bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation and quality assessment of a clinical orthopaedic registry in a public hospital department
Authors: Lee Binglong , Ebrahimi Milad , Ektas Nalan , Ting Chee Han , Cowley MacDougal , Scholes Corey , Bell Christopher 
Published: May 2020

Abstract
Background
The aim of this study was to demonstrate a novel method of assessing data quality for an orthopaedic registry and its effects on data quality metrics.

Methods
A quality controlled clinical patient registry was implemented, comprising six observational cohorts of shoulder and knee pathologies. Data collection procedures were co-developed with clinicians and administrative staff in accordance with the relevant dataset and organised into the registry database software. Quality metrics included completeness, consistency and validity. Data were extracted at scheduled intervals (3 months) and quality metrics reported to stakeholders of the registry.

Results
The first patient was enrolled in July 2017 and the data extracted for analysis over 4 quarters, with the last audit in August 2018 (N = 189). Auditing revealed registry completeness was 100% after registry deficiencies were addressed. However, cohort completeness was less accurate, ranging from 12 to 13% for height & weight to 90–100% for operative variables such as operating surgeon, consulting surgeon and hospital. Consistency and internal validation improved to 100% after issues in registry processes were rectified.

Conclusions
A novel method to assess data quality in a clinical orthopaedic registry identified process shortfalls and improved data quality over time. Real-time communication, a comprehensive data framework and an integrated feedback loop were necessary to ensure adequate quality assurance. This model can be replicated in other registries and serve as a useful quality control tool to improve registry quality and ensure applicability of the data to aid clinical decisions, especially in newly implemented registries.

Trial registration
ACTRN12617001161314; registration date 8/08/2017. Retrospectively registered.
Effectiveness, safety, and major adverse limb events in atrial fibrillation patients with concomitant diabetes mellitus treated with non-vitamin K antagonist oral anticoagulants
Authors: Chan Yi-Hsin , Lee Hsin-Fu , Li Pei-Ru , Liu Jia-Rou , Chao Tze-Fan , Wu Lung-Sheng , Chang Shang-Hung , Yeh Yung-Hsin , Kuo Chi-Tai , See Lai-Chu , Lip Gregory Y. H. 
Published: May 2020

Abstract
Background
Evidence of adverse clinical outcomes for non-vitamin K antagonist oral anticoagulant (NOACs) and warfarin in patients with atrial fibrillation (AF) and diabetes mellitus are limited. We investigated the effectiveness, safety, and major adverse limb events for NOACs versus warfarin among diabetic AF patients.

Methods
In this nationwide retrospective cohort study collected from Taiwan National Health Insurance Research Database, we identified a total of 20,967 and 5812 consecutive AF patients with diabetes taking NOACs and warfarin from June 1, 2012, to December 31, 2017, respectively. We used propensity-score stabilized weighting to balance covariates across study groups.

Results
NOAC was associated with a lower risk of major adverse cardiovascular events (MACE) (adjusted hazard ratio (aHR):0.88; [95% confidential interval (CI) 0.78–0.99]; P = 0.0283), major adverse limb events (MALE) (aHR:0.72;[95% CI 0.57–0.92]; P = 0.0083), and major bleeding (aHR:0.67;[95% CI 0.59–0.76]; P < 0.0001) compared to warfarin. NOACs decreased MACE in patients of ≥ 75 but not in those aged < 75 years (P interaction = 0.01), and in patients with ischemic heart disease (IHD) compared to those without IHD (P interaction < 0.01). For major adverse limb events, the advantage of risk reduction for NOAC over warfarin persisted in high risk subgroups including age ≥ 75 years, chronic kidney disease, IHD, peripheral artery disease, or use of concomitant antiplatelet drugs.

Conclusion
Among diabetic AF patients, NOACs were associated with a lower risk of thromboembolism, major bleeding, and major adverse limb events than warfarin. Thromboprophylaxis with NOACs should be considered in the diabetic AF population with a high atherosclerotic burden.
Serum lipids profiling perturbances in patients with ischemic heart disease and ischemic cardiomyopathy
Authors: Yang Lin , Wang Liang , Deng Yangyang , Sun Lizhe , Lou Bowen , Yuan Zuyi , Wu Yue , Zhou Bo , Liu Junhui , She Jianqing 
Published: May 2020

Abstract
Background
Ischemic heart disease (IHD) is a common cardiovascular disorder associated with inadequate blood supply to the myocardium. Chronic coronary ischemia leads to ischemic cardiomyopathy (ICM). Despite their rising prevalence and morbidity, few studies have discussed the lipids alterations in these patients.

Methods
In this cross-sectional study, we analyzed serum lipids profile in IHD and ICM patients using a lipidomics approach. Consecutive consenting patients admitted to the hospital for IHD and ICM were enrolled. Serum samples were obtained after overnight fasting. Non-targeted metabolomics was applied to demonstrate lipids metabolic profile in control, IHD and ICM patients.

Results
A total of 63 and 62 lipids were detected in negative and positive ion mode respectively. Among them, 16:0 Lyso PI, 18:1 Lyso PI in negative ion mode, and 19:0 Lyso PC, 12:0 SM d18:1/12:0, 15:0 Lyso PC, 17:0 PC, 18:1–18:0 PC in positive ion mode were significantly altered both in IHD and ICM as compared to control. 13:0 Lyso PI, 18:0 Lyso PI, 16:0 PE, 14:0 PC DMPC, 16:0 ceramide, 18:0 ceramide in negative ion mode, and 17:0 PE, 19:0 PC, 14:0 Lyso PC, 20:0 Lyso PC, 18:0 PC DSPC, 18:0–22:6 PC in positive ion mode were significantly altered only in ICM as compared to IHD and control.

Conclusion
Using non-targeted lipidomics profiling, we have successfully identified a group of circulating lipids that were significantly altered in IHD and ICM. The lipids metabolic signatures shed light on potential new biomarkers and therapeutics for preventing and treating ICM.
A comprehensive metabolic profiling of the metabolically healthy obesity phenotype
Authors: Telle-Hansen Vibeke H. , Christensen Jacob J. , Formo Gulla Aase , Holven Kirsten B. , Ulven Stine M. 
Published: May 2020

Abstract
Background
The ever-increasing prevalence of obesity constitutes a major health problem worldwide. A subgroup of obese individuals has been described as “metabolically healthy obese” (MHO). In contrast to metabolically unhealthy obese (MUO), the MHO phenotype has a favorable risk profile. Despite this, the MHO phenotype is still sub-optimally characterized with respect to a comprehensive risk assessment. Our aim was to increase the understanding of metabolic alterations associated with healthy and unhealthy obesity.

Methods
In this cross-sectional study, men and women (18–70 years) with obesity (body mass index (BMI) ≥ 30 kg/m2) or normal weight (NW) (BMI ≤ 25 kg/m2) were classified with MHO (n = 9), MUO (n = 10) or NW (n = 11) according to weight, lipid profile and glycemic regulation. We characterized individuals by comprehensive metabolic profiling using a commercial available high-throughput proton NMR metabolomics platform. Plasma fatty acid profile, including short chain fatty acids, was measured using gas chromatography.

Results
The concentrations of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and low density lipoprotein (LDL) subclasses were overall significantly higher, and high density lipoprotein (HDL) subclasses lower in MUO compared with MHO. VLDL and IDL subclasses were significantly lower and HDL subclasses were higher in NW compared with MHO. The concentration of isoleucine, leucine and valine was significantly higher in MUO compared with MHO, and the concentration phenylalanine was lower in NW subjects compared with MHO. The fatty acid profile in MHO was overall more favorable compared with MUO.

Conclusions
Comprehensive metabolic profiling supports that MHO subjects have intermediate-stage cardiovascular disease risk marker profile compared with NW and MUO subjects.

Clinical trial registration number
NCT01034436, Fatty acid quality and overweight (FO-study).

Graphical abstract
Role of hypoxia-related proteins in adenoid cystic carcinoma invasion
Authors: de Mendonça Raíssa Pinheiro , Chemelo Giordanna Pereira , Mitre Geovanni Pereira , Branco Dimitra Castelo , da Costa Natacha Malu Miranda , Tuji Fabrício Mesquita , da Silva Kataoka Maria Sueli , Mesquita Ricardo Alves , de Melo Alves Júnior Sérgio , de Jesus Viana Pinheiro João 
Published: May 2020

Abstract
Background
Among cancers affecting the oral cavity, adenoid cystic carcinoma (ACC) is a relatively common malignant neoplasm. It has high rates of metastasis and recurrence and is associated with significant morbidity. During the progression of ACC, the oxygen concentration is reduced in specific areas of the tumour microenvironment, leading to intratumoural hypoxia. The expression of NOTCH1, a disintegrin and metalloproteinase 12 (ADAM-12), hypoxia-inducible factor 1 alpha (HIF-1α), and heparin-binding epidermal growth factor (HB-EGF) under hypoxic conditions has been implicated in invadopodia formation, tumour invasiveness, and metastasis. The aim of this study was to analyse the expression of these proteins to elucidate the mechanisms underlying ACC invasiveness.

Methods
Fifteen ACC samples and 10 normal-looking salivary gland (SG) samples were used to investigate the expression of these proteins by immunohistochemistry. Primary antibodies against NOTCH1, ADAM-12, HIF-1α, and HB-EGF were used.

Results
The immunoexpression of all proteins was higher in ACC samples than in SG samples (p < 0.05).

Conclusions
There was increased expression of proteins associated with hypoxia and tumour invasiveness in ACC samples, which indicates a possible role of these proteins in the biological behaviour of this tumour.
A familial case of alveolar capillary dysplasia with misalignment of the pulmonary veins: the clinicopathological features and unusual glomeruloid endothelial proliferation
Authors: Kitano Akiko , Nakaguro Masato , Tomotaki Seiichi , Hanaoka Shintaro , Kawai Masahiko , Saito Akiko , Hayakawa Masahiro , Takahashi Yoshiyuki , Kawasaki Hidenori , Yamada Takahiro , Ikeda Masahiko , Onda Tetsuo , Cho Kazutoshi , Haga Hironori , Nakazawa Atsuko , Minamiguchi Sachiko 
Published: May 2020

Abstract
Background
Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare disorder of pulmonary vascular abnormality with persistent pulmonary hypertension of the newborn. The symptom usually presents within hours after birth, leading to an early demise. Heterozygous de novo point mutations and genomic deletions of the FOXF1 (forkhead box F1) gene or its upstream enhancer have been identified in most patients with ACD/MPV. Most cases of ACD/MPV are sporadic; however, familial cases are also reported in 10% of patients.

Case presentation
We herein report a case of familial ACD/MPV that showed unusual glomeruloid proliferation of endothelial cells. In this family, three of the four siblings died within two to 3 days after birth because of persistent pulmonary hypertension and respiratory failure. Only the second child remains alive and healthy. An autopsy was performed for the third and fourth children, resulting in a diagnosis of ACD/MPV based on the characteristic features, including misalignment of smaller pulmonary veins and lymphangiectasis. In both of these children, glomeruloid endothelial proliferation of vessels was noted in the interlobular septa. The vessels were immunohistochemically positive for D2–40, CD31, Factor VIII, and ERG, suggestive of differentiation for both lymphatic and blood vessels.

Conclusions
Unusual glomeruloid endothelial proliferation was observed in a familial ACD/MPV case. This histologic feature has not been described previously in ACD/MPV or any other pulmonary disease. Although the histogenesis of this histologic feature is unclear, this finding may suggest that ACD/MPV is a compound vascular and lymphovascular system disorder that exhibits various histologic features.
An integrated approach to meet the needs of high-vulnerable families: a qualitative study on integrated care from a professional perspective
Authors: Nooteboom L. A. , van den Driesschen S. I. , Kuiper C. H. Z. , Vermeiren R. R. J. M. , Mulder E. A. 
Published: May 2020

Abstract
Background
To meet the needs of high-vulnerable families with severe and enduring problems across several life domains, professionals must improve their ability to provide integrated care timely and adequately. The aim of this study was to identify facilitators and barriers professionals encounter when providing integrated care.

Methods
Experiences and perspectives of 24 professionals from integrated care teams in the Netherlands were gathered by conducting semi-structured interviews. A theory-driven framework method was applied to systematically code the transcripts both deductively and inductively.

Results
There was a consensus among professionals regarding facilitators and barriers influencing their daily practice, leading to an in depth, thematic report of what facilitates and hinders integrated care. Themes covering the facilitators and barriers were related to early identification and broad assessment, multidisciplinary expertise, continuous pathways, care provision, autonomy of professionals, and evaluation of care processes.

Conclusions
Professionals emphasized the need for flexible support across several life domains to meet the needs of high-vulnerable families. Also, there should be a balance between the use of guidelines and a professional’s autonomy to tailor support to families’ needs. Other recommendations include the need to improve professionals’ ability in timely stepping up to more intensive care and scaling down to less restrictive support, and to further our insight in risk factors and needs of these families.
The effect of glutamine on Dehydroepiandrosterone-induced polycystic ovary syndrome rats
Authors: Wu Gengxiang , Hu Xue , Ding Jinli , Yang Jing 
Published: May 2020

Abstract
Background
Previous studies have shown that chronic inflammation and oxidative stress may play an important role in the pathophysiology of polycystic ovary syndrome (PCOS), and glutamine (Gln) have showed the anti-inflammatory and antioxidant properties. So the aim of this study is to investigate the effect of glutamine supplementation on PCOS rats.

Methods
Female Sprague–Dawley rats were randomly assigned into four groups (n = 10 /group), control group, PCOS group, PCOS+ 0.5 g/kg Gln group and PCOS+ 1.0 g/kg Gln group. All the PCOS rats were administrated with 6 mg/100 g dehydroepiandrosterone (DHEA) for 20 consecutive days, all the PCOS+Gln groups were intraperitoneal injected glutamine twice in the next morning after the last DHEA injection. All the samples were collected 12 h after the last administration. Ovarian histological examinations were analyzed and the concentration of serum hormone, inflammatory and oxidative stress factors were measured.

Results
There was no obvious ovarian histological change among the PCOS group and PCOS+Gln groups. All the detected inflammation factors [C-reactive protein, interleukin (IL)-6, IL-18, tumor necrosis factor] showed significantly higher in all the PCOS groups compared to the control group (P < 0.01), and were significantly decreased with the supplementation of 0.5 g/kg glutamine (P < 0.01). Concentrations of superoxide dismutase were significantly lower in all the PCOS groups (P < 0.01) compared to the control group, and increased significantly with the supplementation of 0.5 g/kg glutamine (P < 0.01). Serum concentrations of malondialdehyde, nitric oxide synthase and nitric oxide were significantly higher in PCOS group (P < 0.01) compared with the control group, and significantly decreased to the comparative levels of control group with supplementation of 0.5 g/kg glutamine (P < 0.01).

Conclusion
There is low-grade inflammation and oxidative stress in DHEA-induced PCOS rats. The supplementation of 0.5 g/kg glutamine could effectively ameliorate the inflammation and oxidative stress conditions of PCOS.
Diffuse large B cell lymphoma involving Meckel’s cave masquerading as biopsy-negative giant cell arteritis: a case report
Authors: Samec Matthew J. , Madrigal Andres G. , Rydberg Charlotte H. , Koster Matthew J. 
Published: May 2020

Abstract
Background
Given the absence of consensus diagnostic criteria for giant cell arteritis, clinicians may encounter difficulty with identification of new-onset headache in patients older than age 50 years presenting with visual changes and elevated inflammatory markers, particularly if temporal artery biopsies are performed and negative.

Case presentation
We present a case of a 57-year-old white man with headache, diplopia, and jaw paresthesia initially diagnosed and managed as steroid-refractory biopsy-negative giant cell arteritis. Further investigation disclosed evidence of soft tissue infiltration into Meckel’s (trigeminal) cave bilaterally. Positron emission tomography suggested the presence of a lymphoproliferative disorder. Histology confirmed the diagnosis of diffuse large B cell lymphoma.

Conclusions
Metastatic involvement in Meckel’s cave in diffuse large B cell lymphoma is extremely rare and presents a diagnostic challenge. Patients with suspicion of giant cell arteritis should undergo advanced imaging, particularly those with negative biopsy, atypical features, or lack of response to standard therapy, in order to assess for the presence of large-vessel vasculitis or other mimicking pathologies.
Association between pesticide exposure and paraoxonase-1 (PON1) polymorphisms, and neurobehavioural outcomes in children: a systematic review
Authors: Banhela Nkosinathi , Naidoo Pragalathan , Naidoo Saloshni 
Published: May 2020

AbstractEnvironmental factors such as pollution, pesticide exposure and socio-demographic location have been implicated as a pressure capable of altering genetic make-up. Altered genetic sequence of genes encoding enzymes may result in single nucleotide polymorphism (SNP). Of peculiar interest is the genetic variance on the paraoxonase-1 gene induced by pre- and postnatal exposure to pesticides. SNP have been reported on the paraoxonase-1 gene and post-xenobiotic exposure and are presumed to alter gene sequence and ultimately enzymatic activity. The altered enzymatic activity may facilitate neurodevelopment disorders. Autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD) are among the neurodevelopment disorders of which prevalence is concurrently associated with increasing environmental xenobiotic exposure. The variance on xenobiotic metabolising genes is associated with altered neurodevelopment outcome and ultimately altered neurobehavioural outcome. Prime interests of this systematic review were to establish an understanding of the sequences on the paraoxonase-1 gene associated with adverse neurobehavioural outcome. An in-depth literature search was conducted using the term combination “pesticide exposure, pre- and postnatal exposure, organophosphates/organophosphorus, single nucleotide polymorphism, paraoxonase-1 (PON-1), neurodevelopment/neurobehavioural outcome in child/infant”. Articles published from the year 2000 to 2018 were considered for review. The result showed that variance on the PON1-108 and 192 alleles could be implicated in the development of altered neurobehavioural outcomes.
Interventions for treatment of COVID-19: a protocol for a living systematic review with network meta-analysis including individual patient data (The LIVING Project)
Authors: Juul Sophie , Nielsen Niklas , Bentzer Peter , Veroniki Areti Angeliki , Thabane Lehana , Linder Adam , Klingenberg Sarah , Gluud Christian , Jakobsen Janus Christian 
Published: May 2020

Abstract
Background
COVID-19 is a rapidly spreading virus infection that has quickly caused extensive burden to individual, families, countries, and the globe. No intervention has yet been proven effective for the treatment of COVID-19. Some randomized clinical trials assessing the effects of different drugs have been published, and more are currently underway. There is an urgent need for a living, dynamic systematic review that continuously evaluates the beneficial and harmful effects of all available interventions for COVID-19.

Methods/design
We will conduct a living systematic review based on searches of major medical databases (e.g., MEDLINE, EMBASE, CENTRAL) and clinical trial registries from their inception onwards to identify relevant randomized clinical trials. We will update the literature search once a week to continuously assess if new evidence is available. Two review authors will independently extract data and perform risk of bias assessment. We will include randomized clinical trials comparing any intervention for the treatment of COVID-19 (e.g., pharmacological interventions, fluid therapy, invasive or noninvasive ventilation, or similar interventions) with any comparator (e.g., an “active” comparator, standard care, placebo, no intervention, or “active placebo”) for participants in all age groups with a diagnosis of COVID-19. Primary outcomes will be all-cause mortality and serious adverse events. Secondary outcomes will be admission to intensive care, mechanical ventilation, renal replacement therapy, quality of life, and non-serious adverse events. The living systematic review will include aggregate data meta-analyses, Trial Sequential Analyses, network meta-analysis, and individual patient data meta-analyses. Risk of bias will be assessed with domains, an eight-step procedure will be used to assess if the thresholds for clinical significance are crossed, and the certainty of the evidence will be assessed by Grading of Recommendations, Assessment, Development and Evaluations (GRADE).

Discussion
COVID-19 has become a pandemic with substantial mortality. A living systematic review evaluating the beneficial and harmful effects of pharmacological and other interventions is urgently needed. This review will continuously inform best practice in treatment and clinical research of this highly prevalent disease.

Systematic review registration
PROSPERO CRD42020178787
An application of Phragmén–Lindelöf theorem to the existence of ground state solutions for the generalized Schrödinger equation with optimal control
Authors: Zhang Chaofeng , Hu Rong 
Published: May 2020

AbstractIn this paper, we develop optimal Phragmén–Lindelöf methods, based on the use of maximum modulus of optimal value of a parameter in a Schrödinger functional, by applying the Phragmén–Lindelöf theorem for a second-order boundary value problems with respect to the Schrödinger operator. Using it, it is possible to find the existence of ground state solutions of the generalized Schrödinger equation with optimal control. In spite of the fact that the equation of this type can exhibit non-uniqueness of weak solutions, we prove that the corresponding Phragmén–Lindelöf method, under suitable assumptions on control conditions of the nonlinear term, is well-posed and admits a nonempty set of solutions.