tbuckley/cabot-search huggingface dataset:
Intravenous Immunoglobulin for Treatment of Severe Coronavirus Disease 19 (COVID-19) – A Literature Overview
Authors: Syed Rizvi, Huub Kreuwel
Journal: Journal of Allergy and Clinical Immunology (2021)

COVID-19 was declared a global pandemic in March 2020. Previous experiences with SARS-Cov-2 showed that the main pathogenesis and pulmonary dysfunction lay in the overall cytokine dysregulation. Intravenous immunoglobulin (IVIg) has been recognized for its anti-inflammatory and immunomodulatory effects Based on evidence, clinicians have hypothesized that IVIg therapy may improve the prognosis of critically-ill COVID-19 patients. A literature search was performed using the search terms: Corona, COVID-19, IVIg, and Immunoglobulin. 10 published reports describing the beneficial effects of IVIg in treating COVID-19 were identified. A retrospective, multicenter cohort study that included 325 adult critical patients demonstrated early high-dose IVIg administration improves the prognosis of critical COVID-19 patients. A retrospective review of 58 patients with severe COVID-19 pneumonia compared outcomes in those receiving high-dose IVIg treatment < 48 hours versus > 48 hours after admission to ICU. Results demonstrated high-dose IVIg received < 48 hours after admission to ICU resulted in reductions in the use of mechanical ventilation, hospital/ICU stay, and 28-day mortality in patients with severe COVID-19 pneumonia. An observational study conducted in 10 COVID-19 patients demonstrated short-term moderate-dose corticosteroid combined with high-dose IVIg reversed severe, deteriorating COVID-19 patients who failed initial low-dose therapy. Three published papers were identified using IVIg in pediatric COVID-19 patients who presented with Kawasaki-like or PMIS (Pediatric COVID-associated Multi-system Inflammatory Syndrome). It may be useful to consider high-dose IVIg at the time of initiation of respiratory distress to potentially promote satisfactory clinical recovery and reduce burden of care for COVID-19 patients.
Therapeutic Manipulation of Tumor-associated Macrophages: Facts and Hopes from a Clinical and Translational Perspective
Authors: Paola Allavena, Clément Anfray, Aldo Ummarino, Fernando Torres Andón
Journal: Clinical Cancer Research (2021)

The stroma of most solid tumors is populated by myeloid cells, which mostly represent macrophages. Tumor-associated macrophages (TAMs), strongly influenced by cancer cell-derived factors, are key drivers of immunosuppression and support tumor growth and spread to distant sites. Their accurate quantification and characterization in the tumor microenvironment are gaining prognostic value: increasing evidence demonstrates their ability to hamper cancer patients' response to chemotherapy, as well as to immunotherapies based on checkpoint inhibition. Therefore, strategies to counteract their negative effects are nowadays gaining momentum at preclinical, translational, and clinical levels. Our knowledge of the biology of TAMs has greatly advanced in the last years; several strategies to target and reprogram their functions to become antitumor effectors have proven successful in experimental preclinical tumor models; on the other hand, few approaches have so far been effectively translated into clinic practice. A growing interest in the therapeutic manipulation of TAMs is evidenced by numerous early-phase clinical trials, which are continuously fueled by new discoveries from basic research. This gives us hope that the targeting and sustained reprogramming of TAMs will be more specific to synergize with current therapies and maximize antitumor responses in patients.
Prevalence of and Factors Associated With Nurse Burnout in the US
Authors: Megha K. Shah, Nikhila Gandrakota, Jeannie P. Cimiotti, Neena Ghose, Miranda Moore, Mohammed K. Ali
Journal: JAMA Network Open (2021)

Clinician burnout is a major risk to the health of the US. Nurses make up most of the health care workforce, and estimating nursing burnout and associated factors is vital for addressing the causes of burnout.To measure rates of nurse burnout and examine factors associated with leaving or considering leaving employment owing to burnout.This secondary analysis used cross-sectional survey data collected from April 30 to October 12, 2018, in the National Sample Survey of Registered Nurses in the US. All nurses who responded were included (N = 50 273). Data were analyzed from June 5 to October 1, 2020.Age, sex, race and ethnicity categorized by self-reported survey question, household income, and geographic region. Data were stratified by workplace setting, hours worked, and dominant function (direct patient care, other function, no dominant function) at work.The primary outcomes were the likelihood of leaving employment in the last year owing to burnout or considering leaving employment owing to burnout.The weighted sample of 50 273 respondents (representing 3 957 661 nurses nationally) was predominantly female (90.4%) and White (80.7%); the mean (SD) age was 48.7 (0.04) years. Among nurses who reported leaving their job in 2017 (n = 418 769), 31.5% reported burnout as a reason, with lower proportions of nurses reporting burnout in the West (16.6%) and higher proportions in the Southeast (30.0%). Compared with working less than 20 h/wk, nurses who worked more than 40 h/wk had a higher likelihood identifying burnout as a reason they left their job (odds ratio, 3.28; 95% CI, 1.61-6.67). Respondents who reported leaving or considering leaving their job owing to burnout reported a stressful work environment (68.6% and 59.5%, respectively) and inadequate staffing (63.0% and 60.9%, respectively).These findings suggest that burnout is a significant problem among US nurses who leave their job or consider leaving their job. Health systems should focus on implementing known strategies to alleviate burnout, including adequate nurse staffing and limiting the number of hours worked per shift.
Group 2 Innate Lymphoid Cells: Team Players in Regulating Asthma
Authors: Noe Rodriguez-Rodriguez, Mayuri Gogoi, Andrew N.J. McKenzie
Journal: Annual Review of Immunology (2021)

Type 2 immunity helps protect the host from infection, but it also plays key roles in tissue homeostasis, metabolism, and repair. Unfortunately, inappropriate type 2 immune reactions may lead to allergy and asthma. Group 2 innate lymphoid cells (ILC2s) in the lungs respond rapidly to local environmental cues, such as the release of epithelium-derived type 2 initiator cytokines/alarmins, producing type 2 effector cytokines such as IL-4, IL-5, and IL-13 in response to tissue damage and infection. ILC2s are associated with the severity of allergic asthma, and experimental models of lung inflammation have shown how they act as playmakers, receiving signals variously from stromal and immune cells as well as the nervous system and then distributing cytokine cues to elicit type 2 immune effector functions and potentiate CD4+ T helper cell activation, both of which characterize the pathology of allergic asthma. Recent breakthroughs identifying stromal- and neuronal-derived microenvironmental cues that regulate ILC2s, along with studies recognizing the potential plasticity of ILC2s, have improved our understanding of the immunoregulation of asthma and opened new avenues for drug discovery.
Nuclear factor erythroid 2–related factor 2 and β‐Catenin Coactivation in Hepatocellular Cancer: Biological and Therapeutic Implications
Authors: Junyan Tao, Yekaterina Krutsenko, Akshata Moghe, Sucha Singh, Minakshi Poddar, Aaron Bell, Michael Oertel, Aatur D. Singhi, David Geller, Xin Chen, Amaia Lujambio, Silvia Liu, Satdarshan P. Monga
Journal: Hepatology (2021)

HCC remains a major unmet clinical need. Although activating catenin beta-1 (CTNNB1) mutations are observed in prominent subsets of HCC cases, these by themselves are insufficient for hepatocarcinogenesis. Coexpression of mutant CTNNB1 with clinically relevant co-occurrence has yielded HCCs. Here, we identify cooperation between β-catenin and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling in HCC.Public HCC data sets were assessed for concomitant presence of CTNNB1 mutations and either mutations in nuclear factor erythroid-2-related factor-2 (NFE2L2) or Kelch like-ECH-associated protein 1 (KEAP1), or Nrf2 activation by gene signature. HCC development in mice and similarity to human HCC subsets was assessed following coexpression of T41A-CTNNB1 with either wild-type (WT)-, G31A-, or T80K-NFE2L2. Based on mammalian target of rapamycin complex 1 activation in CTNNB1-mutated HCCs, response of preclinical HCC to mammalian target of rapamycin (mTOR) inhibitor was investigated. Overall, 9% of HCC cases showed concomitant CTNNB1 mutations and Nrf2 activation, subsets of which were attributable to mutations in NFE2L2/KEAP1. Coexpression of mutated CTNNB1 with mutant NFE2L2, but not WT-NFE2L2, led to HCC development and mortality by 12-14 weeks. These HCCs were positive for β-catenin targets, like glutamine synthetase and cyclin-D1, and Nrf2 targets, like NAD(P)H quinone dehydrogenase 1 and peroxiredoxin 1. RNA-sequencing and pathway analysis showed high concordance of preclinical HCC to human HCC subset showing activation of unique (iron homeostasis and glioblastoma multiforme signaling) and expected (glutamine metabolism) pathways. NFE2L2-CTNNB1 HCC mice were treated with mTOR inhibitor everolimus (5-mg/kg diet ad libitum), which led to >50% decrease in tumor burden.Coactivation of β-catenin and Nrf2 is evident in 9% of all human HCCs. Coexpression of mutant NFE2L2 and mutant CTNNB1 led to clinically relevant HCC development in mice, which responded to mTOR inhibitors. Thus, this model has both biological and therapeutic implications.
Abstract 10959: Adverse Effects of Severe Left Ventricular Diastolic Dysfunction on the Response to Cardiac Resynchronization Therapy
Authors: Hideaki Kanzaki, Takashi Noda, Masashi Amano, Yasuhiro Hamatani, Atsushi Okada, Hiroyuki Takahama, Makoto Amaki, Takuya Hasegawa, Kengo Kusano, Satoshi Yasuda, Chisato Izumi
Journal: Circulation (2018)

Introduction: Cardiac resynchronization therapy (CRT) can benefit patients with left ventricular (LV) systolic heart failure with conduction delay. LV diastolic dysfunction (DD) affects the symptom...
CARD14 is Required for FLG Homeostasis in Human Skin, and the CARD14 Variant Rs11652075 Regulates the Expression of FLG in a Genotype-Dependent Fashion
Authors: Stanley DeVore, Mariana Stevens, Hua He, Jocelyn Biagini Myers, John Kroner, Lisa Martin, Gurjit Khurana Hershey
Journal: Journal of Allergy and Clinical Immunology (2021)
The miR–181a–SFRP4 Axis Regulates Wnt Activation to Drive Stemness and Platinum Resistance in Ovarian Cancer
Authors: Anil Belur Nagaraj, Matthew Knarr, Sreeja Sekhar, R. Shae Connor, Peronne Joseph, Olga Kovalenko, Alexis Fleming, Arshia Surti, Elmar Nurmemmedov, Luca Beltrame, Sergio Marchini, Michael Kahn, Analisa DiFeo
Journal: Cancer Research (2021)

Abstract Wnt signaling is a major driver of stemness and chemoresistance in ovarian cancer, yet the genetic drivers that stimulate its expression remain largely unknown. Unlike other cancers, mutations in the Wnt pathway are not reported in high-grade serous ovarian cancer (HGSOC). Hence, a key challenge that must be addressed to develop effective targeted therapies is to identify nonmutational drivers of Wnt activation. Using an miRNA sensor-based approach, we have identified miR-181a as a novel driver of Wnt/β-catenin signaling. miR-181ahigh primary HGSOC cells exhibited increased Wnt/β-catenin signaling, which was associated with increased stem-cell frequency and platinum resistance. Consistent with these findings, inhibition of β-catenin decreased stem-like properties in miR-181ahigh cell populations and downregulated miR-181a. The Wnt inhibitor SFRP4 was identified as a novel target of miR-181a. Overall, our results demonstrate that miR-181a is a nonmutational activator of Wnt signaling that drives stemness and chemoresistance in HGSOC, suggesting that the miR–181a–SFRP4 axis can be evaluated as a novel biomarker for β-catenin–targeted therapy in this disease. Significance: These results demonstrate that miR-181a is an activator of Wnt signaling that drives stemness and chemoresistance in HGSOC and may be targeted therapeutically in recurrent disease.
After TAVI, aspirin vs. aspirin + clopidogrel for 3 mo reduced bleeding and a composite of bleeding and thrombotic events at 1 y
Authors: Raúl Moreno
Journal: Annals of Internal Medicine (2021)

ACP Journal ClubFebruary 2021After TAVI, aspirin vs. aspirin + clopidogrel for 3 mo reduced bleeding and a composite of bleeding and thrombotic events at 1 yRaúl Moreno, MD, PhDRaúl Moreno, MD, PhDHospital La Paz, IdiPAZ, CIBER-CV, Madrid, Spain (R.M.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJ202102160-021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationBrouwer J, Nijenhuis VJ, Delewi R, et al. Aspirin with or without clopidogrel after transcatheter aortic-valve implantation. N Engl J Med. 2020;383:1447-57. https://pubmed.ncbi.nlm.nih.gov/32865376Clinical Impact RatingsCardiology: Geriatrics: References1 Noble S, Asgar A, Cartier R, et al. Anatomo-pathological analysis after CoreValve Revalving system implantation. EuroIntervention 2009;5:78-85. [PMID: 19577986] Google Scholar2 Grube E, Laborde JC, Gerckens U, et al. Percutaneous implantation of the CoreValve self-expanding valve prosthesis in high-risk patients with aortic valve disease: the Siegburg first-in-man study. Circulation. 2006;114:1616-2. [PMID: 17015786] Google Scholar3 Moreno R, Calvo L, Salinas P, et al. Causes of peri-operative mortality after transcatheter aortic valve implantation: a pooled analysis of 12 studies and 1223 patients. J Invasive Cardiol 2011;23:180-4. [PMID: 21562344] Google Scholar4 Rodés-Cabau J, Masson JB, Welsh RC, et al. Aspirin versus aspirin plus clopidogrel as antithrombotic treatment following transcatheter aortic valve replacement with a balloon-expandable valve: the ARTE randomized clinical trial. JACC Cardiovasc Interv. 2017;10:1357-65. [PMID: 28527771] Google Scholar Author, Article, and Disclosure InformationAffiliations: Hospital La Paz, IdiPAZ, CIBER-CV, Madrid, Spain (R.M.)Disclosures: The commentator has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M20-7313.This article was published at Annals.org on 2 February 2021. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics February 2021Volume 174, Issue 2Page: JC21KeywordsAntiplatelet therapyAortic valve replacementAspirinCoronary stentingHemorrhageIntent to treat analysisIschemic strokeMyocardial infarctionStent implantationThorax ePublished: 2 February 2021 Issue Published: February 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Polydopamine/poly(sulfobetaine methacrylate) Co-deposition coatings triggered by CuSO4/H2O2 on implants for improved surface hemocompatibility and antibacterial activity
Authors: Zhongqiang Zhu, Qiang Gao, Ziyue Long, Qiuyi Huo, Yifan Ge, Ntakirutimana Vianney, Nishimwe Anodine Daliko, Yongchun Meng, Jia Qu, Hao Chen, Bailiang Wang
Journal: Bioactive Materials (2021)

Implanted biomaterials such as medical catheters are prone to be adhered by proteins, platelets and bacteria due to their surface hydrophobicity characteristics, and then induce related infections and thrombosis. Hence, the development of a versatile strategy to endow surfaces with antibacterial and antifouling functions is particularly significant for blood-contacting materials. In this work, CuSO4/H2O2 was used to trigger polydopamine (PDA) and poly-(sulfobetaine methacrylate) (PSBMA) co-deposition process to endow polyurethane (PU) antibacterial and antifouling surface (PU/PDA(Cu)/PSBMA). The zwitterions contained in the PU/PDA(Cu)/PSBMA coating can significantly improve surface wettability to reduce protein adsorption, thereby improving its blood compatibility. In addition, the copper ions released from the metal-phenolic networks (MPNs) imparted them more than 90% antibacterial activity against E. coli and S. aureus. Notably, PU/PDA(Cu)/PSBMA also exhibits excellent performance in vivo mouse catheter-related infections models. Thus, the PU/PDA(Cu)/PSBMA has great application potential for developing multifunctional surface coatings for blood-contacting materials so as to improve antibacterial and anticoagulant properties.
Expansion and Accelerated Evolution of 9-Exon Odorant Receptors in<i>Polistes</i>Paper Wasps
Authors: Andrew W Legan, Christopher M Jernigan, Sara E Miller, Matthieu F Fuchs, Michael J Sheehan
Journal: Molecular Biology and Evolution (2021)

Abstract Independent origins of sociality in bees and ants are associated with independent expansions of particular odorant receptor (OR) gene subfamilies. In ants, one clade within the OR gene family, the 9-exon subfamily, has dramatically expanded. These receptors detect cuticular hydrocarbons (CHCs), key social signaling molecules in insects. It is unclear to what extent 9-exon OR subfamily expansion is associated with the independent evolution of sociality across Hymenoptera, warranting studies of taxa with independently derived social behavior. Here, we describe OR gene family evolution in the northern paper wasp, Polistes fuscatus, and compare it to four additional paper wasp species spanning ∼40 million years of evolutionary divergence. We find 200 putatively functional OR genes in P. fuscatus, matching predictions from neuroanatomy, and more than half of these are in the 9-exon subfamily. Most OR gene expansions are tandemly arrayed at orthologous loci in Polistes genomes, and microsynteny analysis shows species-specific gain and loss of 9-exon ORs within tandem arrays. There is evidence of episodic positive diversifying selection shaping ORs in expanded subfamilies. Values of omega (dN/dS) are higher among 9-exon ORs compared to other OR subfamilies. Within the Polistes OR gene tree, branches in the 9-exon OR clade experience relaxed negative (relaxed purifying) selection relative to other branches in the tree. Patterns of OR evolution within Polistes are consistent with 9-exon OR function in CHC perception by combinatorial coding, with both natural selection and neutral drift contributing to interspecies differences in gene copy number and sequence.
Genomic monitoring of SARS-CoV-2 uncovers an Nsp1 deletion variant that modulates type I interferon response
Authors: Jing-wen Lin, Chao Tang, Han-cheng Wei, Baowen Du, Chuan Chen, Minjin Wang, Yongzhao Zhou, Ming-xia Yu, Lu Cheng, Suvi Kuivanen, Natacha S. Ogando, Lev Levanov, Yuancun Zhao, Chang-ling Li, Ran Zhou, Zhidan Li, Yiming Zhang, Ke Sun, Chengdi Wang, Li Chen, Xia Xiao, Xiuran Zheng, Sha-sha Chen, Zhen Zhou, Ruirui Yang, Dan Zhang, Mengying Xu, Junwei Song, Danrui Wang, Yupeng Li, ShiKun Lei, Wanqin Zeng, Qingxin Yang, Ping He, Yaoyao Zhang, Lifang Zhou, Ling Cao, Feng Luo, Huayi Liu, Liping Wang, Fei Ye, Ming Zhang, Mengjiao Li, Wei Fan, Xinqiong Li, Kaiju Li, Bowen Ke, Jiannan Xu, Huiping Yang, Shusen He, Ming Pan, Yichen Yan, Yi Zha, Lingyu Jiang, Changxiu Yu, Yingfen Liu, Zhiyong Xu, Qingfeng Li, Yongmei Jiang, Jiufeng Sun, Wei Hong, Hongping Wei, Guangwen Lu, Olli Vapalahti, Yunzi Luo, Yuquan Wei, Thomas Connor, Wenjie Tan, Eric J. Snijder, Teemu Smura, Weimin Li, Jia Geng, Binwu Ying, Lu Chen
Journal: Cell Host & Microbe (2021)
Comparison of Corticosteroid Tapering Regimens in Myasthenia Gravis
Authors: Tarek Sharshar, Raphaël Porcher, Sophie Demeret, Christine Tranchant, Antoine Gueguen, Bruno Eymard, Aleksandra Nadaj-Pakleza, Marco Spinazzi, Lamiae Grimaldi, Simone Birnbaum, Diane Friedman, Bernard Clair, Philippe Aegerter, Djillali Annane, Anne-Catherine Aubé-Nathier, Francis Bolgert, Marie Fleury, Marie-Christine Durand, Pierre-Marie Gonnaud, Catherine Goulon-Goeau, Olivier Gout, Frédéric Lofaso, Christophe Marcel, Vivien Pautot, Isabelle Penisson-Besnier, Hélène Prigent, Benjamin Rohaut, Christophe Vial, Nicolas Weiss
Journal: JAMA Neurology (2021)

The tapering of prednisone therapy in generalized myasthenia gravis (MG) presents a therapeutic dilemma; however, the recommended regimen has not yet been validated.To compare the efficacy of the standard slow-tapering regimen of prednisone therapy with a rapid-tapering regimen.From June 1, 2009, to July 31, 2013, a multicenter, parallel, single-blind randomized trial was conducted to compare 2 regimens of prednisone tapering. Data analysis was conducted from February 18, 2019, to January 23, 2020. A total of 2291 adults with a confirmed diagnosis of moderate to severe generalized MG at 7 specialized centers in France were assessed for eligibility.The slow-tapering arm included a gradual increase of the prednisone dose to 1.5 mg/kg every other day and a slow decrease once minimal manifestation status of MG was attained. The rapid-tapering arm consisted of immediate high-dose daily administration of prednisone, 0.75 mg/kg, followed by an earlier and rapid decrease once improved MG status was attained. Azathioprine, up to a maximum dose of 3 mg/kg/d, was prescribed for all participants.The primary outcome was attainment of minimal manifestation status of MG without prednisone at 12 months and without clinical relapse at 15 months. Intention-to-treat analysis was conducted.Of the 2291 patients assessed, 2086 did not fulfill the inclusion criteria, 87 declined to participate, and 1 patient registered after trial closure. A total of 117 patients (58 in the slow-tapering arm and 59 in the rapid-tapering arm) were selected for inclusion by MG specialists and were randomized. The population included 62 men (53%); median age was 65 years (interquartile range, 35-69 years). The proportion of patients having met the primary outcome was higher in the rapid- vs slow-tapering arm (23 [39%] vs 5 [9%]), with a risk ratio of 3.61 (95% CI, 1.64-7.97; P < .001) after adjusting for center and thymectomy. The rapid-tapering regimen allowed sparing of a mean of 1898 mg (95% CI, -3121 to -461 mg) of prednisone over 1 year (ie, 5.3 mg/d per patient, P = .03). The number of serious adverse events did not differ significantly between the slow- vs rapid-tapering group (13 [22%] vs 21 [36%], P = .15).In patients with moderate to severe generalized MG who require high-dose prednisone with azathioprine therapy, rapid tapering of prednisone appears to be feasible, well tolerated, and associated with a good outcome.ClinicalTrials.gov Identifier: NCT00987116.
Abstract 14539: Impact of Tricuspid Regurgitation on Chronic Hepatic and Cardiac Function After Pulmonary Valve Replacement With Repaired Tetralogy of Fallot
Authors: Hideki Tatewaki, Ichiro Sakamoto, Satoshi Fujita, Hiroyuki Tsutsui, Akira Shiose
Journal: Circulation (2018)

Introduction: Tricuspid regurgitation (TR) is a common long-term complication in patients with repaired tetralogy of Fallot (TOF). However, tricuspid valve repair associated to pulmonary valve repl...