bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peripheral Blood RNA Levels of
QSOX1
and
PLBD1
Are New Independent Predictors of Left Ventricular Dysfunction After Acute Myocardial Infarction
Authors: Vanhaverbeke Maarten , Vausort Mélanie , Veltman Denise , Zhang Lu , Wu Ming , Laenen Griet , Gillijns Hilde , Moreau Yves , Bartunek Jozef , Van De Werf Frans , Devaux Yvan , Janssens Stefan , Sinnaeve Peter R. ,   on behalf of EU-CardioRNA COST Action CA17129
Published: December 2019

Background:
The identification of patients with acute myocardial infarction (MI) at risk of subsequent left ventricular (LV) dysfunction remains challenging, but it is important to optimize therapies. The aim of this study was to determine the unbiased RNA profile in peripheral blood of patients with acute MI and to identify and validate new prognostic markers of LV dysfunction.

Methods:
We prospectively enrolled a discovery cohort with acute MI (n=143) and performed whole-blood RNA profiling at different time points. We then selected transcripts on admission that related to LV dysfunction at follow-up and validated them by quantitative polymerase chain reaction in the discovery cohort, in an external validation cohort (n=449), and in a representative porcine MI model with cardiac magnetic resonance–based measurements of infarct size and postmortem myocardial pathology (n=33).

Results:

RNA profiling in the discovery cohort showed upregulation of genes involved in chemotaxis, IL (interleukin)-6, and NF-κB (nuclear factor-κB) signaling in the acute phase of MI. Expression levels of the majority of these transcripts paralleled the rise in cardiac troponin T and decayed at 30 days. RNA levels of
QSOX1
,
PLBD1
, and
S100A8
on admission with MI correlated with LV dysfunction at follow-up. Using quantitative polymerase chain reaction, we confirmed that
QSOX1
and
PLBD1
predicted LV dysfunction (odds ratio, 2.6 [95% CI, 1.1–6.1] and 3.2 [95% CI, 1.4–7.4]), whereas
S100A8
did not. In the external validation cohort, we confirmed
QSOX1
and
PLBD1
as new independent markers of LV dysfunction (odds ratio, 1.41 [95% CI, 1.06–1.88] and 1.43 [95% CI, 1.08–1.89]).
QSOX1
had an incremental predictive value in a model consisting of clinical variables and cardiac biomarkers (including NT-proBNP [N-terminal pro-B-type natriuretic peptide]). In the porcine MI model, whole-blood levels of
QSOX1
and
PLBD1
related to neutrophil infiltration in the ischemic myocardium in an infarct size–independent manner.

Conclusions:

Peripheral blood
QSOX1
and
PLBD1
in acute MI are new independent markers of LV dysfunction post-MI.
Genetic Determinants of Lipids and Cardiovascular Disease Outcomes
Authors: Allara Elias , Morani Gabriele , Carter Paul , Gkatzionis Apostolos , Zuber Verena , Foley Christopher N. , Rees Jessica M.B. , Mason Amy M. , Bell Steven , Gill Dipender , Lindström Sara , Butterworth Adam S. , Di Angelantonio Emanuele , Peters James , Burgess Stephen ,   INVENT consortium
Published: December 2019

Background:
Evidence from randomized trials has shown that therapies that lower LDL (low-density lipoprotein)-cholesterol and triglycerides reduce coronary artery disease (CAD) risk. However, there is still uncertainty about their effects on other cardiovascular outcomes. We therefore performed a systematic investigation of causal relationships between circulating lipids and cardiovascular outcomes using a Mendelian randomization approach.

Methods:
In the primary analysis, we performed 2-sample multivariable Mendelian randomization using data from participants of European ancestry. We also conducted univariable analyses using inverse-variance weighted and robust methods, and gene-specific analyses using variants that can be considered as proxies for specific lipid-lowering medications. We obtained associations with lipid fractions from the Global Lipids Genetics Consortium, a meta-analysis of 188 577 participants, and genetic associations with cardiovascular outcomes from 367 703 participants in UK Biobank.

Results:
For LDL-cholesterol, in addition to the expected positive associations with CAD risk (odds ratio [OR] per 1 SD increase, 1.45 [95% CI, 1.35–1.57]) and other atheromatous outcomes (ischemic cerebrovascular disease and peripheral vascular disease), we found independent associations of genetically predicted LDL-cholesterol with abdominal aortic aneurysm (OR, 1.75 [95% CI, 1.40–2.17]) and aortic valve stenosis (OR, 1.46 [95% CI, 1.25–1.70]). Genetically predicted triglyceride levels were positively associated with CAD (OR, 1.25 [95% CI, 1.12–1.40]), aortic valve stenosis (OR, 1.29 [95% CI, 1.04–1.61]), and hypertension (OR, 1.17 [95% CI, 1.07–1.27]), but inversely associated with venous thromboembolism (OR, 0.79 [95% CI, 0.67–0.93]) and hemorrhagic stroke (OR, 0.78 [95% CI, 0.62–0.98]). We also found positive associations of genetically predicted LDL-cholesterol and triglycerides with heart failure that appeared to be mediated by CAD.

Conclusions:
Lowering LDL-cholesterol is likely to prevent abdominal aortic aneurysm and aortic stenosis, in addition to CAD and other atheromatous cardiovascular outcomes. Lowering triglycerides is likely to prevent CAD and aortic valve stenosis but may increase thromboembolic risk.
Prestroke Disability Predicts Adverse Poststroke Outcome
Authors: Han Thang S. , Fry Christopher H. , Gulli Giosue , Affley Brendan , Robin Jonathan , Irvin-Sellers Melanie , Fluck David , Kakar Puneet , Sharma Sapna , Sharma Pankaj 
Published: December 2019

Background and Purpose—
Information on what effect disability before stroke can have on stroke outcome is lacking. We assessed prestroke disability in relation to poststroke hospital outcome.

Methods—
Analysis of prospectively collected data from the Sentinel Stroke National Audit Programme. A total of 1656 men (mean age ±SD =73.1±13.2 years) and 1653 women (79.3±13.0 years) were admitted to hyperacute stroke units with acute stroke in 4 major UK between 2014 and 2016. Prestroke disability, assessed by modified Rankin Scale (mRS), was tested against poststroke adverse outcomes, adjusted for age, sex, and coexisting morbidities.

Results—

Compared with patients with prestroke mRS score =0, individuals with prestroke mRS scores =3, 4, or 5 had greater adjusted risks of moderately severe or severe stroke on arrival (4.4% versus 16.7%; odds ratio [OR], 3.2 [95% CI, 2.3–4.6]
P
<0.001); urinary tract infection or pneumonia within 7 days of admission (9.6% versus 35.9%; OR, 3.7 [95% CI, 2.8–4.8]
P
<0.001); mortality (7.2% versus 37.1%; OR, 4.9 [95% CI, 3.7–6.5]
P
<0.001); requiring help with activities of daily living on discharge (12.3% versus 26.7%; OR, 3.1 [95% CI, 2.3–4.1]
P
<0.001); and transferred to new care home (2.4% versus 9.4%; OR, 2.1 [95% CI, 1.3–3.3]
P
=0.002). Patients with mRS scores =1 or 2 had intermediate risk of adverse outcomes. Overall, those with a mRS score =1 or 2 had length of stay on hyperacute stroke units extended by 5.3 days (95% CI, 2.8–7.7;
P
<0.001) and mRS score =3, 4 or 5 by 7.2 days (95% CI, 4.0–10.5;
P
<0.001).

Conclusions—
Individuals with evidence of prestroke disability, assessed by mRS, had significantly increased risk of poststroke adverse outcomes and longer length of stay on hyperacute stroke units and higher level of care on discharge.
Fiberoptic Endoscopic Evaluation of Swallowing in Infants and Children: Protocol, Safety, and Clinical Efficacy: 25 Years of Experience
Authors: Miller Claire Kane , Willging Jay Paul 
Published: December 2019

Background: The application of fiberoptic endoscopic evaluation of swallowing (FEES) in the pediatric dysphagia protocol requires specialized knowledge of pediatric conditions that result in dysphagia, recognition of normal and abnormal laryngopharyngeal anatomy and function across ages, and the ability to identify maturational changes in anatomy and function of the aerodigestive tract that pertain to airway protection and swallowing function. Methods: Over the past 25 years, we have performed over 7,000 collaborative Otolaryngology and Speech-Language Pathology FEES examinations in patients ranging from 2 days of age to young adults. During this time period, we have monitored the safety of the procedure, explored the feasibility and utility of FEES across conditions, compared and contrasted FEES to the videofluoroscopic evaluation of swallowing (VFSS), and developed specific pediatric FEES protocols with operational definitions for identification and interpretation of swallowing parameters. Results: FEES has proved to be a safe procedure in patients across ages. There have been no significant adverse events. FEES is comparable to the VFSS in the assessment of events before and after the swallow. It provides unique information regarding laryngopharyngeal anatomy and function, airway protection integrity, sensory threshold, and secretion management ability, as well as pharyngeal swallowing dynamics and the efficacy of compensatory swallowing strategies. Conclusions: There are specific indications and contraindications for pediatric FEES, and unique components that characterize the pediatric FEES protocols across ages and conditions. FEES procedures performed jointly by an Otolaryngologist and Speech-Language pathologist offer a team approach to interpretation and management recommendations.
Social and Health System Complexities Impacting on Decision-Making for Utilization of Oncology and Palliative Care in an African Context: A Qualitative Study
Authors: Agom David A. , Allen Stuart , Neill Sarah , Sixsmith Judith , Poole Helen , Onyeka Tonia C. , Ominyi Jude 
Published: December 2019

Background: There is a dearth of research focusing on identifying the social complexities impacting on oncology and palliative care (PC), and no study has explored how the health-care system in Nigeria or other African contexts may be influencing utilization of these services. Aim: This study explored how social complexities and the organization of health-care influenced the decision-making process for the utilization of oncology and PC in a Nigerian hospital. Methods: This qualitative study used an interpretive descriptive design. Data were collected using semistructured interview guides with 40 participants, comprising health-care professionals, patients, and their families. Thematic analysis was conducted to generate and analyze patterns within the data. Findings: Three themes were identified: dysfunctional structural organization of the health-care delivery system, service-users’ economic status, and the influence of social networks. The interrelationship between the themes result in patients and their family members decisions either to present late to the hospital, miss their clinical appointments, or not to seek oncological health care and PC. Conclusion: This article offers insights into the role of the health-care system, as organized currently in Nigeria, as “autoinhibitory” and not adequately prepared to address the increasing burden of cancer. We therefore argue that there is a need to restructure the Nigerian health-care system to better meet the needs of patients with cancer and their families as failure to do so will strengthen the existing inequalities, discourage usage, and increase mortality.
High-dose biotin in progressive multiple sclerosis: A prospective study of 178 patients in routine clinical practice
Authors: Couloume Laura , Barbin Laetitia , Leray Emmanuelle , Wiertlewski Sandrine , Le Page Emmanuelle , Kerbrat Anne , Ory Solenn , Le Port Damien , Edan Gilles , Laplaud David-Axel , Michel Laure 
Published: December 2019

Background: A recent controlled trial suggested that high-dose biotin supplementation reverses disability progression in patients with progressive multiple sclerosis. Objective: To analyze the impact of high-dose biotin in routine clinical practice on disability progression at 12 months. Methods: Progressive multiple sclerosis patients who started high-dose biotin at Nantes or Rennes Hospital between 3 June 2015 and 15 September 2017 were included in this prospective study. Disability outcome measures, patient-reported outcome measures, relapses, magnetic resonance imaging (MRI) data, and adverse events were collected at baseline, 6, and 12 months. Results: A total of 178 patients were included. At baseline, patients were 52.0 ± 9.4 years old, mean Expanded Disability Status Scale (EDSS) score was 6.1 ± 1.3, mean disease duration was 16.9 ± 9.5 years. At 12 months, 3.8% of the patients had an improved EDSS score. Regarding the other disability scales, scores either remained stable or increased significantly. In total, 47.4% of the patients described stability, 27.6% felt an improvement, and 25% described a worsening. Four patients (2.2%) had a relapse. Of the 74 patients (41.6%) who underwent an MRI, 20 (27.0%) had new T2 lesions, 8 (10.8%) had gadolinium-enhancing lesions. Twenty-five (14%) reported adverse event. Conclusion: In this study, high-dose biotin did not seem to be associated with a clear improvement in disability.
The effect of malocclusion on dating prospects
Authors: Khela Sonia , Newton J Timothy , Jeremiah Huw G 
Published: December 2019

Objective: To establish whether the appearance of malocclusion affected dating prospects. The secondary objective was to identify any significant predictors relating to likelihood of dating. Design: Cross-sectional study. Setting: King’s College London. Participants: A total of 232 undergraduate students. Methods: Participants were shown images of either one man or one woman. The images had been manipulated using computer software to represent one of three differing dental appearances: post-orthodontic aligned teeth; pre-orthodontic crowded teeth; or pre-orthodontic missing teeth (developmentally absent maxillary lateral incisors). Sealed envelopes were randomly assigned to participants, who rated the individual in the image in relation to: attractiveness; intelligence; happiness; nervousness; and how much they would want to go on a date with them. The response format was a 100-mm visual analogue scale. Results: The aligned dental appearance received statistically significant higher ratings of attractiveness ( P < 0.001), intelligence ( P = 0.031), likelihood of dating ( P = 0.017) as well as lower ratings of nervousness ( P = 0.020). There was no statistically significant difference in relation to happiness ( P = 0.43), neither were there any statistically significant differences between the crowded and missing dental appearances. Regression analysis revealed that rated attractiveness was the most significant predictor in relation to likelihood of dating ( P < 0.001). Conclusion: Malocclusion did influence dating prospects. Photographs of individuals with aligned teeth were more likely to be rated highly in relation to attractiveness, intelligence and likelihood of dating, when compared with images of malocclusions. The most significant predictor of likelihood of dating was rated attractiveness.
Joint sparing Kirschner-wire fixation for displaced proximal phalangeal neck fractures: randomized prospective comparative study
Authors: Sadek Ahmed Fathy 
Published: December 2019

The aim of this study was to compare two joint sparing Kirschner-wire fixation techniques for displaced proximal phalangeal neck fractures. Forty-six patients with proximal phalangeal neck fractures managed by either percutaneous antegrade flexible intramedullary nailing (Group I) or crossed Kirschner-wires (Group II) were recruited for a randomized prospective comparative study. Clinical and radiological assessment of all patients was done in addition to the Kang scoring system, Disability of Arm, Shoulder and Hand score and total active motion. The mean time for radiological union for both groups was 5.8 weeks. The mean postoperative total active motion, Kang and the Disability of Arm, Shoulder and Hand scores were better in Group I patients, but without any statistically significant differences. Closed reduction and percutaneous Kirschner-wire fixation by a joint sparing approach will yield good functional results with no or minimal complications in proximal phalangeal neck fractures. Level of evidence: II
Representation learning for clinical time series prediction tasks in electronic health records
Authors: Ruan Tong , Lei Liqi , Zhou Yangming , Zhai Jie , Zhang Le , He Ping , Gao Ju 
Published: December 2019

Abstract
Background
Electronic health records (EHRs) provide possibilities to improve patient care and facilitate clinical research. However, there are many challenges faced by the applications of EHRs, such as temporality, high dimensionality, sparseness, noise, random error and systematic bias. In particular, temporal information is difficult to effectively use by traditional machine learning methods while the sequential information of EHRs is very useful.

Method
In this paper, we propose a general-purpose patient representation learning approach to summarize sequential EHRs. Specifically, a recurrent neural network based denoising autoencoder (RNN-DAE) is employed to encode inhospital records of each patient into a low dimensional dense vector.

Results
Based on EHR data collected from Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, we experimentally evaluate our proposed RNN-DAE method on both mortality prediction task and comorbidity prediction task. Extensive experimental results show that our proposed RNN-DAE method outperforms existing methods. In addition, we apply the “Deep Feature” represented by our proposed RNN-DAE method to track similar patients with t-SNE, which also achieves some interesting observations.

Conclusion
We propose an effective unsupervised RNN-DAE method to summarize patient sequential information in EHR data. Our proposed RNN-DAE method is useful on both mortality prediction task and comorbidity prediction task.
High-sensitivity troponin I and B-type natriuretic peptide biomarkers for prediction of cardiovascular events in patients with coronary artery disease with and without diabetes mellitus
Authors: Wong Yuen-Kwun , Cheung Chloe Y. Y. , Tang Clara S. , Hai JoJo S. H. , Lee Chi-Ho , Lau Kui-Kai , Au Ka-Wing , Cheung Bernard M. Y. , Sham Pak-Chung , Xu Aimin , Lam Karen S. L. , Tse Hung-Fat 
Published: December 2019

Abstract
Background
High-sensitivity troponin I (hs-Tnl) and B-type natriuretic peptide (BNP) are promising prognostic markers for coronary artery disease (CAD). This prospective cohort study investigated whether a combination of these cardiac biomarkers with conventional risk factors would add incremental value for the prediction of secondary major adverse cardiovascular events (MACEs) in patients with CAD, with and without type 2 diabetes mellitus (T2DM).

Methods
Baseline plasma level of hs-Tnl and BNP was measured in 2275 Chinese patients with stable CAD. Patients were monitored for new-onset of MACE over a median of 51 months. Cox proportional hazard model and area under the receiver operating characteristic curve (AUC) were used to assess the association of cardiac biomarkers with MACE and their predictive values in relationship with or without T2DM.

Results
During the follow up period 402 (18%) patients experienced a new-onset MACE with hs-Tnl and BNP level significantly higher than in those without MACE. In multivariable analyses, patients with elevated hs-Tnl (hazard ratio, 1.75 [95% CI 1.41–2.17]; P < 0.001) and BNP (hazard ratio, 1.42 [95% CI 1.15–1.75]; P = 0.001) were significantly associated with an increased risk of MACE after adjustment for variables of a risk factor model of age, sex, T2DM and hypertension. The risk factor model had an AUC of 0.64 for MACE prediction. The AUC significantly increased to 0.68 by the addition of hs-Tnl to the risk factor model. Subgroup analyses showed that hs-Tnl and BNP remained significant predictors of MACE in both patients with and without T2DM in multivariable models with higher risk of MACE evident in those without T2DM. Among patients without T2DM, addition of each biomarker yielded greater predictive accuracy than in T2DM patients, with AUC further increased to 0.75 when a combination of hs-Tnl and BNP was added to the risk factor model (age, sex and hypertension).

Conclusions
Elevated hs-Tnl and BNP level are independent predictors of new-onset MACE in CAD patients, irrespective of diabetes status. Among CAD patients without T2DM, a combination of cardiac biomarkers hs-Tnl and BNP yield the greatest predictive value beyond conventional risk factors.
Carbonic anhydrase 2 (CAII) supports tumor blood endothelial cell survival under lactic acidosis in the tumor microenvironment
Authors: Annan Dorcas A. , Maishi Nako , Soga Tomoyoshi , Dawood Randa , Li Cong , Kikuchi Hiroshi , Hojo Takayuki , Morimoto Masahiro , Kitamura Tetsuya , Alam Mohammad Towfik , Minowa Kazuyuki , Shinohara Nobuo , Nam Jin-Min , Hida Yasuhiro , Hida Kyoko 
Published: December 2019

AbstractBackgroundTumor endothelial cells (TECs) perform tumor angiogenesis, which is essential for tumor growth and metastasis. Tumor cells produce large amounts of lactic acid from glycolysis; however, the mechanism underlying the survival of TECs to enable tumor angiogenesis under high lactic acid conditions in tumors remains poorly understood.MethodologyThe metabolomes of TECs and normal endothelial cells (NECs) were analyzed by capillary electrophoresis time-of-flight mass spectrometry. The expressions of pH regulators in TECs and NECs were determined by quantitative reverse transcription-PCR. Cell proliferation was measured by the MTS assay. Western blotting and ELISA were used to validate monocarboxylate transporter 1 and carbonic anhydrase 2 (CAII) protein expression within the cells, respectively. Human tumor xenograft models were used to access the effect of CA inhibition on tumor angiogenesis. Immunohistochemical staining was used to observe CAII expression, quantify tumor microvasculature, microvessel pericyte coverage, and hypoxia.ResultsThe present study shows that, unlike NECs, TECs proliferate in lactic acidic. TECs showed an upregulated CAII expression both in vitro and in vivo. CAII knockdown decreased TEC survival under lactic acidosis and nutrient-replete conditions. Vascular endothelial growth factor A and vascular endothelial growth factor receptor signaling induced CAII expression in NECs. CAII inhibition with acetazolamide minimally reduced tumor angiogenesis in vivo. However, matured blood vessel number increased after acetazolamide treatment, similar to bevacizumab treatment. Additionally, acetazolamide-treated mice showed decreased lung metastasis.ConclusionThese findings suggest that due to their effect on blood vessel maturity, pH regulators like CAII are promising targets of antiangiogenic therapy.Graphical abstract