tbuckley/cabot-search huggingface dataset:
Cardiovascular diseases, lipid-lowering therapies and European registries in the COVID-19 pandemic
Authors: Henning Morawietz, Ulrich Julius, Stefan R Bornstein
Journal: Cardiovascular Research (2020)

Since December 2019 the coronavirus disease 2019 (COVID-19) which emerged in Wuhan, China, has rapidly spread around the globe.With >10 000 000 confirmed cases in >180 countries and an estimated mortality rate of 2-5%, it has had an enormous economic and social impact worldwide.Clinical risk factors and diseases which predispose to severe COVID-19 are pulmonary diseases, advanced age, hypertension, coronary artery disease, diabetes mellitus, and smoking (Figure 1). 1 These factors might affect the susceptibility to infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the subsequent critical clinical complications. 2 Approximately 80% of patients after SARS-CoV-2 infection develop mild to moderate symptoms, 15% severe, and 5% life-threatening clinical complications.Severe clinical problems of COVID-19 patients could involve the difficult management of acute myocardial infarction, acute pulmonary embolism, cardiac tamponade complicating myo-pericarditis, and heart failure.The infection involves binding of the SARS-CoV-2 spike protein to the cell receptor angiotensin-converting enzyme 2 (ACE2). 3Because ACE inhibitors and angiotensin receptor blockers (ARBs) can increase ACE2 expression in experimental studies, this observation has raised discussions about the safety of these important antihypertensive drugs in the current COVID-19 pandemic. 3It should be emphasized that such discontinuation of ACE inhibitor or ARB therapy in patients with heart failure or coronary disease could lead to unnecessary worsening of cardiac conditions and hospitalization.Recent position statements from the European Society of Cardiology (https://www.escardio.org/Councils/Council-on-Hypertension-(CHT)/News/position-statement-of-theesc-council-on-hypertension-on-ace-inhibitors-and-ang), the Eur
Abstract TMIM-064: AMPKA-LIKE PROTEINS IN OVARIAN CANCER TUMORIGENESIS AND NECROPTOSIS
Authors: Anmbreen Jamroze, Mikhail Chesnokov, Ilana Chefetz
Journal: Clinical Cancer Research (2019)

Abstract In our previous research we characterized novel ALDH1A inhibitors (1A1, 1A2, 1A3) 673A that specifically target Ovarian Cancer Stem cells (OvCSC) and trigger cell programmed necrosis (necroptosis). Following ALDH1A inhibition CD133+ (A2780) FACS sorted cells we detected increase in phospho LKB1 while its major downstream target AMPKa did not exhibit changes in phosphorylation level. In addition to AMPKa, which is most known downstream target of LKB1, there are 11 AMPKa-like proteins that can be phosphorylated by LKB1. These proteins have been studied mostly in brain development. To detect AMPKa-like relevancy to high grade serous ovarian cancer, we next analyzed TCGA data. Surprisingly we identified many alterations in all 12 genes, including LKB1 (STK11). We only focused on alterations that exhibit gene amplifications or mRNA upregulation. Based on TCGA data, all AMPKa-like genes have many alterations in ovarian tumors suggesting importance of these genes to ovarian cancer tumorigenesis. We next continued to analyze combinations of any two genes to test their co-occurrence or mutual exclusivity. We detected 9 gene combinations, in which amplification or mRNA upregulation in AMPKa-like genes co-occur (p&amp;lt;0.5) in patient tumors. We next validated expression of AMPKa-like genes in ovarian cancer cell lines and confirmed their expression in PEO-4, Ovcar8, and Ovsaho. We next treated Ovsaho, PEO4 and OvCAR8 cells with ALDH1A inhibitor 673A for 8 and 14 hr, and profiled expression of AMPKa-like genes following ALDH1A inhibition. We detected significant changes in AMPKa-like genes, suggesting their role in cell programmed necrosis. To confirm our bioinformatic findings, we established cell lines that mimic patient tumors with most frequent co-occurrence of AMPKa genes. We have been studying these cell lines in terms of cell proliferation, stemness and role in cell death. Citation Format: Anmbreen Jamroze, Mikhail Chesnokov, Ilana Chefetz. AMPKA-LIKE PROTEINS IN OVARIAN CANCER TUMORIGENESIS AND NECROPTOSIS [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr TMIM-064.
Tracing and analysis of 288 early SARS-CoV-2 infections outside China: A modeling study
Authors: Francesco Pinotti, Laura Di Domenico, Ernesto Ortega, Marco Mancastroppa, Giulia Pullano, Eugenio Valdano, Pierre-Yves Boëlle, Chiara Poletto, Vittoria Colizza
Journal: PLoS Medicine (2020)

Background In the early months of 2020, a novel coronavirus disease (COVID-19) spread rapidly from China across multiple countries worldwide. As of March 17, 2020, COVID-19 was officially declared a pandemic by the World Health Organization. We collected data on COVID-19 cases outside China during the early phase of the pandemic and used them to predict trends in importations and quantify the proportion of undetected imported cases. Methods and findings Two hundred and eighty-eight cases have been confirmed out of China from January 3 to February 13, 2020. We collected and synthesized all available information on these cases from official sources and media. We analyzed importations that were successfully isolated and those leading to onward transmission. We modeled their number over time, in relation to the origin of travel (Hubei province, other Chinese provinces, other countries) and interventions. We characterized the importation timeline to assess the rapidity of isolation and epidemiologically linked clusters to estimate the rate of detection. We found a rapid exponential growth of importations from Hubei, corresponding to a doubling time of 2.8 days, combined with a slower growth from the other areas. We predicted a rebound of importations from South East Asia in the successive weeks. Time from travel to detection has considerably decreased since first importation, from 14.5 ± 5.5 days on January 5, 2020, to 6 ± 3.5 days on February 1, 2020. However, we estimated 36% of detection of imported cases. This study is restricted to the early phase of the pandemic, when China was the only large epicenter and foreign countries had not discovered extensive local transmission yet. Missing information in case history was accounted for through modeling and imputation. Conclusions Our findings indicate that travel bans and containment strategies adopted in China were effective in reducing the exportation growth rate. However, the risk of importation was estimated to increase again from other sources in South East Asia. Surveillance and management of traveling cases represented a priority in the early phase of the epidemic. With the majority of imported cases going undetected (6 out of 10), countries experienced several undetected clusters of chains of local transmissions, fueling silent epidemics in the community. These findings become again critical to prevent second waves, now that countries have reduced their epidemic activity and progressively phase out lockdown.
Long-Term Mortality Following Transcatheter Atrial Septal Defects Closure in Comparison to the General Population
Authors: Sami Alnasser, Douglas S. Lee, Mark Osten, Peter C. Austin, Ashish Shah, Yvonne Bach, Lusine Abrahamyan, Bing Yu, Lee Benson, Eric M. Horlick
Journal: Journal of the American College of Cardiology (2020)
High-loading Gα <sub>13</sub> -binding EXE peptide nanoparticles prevent thrombosis and protect mice from cardiac ischemia/reperfusion injury
Authors: Aiming Pang, Ni Cheng, Yujie Cui, Yanyan Bai, Zhigang Hong, M. Keegan Delaney, Yaping Zhang, Claire Chang, Can Wang, Chang Liu, Paola Leon Plata, Alexander Zakharov, Kasim Kabirov, Jalees Rehman, Randal A. Skidgel, Asrar B. Malik, Ying Liu, Aleksander Lyubimov, Minyi Gu, Xiaoping Du
Journal: Science Translational Medicine (2020)

In vivo high-loading peptide nanoparticle administration prevented thrombosis and myocardial injury without causing bleeding in mice.
T <sub>H</sub> 17 cells require ongoing classic IL-6 receptor signaling to retain transcriptional and functional identity
Authors: Stacey N. Harbour, Daniel F. DiToro, Steven J. Witte, Carlene L. Zindl, Min Gao, Trenton R. Schoeb, Gareth W. Jones, Simon A. Jones, Robin D. Hatton, Casey T. Weaver
Journal: Science Immunology (2020)

Ongoing classic IL-6 receptor signaling is required to maintain the T H 17 program, acting upstream of IL-23 to sustain RORγt expression.
Prevalence of Clinical Signs Within Reference Ranges Among Hospitalized Patients Prescribed Antibiotics for Pneumonia
Authors: Michael Klompas, Aileen Ochoa, Wenjing Ji, Caroline McKenna, Roger Clark, Erica S. Shenoy, David Hooper, Chanu Rhee
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Antibiotics are frequently prescribed for suspected pneumonia, but overdiagnosis is common and fixed regimens are often used despite randomized trials suggesting it is safe to stop antibiotics once clinical signs are normalizing. <h3>Objective</h3> To quantify potential excess antibiotic prescribing by characterizing antibiotic use relative to patients’ initial clinical signs and subsequent trajectories. <h3>Design, Setting, and Participants</h3> An observational cohort study was conducted in 2 tertiary and 2 community hospitals in Eastern Massachusetts. All nonventilated adult patients admitted between May 1, 2017, and July 1, 2018 (194 521 hospitalizations), were included. <h3>Main Outcomes and Measures</h3> Identification of all antibiotic starts for possible community-acquired pneumonia (CAP) or hospital-acquired pneumonia (HAP) per clinicians’ stated indications. Potential excess antibiotic prescribing was quantified by characterizing the frequency of patients in whom all clinical signs were within reference ranges on the first day of antibiotic therapy and by how long antibiotic therapy was continued after all clinical signs were normal, including postdischarge antibiotics. <h3>Results</h3> Among 194 521 hospitalizations, 9540 patients were treated for possible CAP (4574 [48.0%] women; mean [SD] age, 67.6 [17.0] years) and 2733 for possible HAP (1211 [44.3%] women; mean [SD] age, 66.7 [16.2] years). Temperature, respiratory rate, oxygen saturation, and white blood cell count were all within reference ranges on the first day of antibiotics in 1779 of 9540 (18.6%) episodes of CAP and 370 of 2733 (13.5%) episodes of HAP. Antibiotics were continued for 3 days or longer after all clinical signs were normal in 3322 of 9540 (34.8%) episodes of CAP and 1050 of 2733 (38.4%) episodes of HAP. Up to 24 978 of 71 706 (34.8%) antibiotic-days prescribed for possible pneumonia may have been unnecessary. <h3>Conclusions and Relevance</h3> In this study, almost one-fifth of hospitalized patients treated for pneumonia did not have any of the cardinal signs of pneumonia on the first day of treatment and antibiotics were continued for 3 days or longer after all signs were normal in more than a third of patients. These observations suggest substantial opportunities to improve antibiotic prescribing.
SAT0103 Acromegalic arthropathy: an italian study in 20 patients
Authors: F Schiavon, H Marotta, P Maffei, C Martini, C Menegazzo, N Sicolo, R Ragazzi, S Todesco
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Acromegaly is frequently complicated by axial and peripheral joint abnormalities. Although usually mild, severe handicap is not infrequent. In addition soft tissue, cartilage and bony proliferation make acromegaly a peculiar model of non-inflammatory joint disease, which is reflected by clinical and radiological findings. <h3>Objectives</h3> The aim of this study was to compare the clinical and radiographic features of Italian acromegalic patients with the well- known literature studies. <h3>Methods</h3> We studied 20 patients (10 men and 10 women) with acromegaly, admitted to our Department. The diagnosis of acromegaly and the status of the disease were based on clinical, hormonal and radiological features. The duration of disease was assumed as the interval between the clinical onset and the time of the diagnosis and was 5.43 ± 2.76 year for men and 8.50 ± 5.66 year for women. Physical examination of peripheral and axial joints and radiological assessment of hands, wrists, shoulders, spine, pelvis hips and knee was performed. Moreover a ultrasonographyc shoulder's study in 8 patients was carried out. All the patients were submitted to a global self assessment of disease status or activity with WOMAC. <h3>Results</h3> We found 70% of acromegalic gave a history of peripheral joint pain, often mild and intermittent and 65% described spine involvement. At the examination 12 patients described spine pain, mostly mild and poorly localised, 9 shoulder pain with severely disabling symptoms, 4 mild localised knee joint pain, 2 hip pain. Only 2 patients reported hand pain. Over 50% of patients presented joint hypermobility. We are able to find a correlation between the severity of peripheral joint or spinal abnormalities, WOMAC physical function and stiffness scale score and activity of acromegaly (GH and IGF-1 blood levels) (p &lt; 0.001). In our patients the shoulder represents one of the most painful and disabling joint. Radiographic abnormalities included narrowing of glenohumeral joint, beak-like osteophytes and, in 4 patients, a destructive arthropathy with oval deformation of humeral head. Ultrasonographic studies were carried out in 8 patients and revealed tendons involvement in all the patients, even without radiological abnormalities. We found supraspinatus tendon tear in 3 patients, rotator cuff and bicipital tendinitis in 7 patients and subacromial bursitis in 2 patients. <h3>Conclusion</h3>
Predicted Prognosis of Pancreatic Cancer Patients by Machine Learning—Letter
Authors: Julius M. Kernbach, Victor E. Staartjes
Journal: Clinical Cancer Research (2020)

We recently read the article by Yokoyama and colleagues ([1][1]), in which the authors report a predictive model integrating DNA methylation status of three mucin genes to predict overall survival at a designated 5-year interval in pancreatic cancer. They collected samples from 191 patients and
Ultrasound shows rapid reduction of crystal depositions during a treat-to-target approach in gout patients: 12-month results from the NOR-Gout study
Authors: Hilde Berner Hammer, Lars Karoliussen, Lene Terslev, Espen A Haavardsholm, Tore K Kvien, Till Uhlig
Journal: Annals of the Rheumatic Diseases (2020)

As ultrasound is sensitive for detecting crystal depositions in patients with gout, our objectives were to explore the main locations for depositions and the extent of dissolution of depositions during a treat-to-target approach with urate lowering treatment (ULT) in patients with gout.Patients with a recent flare of gout were consecutively included in this single-centre study and managed by a treat-to-target approach with ULT. All patients were assessed at baseline, 3, 6 and 12 months including bilateral ultrasound examinations of joints/tendons/entheses of hands, elbows, knees, ankles and feet. A new semiquantitative scoring system of 0-3 of elementary lesions (double contour (DC), tophi and aggregates) was applied to quantify the amount of depositions during the follow-up.209 of the patients were evaluated with ultrasound at baseline (mean (SD) age 56.4 (13.8) years and disease duration 7.9 (7.7) years, 95.2% men). The serum urate levels decreased from baseline to 12 months (mean (SD) 500 (77) to 312 (49) µmol/L) (p<0.001)). The first metatarsophalangeal joint was the most frequent location for all the elementary lesions and erosions were associated with higher levels of crystal depositions. From baseline to 12 months, mean sum scores decreased for DC (4.3 to 1.3), tophi (6.5 to 3.8) and aggregates (9.3 to 6.7) (p<0.001 for all), with DC being most sensitive to change.The ultrasound scoring system for crystal depositions was sensitive to change and showed that a treat-to-target approach with ULT resulted in significant reductions of all the depositions, most extensively for DC.
AB0061 Circulating adenosine levels after initiation of methotrexate and anti-tnf therapy in ra
Authors: P Barrera, AE Van Ede, M Creemers, RF Laan, RA De Abreu, LB Van de Putte
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Adenosine exerts strong anti-inflammatory effects. <i>In vitro</i> and animal studies suggest that adenosine release is implicated in the mechanism of action of methotrexate (MTX) and sulfasalazine. Whether blocking TNF has any effect on this pathway has not been investigated yet. <h3>Objectives</h3> To assess the short anf mid-term effect of MTX and anti-TNF therapy on the circulating levels of adenosine and aminoimidazolcarboximide ribotide (AICAR) in rheumatoid arthritis (RA). <h3>Methods</h3> Patients starting therapy with MTX (n = 10; dose 15 mg/kg im) or infliximab (n = 10, dose 3 mg/kg) were enrolled in the study. Blood samples were drawn immediately before and 2, 6, 24 and 48 h and 4 weeks after the first administration of MTX or anti-TNF. Measurements before and 2 and 6 h after administration were also performed on week 12. To avoid adenosine degradation, blood was directly mixed with a solution containing EHNA 10 μM, dipyridamole 20 μM and indomethacin 2 mg/L. Adenosine and AICAR were measured using sensitive HPLC methods. Response to therapy was assessed at week 4 and 12 using the EULAR criteria. <h3>Results</h3> Baseline adenosine levels were similar in both patient groups (median, [p25 – p75] 213 [146 – 302] and 230 [71 – 291] nmol/L for MTX and anti-TNF respectively). Adenosine levels showed marked inter- and intra-individual variability (75% and 49% respectively). In 3 patients, adenosine concentrations raised markedly 2 h after the first MTX dose. Nevertheless, no consistent changes were observed in the whole MTX group or after anti-TNF administration. Within the study period, 55% and 64% of the patients receiving MTX and anti-TNF showed clinical response. The latter was also not reflected in the levels of adenosine. AICAR could not be detected in any of the samples. <h3>Conclusion</h3> In patients with RA, neither MTX therapy nor its effectivity are mirrored by consistent changes in circulating adenosine levels. The same holds true for anti-TNF treatment. This does not exclude the possibility of a modulation of adenosine release at the target organ.
Apicularen A induces cell death via caspase-dependent apoptosis and down-regulation of tubulin synthesis in HeLa human cervical carcinoma cells
Journal: Cancer Research (2007)

3592  Apicularen A is a newly identified highly cytotoxic metabolite from the myxobacterial genus Chondromyces, has been shown to cause growth inhibition in several cancer cell lines and apoptosis. Also, apicularen A was recently reported to be a vacuolar ATPase inhibitor. However, the molecular pathway that lead to cell death by apicularen A are limited. In this study, we investigated the molecular mechanisms of apicularen A-induced cell death in HeLa human cervix cancer cells. To determine the mechanism of cytotoxicity of apicularen A in cervical carcinoma cell, effects of apicularen A on the cell growth and apoptosis-related molecules were examined in HeLa cells. Apicularen A inhibited a time and dose dependently HeLa cell growth. Also Apicularen A induced DNA fragmentation and PARP cleavage. Flow cytometric analysis showed that accumulation of cells in sub-G1 was caused and decreased in sub-G1 by pancaspase inhibitor. The activation of caspase-3,-8,-9 and upregulation of Fas (CD95/Apo-1), and the loss of mitochondrial transmembrane potential (Δψm) were also observed. However, apicularen A induced-cell death was not effected by NOK-1 antibody. Total amount of β-tubulin protein and mRNA were decreased. Concurrently, immunofluorescence microscopy indicated that HeLa cell had disrupted microtubule architectures and decreased density of microtubule, almost eccentric nucleus and irregular nuclear membrane by apicularen A. From the above results, apicularen A induces cell death of HeLa human cervical carcinoma cells by activation of caspase and disruption of microtubule architecture with down-regulation of tubulin levels.
Symptom Profiles of a Convenience Sample of Patients with COVID-19 — United States, January–April 2020
Authors: Rachel M. Burke, Marie E. Killerby, Suzanne Newton, Candace E. Ashworth, Abby L. Berns, Skyler Brennan, Jonathan M. Bressler, Erica Bye, Richard Crawford, Laurel Harduar Morano, Nathaniel M. Lewis, Tiffanie M. Markus, Jennifer S. Read, Tamara Rissman, Joanne Taylor, Jacqueline E. Tate, Claire M. Midgley, Neha Balachandran, Rebecca M. Dahl, Mary Dott, Zunera Gilani, Aaron Grober, Jessica Leung, Michelle O’Hegarty, John Person, Jessica N. Ricaldi, Nicole M. Roth, James J. Sejvar, Tom Shimabukuro, Cuc H. Tran, John T. Watson, Hilary Whitham, Howard Chiou, Paula Clogher, Lindsey M. Duca, Alissa Dratch, Amanda Feldpausch, Mary-Margaret Fill, Isaac Ghinai, Michelle Holshue, Sarah Scott, Ryan Westergaard
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Case Investigation Form Working GroupCoronavirus disease 2019 (COVID-19) was first detected in the United States in January 2020 (1), and by mid-July, approximately 3.4 million cases had been reported in the United States (2).Information about symptoms among U.S. COVID-19 patients is limited, especially among nonhospitalized patients.To better understand symptom profiles of patients with laboratory-confirmed COVID-19 in the United States, CDC used an optional questionnaire to collect detailed information on a convenience sample of COVID-19 patients from participating states.Symptom data were analyzed by age group, sex, hospitalization status, and symptom onset date relative to expansion of testing guidelines on March 8, 2020 (3).Among 164 symptomatic patients with known onset during January 14-April 4, 2020, a total of 158 (96%) reported fever, cough, or shortness of breath.Among 57 hospitalized adult patients (aged ≥18 years), 39 (68%) reported all three of these symptoms, compared with 25 (31%) of the 81 nonhospitalized adult patients.Gastrointestinal (GI) symptoms and other symptoms, such as chills, myalgia, headache, and fatigue, also were commonly reported, especially after expansion of testing guidelines.To aid prompt recognition of COVID-19, clinicians and public health professionals should be aware that COVID-19 can cause a wide variety of symptoms.The CDC COVID-19 case investigation form is a detailed questionnaire that was completed as an optional activity by participating states* for a subset of laboratory-confirmed COVID-19 cases identified through care-seeking, surveillance, or contact tracing.This subset of cases was selected at the state level through convenience sampling, with guidance to include cases with a range of ages and severities.Staff members at local or state health departments or CDC personnel deployed to support health departments interviewed patients or their proxies and reviewed medical records to complete the case investigation form.The case investigation form was used to collect demographic, epidemiologic, and clinical information (including symptoms) about COVID-19 patients.Patients were asked about a series of commonly and less commonly