bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of riociguat in combination therapy for patients with pulmonary arterial hypertension (PATENT studies)
Authors: Ghofrani Hossein‐Ardeschir , Grünig Ekkehard , Jansa Pavel , Langleben David , Rosenkranz Stephan , Preston Ioana R. , Rahaghi Franck , Sood Namita , Busse Dennis , Meier Christian , Humbert Marc 
Published: July 2020

Many patients with pulmonary arterial hypertension do not achieve treatment goals with monotherapy, and therefore combination therapy is becoming the standard of care. The soluble guanylate cyclase stimulator riociguat is licensed for the treatment of pulmonary arterial hypertension; here we present findings from patients who were receiving combined riociguat plus endothelin receptor antagonists or non‐intravenous prostanoids in the randomized, placebo‐controlled PATENT‐1 study and its open‐label extension (PATENT‐2). Moreover, we include new data from patients receiving early sequential combination therapy (three to six months of endothelin receptor antagonist treatment) or long‐term background endothelin receptor antagonist therapy (>6 months). Patients were randomized to riociguat 2.5 mg–maximum (N = 131 pretreated patients) and placebo (N = 60 pretreated patients). Riociguat improved 6‐min walking distance (PATENT‐1 primary endpoint), functional capacity, and hemodynamics after 12 weeks in pretreated patients. The placebo‐corrected changes in 6‐min walking distance were +24 m in endothelin receptor antagonist‐pretreated patients and +106 m in the small group of prostanoid‐pretreated patients. In the early sequential combination and long‐term background endothelin receptor antagonist groups, the placebo‐corrected changes in 6‐min walking distance were +65 m (95% CI: 17 to 113 m) and +13 m (95% CI: –8 to 33 m), respectively. In conclusion, these data suggest that early sequential combination of an endothelin receptor antagonist plus riociguat is a feasible treatment option. Both early sequential therapy and long‐term background endothelin receptor antagonist plus riociguat were well tolerated in the PATENT studies.
Effect of persistent opium consumption after surgery on the long-term outcomes of surgical revascularisation
Authors: Masoudkabir Farzad , Yavari Negin , Pashang Mina , Sadeghian Saeed , Jalali Arash , Poorhosseini Hamidreza , Tafti Seyed Hossein Ahmadi , Bagheri Jamshid , Abbasi Kiomars , Omran Abbas Salehi , Mansourian Soheil , Momtahan Shahram , Mortazavi Seyedeh Hamideh , Karimi Abbasali 
Published: July 2020

Background
A wrong traditional belief persists among people that opium consumption beneficially affects cardiovascular disease and its risk factors. However, no evidence exists regarding the effect of opium consumption or cessation on the long-term risk of major adverse cardio-cerebrovascular events after coronary artery bypass grafting. We therefore aimed to evaluate the effect of persistent opium consumption after surgery on the long-term outcomes of coronary artery bypass grafting.

Methods
The study population consisted of 28,691 patients (20,924 men, mean age 60.9 years), who underwent coronary artery bypass grafting between 2007 and 2016 at our centre. The patients were stratified into three groups according to the status of opium consumption: never opium consumers (n = 23,619), persistent postoperative opium consumers (n = 3636) and enduring postoperative opium withdrawal (n = 1436). Study endpoints were 5-year mortality and 5-year major adverse cardio-cerebrovascular events, comprising all-cause mortality, acute coronary syndrome, cerebrovascular accident and revascularisation.

Results
After surgery, 3636 patients continued opium consumption, while 1436 patients persistently avoided opium use. The multivariable survival analysis demonstrated that persistent post-coronary artery bypass grafting opium consumption increased 5-year mortality and 5-year major adverse cardio-cerebrovascular events by 28% (hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.06–1.54; P = 0.009) and 25% (HR 1.25, 95% CI 1.13–1.40; P &lt; 0.0001), respectively. It also increased the 5-year risk of acute coronary syndrome by 34% (sub-distribution HR 1.34, 95% CI 1.16–1.55; P &lt; 0.0001).

Conclusions
The present data suggest that persistent post-coronary artery bypass grafting opium consumption may significantly increase mortality, major adverse cardio-cerebrovascular events and acute coronary syndrome in the long term. Future studies are needed to confirm our findings.
Linked Double-Row Equivalent Arthroscopic Rotator Cuff Repair Leads to Significantly Improved Patient Outcomes
Authors: Endo Atsushi , Hoogervorst Paul , Safranek Conrad , Sochacki Kyle R. , Safran Marc R. , Sherman Seth L. , Donahue Joseph 
Published: July 2020

Background: Biomechanical studies have demonstrated that arthroscopic rotator cuff repair using a linked double-row equivalent construct results in significantly higher load to failure compared with conventional transosseous-equivalent constructs. Purpose: To determine the patient-reported outcomes (PROs), reoperation rates, and complication rates after linked double-row equivalent rotator cuff repair for full-thickness rotator cuff tears. Study Design: Case series; Level of evidence, 4. Methods: Consecutive patients who underwent linked double-row equivalent arthroscopic rotator cuff repair with minimum 2-year follow-up were included. The primary outcome was the American Shoulder and Elbow Surgeons (ASES) score at final follow-up. Secondary outcomes included the Simple Shoulder Test (SST), shortened Disabilities of the Arm, Shoulder and Hand (QuickDASH) questionnaire, visual analog scale (VAS), reoperations, and complications. Clinical relevance was defined by the minimally clinically important difference (MCID). Comparisons on an individual level that exceeded MCID (individual-level scores) were deemed clinically relevant. Comparisons between preoperative and postoperative scores were completed using the Student t test. All P values were reported with significance set at P < .05. Results: A total of 42 shoulders in 41 consecutive patients were included in this study (21 male patients [51.2%]; mean age, 64.5 ± 11.9 years; mean follow-up, 29.7 ± 4.5 months). All patients (100%) completed the minimum 2-year follow-up. The rotator cuff tear measured on average 15.2 ± 8.9 mm in the coronal plane and 14.6 ± 9.8 mm in the sagittal plane. The ASES score improved significantly from 35.5 ± 18.2 preoperatively to 93.4 ± 10.6 postoperatively ( P < .001). The QuickDASH ( P < .001), SST ( P < .001), and VAS ( P < .001) scores also significantly improved after surgery. All patients (42/42 shoulders; 100%) achieved clinically relevant improvement (met or exceeded MCID) on ASES and SST scores postoperatively. There were no postoperative complications (0.0%) or reoperations (0.0%) at final follow-up. Conclusion: Arthroscopic repair of full-thickness rotator cuff tears with the linked double-row equivalent construct results in statistically significant and clinically relevant improvements in PRO scores with low complication rates (0.0%) and reoperation rates (0.0%) at short-term follow-up.
QTL Mapping and Candidate Gene Analysis for Alkali Tolerance in Japonica Rice at the bud Stage Based on Linkage Mapping and Genome-Wide Association Study
Authors: Li Xianwei , Zheng Hongliang , Wu Wenshen , Liu Hualong , Wang Jingguo , Jia Yan , Li Jiaming , Yang Luomiao , Lei Lei , Zou Detang , Zhao Hongwei 
Published: July 2020

Abstract
Background
Salinity-alkalinity stress is one of the major factors limiting rice production. Damage caused by alkaline salt stress is more severe than that caused by neutral salt stress. Alkali tolerance at the bud stage in rice directly affects seedling survival and final yield when using the direct seeding cultivation model. However, genetic resources (QTLs and genes) for rice breeders to improve alkali tolerance are limited. In this study, we combined linkage mapping and a genome-wide association study (GWAS) to analyze the genetic structure of this trait in japonica rice at the bud stage.

Results
A population of 184 recombinant inbred lines (RILs) was utilized to map quantitative trait loci (QTLs) for the root length under control condition (RL), alkaline stress (ARL) and relative root length (RRL) at the bud stage. A major QTL related to alkali tolerance at the rice bud stage, qAT11, was detected on chromosome 11. Interestingly, a GWAS identified a lead SNP (Chr_21,999,659) in qAT11 that was significantly associated with alkaline tolerance. After filtering by linkage disequilibrium (LD), haplotype analysis, quantitative real-time PCR, we obtained three candidate genes (LOC_Os11g37300, LOC_Os11g37320 and LOC_Os11g37390). In addition, we performed phenotype verification on the CRISPR/Cas9 mutant of LOC_Os11g37390.

Conclusion
Based on these results, LOC_Os11g37300, LOC_Os11g37320 and LOC_Os11g37390 were the candidate genes contributing to alkaline tolerance in japonica rice. This study provides resources for breeding aimed at improving rice responses to alkalinity stress.
Incorporating representation learning and multihead attention to improve biomedical cross-sentence n-ary relation extraction
Authors: Zhao Di , Wang Jian , Zhang Yijia , Wang Xin , Lin Hongfei , Yang Zhihao 
Published: July 2020

AbstractBackgroundMost biomedical information extraction focuses on binary relations within single sentences. However, extracting n-ary relations that span multiple sentences is in huge demand. At present, in the cross-sentence n-ary relation extraction task, the mainstream method not only relies heavily on syntactic parsing but also ignores prior knowledge.ResultsIn this paper, we propose a novel cross-sentence n-ary relation extraction method that utilizes the multihead attention and knowledge representation that is learned from the knowledge graph. Our model is built on self-attention, which can directly capture the relations between two words regardless of their syntactic relation. In addition, our method makes use of entity and relation information from the knowledge base to impose assistance while predicting the relation. Experiments on n-ary relation extraction show that combining context and knowledge representations can significantly improve the n-ary relation extraction performance. Meanwhile, we achieve comparable results with state-of-the-art methods.ConclusionsWe explored a novel method for cross-sentence n-ary relation extraction. Unlike previous approaches, our methods operate directly on the sequence and learn how to model the internal structures of sentences. In addition, we introduce the knowledge representations learned from the knowledge graph into the cross-sentence n-ary relation extraction. Experiments based on knowledge representation learning show that entities and relations can be extracted in the knowledge graph, and coding this knowledge can provide consistent benefits.
Novel ECHS1 mutations in Leigh syndrome identified by whole-exome sequencing in five Chinese families: case report
Authors: Sun Dan , Liu Zhimei , Liu Yongchu , Wu Miaojuan , Fang Fang , Deng Xianbo , Liu Zhisheng , Song Liang , Murayama Kei , Zhang Chunhua , Zhu Yuanyuan 
Published: July 2020

Abstract
Background
Short-chain enoyl-CoA hydratase deficiency (ECHS1D), also known as ECHS1 deficiency, is a rare inborn metabolic disorder with clinical presentations characterized by Leigh syndrome (LS). Thirty-four different pathogenic mutations have been identified from over 40 patients to date.

Case presentation
Here, we report five Chinese patients with clinical syndromes typified as LS. Despite different initial symptoms, all patients presented developmental regression, dystonia, common radiological features such as symmetrical bilateral brain abnormalities, and similar metabolic results such as elevated plasma lactate and 2,3-dihydroxy-2-methylbutyrate. Utilizing whole-exome sequencing (WES), we identified eight distinct variants in ECHS1, with six novel variants, and the remaining two variants have been previously reported. Interestingly, one of the six novel variants, c.463G > A (p.Gly155Ser), was detected in three patients from unrelated families, suggesting a potential founder effect already described for a few mutations in LS. Incorporating both genetic analysis and medical results, including magnetic resonance imaging (MRI), electroencephalography (EEG), and biochemical testing, our study enriched the mutation spectrum of the ECHS1 gene and confirmed the phenotypic presentations of LS.

Conclusions
The severity of ECHS1 deficiency seems to vary. It was affected by both genetics and external environmental factors that lead to increased metabolism. Our study enriched the mutation spectrum of the ECHS1 gene, confirmed the phenotypic presentations, and highlighted the importance of the valine catabolic pathway in Leigh syndrome. Further studies are required to examine the potential founder mutation c.463G > A (p.Gly155Ser) and the role of ECHS1 in relevant pathways.
Developing a competency profile for newly graduated registered nurses in South Africa
Authors: Rabie Gerhard Hendrik , Rabie Tinda , Dinkelmann Monica 
Published: July 2020

Abstract
Background
Newly graduated registered nurses experience various challenges when entering the clinical practice environment. Typical challenges include lack of specific knowledge, skills and attitude competencies which is aggravated further by factors such as transition problems, workloads, lack of confidence and independence which potentially causes poor quality care. The aim of the study was to develop a competency profile for newly graudated registered nures, based on the perceptions of both nurse educators and final-year nursing students regarding the knowledge, skills and attitudes needed to deliver quality patient care in South Africa.

Methods
A qualitative descriptive design was used. Semi-structured individual interviews were conducted with 42 participants consisting of 23 nurse educators and 19 final-year nursing students at three nursing education institutions. The interviews were guided by an interview guide that examined three predetermined themes: knowledge, skills and attitudes as competencies to deliver quality patient care. Data were processed using thematic analysis.

Results
The predetermined theme knowledge, was broken down into themes: theoretical knowledge, holistic care, cultural diversity and code of conduct, with its relating sub-themes. The predetermined theme skills delivered the following themes: interpersonal, management, administrative, practical and personal skills with its sub-themes. Attitudes unpacked into the following themes: being positive, caring, humble, friendly, empathetic, life-long learning, going the extra mile, compassionate, having passion, approachable, sensitive, helpful, and non-judgemental.

Conclusions
Rich, in-depth knowledge, skills and attitudes were identified to develop a competency profile that may assist newly graduated registered nurses when entering the clinical practice environment to deliver quality patient care.
Circulating vaccine-derived poliovirus: a menace to the end game of polio eradication
Authors: Ming Long Chiau , Hussain Zahid , Yeoh Siang Fei , Koh David , Lee Kah Seng 
Published: July 2020

AbstractThe World Health Organisation Western Pacific Region countries were declared free of polio in 2000 until a polio outbreak involving 305 cases occurred in Indonesia in 2006. It was not until 2014 that the World Health Organisation South East Asia region was officially declared polio-free again. However, in February 2019, the Global Polio Eradication Initiative announced a new circulating vaccine-derived poliovirus outbreak in the Papua province of Indonesia. To make matter worse, the outbreak responses were tardy and led to transmission among migrating communities to other cities. The pressing regional issues of polio outbreak caused by circulating vaccine-derived poliovirus and use of oral polio vaccine have not been well presented. Our letter highlighted the suboptimal outbreak responses as well as the necessity of cross-border vaccination to curb continued poliovirus transmission.
Can levosimendan reduce ECMO weaning failure in cardiogenic shock?: a cohort study with propensity score analysis
Authors: Guilherme Enrique , Jacquet-Lagrèze Matthias , Pozzi Matteo , Achana Felix , Armoiry Xavier , Fellahi Jean-Luc 
Published: July 2020

Abstract
Background
Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has been increasingly used over the last decade in patients with refractory cardiogenic shock. ECMO weaning can, however, be challenging and lead to circulatory failure and death. Recent data suggest a potential benefit of levosimendan for ECMO weaning. We sought to further investigate whether the use of levosimendan could decrease the rate of ECMO weaning failure in adult patients with refractory cardiogenic shock.

Methods
We performed an observational single-center cohort study. All patients undergoing VA-ECMO from January 2012 to December 2018 were eligible and divided into two groups: group levosimendan and group control (without levosimendan). The primary endpoint was VA-ECMO weaning failure defined as death during VA-ECMO treatment or within 24 h after VA-ECMO removal. Secondary outcomes were mortality at day 28 and at 6 months. The two groups were compared after propensity score matching. P < 0.05 was considered statistically significant.

Results
Two hundred patients were analyzed (levosimendan group: n = 53 and control group: n = 147). No significant difference was found between groups on baseline characteristics except for ECMO duration, which was longer in the levosimendan group (10.6 ± 4.8 vs. 6.5 ± 4.7 days, p < 0.001). Levosimendan administration started 6.6 ± 5.4 days on average following ECMO implantation. After matching of 48 levosimendan patients to 78 control patients, the duration of ECMO was similar in both groups. The rate of weaning failure was 29.1% and 35.4% in levosimendan and control groups, respectively (OR: 0.69, 95%CI: 0.25–1.88). No significant difference was found between groups for all secondary outcomes.

Conclusion
Levosimendan did not improve the rate of successful VA-ECMO weaning in patients with refractory cardiogenic shock.

Trial registration
ClinicalTrials.gov, NCT04323709.
Development and validation of a risk factor-based system to predict short-term survival in adult hospitalized patients with COVID-19: a multicenter, retrospective, cohort study
Authors: Zhang Shuai , Guo Mengfei , Duan Limin , Wu Feng , Hu Guorong , Wang Zhihui , Huang Qi , Liao Tingting , Xu Juanjuan , Ma Yanling , Lv Zhilei , Xiao Wenjing , Zhao Zilin , Tan Xueyun , Meng Daquan , Zhang Shujing , Zhou E , Yin Zhengrong , Geng Wei , Wang Xuan , Zhang Jianchu , Chen Jianguo , Zhang Yu , Jin Yang 
Published: July 2020

Abstract
Background
Coronavirus disease 2019 (COVID-19) has become a public health emergency of global concern. We aimed to explore the risk factors of 14-day and 28-day mortality and develop a model for predicting 14-day and 28-day survival probability among adult hospitalized patients with COVID-19.

Methods
In this multicenter, retrospective, cohort study, we examined 828 hospitalized patients with confirmed COVID-19 hospitalized in Wuhan Union Hospital and Central Hospital of Wuhan between January 12 and February 9, 2020. Among the 828 patients, 516 and 186 consecutive patients admitted in Wuhan Union Hospital were enrolled in the training cohort and the validation cohort, respectively. A total of 126 patients hospitalized in Central Hospital of Wuhan were enrolled in a second external validation cohort. Demographic, clinical, radiographic, and laboratory measures; treatment; proximate causes of death; and 14-day and 28-day mortality are described. Patients’ data were collected by reviewing the medical records, and their 14-day and 28-day outcomes were followed up.

Results
Of the 828 patients, 146 deaths were recorded until May 18, 2020. In the training set, multivariate Cox regression indicated that older age, lactate dehydrogenase level over 360 U/L, neutrophil-to-lymphocyte ratio higher than 8.0, and direct bilirubin higher than 5.0 μmol/L were independent predictors of 28-day mortality. Nomogram scoring systems for predicting the 14-day and 28-day survival probability of patients with COVID-19 were developed and exhibited strong discrimination and calibration power in the two external validation cohorts (C-index, 0.878 and 0.839).

Conclusion
Older age, high lactate dehydrogenase level, evaluated neutrophil-to-lymphocyte ratio, and high direct bilirubin level were independent predictors of 28-day mortality in adult hospitalized patients with confirmed COVID-19. The nomogram system based on the four factors revealed good discrimination and calibration, suggesting good clinical utility.
Presence of autoantibodies in “seronegative” rheumatoid arthritis associates with classical risk factors and high disease activity
Authors: Reed Evan , Hedström Anna Karin , Hansson Monika , Mathsson-Alm Linda , Brynedal Boel , Saevarsdottir Saedis , Cornillet Martin , Jakobsson Per-Johan , Holmdahl Rikard , Skriner Karl , Serre Guy , Alfredsson Lars , Rönnelid Johan , Lundberg Karin 
Published: July 2020

Abstract
Background
Rheumatoid arthritis (RA) is classified as seropositive or seronegative, depending on the presence/absence of rheumatoid factor (RF), primarily IgM RF, and/or anti-citrullinated protein antibodies (ACPA), commonly detected using anti-cyclic citrullinated peptide (CCP) assays. Known risk factors associate with the more severe seropositive form of RA; less is known about seronegative RA. Here, we examine risk factors and clinical phenotypes in relation to presence of autoantibodies in the RA subset that is traditionally defined as seronegative.

Methods
Anti-CCP2 IgG, 19 ACPA fine-specificities, IgM/IgG/IgA RF, anti-carbamylated-protein (CarP) antibodies, and 17 other autoantibodies, were analysed in 2755 RA patients and 370 controls. Antibody prevalence, levels, and co-occurrence were examined, and associations with risk factors and disease activity during 5 years were investigated for different antibody-defined RA subsets.

Results
Autoantibodies were detected in a substantial proportion of the traditionally defined seronegative RA subset, with ACPA fine-specificities found in 30%, IgA/IgG RF in 9.4%, and anti-CarP antibodies in 16%, with a 9.6% co-occurrence of at least two types of RA-associated autoantibodies. HLA-DRB1 shared epitope (SE) associated with the presence of ACPA in anti-CCP2-negative RA; in anti-CCP2-positive RA, the SE association was defined by six ACPA fine-specificities with high co-occurrence. Smoking associated with RF, but not with ACPA, in anti-CCP2-negative RA. Presence of ACPA and RF, but not anti-CarP antibodies, in conventionally defined “seronegative” RA, associated with worse clinical outcome.

Conclusions
“Seronegative” RA is not truly a seronegative disease subset. Additional screening for ACPA fine-specificities and IgA/IgG RF defines a group of patients that resembles seropositive patients with respect to risk factors and clinical picture and may contribute to earlier diagnosis for a subset of anti-CCP2−/IgM RF− patients with a high need for active treatment.
A note on the impact of late diagnosis on HIV/AIDS dynamics: a mathematical modelling approach
Authors: Mushanyu J. 
Published: July 2020

Abstract
Objectives:
The global incidence of HIV infection is not significantly decreasing, especially in sub-Saharan African countries. Though there is availability and accessibility of free HIV services, people are not being diagnosed early for HIV, and hence HIV-related mortality remains significantly high. We formulate a mathematical model for the spread of HIV using non linear ordinary differential equations in order to investigate the impact of late diagnosis of HIV on the spread of HIV.

Results:
The results suggest the need to encourage early initiation into HIV treatment as well as promoting HIV self-testing programs that enable more undiagnosed people to know their HIV status in order to curtail the continued spread of HIV.