tbuckley/cabot-search huggingface dataset:
Viable SARS-CoV-2 in various specimens from COVID-19 patients
Authors: Hye Won Jeong, Se-Mi Kim, Hee-Sung Kim, Young-Il Kim, Jun Hyoung Kim, Jun Yeon Cho, Sun-hyung Kim, Hyeran Kang, Seong-Gyu Kim, Su-Jin Park, Eun-Ha Kim, Young Ki Choi
Journal: Clinical Microbiology and Infection (2020)

ObjectivesThe aim was to determine whether various clinical specimens obtained from COVID-19 patients contain the infectious virus.MethodsTo demonstrate whether various clinical specimens contain the viable virus, we collected naso/oropharyngeal swabs and saliva, urine and stool samples from five COVID-19 patients and performed a quantitative polymerase chain reaction (qPCR) to assess viral load. Specimens positive with qPCR were subjected to virus isolation in Vero cells. We also used urine and stool samples to intranasally inoculate ferrets and evaluated the virus titres in nasal washes on 2, 4, 6 and 8 days post infection.ResultsSARS-CoV-2 RNA was detected in all naso/oropharyngeal swabs and saliva, urine and stool samples collected between days 8 and 30 of the clinical course. Notably, viral loads in urine, saliva and stool samples were almost equal to or higher than those in naso/oropharyngeal swabs (urine 1.08 ± 0.16–2.09 ± 0.85 log10 copies/mL, saliva 1.07 ± 0.34–1.65 ± 0.46 log10 copies/mL, stool 1.17 ± 0.32 log10 copies/mL, naso/oropharyngeal swabs 1.18 ± 0.12–1.34 ± 0.30 log10 copies/mL). Further, viable SARS-CoV-2 was isolated from naso/oropharyngeal swabs and saliva of COVID-19 patients, as well as nasal washes of ferrets inoculated with patient urine or stool.DiscussionViable SARS-CoV-2 was demonstrated in saliva, urine and stool samples from COVID-19 patients up to days 11–15 of the clinical course. This result suggests that viable SARS-CoV-2 can be secreted in various clinical samples and respiratory specimens.
AB0071 Lymphocytotoxic antibody (lca) among iraqi sle patients and their relatives
Authors: MM Hasan, KM Mousawy, S Salman, A Al-Wahab, AR Al-Shaikly
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To study the Lymphocytotoxic antibodies (LCA) in SLE patients and their first degree relatives compared to matching controls. <h3>Methods</h3> Complement dependent microcytotoxicity test was used to assess the presence of LCA, their temperature dependence in addition to HLA specificity among 40 SLE patients, 184 of their first degree relatives in comparison to 100 subjects of a blood bank donor as a healthy control. <h3>Results</h3> Lyphocytotoxic activity was manifested in 70% of patients, 33.36% of relatives compared to 80% of control group. While cold dependent antibodies were higher among patients group (92.8%) compared to 35% of their relatives. The presence of these antibodies in a control group was less temperature dependent, since 62.5% of them reacted both at 22C° and 15C° and only 12.5% of them exhibited a sole reactivity of 15C°. No association between LCA and and of HLA antigen of both classes was detected, however, patients had a tendency to react with a large number of lymphocyte samples than did positive sera from other group. Generally, females had a higher percentage of LCA (42.15%). Yet, the highest percentage was reported among sisters, followed by mothers, while brothers exhibited the least frequency (15.15%). In contrast to females, male subjects reported the highest frequency of these antibodies among age group of &gt; 50 years. <h3>Conclusion</h3> Patients expressed a high positivity rate of cold LCA. Moreover, female first degree relatives showed higher positivity rates than male relatives or controls.
Gout and pseudo-gout-related crystals promote GLUT1-mediated glycolysis that governs NLRP3 and interleukin-1β activation on macrophages
Authors: Felix Renaudin, Lucie Orliaguet, Florence Castelli, François Fenaille, Aurelie Prignon, Fawaz Alzaid, Christele Combes, Aurélie Delvaux, Yasmina Adimy, Martine Cohen-Solal, Pascal Richette, Thomas Bardin, Jean-Pierre Riveline, Nicolas Venteclef, Frédéric Lioté, Laure Campillo-Gimenez, Hang-Korng Ea
Journal: Annals of the Rheumatic Diseases (2020)

Macrophage activation by monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals mediates an interleukin (IL)-1β-dependent inflammation during gout and pseudo-gout flare, respectively. Since metabolic reprogramming of macrophages goes along with inflammatory responses dependently on stimuli and tissue environment, we aimed to decipher the role of glycolysis and oxidative phosphorylation in the IL-1β-induced microcrystal response.Briefly, an in vitro study (metabolomics and real-time extracellular flux analysis) on MSU and CPP crystal-stimulated macrophages was performed to demonstrate the metabolic phenotype of macrophages. Then, the role of aerobic glycolysis in IL-1β production was evaluated, as well in vitro as in vivo using 18F-fluorodeoxyglucose positron emission tomography imaging and glucose uptake assay, and molecular approach of glucose transporter 1 (GLUT1) inhibition.We observed that MSU and CPP crystals led to a metabolic rewiring toward the aerobic glycolysis pathway explained by an increase in GLUT1 plasma membrane expression and glucose uptake on macrophages. Also, neutrophils isolated from human synovial fluid during gout flare expressed GLUT1 at their plasma membrane more frequently than neutrophils isolated from bloodstream. Both glucose deprivation and treatment with either 2-deoxyglucose or GLUT1 inhibitor suppressed crystal-induced NLRP3 activation and IL-1β production, and microcrystal inflammation in vivo.In conclusion, we demonstrated that GLUT1-mediated glucose uptake is instrumental during the inflammatory IL-1β response induced by MSU and CPP crystals. These findings open new therapeutic paths to modulate crystal-related inflammation.
Single-Cell Analyses Identify Dysfunctional CD16+ CD8 T Cells in Smokers
Authors: Suzanne N. Martos, Michelle R. Campbell, Oswaldo A. Lozoya, Xuting Wang, Brian D. Bennett, Isabel J.B. Thompson, Ma Wan, Gary S. Pittman, Douglas A. Bell
Journal: Cell Reports Medicine (2020)

Tobacco smoke exposure contributes to the global burden of communicable and chronic diseases. To identify immune cells affected by smoking, we use single-cell RNA sequencing on peripheral blood from smokers and nonsmokers. Transcriptomes reveal a subpopulation of FCGR3A (CD16)-expressing Natural Killer (NK)-like CD8 T lymphocytes that increase in smokers. Mass cytometry confirms elevated CD16+ CD8 T cells in smokers. Inferred as highly differentiated by pseudotime analysis, NK-like CD8 T cells express markers characteristic of effector memory re-expressing CD45RA T (TEMRA) cells. Indicative of immune aging, smokers' CD8 T cells are biased toward differentiated cells and smokers have fewer naïve cells than nonsmokers. DNA methylation-based models show that smoking dose is associated with accelerated aging and decreased telomere length, a biomarker of T cell senescence. Immune aging accompanies T cell senescence, which can ultimately lead to impaired immune function. This suggests a role for smoking-induced, senescence-associated immune dysregulation in smoking-mediated pathologies.
FRI0164 Antibodies to proteinase-3, myeloperoxidase and b2gpi
Authors: AA Baranov, SY Kirdyanov, EL Nassonov, TV Beketova, MS Gurieva, OV Bashina, NE Abaytova
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To investigate the relationship between antibodies to proteinase-3 (anti-PR3), myeloperoxidase (anti-MPO) and b2GPI (anti-b2GPI) in patients (pts) with systemic vasculitis and primary antiphospholipid syndrome (PAPS). <h3>Methods</h3> The sera from 18 pts with polyarteritis nodosa (PAN), 18 pts with Takayasu's arteritis (TA), 21 pts with thromboangiitis obliterans (TAO), 21 pts with Henoch-Schonlein purpura (HSP), 20 pts with Wegener's granulomatosis (WG) (ACR,1990) and 8 pts with define PAPS (1998) and 20 donors were surveyed. IgG anti-PR3, anti-MPO and anti-b2GPI by ELISA (Orgentec, Germany) were studied. <h3>Results</h3> anti-PR3 in 1 (5,6%) pts with PAN and in 3 (14,3%) pts with HSP in low titers were found. anti-PR3 in 13 (61,9%) of 21 pts with WG (in 10 (71,4%) of 14 pts with generalized and in 3 (50%) of 6 local forms) in medium or high titers were observed. anti-MPO in 1 (5,6%) pts with PAN, in 2 (11,2%) pts with TA, in 1 (4,8%) pts with TAO and in 3 (14,3%) pts with HSP in low titers were found. anti-b2GPI in low titers in 4 (22,4%) pts with HSP and in medium or high titers in 8 (100%) pts with PAPS were observed only. anti-PR3 and anti-MPO in 1 pts sera with PAN were attended simultaneously. In HSP 1 pts had anti-PR3, anti-MPO, anti-b2GPI and 1 pts had anti-PR3 and anti-b2GPI simultaneously as well. In the serum from pts with TA, TAO, WG and PAPS anti-PR3 or anti-MPO or anti-b2GPI were attended alone. <h3>Conclusion</h3> So, in some pts with PAN and HSP anti-MPO, anti-PR3 and anti-b2GPI in low titers are attended simultaneously but their clinical significance are not obscure.
Efficacy and Safety of Locoregional Radiotherapy With Chemotherapy vs Chemotherapy Alone in De Novo Metastatic Nasopharyngeal Carcinoma
Authors: Rui You, You-Ping Liu, Pei-Yu Huang, Xiong Zou, Rui Sun, Yu-Xiang He, Yi-Shan Wu, Guo-Ping Shen, Hong-Dan Zhang, Chong-Yang Duan, Sze Huey Tan, Jing-Yu Cao, Ji-Bin Li, Yu-Long Xie, Yi-Nuan Zhang, Zhi-Qiang Wang, Qi Yang, Mei Lin, Rou Jiang, Meng-Xia Zhang, Yi-Jun Hua, Lin-Quan Tang, Ai-Hua Zhuang, Qiu-Yan Chen, Ling Guo, Hao-Yuan Mo, Yong Chen, Hai-Qiang Mai, Li Ling, Qing Liu, Melvin Lee Kiang Chua, Ming-Yuan Chen
Journal: JAMA Oncology (2020)

The role of locoregional radiotherapy in patients with de novo metastatic nasopharyngeal carcinoma (mNPC) is unclear.To investigate the efficacy and safety of locoregional radiotherapy in de novo mNPC.Patients with biopsy-proven mNPC, who demonstrated complete or partial response (RECIST v1.1) following 3 cycles of cisplatin and fluorouracil chemotherapy, were enrolled. Eligible patients were randomly assigned (1:1) to receive either chemotherapy plus radiotherapy or chemotherapy alone. Overall, 126 of 173 patients screened were eligible to the study, and randomized to chemotherapy plus radiotherapy (n = 63) or chemotherapy alone (n = 63). Median (IQR) follow-up duration was 26.7 (17.2-33.5) months.The chemotherapy regimens were fluorouracil continuous intravenous infusion at 5 g/m2 over 120 hours and 100 mg/m2 intravenous cisplatin on day 1, administered every 3 weeks for 6 cycles. Patients assigned to the chemotherapy plus radiotherapy group received intensity-modulated radiotherapy (IMRT) after chemotherapy.The primary end point of the study was overall survival (OS). The secondary end point was progression-free survival (PFS) and safety.Overall, 126 patients were enrolled (105 men [83.3%] and 21 women [16.7%]; median [IQR] age, 46 [39-52] years). The 24-month OS was 76.4% (95% CI, 64.4%-88.4%) in the chemotherapy plus radiotherapy group, compared with 54.5% (95% CI, 41.0%-68.0%) in the chemotherapy-alone group. The study met its primary end point of improved OS (stratified hazard ratio [HR], 0.42; 95% CI, 0.23-0.77; P = .004) in favor of chemotherapy plus radiotherapy. Progression-free survival was also improved in the chemotherapy plus radiotherapy group compared with the chemotherapy-alone group (stratified HR, 0.36; 95% CI, 0.23-0.57). No significant differences in acute hematological or gastrointestinal toxic effects were observed between the treatment arms. The frequency of acute grade 3 or higher dermatitis, mucositis, and xerostomia was 8.1%, 33.9%, and 6.5%, respectively, in the chemotherapy plus radiotherapy group. The frequency of late severe grade 3 or higher hearing loss and trismus was 5.2% and 3.4%, respectively, in the chemotherapy plus radiotherapy group.In this randomized clinical trial, radiotherapy added to chemotherapy significantly improved OS in chemotherapy-sensitive patients with mNPC.ClinicalTrials.gov Identifier: NCT02111460.
Association of Cardiac Infection With SARS-CoV-2 in Confirmed COVID-19 Autopsy Cases
Authors: Diana Lindner, Antonia Fitzek, Hanna Bräuninger, Ganna Aleshcheva, Caroline Edler, Kira Meissner, Katharina Scherschel, Paulus Kirchhof, Felicitas Escher, Heinz-Peter Schultheiss, Stefan Blankenberg, Klaus Püschel, Dirk Westermann
Journal: JAMA Cardiology (2020)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be documented in various tissues, but the frequency of cardiac involvement as well as possible consequences are unknown.To evaluate the presence of SARS-CoV-2 in the myocardial tissue from autopsy cases and to document a possible cardiac response to that infection.This cohort study used data from consecutive autopsy cases from Germany between April 8 and April 18, 2020. All patients had tested positive for SARS-CoV-2 in pharyngeal swab tests.Patients who died of coronavirus disease 2019.Incidence of SARS-CoV-2 positivity in cardiac tissue as well as CD3+, CD45+, and CD68+ cells in the myocardium and gene expression of tumor necrosis growth factor α, interferon γ, chemokine ligand 5, as well as interleukin-6, -8, and -18.Cardiac tissue from 39 consecutive autopsy cases were included. The median (interquartile range) age of patients was 85 (78-89) years, and 23 (59.0%) were women. SARS-CoV-2 could be documented in 24 of 39 patients (61.5%). Viral load above 1000 copies per μg RNA could be documented in 16 of 39 patients (41.0%). A cytokine response panel consisting of 6 proinflammatory genes was increased in those 16 patients compared with 15 patients without any SARS-CoV-2 in the heart. Comparison of 15 patients without cardiac infection with 16 patients with more than 1000 copies revealed no inflammatory cell infiltrates or differences in leukocyte numbers per high power field.In this analysis of autopsy cases, viral presence within the myocardium could be documented. While a response to this infection could be reported in cases with higher virus load vs no virus infection, this was not associated with an influx of inflammatory cells. Future investigations should focus on evaluating the long-term consequences of this cardiac involvement.
The CDK4/6-EZH2 pathway is a potential therapeutic target for psoriasis
Authors: Anne Müller, Antje Dickmanns, Claudia Resch, Knut Schäkel, Stephan Hailfinger, Matthias Dobbelstein, Klaus Schulze-Osthoff, Daniela Kramer
Journal: Journal of Clinical Investigation (2020)

Psoriasis is a frequent, inflammatory skin disease characterized by keratinocyte hyperproliferation and a disease-related infiltration of immune cells. Here, we identified a novel proinflammatory signaling pathway driven by cyclin-dependent kinase 4 (CDK4) and CDK6 and the methyltransferase EZH2 as a valid target for psoriasis therapy. Delineation of the pathway revealed that CDK4/6 phosphorylated EZH2 in keratinocytes, thereby triggering a methylation-induced activation of STAT3. Subsequently, active STAT3 resulted in the induction of IκBζ, which is a key proinflammatory transcription factor required for cytokine synthesis in psoriasis. Pharmacological or genetic inhibition of CDK4/6 or EZH2 abrogated psoriasis-related proinflammatory gene expression by suppressing IκBζ induction in keratinocytes. Importantly, topical application of CDK4/6 or EZH2 inhibitors on the skin was sufficient to fully prevent the development of psoriasis in various mouse models by suppressing STAT3-mediated IκBζ expression. Moreover, we found a hyperactivation of the CDK4/6-EZH2 pathway in human and mouse psoriatic skin lesions. Thus, this study not only identifies a novel psoriasis-relevant proinflammatory pathway, but also proposes the repurposing of CDK4/6 or EZH2 inhibitors as a new therapeutic option for patients with psoriasis.
SAT0188 Chronic plantar fasciitis: evaluation by ultrasound and mri. treatment with ultrasound guided injection
Authors: R Ghozlan, M Dupuis, C Lecarpentier, M Delain
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Chronic plantar fasciitis is not very known and the diagnosis is frequently missed. Trends for the diagnosis have been performed with the new methods of imaging. <h3>Objectives</h3> Determine the abnormal features of the chronic plantar fasciitis and find an efficient and accurate method of treatment. <h3>Methods</h3> 12 patients with chronic plantar fasciitis have been referred to us: men 7, women 5; mean age 55 years; mean duration of the disease 10 months. Ultrasound has been performed in 5 cases and MRI in 7 cases. <h3>Results</h3> Imaging showed increased thickness, reduced echogenicity of the plantar fasciitis and/or inflammatory changes. Ultrasound guided injection of steroids of the enlarged, hypoechoic plantar fascia, has been performed in 7 patients who had failed to conservative treatment. <h3>Conclusion</h3> The procedure resulted in complete relief of symptoms in 6 of 7 patients.
Pulmonary vascular resistance and clinical outcomes in patients with pulmonary hypertension: a retrospective cohort study
Authors: Bradley A Maron, Evan L Brittain, Edward Hess, Stephen W Waldo, Anna E Barón, Shi Huang, Ronald H Goldstein, Tufik Assad, Bradley M Wertheim, George A Alba, Jane A Leopold, Horst Olschewski, Nazzareno Galiè, Gerald Simonneau, Gabor Kovacs, Ryan J Tedford, Marc Humbert, Gaurav Choudhary
Journal: The Lancet Respiratory Medicine (2020)
JAK Inhibition for the Treatment of Myelofibrosis: Limitations and Future Perspectives
Authors: Prithviraj Bose, Srdan Verstovsek
Journal: HemaSphere (2020)

The 2011 approval of ruxolitinib ushered in the Janus kinase (JAK) inhibitor era in the treatment of myelofibrosis (MF), and 2019 saw the US approval of fedratinib. The first therapeutic agents approved by regulatory authorities for MF, these drugs attenuate the overactive JAK-signal transducer and activator of transcription (STAT) signaling universally present in these patients, translating into major clinical benefits in terms of spleen shrinkage and symptom improvement. These, in turn, confer a survival advantage on patients with advanced disease, demonstrated in the case of ruxolitinib, for which long-term follow-up data are available. However, JAK inhibitors do not improve cytopenias in most patients, have relatively modest effects on bone marrow fibrosis and driver mutation allele burden, and clinical resistance eventually develops. Furthermore, they do not modify the risk of transformation to blast phase; indeed, their mechanism of action may be more anti-inflammatory than truly disease-modifying. This has spurred interest in rational combinations of JAK inhibitors with other agents that may improve cytopenias and drugs that could potentially modify the natural history of MF. Newer JAK inhibitors that are distinguished from ruxolitinib and fedratinib by their ability to improve anemia (eg, momelotinib) or safety and efficacy in severely thrombocytopenic patients (eg, pacritinib) are in phase 3 clinical trials. There is also interest in developing inhibitors that are highly selective for mutant JAK2, as well as "type II" JAK2 inhibitors. Overall, although current JAK inhibitors have limitations, they will likely continue to form the backbone of MF therapy for the foreseeable future.
Chronic ethanol consumption and HBV induce abnormal lipid metabolism through HBx/SWELL1/arachidonic acid signaling and activate Tregs in HBV-Tg mice
Authors: Zixian Liu, Jiapei Wang, Lei Liu, Hongfeng Yuan, Yanan Bu, Jinyan Feng, Yunxia Liu, Guang Yang, Man Zhao, Ying Yuan, Huihui Zhang, Haolin Yun, Xiaodong Zhang
Journal: Theranostics (2020)

Rationale: Chronic ethanol consumption as a public health problem worldwide boosts the development of chronic liver diseases in hepatitis B virus (HBV)-infected patients. Arachidonic acid metabolite prostaglandin E2 (PGE2) activates regulatory T cells (Tregs) function. Here, we aim to investigate the underlying mechanism by which chronic ethanol consumption enriches the HBV-induced abnormal lipid metabolism and Tregs. Methods: The si-RNAs were used to weaken the expression of SWELL1 in HepG2, HepG2.2.15 and K180 cancer cell lines, followed by RNA sequencing from HepG2 cells. Arachidonic acid metabolite PGE2 and LTD4 were measured by ELISA assay in vivo and in vitro. Western blot analysis and RT-qPCR were used to examine HBx and SWELL1 and transcriptional factor Sp1 in clinical HCC samples and cell lines. The effect of chronic ethanol consumption on Tregs was tested by flow cytometry in HBV-Tg mice. The splenic Tregs were collected and analyzed by RNA sequencing. Results: The cooperative effect of ethanol and HBV in abnormal lipid metabolism was observed in vivo and in vitro. The depression of SWELL1 (or HBx) resulted in the reduction of lipid content and arachidonic acid metabolite, correlating with suppression of relative gene atlas. Ethanol and SWELL1 elevated the levels of PGE2 or LTD4 in the liver of mice and cell lines. Interestingly, the ethanol modulated abnormal lipid metabolism through activating HBx/Sp1/SWELL1/arachidonic acid signaling. Chronic ethanol consumption remarkably increased the population of PBL Tregs and splenic Tregs in HBV-Tg mice, consistently with the enhanced expression of PD-L1 in vivo and in vitro. Mechanically, RNA-seq data showed that multiple genes were altered in the transcriptomic atlas of Tregs sorting from ethanol-fed mice or HBV-Tg mice. Conclusion: The chronic ethanol intake enriches the HBV-enhanced abnormal lipid metabolism through HBx/SWELL1/arachidonic acid signaling and activates Tregs in mice.
Social touch promotes interfemale communication via activation of parvocellular oxytocin neurons
Authors: Yan Tang, Diego Benusiglio, Arthur Lefevre, Louis Hilfiger, Ferdinand Althammer, Anna Bludau, Daisuke Hagiwara, Angel Baudon, Pascal Darbon, Jonas Schimmer, Matthew K. Kirchner, Ranjan K. Roy, Shiyi Wang, Marina Eliava, Shlomo Wagner, Martina Oberhuber, Karl K. Conzelmann, Martin Schwarz, Javier E. Stern, Gareth Leng, Inga D. Neumann, Alexandre Charlet, Valery Grinevich
Journal: Nature Neuroscience (2020)
Abstract P236: Impact of Acculturation and Health Literacy on Prevalent Fasting Glycemia Among Latinos: Results From the Boston Area Community Health (BACH) Survey
Authors: Lenny Lopez, Lisa Marceau, Rebecca Piccolo, Gretchen Liu, Jason Vassy, Richard Grant, James B Meigs, John McKinlay
Journal: Circulation (2013)

Background Acculturation is the process by which immigrant groups adopt the cultural practices and values of the host country. We hypothesized higher acculturation is associated with higher prevale...
Randomized Trials Versus Common Sense and Clinical Observation
Authors: Alexander C. Fanaroff, Robert M. Califf, Robert A. Harrington, Christopher B. Granger, John J.V. McMurray, Manesh R. Patel, Deepak L. Bhatt, Stephan Windecker, Adrian F. Hernandez, C. Michael Gibson, John H. Alexander, Renato D. Lopes
Journal: Journal of the American College of Cardiology (2020)
The BMJ Awards 2020: Research paper of the year
Authors: Matthew Limb
Journal: BMJ (2020)

Using a single dose of prophylactic antibiotic after assisted vaginal birth would prevent thousands of infections and cut overall antibiotic use by 17%, concluded the winning paper in the research paper of the year award in this year's BMJ Awards.To find out more go to thebmjawards.bmj.com. 1