bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact on renal function after long-term use of anticoagulants in atrial fibrillation patients
Authors: Lee Wei-Chieh , Lee Pai-Wei , Wu Po-Jui , Fang Yen-Nan , Chen Huang-Chung , Lin Yu-Sheng , Fang Hsiu-Yu , Chang Shang-Hung , Liu Ping-Yen , Chen Mien-Cheng 
Published: December 2021

Abstract
Objective
Long-term oral anticoagulant should be considered or recommended in patients with atrial fibrillation (AF) and CHA2DS2VASc score ≥ 1 for stroke prevention. Warfarin and different direct oral anticoagulants (DOACs) are metabolized differently by the kidney. The impact on renal function after long-term use of anticoagulants in the patients with AF remains unclear. This study aimed to compare DOACs and warfarin’s impact on the decline in renal function from a large cohort with AF.

Methods
This study included patients with nonvalvular AF from 2000 to 2018, mainly through the medical history (ICD code) of the Chang Gung Research Database. Baseline estimated glomerular filtration rate (eGFR), follow-up eGFR and the change in eGFR between 2-year eGFR and baseline eGFR were compared between different DOACs and warfarin after propensity score matching. The primary study endpoint was acute kidney injury (AKI).

Results
3657 patients were enrolled in this study and the mean observation time was 3.3 ± 0.9 years. During the observation period, there was a significantly higher incidence of AKI during follow-up in the warfarin group than in the different DOAC groups before and after propensity score matching (before: warfarin vs. DOAC: 9.2% vs. 5.2%, p <  0.001; after: warfarin vs. DOAC: 8.9% vs. 4.4%, p <  0.001). There was no difference in the incidence of AKI between dabigatran group and anti-factor Xa inhibitor group after propensity score matching. The incidence of AKI was similar among rivaroxaban, apixaban and edoxaban groups after propensity score matching. The change in eGFR between 2-year eGFR and baseline eGFR did not differ between the warfarin and DOAC groups after propensity score matching (warfarin vs. DOAC: − 1.27 ± 20.32 vs. -1.94 ± 17.24 mL/min/1.73 m2, p = 0.461).

Conclusions
During the mean observation time of 3.3 ± 0.9 years, warfarin was associated with a higher incidence of AKI compared with DOACs. The decline in renal function did not differ among warfarin and different DOAC groups.
Measuring health science research and development in Africa: mapping the available data
Authors: Wenham Clare , Wouters Olivier , Jones Catherine , Juma Pamela A. , Mijumbi-Deve Rhona M. , Sobngwi-Tambekou Joëlle L. , Parkhurst Justin 
Published: December 2021

Abstract
Background
In recent years there have been calls to strengthen health sciences research capacity in African countries. This capacity can contribute to improvements in health, social welfare and poverty reduction through domestic application of research findings; it is increasingly seen as critical to pandemic preparedness and response. Developing research infrastructure and performance may reduce national economies’ reliance on primary commodity and agricultural production, as countries strive to develop knowledge-based economies to help drive macroeconomic growth. Yet efforts to date to understand health sciences research capacity are limited to output metrics of journal citations and publications, failing to reflect the complexity of the health sciences research landscape in many settings.

Methods
We map and assess current capacity for health sciences research across all 54 countries of Africa by collecting a range of available data. This included structural indicators (research institutions and research funding), process indicators (clinical trial infrastructures, intellectual property rights and regulatory capacities) and output indicators (publications and citations).

Results
While there are some countries which perform well across the range of indicators used, for most countries the results are varied—suggesting high relative performance in some indicators, but lower in others. Missing data for key measures of capacity or performance is also a key concern. Taken as a whole, existing data suggest a nuanced view of the current health sciences research landscape on the African continent.

Conclusion
Mapping existing data may enable governments and international organizations to identify where gaps in health sciences research capacity lie, particularly in comparison to other countries in the region. It also highlights gaps where more data are needed. These data can help to inform investment priorities and future system needs.
γ-Enolase enhances Trk endosomal trafficking and promotes neurite outgrowth in differentiated SH-SY5Y cells
Authors: Pišlar Anja , Kos Janko 
Published: December 2021

Abstract
Background
Neurotrophins can activate multiple signalling pathways in neuronal cells through binding to their cognate receptors, leading to neurotrophic processes such as cell survival and differentiation. γ-Enolase has been shown to have a neurotrophic activity that depends on its translocation towards the plasma membrane by the scaffold protein γ1-syntrophin. The association of γ-enolase with its membrane receptor or other binding partners at the plasma membrane remains unknown.

Methods
In the present study, we used immunoprecipitation and immunofluorescence to show that γ-enolase associates with the intracellular domain of the tropomyosin receptor kinase (Trk) family of tyrosine kinase receptors at the plasma membrane of differentiated SH-SY5Y cells.

Results
In differentiated SH-SY5Y cells with reduced expression of γ1-syntrophin, the association of γ-enolase with the Trk receptor was diminished due to impaired translocation of γ-enolase towards the plasma membrane or impaired Trk activity. Treatment of differentiated SH-SY5Y cells with a γ-Eno peptide that mimics γ-enolase neurotrophic activity promoted Trk receptor internalisation and endosomal trafficking, as defined by reduced levels of Trk in clathrin-coated vesicles and increased levels in late endosomes. In this way, γ-enolase triggers Rap1 activation, which is required for neurotrophic activity of γ-enolase. Additionally, the inhibition of Trk kinase activity by K252a revealed that increased SH-SY5Y cell survival and neurite outgrowth mediated by the γ-Eno peptide through activation of signalling cascade depends on Trk kinase activity.

Conclusions
These data therefore establish the Trk receptor as a binding partner of γ-enolase, whereby Trk endosomal trafficking is promoted by γ-Eno peptide to mediate its neurotrophic signalling.

Graphical Abstract
Long-term efficacy of autologous bone marrow mesenchymal stromal cells for treatment of knee osteoarthritis
Authors: Lamo-Espinosa José María , Prósper Felipe , Blanco Juan F. , Sánchez-Guijo Fermín , Alberca Mercedes , García Verónica , González-Vallinas Margarita , García-Sancho Javier 
Published: December 2021

AbstractKnee osteoarthritis is the most prevalent joint disease and a frequent cause of pain, functional loss and disability. Conventional treatments have demonstrated only modest clinical benefits whereas cell-based therapies have shown encouraging results, but important details, such as dose needed, long-term evolution or number of applications required are scarcely known. Here we have reanalyzed results from two recent pilot trials with autologous bone marrow-derived mesenchymal stromal cells using the Huskisson plot to enhance quantification of efficacy and comparability. We find that cell doses of 10, 40 and 100 million autologous cells per knee provided quite similar healing results and that much of the effect attained 1 year after cell application remained after 2 and 4 years. These results are encouraging because they indicate that, apart from safety and simplicity: (i) the beneficial effect is both significant and sizeable, (ii) it can be achieved with a single injection of cells, and (iii) the effect is perdurable for years.Trial registration: EudraCT 2009-017405-11; NCT02123368. Registered 25 April 2014—Prospectively registered, https://clinicaltrials.gov/ct2/show/NCT02123368?term=02123368&draw=2&rank=1
Physical activity dimensions after stroke: patterns and relation with lower limb motor function
Authors: Braakhuis Hanneke E. M. , Berger Monique A. M. , Regterschot Ruben G. R. H. , van Wegen Erwin E. H. , Selles Ruud W. , Ribbers Gerard M. , Bussmann Johannes B. J. ,   the PROFITS research group, Meskers Carel , Kwakkel Gert , van Wegen Erwin E. H. , Nijland Rinske , Andinga Aukje , Zonjee Valentijn , Koolstra-Rutgers Muriel , van den Berg-Vos Renske 
Published: December 2021

AbstractBackgroundStroke survivors show deteriorated physical functioning and physical activity levels. Physical activity levels of stroke survivors are generally low. It is increasingly recognized that physical activity is a multidimensional construct that cannot be captured in a single outcome. In-depth insight into multidimensional physical activity patterns may guide the development and timing of targeted rehabilitation interventions. This longitudinal cohort study explored how multidimensional physical activity outcomes develop during recovery in the subacute phase after stroke and if changes in physical activity were correlated to recovery of lower limb motor function.MethodsPatients were recruited during inpatient rehabilitation. At 3, 12, and 26 weeks post-onset, motor function was measured by the Fugl-Meyer Lower Extremity Assessment (FMA-LE). Physical activity was measured with the Activ8 accelerometer in multiple outcomes: counts per minute during walking (CPMwalking; a measure of Intensity), number of active bouts (Frequency), mean length of active bouts (Distribution) and % of waking time in upright positions (Duration). Generalized estimating equations (GEE) were used to study changes in physical activity over time and the relation with the change in lower limb motor recovery.ResultsThirty-nine patients (age 56 ± 9, 77% male, 89% ischemic stroke) were included. GEE models showed a significant main effect of time for PA Intensity (+ 13%, p = 0.007) and Duration (+ 64%, p = 0.012) between 3 and 12 weeks. Motor function did not show a significant effect in all PA models across the 3 timepoints (p > 0.020). A significant interaction effect of time × motor function was observed (p < 0.001).ConclusionsPatterns of PA recovery depend on the PA dimensions: PA Intensity and Duration increased mostly between 3 and 12 weeks post-stroke, whereas Frequency and Distribution did not show substantial changes. Further, no strong associations with motor recovery and high inter-individual variability were documented, which underlies the need to consider factors specific to the disease, the individual patient and the context.
Machine learning approaches for the genomic prediction of rheumatoid arthritis and systemic lupus erythematosus
Authors: Chung Chih-Wei , Hsiao Tzu-Hung , Huang Chih-Jen , Chen Yen-Ju , Chen Hsin-Hua , Lin Ching-Heng , Chou Seng-Cho , Chen Tzer-Shyong , Chung Yu-Fang , Yang Hwai-I , Chen Yi-Ming 
Published: December 2021

Abstract
Background
Rheumatoid arthritis (RA) and systemic lupus erythematous (SLE) are autoimmune rheumatic diseases that share a complex genetic background and common clinical features. This study’s purpose was to construct machine learning (ML) models for the genomic prediction of RA and SLE.

Methods
A total of 2,094 patients with RA and 2,190 patients with SLE were enrolled from the Taichung Veterans General Hospital cohort of the Taiwan Precision Medicine Initiative. Genome-wide single nucleotide polymorphism (SNP) data were obtained using Taiwan Biobank version 2 array. The ML methods used were logistic regression (LR), random forest (RF), support vector machine (SVM), gradient tree boosting (GTB), and extreme gradient boosting (XGB). SHapley Additive exPlanation (SHAP) values were calculated to clarify the contribution of each SNPs. Human leukocyte antigen (HLA) imputation was performed using the HLA Genotype Imputation with Attribute Bagging package.

Results
Compared with LR (area under the curve [AUC] = 0.8247), the RF approach (AUC = 0.9844), SVM (AUC = 0.9828), GTB (AUC = 0.9932), and XGB (AUC = 0.9919) exhibited significantly better prediction performance. The top 20 genes by feature importance and SHAP values included HLA class II alleles. We found that imputed HLA-DQA1*05:01, DQB1*0201 and DRB1*0301 were associated with SLE; HLA-DQA1*03:03, DQB1*0401, DRB1*0405 were more frequently observed in patients with RA.

Conclusions
We established ML methods for genomic prediction of RA and SLE. Genetic variations at HLA-DQA1, HLA-DQB1, and HLA-DRB1 were crucial for differentiating RA from SLE. Future studies are required to verify our results and explore their mechanistic explanation.
The effectiveness and safety of paediatric prehospital pain management: a systematic review
Authors: Abebe Yonas , Hetmann Fredrik , Sumera Kacper , Holland Matt , Staff Trine 
Published: December 2021

Abstract
Background
Clinically meaningful pain reduction with respect to severity and the adverse events of drugs used in prehospital pain management for children are areas that have not received sufficient attention. The present systematic review therefore aims to perform a comprehensive search of databases to examine the preferable drugs for prehospital pain relief in paediatric patients with acute pain, irrespective of aetiology.

Methods
The systematic review includes studies from 2000 and up to 2020 that focus on children’s prehospital pain management. The study protocol is registered in PROSPERO with registration no. CRD42019126699. Pharmacological pain management using any type of analgesic drug and in all routes of administration was included. The main outcomes were (1) measurable pain reduction (effectiveness) and (2) no occurrence of any serious adverse events. Searches were conducted in PubMed, Medline, Embase, CINAHL, Epistemonikos and Cochrane library. Finally, the risk of bias was assessed using the Joanna Briggs Institute (JBI) checklist and a textual narrative analysis was performed due to the heterogeneity of the results.

Results
The present systematic review on the effectiveness and safety of analgesic drugs in prehospital pain relief in children identified a total of eight articles. Most of the articles reviewed identified analgesic drugs such as fentanyl (intranasal/IV), morphine (IV), methoxyflurane (inhalational) and ketamine (IV/IM). The effects of fentanyl, morphine and methoxyflurane were examined and all of the included analgesic drugs were evaluated as effective. Adverse events of fentanyl, methoxyflurane and ketamine were also reported, although none of these were considered serious.

Conclusion
The systematic review revealed that fentanyl, morphine, methoxyflurane and combination drugs are effective analgesic drugs for children in prehospital settings. No serious adverse events were reported following the administration of fentanyl, methoxyflurane and ketamine. Intranasal fentanyl and inhalational methoxyflurane seem to be the preferred drugs for children in pre-hospital settings due to their ease of administration, similar effect and safety profile when compared to other analgesic drugs. However, the level of evidence (LOE) in the included studies was only three or four, and further studies are therefore necessary.
Treatment of urinary incontinence in women with chronic obstructive pulmonary disease—a randomised controlled study
Authors: Haukeland-Parker Stacey , Frisk Bente , Spruit Martijn A. , Stafne Signe Nilssen , Johannessen Hege Hølmo 
Published: December 2021

Abstract
Background
Little is known regarding treatment of urinary incontinence (UI) in women with chronic obstructive pulmonary disease (COPD). The aim of the study was to explore the efficacy of pelvic floor muscle training (PFMT) or cough-suppression techniques (CST) on UI in women with COPD.

Methods
A three-armed, two-centred, single-blinded, randomised controlled study was performed. Subjects were randomised to (a) PFMT for 16 weeks, (b) 2–3 educational sessions in CST, or (c) written information only. All participants completed questionnaires about UI, cough symptoms, and health status and underwent clinical examinations to evaluate the strength of the pelvic floor muscles and exercise capacity. Daily physical activity levels were measured using an activity monitor and lung function with spirometry. With a significance level of 5% and an 80% chance of detecting a significant difference between groups of 2.5 points on the ICIQ UI SF score, our sample size calculation showed that a total of 78 women, 26 in each group, was required to complete the study.

Results
During the period 2016 to 2018, 95 women were invited to the study. A total of 42 were recruited, three were excluded and 10 (24%) dropped out during the follow-up period. Mean ICIQ-UI SF total baseline score was 9.6 (range: 1–17) and 7.0 (range: 0–16) at follow-up. Changes in subjective UI as measured with the ICIQ-UI SF questionnaire were seen in the PFMT group and control group, but not in the CST group.

Conclusion
Due to the low number of available participants and recruitment difficulties including practical issues such as travel distance, lack of interest, poor state of health, and high number of comorbidities, our results are inconclusive. However, reduced subjective UI was observed in the PFMT and control groups with a trend towards best effect in the PFMT group. Screening for UI is advisable in all women with COPD to be able to identify and treat these women to reduce symptom burden and improve quality of life. Future studies should focus on barriers to recruitment as well as randomised controlled studies with larger sample sizes.

Trial registration
ClinicalTrials.gov NCT02614105. 25th November 2015.
Atorvastatin combined with dexamethasone in chronic subdural haematoma (ATOCH II): study protocol for a randomized controlled trial
Authors: Jiang Rong Cai , Wang Dong , Zhao Shi Guang , Wang Ren Zhi , Kang De Zhi , Zhu Xin Gen , Zhao Zong Mao , Wei Jun Ji , Huang Ying , Qu Yan , Sun Xiao Chuan , Ji Hong Ming , Jiang Xiao Chun , Liu Jin Fang , De Zhu Xi , Wang Jian Jun , Tian Ye , Gao Chuang , Wei Hui Jie , Zhang Shu , Quan Wei , Yue Shu Yuan , Lei Ping , Li Xian , Song Li Li , Anderson Craig S. , Zhang Jian Ning 
Published: December 2021

AbstractBackgroundChronic subdural haematoma (CSDH) is a common condition in the elderly that often requires neurosurgical management. For small CSDH, evidence has emerged that statins may reduce haematoma volume and improve outcomes, presumably by reducing local inflammation and promoting vascular repair. We wish to extend this evidence in a study that aims to determine the efficacy and safety of atorvastatin combined with low-dose dexamethasone in patients with CSDH.MethodsThe second ATorvastatin On Chronic subdural Hematoma (ATOCH-II) study is a multi-centre, randomized, placebo-controlled, double-blind trial which aims to enrol 240 adult patients with a conservative therapeutic indication for CSDH, randomly allocated to standard treatment with atorvastatin 20 mg combined with low-dose dexamethasone (or matching placebos) daily for 28 days, and with 152 days of follow-up. The primary outcome is a composite good outcome defined by any reduction from baseline in haematoma volume and survival free of surgery at 28 days. Secondary outcomes include functional outcome on the modified Rankin scale (mRS) and modified Barthel Index at 28 days, surgical transition and reduction in haematoma volumes at 14, 28 and 90 days.DiscussionThis multi-centre clinical trial aims to provide high-quality evidence on the efficacy and safety of the combined treatment of atorvastatin and low-dose dexamethasone to reduce inflammation and enhance angiogenesis in CSDH.Trial registrationChiCTR,ChiCTR1900021659. Registered on 3 March 2019,http://www.chictr.org.cn/showproj.aspx?proj=36157.
Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression (CREST-MST): protocol for identification of novel biomarkers via neurophysiology
Authors: Daskalakis Zafiris J. , McClintock Shawn M. , Hadas Itay , Kallioniemi Elisa , Zomorrodi Reza , Throop Alanah , Palmer Lucy , Farzan Faranak , Thorpe Kevin E. , Tamminga Carol , Blumberger Daniel M. 
Published: December 2021

Abstract
Background
Electroconvulsive therapy (ECT) is the most effective treatment for treatment-resistant depression (TRD), especially for acute suicidal ideation, but the associated cognitive adverse effects and negative stigma limit its use. Another seizure therapy under development is magnetic seizure therapy (MST), which could potentially overcome the restrictions associated with ECT with similar efficacy. The neurophysiological targets and mechanisms of seizure therapy, however, remain poorly understood.

Methods/design
This neurophysiological study protocol is published as a companion to the overall Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression (CREST-MST) protocol that describes our two-site, double-blind, randomized, non-inferiority clinical trial to develop MST as an effective and safe treatment for TRD. Our aim for the neurophysiological component of the study is to evaluate two biomarkers, one to predict remission of suicidal ideation (primary outcome) and the other to predict cognitive impairment (secondary outcome). Suicidal ideation will be assessed through cortical inhibition, which according to our preliminary studies, correlates with remission of suicidal ideation. Cortical inhibition will be measured with simultaneous transcranial magnetic stimulation (TMS) and electroencephalography (EEG), TMS-EEG, which measures TMS-evoked EEG activity. Cognitive adverse effects associated with seizure therapy, on the contrary, will be evaluated via multiscale entropy analysis reflecting the complexity of ongoing resting-state EEG activity.

Discussion
ECT and MST are known to influence cortical inhibition associated with depression, suicidal ideation severity, and clinical outcome. Therefore, evaluating cortical inhibition and brain temporal dynamics will help understand the pathophysiology of depression and suicidal ideation and define new biological targets that could aid clinicians in diagnosing and selecting treatments. Resting-state EEG complexity was previously associated with the degree of cognitive side effects after a seizure therapy. This neurophysiological metric may help clinicians assess the risk for adverse effects caused by these useful and effective treatments.

Trial registration
ClinicalTrials.govNCT03191058. Registered on June 19, 2017.