specific ablation of miR-21 in mice driven by Cx3cr1-Cre was used to determine the function of miR-21 in this cell type. As a disease model, mice were subjected to pressure overload for 6 and 28 days. Cardiac function was assessed in vivo by echocardiography, followed by histological analyses and single-cell sequencing. Cocultures of macrophages and cardiac fibroblasts were used to study macrophage-to-fibroblast signaling.Mice with macrophage-specific genetic deletion of miR-21 were protected from interstitial fibrosis and cardiac dysfunction when subjected to pressure overload of the left ventricle. Single-cell sequencing of pressure-overloaded hearts from these mice revealed that miR-21 in macrophages is essential for their polarization toward a M1-like phenotype. Systematic quantification of intercellular communication mediated by ligand-receptor interactions across all cell types revealed that miR-21 primarily determined macrophage-fibroblast communication, promoting the transition from quiescent fibroblasts to myofibroblasts. Polarization of isolated macrophages in vitro toward a proinflammatory (M1-like) phenotype activated myofibroblast transdifferentiation of cardiac fibroblasts in a paracrine manner and was dependent on miR-21 in cMPs.Our data indicate a critical role of cMPs in pressure overload-induced cardiac fibrosis and dysfunction and reveal macrophage miR-21 as a key molecule for the profibrotic role of cMPs.
Abstract 20099: Gender Differences in Clinical Outcomes and Echocardiographic Profile of Patients With Medically-Managed Severe Aortic Stenosis
Authors: Nicholas Ngiam, Benjamin Tan, Hui-Wen Sim, Ching-Hui Sia, Ting-Ting Low, William K Kong, Kian-Keong Poh
Journal: Circulation (2017)

Background: Gender differences in valvular heart disease are increasingly recognised. Prior study has suggested better surgical outcomes in women with symptomatic severe aortic stenosis (AS). We in...
NSCs Migration Promoted and Drug Delivered Exosomes‐Collagen Scaffold via a Bio‐Specific Peptide for One‐Step Spinal Cord Injury Repair
Authors: Lulu Zhang, Caixia Fan, Wangping Hao, Yan Zhuang, Xiru Liu, Yannan Zhao, Bing Chen, Zhifeng Xiao, Yanyan Chen, Jianwu Dai
Journal: Advanced Healthcare Materials (2021)

Abstract Spinal cord injury (SCI) is plaguing medical professionals globally due to the complexity of injury progression. Based on tissue engineering technology, there recently emerges a promising way by integrating drugs with suitable scaffold biomaterials to mediate endogenous neural stem cells (NSCs) to achieve one‐step SCI repair. Herein, exosomes extracted from human umbilical cord‐derived mesenchymal stem cells (MExos) are found to promote the migration of NSCs in vitro / in vivo. Utilizing MExos as drug delivery vehicles, a NSCs migration promoted and paclitaxel (PTX) delivered MExos‐collagen scaffold is designed via a novel dual bio‐specificity peptide (BSP) to effectively retain MExos within scaffolds. By virtue of the synergy that MExos recruit endogenous NSCs to the injured site, and PTX induce NSCs to give rise to neurons, this multifunctional scaffold has shown superior performance for motor functional recovery after complete SCI in rats by enhancing neural regeneration and reducing scar deposition. Besides, the dual bio‐specific peptide demonstrates the capacity of tethering other cells‐derived exosomes on collagen scaffold, such as erythrocytes‐derived or NSCs‐derived exosomes on collagen fibers or membranes. The resulting exosomes‐collagen scaffold may serve as a potential multifunctional therapy modality for various disease treatments including SCI.
Reply to “Dermatologists in social media: A study on top influencers, posts, and user engagement”: Dermatologist influencers on TikTok
Authors: Colby L. Presley, Kayd J. Pulsipher, Hope R. Rietcheck, Mindy D. Szeto, Melissa R. Laughter, Robert P. Dellavalle
Journal: Journal of the American Academy of Dermatology (2021)
Integrated immune dynamics define correlates of COVID-19 severity and antibody responses
Authors: Marios Koutsakos, Louise C. Rowntree, Luca Hensen, Brendon Y. Chua, Carolien E. van de Sandt, Jennifer R. Habel, Wuji Zhang, Xiaoxiao Jia, Lukasz Kedzierski, Thomas M. Ashhurst, Givanna H. Putri, Felix Marsh-Wakefield, Mark N. Read, Davis N. Edwards, E. Bridie Clemens, Chinn Yi Wong, Francesca L. Mordant, Jennifer A. Juno, Fatima Amanat, Jennifer Audsley, Natasha E. Holmes, Claire L. Gordon, Olivia C. Smibert, Jason A. Trubiano, Carly M. Hughes, Mike Catton, Justin T. Denholm, Steven Y.C. Tong, Denise L. Doolan, Tom C. Kotsimbos, David C. Jackson, Florian Krammer, Dale I. Godfrey, Amy W. Chung, Nicholas J.C. King, Sharon R. Lewin, Adam K. Wheatley, Stephen J. Kent, Kanta Subbarao, James McMahon, Irani Thevarajan, Thi H.O. Nguyen, Allen C. Cheng, Katherine Kedzierska
Journal: Cell Reports Medicine (2021)

SARS-CoV-2 causes a spectrum of COVID-19 disease, the immunological basis of which remains ill defined. We analyzed 85 SARS-CoV-2-infected individuals at acute and/or convalescent time points, up to 102 days after symptom onset, quantifying 184 immunological parameters. Acute COVID-19 presented with high levels of IL-6, IL-18, and IL-10 and broad activation marked by the upregulation of CD38 on innate and adaptive lymphocytes and myeloid cells. Importantly, activated CXCR3+cTFH1 cells in acute COVID-19 significantly correlate with and predict antibody levels and their avidity at convalescence as well as acute neutralization activity. Strikingly, intensive care unit (ICU) patients with severe COVID-19 display higher levels of soluble IL-6, IL-6R, and IL-18, and hyperactivation of innate, adaptive, and myeloid compartments than patients with moderate disease. Our analyses provide a comprehensive map of longitudinal immunological responses in COVID-19 patients and integrate key cellular pathways of complex immune networks underpinning severe COVID-19, providing important insights into potential biomarkers and immunotherapies.
Fine-tuning the cardiac O-GlcNAcylation regulatory enzymes governs the functional and structural phenotype of the diabetic heart
Authors: Darnel Prakoso, Shiang Y Lim, Jeffrey R Erickson, Rachel S Wallace, Jarmon G Lees, Mitchel Tate, Helen Kiriazis, Daniel G Donner, Darren C Henstridge, Jonathan R Davey, Hongwei Qian, Minh Deo, Laura J Parry, Amy J Davidoff, Paul Gregorevic, John C Chatham, Miles J De Blasio, Rebecca H Ritchie
Journal: Cardiovascular Research (2021)

Abstract Aims The glucose-driven enzymatic modification of myocardial proteins by the sugar moiety, β-N-acetylglucosamine (O-GlcNAc), is increased in pre-clinical models of diabetes, implicating protein O-GlcNAc modification in diabetes-induced heart failure. Our aim was to specifically examine cardiac manipulation of the two regulatory enzymes of this process on the cardiac phenotype, in the presence and absence of diabetes, utilising cardiac-targeted recombinant-adeno-associated viral-vector-6 (rAAV6)-mediated gene delivery. Methods and results In human myocardium, total protein O-GlcNAc modification was elevated in diabetic relative to non-diabetic patients, and correlated with left ventricular (LV) dysfunction. The impact of rAAV6-delivered O-GlcNAc transferase (rAAV6-OGT, facilitating protein O-GlcNAcylation), O-GlcNAcase (rAAV6-OGA, facilitating de-O-GlcNAcylation), and empty vector (null) were determined in non-diabetic and diabetic mice. In non-diabetic mice, rAAV6-OGT was sufficient to impair LV diastolic function and induce maladaptive cardiac remodelling, including cardiac fibrosis and increased Myh-7 and Nppa pro-hypertrophic gene expression, recapitulating characteristics of diabetic cardiomyopathy. In contrast, rAAV6-OGA (but not rAAV6-OGT) rescued LV diastolic function and adverse cardiac remodelling in diabetic mice. Molecular insights implicated impaired cardiac PI3K(p110α)-Akt signalling as a potential contributing mechanism to the detrimental consequences of rAAV6-OGT in vivo. In contrast, rAAV6-OGA preserved PI3K(p110α)-Akt signalling in diabetic mouse myocardium in vivo and prevented high glucose-induced impairments in mitochondrial respiration in human cardiomyocytes in vitro. Conclusion Maladaptive protein O-GlcNAc modification is evident in human diabetic myocardium, and is a critical regulator of the diabetic heart phenotype. Selective targeting of cardiac protein O-GlcNAcylation to restore physiological O-GlcNAc balance may represent a novel therapeutic approach for diabetes-induced heart failure.
Author Correction: NF-κB-inducing kinase maintains T cell metabolic fitness in antitumor immunity
Authors: Meidi Gu, Xiaofei Zhou, Jee Hyung Sohn, Lele Zhu, Zuliang Jie, Jin-Young Yang, Xiaofeng Zheng, Xiaoping Xie, Jie Yang, Yaoyao Shi, Hans D. Brightbill, Jae Bum Kim, Jing Wang, Xuhong Cheng, Shao-Cong Sun
Journal: Nature Immunology (2021)
Case 4-2021: A 70-Year-Old Woman with Dyspnea on Exertion and Abnormal Findings on Chest Imaging
Authors: Richard M. Schwartzstein, Benjamin D. Medoff, Amita Sharma, Yolonda L. Colson, Justin Gainor, Lida P. Hariri
Journal: New England Journal of Medicine (2021)

A 70-year-old woman was evaluated because of increasing dyspnea on exertion and abnormal findings on chest imaging. Eleven years before this evaluation, mild mosaic attenuation at the lung bases was identified incidentally. Three years later, dyspnea on exertion developed and pulmonary function worsened. Diagnostic tests were performed.
Chromosome 17q12-21 Variants Are Associated with Multiple Wheezing Phenotypes in Childhood
Authors: Brian Hallmark, Ganesa Wegienka, Suzanne Havstad, Dean Billheimer, Dennis Ownby, Eneida A. Mendonca, Lisa Gress, Debra A. Stern, Jocelyn Biagini Myers, Gurjit K. Khurana Hershey, Lori Hoepner, Rachel L. Miller, Robert F. Lemanske, Daniel J. Jackson, Diane R. Gold, George T. O’Connor, Dan L. Nicolae, James E. Gern, Carole Ober, Anne L. Wright, Fernando D. Martinez
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Birth cohort studies have identified several temporal patterns of wheezing, only some of which are associated with asthma. Whether 17q12-21 genetic variants, which are closely associated with asthma, are also associated with childhood wheezing phenotypes remains poorly explored.Objectives: To determine whether wheezing phenotypes, defined by latent class analysis (LCA), are associated with nine 17q12-21 SNPs and if so, whether these relationships differ by race/ancestry.Methods: Data from seven U.S. birth cohorts (n = 3,786) from the CREW (Children's Respiratory Research and Environment Workgroup) were harmonized to represent whether subjects wheezed in each year of life from birth until age 11 years. LCA was then performed to identify wheeze phenotypes. Genetic associations between SNPs and wheeze phenotypes were assessed separately in European American (EA) (n = 1,308) and, for the first time, in African American (AA) (n = 620) children.Measurements and Main Results: The LCA best supported four latent classes of wheeze: infrequent, transient, late-onset, and persistent. Odds of belonging to any of the three wheezing classes (vs. infrequent) increased with the risk alleles for multiple SNPs in EA children. Only one SNP, rs2305480, showed increased odds of belonging to any wheezing class in both AA and EA children.Conclusions: These results indicate that 17q12-21 is a "wheezing locus," and this association may reflect an early life susceptibility to respiratory viruses common to all wheezing children. Which children will have their symptoms remit or reoccur during childhood may be independent of the influence of rs2305480.
Active Eosinophilic Esophagitis is Associated with Increased Asthma Severity and Lower Lung Function in Children with Comorbid Asthma
Authors: Karyn Parsons, Katharine Guarnieri, Dawit Tadesse, Md Monir Hossain, Vincent Mukkada, Marc Rothenberg, Theresa Guilbert, Sandy Durrani
Journal: Journal of Allergy and Clinical Immunology (2021)
The COVID-19 immune landscape is dynamically and reversibly correlated with disease severity
Authors: Hamid Bolouri, Cate Speake, David Skibinski, S. Alice Long, Anne M. Hocking, Daniel J. Campbell, Jessica A. Hamerman, Uma Malhotra, Jane H. Buckner
Journal: Journal of Clinical Investigation (2021)

BACKGROUND. Despite a rapidly growing body of literature on coronavirus disease 2019 (COVID-19), our understanding of the immune correlates of disease severity, course, and outcome remains poor.
Systematic Detection of Large-Scale Multigene Horizontal Transfer in Prokaryotes
Authors: Lina Kloub, Sophia Gosselin, Matthew Fullmer, Joerg Graf, Johann Peter Gogarten, Mukul S Bansal
Journal: Molecular Biology and Evolution (2021)

Abstract Horizontal gene transfer (HGT) is central to prokaryotic evolution. However, little is known about the “scale” of individual HGT events. In this work, we introduce the first computational framework to help answer the following fundamental question: How often does more than one gene get horizontally transferred in a single HGT event? Our method, called HoMer, uses phylogenetic reconciliation to infer single-gene HGT events across a given set of species/strains, employs several techniques to account for inference error and uncertainty, combines that information with gene order information from extant genomes, and uses statistical analysis to identify candidate horizontal multigene transfers (HMGTs) in both extant and ancestral species/strains. HoMer is highly scalable and can be easily used to infer HMGTs across hundreds of genomes. We apply HoMer to a genome-scale data set of over 22,000 gene families from 103 Aeromonas genomes and identify a large number of plausible HMGTs of various scales at both small and large phylogenetic distances. Analysis of these HMGTs reveals interesting relationships between gene function, phylogenetic distance, and frequency of multigene transfer. Among other insights, we find that 1) the observed relative frequency of HMGT increases as divergence between genomes increases, 2) HMGTs often have conserved gene functions, and 3) rare genes are frequently acquired through HMGT. We also analyze in detail HMGTs involving the zonula occludens toxin and type III secretion systems. By enabling the systematic inference of HMGTs on a large scale, HoMer will facilitate a more accurate and more complete understanding of HGT and microbial evolution.
Whole genome sequencing identifies novel genetic mutations in patients with eczema herpeticum
Authors: Lianghua Bin, Claire Malley, Patricia Taylor, Meher Preethi Boorgula, Sameer Chavan, Michelle Daya, Malaika Mathias, Gautam Shankar, Nicholas Rafaels, Candelaria Vergara, Joseph Potee, Monica Campbell, Jon M. Hanifin, Eric Simpson, Lynda C. Schneider, Richard L. Gallo, Tissa Hata, Amy S. Paller, Anna De Benedetto, Lisa A. Beck, Peck Y. Ong, Emma Guttman‐Yassky, Brittany Richers, David Baraghoshi, Ingo Ruczinski, Kathleen C. Barnes, Donald Y. M. Leung, Rasika A. Mathias
Journal: Allergy (2021)

Eczema herpeticum (EH) is a rare complication of atopic dermatitis (AD) caused by disseminated herpes simplex virus (HSV) infection. The role of rare and/or deleterious genetic variants in disease etiology is largely unknown. This study aimed to identify genes that harbor damaging genetic variants associated with HSV infection in AD with a history of recurrent eczema herpeticum (ADEH+).Whole genome sequencing (WGS) was performed on 49 recurrent ADEH+ (≥3 EH episodes), 491 AD without a history of eczema herpeticum (ADEH-) and 237 non-atopic control (NA) subjects. Variants were annotated, and a gene-based approach (SKAT-O) was used to identify genes harboring damaging genetic variants associated with ADEH+. Genes identified through WGS were studied for effects on HSV responses and keratinocyte differentiation.Eight genes were identified in the comparison of recurrent ADEH+to ADEH-and NA subjects: SIDT2, CLEC7A, GSTZ1, TPSG1, SP110, RBBP8NL, TRIM15, and FRMD3. Silencing SIDT2 and RBBP8NL in normal human primary keratinocytes (NHPKs) led to significantly increased HSV-1 replication. SIDT2-silenced NHPKs had decreased gene expression of IFNk and IL1b in response to HSV-1 infection. RBBP8NL-silenced NHPKs had decreased gene expression of IFNk, but increased IL1b. Additionally, silencing SIDT2 and RBBP8NL also inhibited gene expression of keratinocyte differentiation markers keratin 10 (KRT10) and loricrin (LOR).SIDT2 and RBBP8NL participate in keratinocyte's response to HSV-1 infection. SIDT2 and RBBP8NL also regulate expression of keratinocyte differentiation genes of KRT10 and LOR.
Head-to-head comparison of SARS-CoV-2 antigen-detecting rapid test with professional-collected nasal<i>versus</i>nasopharyngeal swab
Authors: Andreas K. Lindner, Olga Nikolai, Chiara Rohardt, Susen Burock, Claudia Hülso, Alisa Bölke, Maximilian Gertler, Lisa J. Krüger, Mary Gaeddert, Frank Tobian, Federica Lainati, Joachim Seybold, Terry C. Jones, Jörg Hofmann, Jilian A. Sacks, Frank P. Mockenhaupt, Claudia M. Denkinger
Journal: European Respiratory Journal (2021)

<b>Professional nasal sampling is a reliable alternative to nasopharyngeal sampling when using a WHO-listed SARS-CoV-2 antigen-detecting rapid test. This less invasive method needs less training to facilitate rapid scaling of testing strategies.</b>https://bit.ly/3pEVlUL
REPLY:
Authors: Angela Lamarca, Alvaro Santos‐Laso, Kirsten Utpatel, Adelaida La Casta, Simone Stock, Alejandro Forner, Jorge Adeva, Trine Folseraas, Luca Fabris, Rocio I. R. Macias, Marcin Krawczyk, Marek Krawczyk, Vincenzo Cardinale, Chiara Braconi, Domenico Alvaro, Matthias Evert, Jesus M. Banales, Juan W. Valle
Journal: Hepatology (2021)

Rather than categorizing all multifocal disease as "liver metastasis," patients with multiple ICC can harbor "true" multifocal tumors, a solitary tumor with satellite lesions, as well as intrahepatic liver metastasis.Failing to differentiate "multifocal tumors" into separate categories may have conflated three different clinical scenarios.Resection of multifocal ICC has been associated with worse outcomes versus patients who underwent surgery for a solitary tumor (5-year survival 30% versus 19%). (2)Survival was particularly poor in the setting of > 3 tumor nodules, nodal metastasis, and poor differentiation.However, patients with multifocal disease who had none of these factors had 5-year survival of 28% after resection-similar to patients with a solitary tumor.As such, patients with multifocal disease likely represent a heterogeneous population.Unfortunately, in the study by Lamarca et al. treatment details were not elucidated, which would have been important to understand relative to long-term survival.The authors also did not thoroughly examine the impact of multiple ICC tumors relative to nodal status.Our group has long advocated for routine performance of lymphadenectomy. (3,4)Pathological assessment of the nodal basin is critical to staging as nodal status is among the strongest ICC prognostic factors. (5)Patients with concurrent multifocal tumors and lymph node metastases had a 5-year survival of 3.2%, which was worse than patients with either risk factor alone (12.8%) or patients with unifocal disease and no lymph node metastasis (28.8%). ( 2 Categorizing all patients with multifocal disease-regardless of nodal status-as M1a may not be accurate.In sum, the authors' attempt to refine the current American Joint Committee on Cancer staging system relative to patients with multifocal disease is provocative.However, rather than simply categorizing all patients with multiple lesions as having M1a disease, a more nuanced approached informed by anatomic location of the lesions, other competing risk factors, as well as emerging molecular profiling will be needed.
Ceftriaxone Allergy in Pediatric Population
Authors: Morgan Gold, Daniel Sehayek, Sofianne Gabrielli, Elissa Abrams, Andrew O’Keefe, Jennifer Protudjer, E.L.A.N.A. LAVINE, Tracy Pitt, A.D.E.L.L.E. ATKINSON, Thomas Eiwegger, Christine McCusker, Moshe Ben-Shoshan
Journal: Journal of Allergy and Clinical Immunology (2021)
COVID-19-Associated Hospitalization and Outcomes in Patients with Asthma: A Systematic Review and Meta-analysis
Authors: Andrea Sitek, Justine Ade, Mitchell M. Pitlick, Sergio Chiarella, Rohit Divekar, Vivek Iyer, Zhen Wang, Avni Joshi
Journal: Journal of Allergy and Clinical Immunology (2021)

It remains unclear if asthma is a risk factor associated with poor outcomes among patients with COVID-19. We performed a comprehensive database search for COVID-19 studies published through October 2, 2020. We included studies with COVID-19-diagnosed patients with and without underlying asthma. Outcomes of interest included need for hospitalization, length of hospitalization, intensive care unit (ICU) admission and death. Meta-analysis was conducted using random-effects method. A total of 389 studies were identified through database searches. After abstract and full-text screening, 18 observational studies with 76,393 patients were included in the analysis. Of the 18 studies, 17 were retrospective, and 1 was a prospective cohort. The average age was 37.7; 63% were female. Two of the studies specifically evaluated pregnant patients, and two included only pediatric patients. Among patients with COVID-19 infection, the presence of asthma was not associated with significant increased risk of hospitalization (odds ratio (OR) 1.46 [95% confidence interval, 0.29, 7.28]), length of hospitalization (1.59 days [-0.55, 3.74]), ICU admission (OR 1.65 [0.56, 4.17]) or death (OR 0.73 [0.38, 1.40]). The overall risk of bias of the included studies is high. Among patients with COVID-19 infection, asthma did not significantly increase the risk of adverse outcomes. The role of type 2 inflammation and inhaled corticosteroid use in this population needs to be further explored.