bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of rivaroxaban plus aspirin in women and men with chronic coronary or peripheral artery disease
Authors: Liang Yan , Zhu Jun , Liu Lisheng , Anand Sonia S , Connolly Stuart J , Bosch Jackie , Guzik Tomasz J , O’Donnell Martin , Dagenais Gilles R , Fox Keith Aa , Shestakovska Olga , Berkowitz Scott D , Muehlhofer Eva , Keller Lars , Yusuf Salim , Eikelboom John W ,   for the COMPASS Investigators
Published: April 2020

Abstract

Aims
The COMPASS trial demonstrated that the combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg once daily compared with aspirin 100 mg once daily reduced major adverse cardiovascular events (MACE) in patients with chronic coronary artery disease or peripheral artery disease by 24% during a mean follow-up of 23 months. We explored whether this effect varies by sex.

Methods and results
The effects were examined in women and men using log-rank tests and Kaplan–Meier curve. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were obtained from stratified Cox proportional hazards models to explore subgroup effects including subgroup of women and men according to baseline modified REACH risk score. Of 27 395 patients randomized, 18 278 were allocated to receive rivaroxaban plus aspirin (n = 9152) or aspirin alone (n = 9126), and of these, 22.1% were women. Women compared with men had similar incidence rates for MACE and major bleeding but borderline lower rates for myocardial infarction (1.7% vs. 2.2%, P = 0.05). The effect of combination therapy compared with aspirin in women and men was consistent for MACE (women: 3.8% vs. 5.2%, HR 0.72, 95% CI 0.54–0.97; men: 4.2% vs. 5.5%, HR 0.76, 95% CI 0.66–0.89; P interaction 0.75) and major bleeding (women: 3.1% vs. 1.4%, HR 2.22, 95% CI 1.42–3.46; men: 3.2% vs. 2.0%, HR 1.60, 95% CI 1.29–1.97; P interaction 0.19). There was no significant interaction between randomized treatment and baseline modified REACH score above or below the median for MACE or major bleeding.

Conclusion
In patients with stable coronary artery disease or peripheral artery disease, the combination of rivaroxaban (2.5 mg twice daily) and aspirin compared with aspirin alone appears to produce consistent benefits in women and men, independent of baseline cardiovascular risk.
Effect of beta-blocker therapy in patients with or without left ventricular systolic dysfunction after acute myocardial infarction
Authors: Joo Seung-Jae , Kim Song-Yi , Choi Joon-Hyouk , Park Hyeung Keun , Beom Jong Wook , Lee Jae-Geun , Chae Shung Chull , Kim Hyo-Soo , Kim Young Jo , Cho Myeong Chan , Kim Chong Jin , Rha Seung-Woon , Yoon Junghan , Jeong Myung Ho 
Published: April 2020

Abstract

Aims
This observational study aimed to investigate the association between beta-blocker therapy and clinical outcomes in patients with acute myocardial infarction (AMI), especially with mid-range or preserved left ventricular systolic function.

Methods and results
Among 13 624 patients enrolled in the Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH), 12 200 in-hospital survivors were selected. Patients with beta-blockers showed significantly lower 1-year major adverse cardiac events (MACE), which was a composite of cardiac death, MI, revascularization, and readmission due to heart failure [9.7 vs. 14.3/100 patient-year; hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.72–0.97; P = 0.022). However, this association had a significant interaction with left ventricular ejection fraction (LVEF). Beta-blocker therapy at discharge was associated with lower 1-year MACE in patients with LVEF ≤40% (HR 0.63, 95% CI 0.48–0.81; P &lt; 0.001), and 40% &lt;LVEF &lt; 50% (HR 0.69, 95% CI 0.51–0.94; P = 0.020), but not in patients with LVEF ≥50% (HR 1.16, 95% CI 0.91–1.48; P = 0.234).

Conclusions
Beta-blocker therapy at discharge was associated with better 1-year clinical outcomes in patients with reduced or mid-range LVEF after AMI, but not in patients with preserved LVEF. These data suggested that the long-term beta-blocker therapy may be guided by LVEF.
The ‘votive antiphon’ among other sacred textual forms
Authors: Bowers Roger 
Published: April 2020

Abstract
Alongside settings of liturgical texts effected in manners strictly consistent with liturgical performance, there survive large numbers of early vocal pieces engaging Latin words of a religious or devotional nature all commonly subsumed together, both then and now, under the ‘catch-all’ term of ‘motet’. These, however, encompassed a remarkably diverse range of textual content, each destined for a distinct performance occasion and purpose no less likely to have been domestic than ecclesiastical; and these textual types, in turn, possess potential to have been reflected in corresponding distinctions of musical style and texture. Except in isolated instances, modern scholarship has paid only limited attention to these diversities of text and function, with the result that many musical works are classified together with little examination of the criteria by which compositional distinctions apparent between them might be explained. This article examines the category of ‘votive antiphon’ alongside other categories of Latin composition, and reflects upon the need to ask, of any such piece, the question ‘what was it for?’.
Restoration of sinus rhythm by pulmonary vein isolation improves heart failure with preserved ejection fraction in atrial fibrillation patients
Authors: Rattka Manuel , Pott Alexander , Kühberger Anna , Weinmann Karolina , Scharnbeck Dominik , Stephan Tilman , Baumhardt Michael , Bothner Carlo , Iturbe Orbe Mario , Rottbauer Wolfgang , Dahme Tillman 
Published: April 2020

Abstract

Aims
Atrial fibrillation (AF) in patients suffering from heart failure with preserved ejection fraction (HFpEF) is associated with increased symptoms and higher morbidity and mortality. Effective treatment strategies for this patient population have not yet been established.

Methods and results
We analysed clinical outcomes and echocardiographic parameters of patients with AF and HFpEF who underwent pulmonary vein isolation (PVI). Out of 374 PVI patients, we identified 35 patients suffering from concomitant HFpEF. Freedom from atrial tachyarrhythmia (AT) after 1 year was 80%. Heart failure symptoms assessed by New York Heart Association class significantly improved from 2.7 ± 0.7 to 1.7 ± 0.9 (P &lt; 0.001). We observed regression of diastolic dysfunction by echocardiography 12 months after the index procedure. Moreover, 15 patients (42.9%) experienced complete resolution of HFpEF after a single ablation procedure. Multivariate logistic regression revealed absence of AT recurrence as an independent predictor of recovery from HFpEF (hazard ratio 11.37, 95% confidence interval 1.70–75.84, P = 0.009). Furthermore, resolution of HFpEF by achieving freedom from AT recurrence by PVI, including multiple procedures, led to a significant reduction of hospitalizations.

Conclusion
Our results suggest that restoration of sinus rhythm by PVI in HFpEF patients with concomitant AF induces reverse remodelling, improvement of symptoms, resolution of HFpEF and subsequently decrease of hospitalizations. Randomized controlled trials are warranted to confirm our results.
EER test and analysis of surface ice cooling system for coal mine
Authors: Qi Yudong , Wang Minghong 
Published: April 2020

Abstract
With the depth increasing and the improvement of mining mechanization of the coal mine, heat hazard is becoming more and more serious, the ice cooling system is gradually promoted and applied in China for recent years, but the cooling capacity and energy efficiency ratio (EER) test and analysis for such system is seldom reported. The cooling capacity and EER of the refrigerating equipment of an ice cooling system of a coal mine are tested and analyzed in Shandong Province in this paper. The test result indicates that the refrigerating capacity and EER are lower and both the pre-cooling units and the ice making system have a large variable range. It points out that it should not evaluate the ice cooling system by the test data only in this mine but expect more test data and analysis of the ice cooling system in other coal mines to get a more scientific conclusion. And the test, analysis and comparison for different kinds of cooling system are also expected to explore suitable cooling system while a full consideration of the geological conditions and other factors of the mine are taken into consideration.
Characterizing Environmental Surveillance Sites in Nigeria and Their Sensitivity to Detect Poliovirus and Other Enteroviruses
Authors: Hamisu Abdullahi Walla , Blake Isobel M , Sume Gerald , Braka Fiona , Jimoh Abdullateef , Dahiru Habu , Bonos Mohammed , Dankoli Raymond , Mamuda Bello Ahmed , Yusuf Kabir M , Lawal Namadi M , Ahmed Fatimah , Aliyu Zainab , John Doris , Nwachukwu Theresa E , Ayeni Michael F , Gumede-Moeletsi Nicksy , Veltsos Philippe , Giri Sidhartha , Praharaj Ira , Metilda Angeline , Bandyopadhyay Ananda , Diop Ousmane M , Grassly Nicholas C 
Published: April 2020

Abstract

Background
Environmental surveillance (ES) for poliovirus is increasingly important for polio eradication, often detecting circulating virus before paralytic cases are reported. The sensitivity of ES depends on appropriate selection of sampling sites, which is difficult in low-income countries with informal sewage networks.

Methods
We measured ES site and sample characteristics in Nigeria during June 2018–May 2019, including sewage physicochemical properties, using a water-quality probe, flow volume, catchment population, and local facilities such as hospitals, schools, and transit hubs. We used mixed-effects logistic regression and machine learning (random forests) to investigate their association with enterovirus isolation (poliovirus and nonpolio enteroviruses) as an indicator of surveillance sensitivity.

Results
Four quarterly visits were made to 78 ES sites in 21 states of Nigeria, and ES site characteristic data were matched to 1345 samples with an average enterovirus prevalence among sites of 68% (range, 9%–100%). A larger estimated catchment population, high total dissolved solids, and higher pH were associated with enterovirus detection. A random forests model predicted “good” sites (enterovirus prevalence &gt;70%) from measured site characteristics with out-of-sample sensitivity and specificity of 75%.

Conclusions
Simple measurement of sewage properties and catchment population estimation could improve ES site selection and increase surveillance sensitivity.
Association of Antibiotic Exposure With Survival and Toxicity in Patients With Melanoma Receiving Immunotherapy
Authors: Mohiuddin Jahan J , Chu Brian , Facciabene Andrea , Poirier Kendra , Wang Xingmei , Doucette Abigail , Zheng Cathy , Xu Wei , Anstadt Emily J , Amaravadi Ravi K , Karakousis Giorgos C , Mitchell Tara C , Huang Alexander C , Shabason Jacob E , Lin Alexander , Swisher-McClure Samuel , Maity Amit , Schuchter Lynn M , Lukens John N 
Published: April 2020

Abstract

Background
Gut microbial diversity is associated with improved response to immune checkpoint inhibitors (ICI). Based on the known detrimental impact that antibiotics have on microbiome diversity, we hypothesized that antibiotic receipt prior to ICI would be associated with decreased survival.

Methods
Patients with stage III and IV melanoma treated with ICI between 2008 and 2019 were selected from an institutional database. A window of antibiotic receipt within 3 months prior to the first infusion of ICI was prespecified. The primary outcome was overall survival (OS), and secondary outcomes were melanoma-specific mortality and immune-mediated colitis requiring intravenous steroids. All statistical tests were two-sided.

Results
There were 568 patients in our database of which 114 received antibiotics prior to ICI. Of the patients, 35.9% had stage III disease. On multivariable Cox proportional hazards analysis of patients with stage IV disease, the antibiotic-exposed group had statistically significantly worse OS (hazard ratio [HR] = 1.81, 95% confidence interval [CI] = 1.27 to 2.57; P &lt;.001). The same effect was observed among antibiotic-exposed patients with stage III disease (HR = 2.78, 95% CI = 1.31 to 5.87; P =.007). When limited to only patients who received adjuvant ICI (n = 89), antibiotic-exposed patients also had statistically significantly worse OS (HR = 4.84, 95% CI = 1.09 to 21.50; P =.04). The antibiotic group had a greater incidence of colitis (HR = 2.14, 95% CI = 1.02 to 4.52; P =.046).

Conclusion
Patients with stage III and IV melanoma exposed to antibiotics prior to ICI had statistically significantly worse OS than unexposed patients. Antibiotic exposure was associated with greater incidence of moderate to severe immune-mediated colitis. Given the large number of antibiotics prescribed annually, physicians should be judicious with their use in cancer populations likely to receive ICI.
Extinction of all infectious HIV in cell culture by the CRISPR-Cas12a system with only a single crRNA
Authors: Gao Zongliang , Fan Minghui , Das Atze T , Herrera-Carrillo Elena , Berkhout Ben 
Published: April 2020

Abstract
The CRISPR-Cas9 system has been used for genome editing of various organisms. We reported inhibition of the human immunodeficiency virus (HIV) in cell culture infections with a single guide RNA (gRNA) and subsequent viral escape, but complete inactivation of infectious HIV with certain combinations of two gRNAs. The new RNA-guided endonuclease system CRISPR-Cas12a (formerly Cpf1) may provide a more promising tool for genome engineering with increased activity and specificity. We compared Cas12a to the original Cas9 system for inactivation of the integrated HIV DNA genome. Superior antiviral activity is reported for Cas12a, which can achieve full HIV inactivation with only a single gRNA (called crRNA). We propose that the different architecture of Cas9 versus Cas12a endonuclease explains this effect. We also disclose that DNA cleavage by the Cas12a endonuclease and subsequent DNA repair causes mutations with a sequence profile that is distinct from that of Cas9. Both CRISPR systems can induce the typical small deletions around the site of DNA cleavage and subsequent repair, but Cas12a does not induce the pure DNA insertions that are routinely observed for Cas9. Although these typical signatures are apparent in many literature studies, this is the first report that documents these striking differences.
Peptides containing the PCNA interacting motif APIM bind to the β-clamp and inhibit bacterial growth and mutagenesis
Authors: Nedal Aina , Ræder Synnøve B , Dalhus Bjørn , Helgesen Emily , Forstrøm Rune J , Lindland Kim , Sumabe Balagra K , Martinsen Jacob H , Kragelund Birthe B , Skarstad Kirsten , Bjørås Magnar , Otterlei Marit 
Published: April 2020

Abstract
In the fight against antimicrobial resistance, the bacterial DNA sliding clamp, β-clamp, is a promising drug target for inhibition of DNA replication and translesion synthesis. The β-clamp and its eukaryotic homolog, PCNA, share a C-terminal hydrophobic pocket where all the DNA polymerases bind. Here we report that cell penetrating peptides containing the PCNA-interacting motif APIM (APIM-peptides) inhibit bacterial growth at low concentrations in vitro, and in vivo in a bacterial skin infection model in mice. Surface plasmon resonance analysis and computer modeling suggest that APIM bind to the hydrophobic pocket on the β-clamp, and accordingly, we find that APIM-peptides inhibit bacterial DNA replication. Interestingly, at sub-lethal concentrations, APIM-peptides have anti-mutagenic activities, and this activity is increased after SOS induction. Our results show that although the sequence homology between the β-clamp and PCNA are modest, the presence of similar polymerase binding pockets in the DNA clamps allows for binding of the eukaryotic binding motif APIM to the bacterial β-clamp. Importantly, because APIM-peptides display both anti-mutagenic and growth inhibitory properties, they may have clinical potential both in combination with other antibiotics and as single agents.
Biomechanical research into lamina cribrosa in glaucoma
Authors: Li Long , Song Fan 
Published: April 2020

Summary
Glaucoma, a leading cause of irreversible blindness, poses a considerable public health challenge and burden. Mechanical models of the lamina cribrosa under elevated intraocular pressure at different scales, contributing significantly to uncovering the glaucomatous pathogenesis, are discussed. Meanwhile, the open issues and avenues for further development are highlighted.
Interleukin-23 drives expansion of Thelper 17 cells through epigenetic regulation by signal transducer and activators of transcription 3 in lupus patients
Authors: Lee Seunghyun , Nakayamada Shingo , Kubo Satoshi , Yamagata Kaoru , Yoshinari Hiroko , Tanaka Yoshiya 
Published: April 2020

Abstract

Objectives
To elucidate the molecular mechanisms underlying pathogenic Th17 cells, we investigated the modulation of epigenetic modifications and its association with SLE.

Methods
Naive CD4+ T cells were cultured in Th17 polarizing conditions for 5 days and then treated with various cytokines, including IL-23. Expression of Th17 cell–related markers and phosphorylation of signal transducers and activators of transcription (pSTATs) were analysed using flow cytometry and quantitative PCR. Histone modifications were assessed using chromatin immunoprecipitation PCR. T cell phenotypes and pSTATs were analysed in blood samples of patients with SLE (n = 28). Finally, the effects of baricitinib on memory Th17 cells were investigated in SLE patients (n = 12).

Results
Stimulation of resting Th17 cells with IL-23 promoted maturation of these cells (P &lt; 0.0001). IL-23 induced pSTAT3, but not pSTAT4, during Th17 cell maturation (P &lt; 0.05). IL-23-induced STAT3 directly bound the RORγT gene locus. This was accompanied by induction of the H3H4me3 permissive mark and reduction of the H3K27me3 repressive mark, leading to enhanced RORγT gene expression. IL-23-induced expansion of Th17 cells and pSTAT3 were suppressed by the addition of baricitinib in a concentration-dependent manner (P &lt; 0.05). In memory Th17 cells from SLE patients, pSTAT3 was hypersensitized by IL-23 stimulation and inhibited by baricitinib (P &lt; 0.05).

Conclusion
The results of this study indicate that IL-23/STAT3 signalling plays a fundamental role in Th17 cell maturation through transcriptional and epigenetic modifications in patients with SLE. This mechanism may underlie pathogenic Th17 cell expansion and may lead to identification of novel therapeutic targets for SLE.
Insolvency within your trust: bankrupt settlors, insolvent companies and insolvent trusts
Authors: Barton QC Zoë , Taylor Tara 
Published: April 2020

Abstract
Anecdotally at least, there seems to be a trend towards increased litigation involving insolvency practitioners pitted against trustees. This article considers the so-called ‘insolvent trust’ and the challenges these present to their trustees, with particular reference to the Z Trust litigation. It goes on to discuss certain claims that may be faced by insolvent settlors and companies involving the adjustment of antecedent transactions for the benefit of creditors, and how trustees can protect themselves in the face of such claims.
An interacting conformal chiral 2-form electrodynamics in six dimensions
Authors: Townsend Paul K. 
Published: April 2020

The strong-field limit for the 2-form potential on an M5-brane yields a conformal chiral 2-form electrodynamics in six dimensions, with gauge-invariant self-interactions but no adjustable coupling constant; the stress tensor is that of a null fluid. Lorentz invariance can be made manifest via an interpretation as a tensionless ‘space-filling M5-brane’, or as a truncation of the infrared dynamics of an M5-brane in AdS
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Spherization of red blood cells and platelets margination in COPD patients
Authors: Boudjeltia Karim Zouaoui , Kotsalos Christos , Ribeiro Daniel , Rousseau Alexandre , Lelubre Christophe , Sartenaer Olivier , Piagnerelli Michael , Dohet-Eraly Jerôme , Dubois Frank , Tasiaux Nicole , Chopard Bastien , Van Meerhaeghe Alain 
Published: April 2020

AbstractRationaleThere are important interactions between Red Blood Cells (RBCs) and platelets in the bloodstream. These interactions lead to a phenomenon called margination. RBCs in pathological situations undergo biochemical and conformational changes leading to alterations in blood rheology.AimRBCs shape in volunteers (21), stable (42) and exacerbated (31) COPD patients was analyzed. We studied the effect of the RBCs spherization on the platelets transport experimentally, in vitro, and by using numerical simulations.MethodsRBC shape was estimated by the second moment of Pearson obtained through flow cytometry on fsc histogram. In vitro experiments were performed to analyze the effect of RBC shape on platelets adhesion/aggregation in dynamic conditions. Neuraminidase treatment was used to induce RBCs spherization. Numerical simulation were performed to determine the effect of RBCs spherization on platelets mean square displacement (MSD) to provide a physical explanation.ResultsSignificant increase of RBC sphericity was observed in COPD patients compared to volunteers (Kruskal-Wallis: p<0.0001). In vitro experiments, at shear rate of 100 s-1, we observed that RBCs treated with neuraminidase mainly affect the number of platelet aggregates (p = 0.004). There was no change in the aggregates size. At a shear rate of 400 sec-1 neuraminidase treatment changes both the size of the aggregates (p = 0.009) and the number of platelet aggregates (p = 0.008).Numerical simulations indicated that RBCs spherization induces an increase of MSD and the effect was more pronounced when the shear rate increased.ConclusionOur results show that the RBCs of COPD patients are more spherical than those of healthy volunteers. Experimentally we observe that the RBCs spherization induces an increase platelet transport to the wall. Additional studies are needed to better understand the possible association between the RBCs effect on the platelets transport and the increased cardiovascular events observed in COPD patients.
A model to predict SARS-CoV-2 infection based on the first three-month surveillance data in Brazil
Authors: Diaz-Quijano Fredi A. , da Silva José Mário Nunes , Ganem Fabiana , Oliveira Silvano , Vesga-Varela Andrea L. , Croda Julio 
Published: April 2020

AbstractBackgroundCOVID-19 diagnosis is a critical problem, mainly due to the lack or delay in the test results. We aimed to obtain a model to predict SARS-CoV-2 infection in suspected patients reported to the Brazilian surveillance system.MethodsWe analyzed suspected patients reported to the National Surveillance System that corresponded to the following case definition: patients with respiratory symptoms and fever, who traveled to regions with local or community transmission or who had close contact with a suspected or confirmed case. Based on variables routinely collected, we obtained a multiple model using logistic regression. The area under the receiver operating characteristic curve (AUC) and accuracy indicators were used for validation.ResultsWe described 1468 COVID-19 cases (confirmed by RT-PCR) and 4271 patients with other illnesses. With a data subset, including 80% of patients from Sao Paulo (SP) and Rio Janeiro (RJ), we obtained a function which reached an AUC of 95.54% (95% CI: 94.41% - 96.67%) for the diagnosis of COVID-19 and accuracy of 90.1% (sensitivity 87.62% and specificity 92.02%). In a validation dataset including the other 20% of patients from SP and RJ, this model exhibited an AUC of 95.01% (92.51% – 97.5%) and accuracy of 89.47% (sensitivity 87.32% and specificity 91.36%).ConclusionWe obtained a model suitable for the clinical diagnosis of COVID-19 based on routinely collected surveillance data. Applications of this tool include early identification for specific treatment and isolation, rational use of laboratory tests, and input for modeling epidemiological trends.