bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reference SVA insertion polymorphisms are associated with dopaminergic degeneration in Parkinson’s Disease and differential gene expression in the PPMI cohort
Authors: Pfaff Abigail L , Bubb Vivien J. , Quinn John P. , Koks Sulev 
Published: July 2020

Abstract
Background: The development of Parkinson’s disease (PD) involves a complex interaction of genetic and environmental factors. The majority of studies investigating the genetic component of complex diseases, including PD, have focused on single nucleotide polymorphisms as this enables genome wide analysis of a large number of samples. Genome wide association studies have been crucial in identifying PD risk variants, however a large proportion of the heritability of PD remains to be identified. To investigate the component of PD that may involve complex genetic variants we characterised SINE-VNTR-Alus (SVAs), a retrotransposon known to affect gene expression, in the Parkinson’s Progression Markers Initiative (PPMI) cohort.Results: Utilising whole genome sequencing from the PPMI cohort that consisted of 179 healthy controls, 371 individuals with PD and 58 individuals classified as SWEDD (scans without evidence of dopaminergic deficit) we genotyped SVAs in the reference genome for their presence or absence identifying 81 such SVAs. Seven of these SVAs were associated with progression of the disease, including four whose specific genotypes were linked to an increase in the gradient of dopaminergic loss when comparing the caudate to putamen from DaTscan imaging analysis. These seven SVAs also demonstrated regulatory properties as they were associated with differential gene expression in whole blood RNA sequencing data.Conclusion: This study highlights the importance of addressing variation of SVAs and potentially other types of retrotransposons in PD genetics, furthermore these SVA elements should be considered as regulatory domains that could play a role in disease progression.
P38 Initiates Diabetic Neurodegeneration Through Glutamatergic and GABAergic Neurons
Authors: Farhadi Aisan , Totonchi Mehdi , Nabavi Seyed Masood , Baharvand Hossein , Pakdaman Hossein , Hajizadeh-Saffar Ensiyeh , Mousavi Ahmad , Hadi Fatemeh , Al-Sinawi Hamed , Li Quan , Zhang Jin-San , Tahamtani Yaser , Shahpasand Koorosh 
Published: July 2020

Abstract
Background: Diabetes mellitus may cause neurodegeneration, but the exact mechanism by which diabetic conditions induce neuronal cell death remains unclear. Tau protein hyperphosphorylation is considered to be a major pathological hallmark of neurodegeneration and can be triggered by diabetes. Various tau-directed kinases, including P38, can be activated upon diabetic stress and induce tau hyperphosphorylation. Despite extensive research efforts and the known importance of tau pathology in neurodegeneration, the exact tau specie(s) and kinases driving neurodegeneration in diabetes mellitus have not been clearly elucidated. Methods: We herein employed protein expression data analysis as well as immunofluorescence and immunoblotting techniques to determine the exact molecular mechanism of tau pathology triggered by diabetes in both in vitro and in vivo systems.Results: We found that P38, a major tau kinase, was increased in Glutamatergic & GABAergic neuron subtypes under diabetic conditions. This rendered them more responsive to oxidative stress caused by diabetes. We observed that oxidative stress activated P38, which in turn directly and indirectly drove tau pathology in the brainstem (enriched by Glutamatergic & GABAergic neurons), which gradually spread to neighboring brain areas. Notably, P38 inhibition suppressed tau pathogenicity and neurodegeneration in diabetic mouse models. Conclusion: The data establish P38 as a central mediator of diabetes mellitus induced tau pathology. Furthermore, the inhibition of P38 at early stages of diabetes-induced stress can inhibit tau pathology. Our findings provide mechanistic insight on the consequences of this metabolic disorder on the nervous system.
Effect of sham feeding on postoperative ileus
Authors: Ozgur Ilker , Karip Bora , Keskin Metin , Iscan Ahmet Yalin , Balik Emre 
Published: July 2020

Abstract
Background: To evaluate the effects of different sham feeding methods on postoperative ileus after low anterior resection and diverting ileostomy for rectal cancer.Methods: 72 patients who underwent low anterior resection with a diverting ileostomy were randomized into 4 groups as: control (n = 16), ice cream (n = 18), gum (n = 17) and nicotine gum (n = 17). Four patients were excluded due to a lack of data. Patients’ demographics, constipation scores, neoadjuvant treatment, amount of perioperative bleeding, fluid administration, drain placement, time of intestinal movement, ileostomy discharge, and return of appetite were compared.Results: Patients’ demographics, constipation scores, neoadjuvant treatment existence, amount of perioperative bleeding, fluid administration, drain placement were similar between groups (p > 0,05). The first sense of intestinal movement was shorter in the nicotine group than control and gum groups (p=0,004 and 0,046, respectively). The average time to first ileostomy discharge and first appetite was shortest in the nicotine gum group. Diverting ileostomy discharge time was significantly shorter in the nicotine gum group than the control group (p=0,011). Return of appetite time was shorter in the nicotine gum group when compared to the gum group (p=0.036).Conclusions: Nicotine gum chewing is an effective method to resolve postoperative ileus after rectal surgery. Other methods such as ice-cream feeding and gum chewing showed no benefit compared to control.
Is a further reduction of radiation exposure in scoliosis monitoring achievable using flat detector and pulsed fluoroscopy technology? - A feasibility study on human specimen
Authors: Walter Christian , Schaefer Juergen F. , Tsiflikas Ilias 
Published: July 2020

Abstract
Background: In the case of scoliosis therapy, frequent radiological monitoring of the spine is necessary. However, x-ray requires high radiation doses; therefore digital pulsed fluoroscopy with flat detector technique can be used alternatively. The latest developments in this technology lead to further dose reduction with an improved image quality. To evaluate the new system, we asked if there is a difference in dose area product (DAP) concerning the opening area (OA) and image quality settings (IQS). Further we wanted to investigate the inter-observer reliability using an established scoring system and correlate the DAP with the point value. Methods Therefore, we examined 4 cadaver spines (T1 to sacrum) with the flat detector technique using digital pulsed fluoroscopy and simulated the abdominal soft tissues with water bags. The images were merged calculating whole spine images from several digital single images and evaluated by 3 different investigators (spine surgeon, experienced pediatric radiologist, assistant physician) using an established scoring system. For comparison and validation of our model, we used digital radiography images of the cadaver spines. Results The values for the DAP increased from the small OA (33%; 0.56 µGy·m²) to the maximum OA (100%; 0.82 µGy·m²) by 45% (p = .003) and from low IQS (0.57 µGy·m²) to high IQS (0.84 µGy·m²) by 48% (p = .028). The inter-observer reliability was strong (3 vs. 1: ρ = .818; 3 vs. 2: ρ = .742; 2 vs. 1: ρ = .586; p <.001), but there was no correlation between DAP and point value (ρ = -.053, p = .588). Despite the low DAP, the setting 33% OA achieved the best point values, therefore this setting is preferred. Conclusions Using a digital fluoroscopy system allows a significant reduction of radiation exposure for whole spine images by a factor of 7.5 (3.88 µGy·m² to 0.5 µGy·m²) compared to slot-scanning x-ray (EOS).
Measurement and calibration of the nucleus position and its cross-sectional area ratio to increase the accuracy of finite element analysis
Authors: Li Jingchi , Xi Zhipeng , Zhang Xiaoyu , Zhang Ke , Sun Shenglu , Fang Xiaoyang , Xie Lin , Liu Yang 
Published: July 2020

Abstract
Backgrounds: As a widely used biomechanical research method, finite element analysis (FEA) is an important tool for investigating the pathogenesis of disc degenerative diseases and optimizing spine surgical methods. However, the definitions of the relative nucleus position and its cross-sectional area ratio do not conform to a uniform standard, thus affecting the accuracy (ACC) of the FEA.Objectives: This study aimed to determine a precise definition of the relative nucleus position and its cross-sectional area ratio to increase the ACC of the following FEA studies.Methods: The lumbar relative nucleus position and its cross-sectional area ratio were measured from magnetic resonance imaging data and then calibrated and validated via FEA. Imaging data from patients without disc degeneration were used. The L4-L5 nucleus and disc cross-sectional areas and the distances between the edges of the annulus and nucleus were measured; the ratios between these values were calculated as P1 and P2, respectively. The FEA model was constructed using these measured values, and the relative nucleus position was calibrated by estimating the differences in the range of motion (ROM) between the model, wherein the ligaments, facet joints and nucleus were suppressed, and that of an in vitro study. Then, the ACC was re-estimated in the model with all non-bony structures by comparing the ROM, the intradiscal pressure (IDP), the facet contact force (FCF) and the disc compression (DC) under different sizes and directions of moments magnitudes to validate the measured and calibrated indicators.Results: The interobserver homogeneity was acceptable, and the measured P1 and P2 values were 1.22 and 38%, respectively. Furthermore, an ACC of up to 99% was attained for the model under flexion–extension conditions when the calibrated P1 value (1.62) was used, with a model validation of greater than 90% attained under almost all of the loading conditions considering the different indicators and moment magnitudes.Conclusions: The measured and calibrated relative nucleus position and its cross-sectional area ratio increase the ACC of the FEA model and can therefore be used in subsequent studies.
The comparative efficacies of intravenous administration and intra-articular injection of tranexamic acid during anterior cruciate ligament reconstruction for reducing postoperative hemarthrosis
Authors: Ma Rui , Wu Mengjun , Li Yongwei , Wang Jialin , Wang Wei , Yang Pei , Wang Kunzheng 
Published: July 2020

Abstract
Background

Hemarthrosis after anterior cruciate ligament (ACL) reconstruction can create many adverse joint effects. Tranexamic acid (TXA) can be used to minimize hemarthrosis and associated pain after ACL reconstruction. We aimed to compare the efficacies of intravenous (IV) administration and intra-articular (IA) injection of TXA during ACL reconstruction for reducing postoperative hemarthrosis.
Methods

A total of 120 patients who underwent arthroscopic ACL reconstruction were included in this prospective and randomized study. All patients were randomized into three groups: IV group, IA group and placebo group. Patients in the IV group received intravenously administered TXA (15 mg/kg in 100 mL of saline solution) 10 minutes before tourniquet release; patients in the IA group received intra-articular TXA (15 mg/kg in 100 mL of saline solution) injected via the drainage tube; and patients in the placebo group received an equivalent volume of normal saline administered into the knee joint cavity and intravenously. Drainage tubes were removed 24 hours after surgery, and all enrolled patients experienced a 4-week follow-up period. The drain output volume, visual analogue scale (VAS) score, patellar circumference, hemarthrosis grade and Lysholm score of all patients were recorded.
Results

Both the IV group and the IA group had significantly lower drain output volumes at day 1, lower VAS scores at weeks 1 and 2, smaller patellar circumferences at weeks 1 and 2, and lower hemarthrosis grades at weeks 1 and 2 than the placebo group. There were no significant differences in drain output volume, VAS score, patellar circumference or hemarthrosis grade between the IV group and the IA group at any time point. No obvious differences in Lysholm score were observed between any pair of groups at week 4. Neither infection nor deep vein thrombosis occurred in any group.
Conclusion

Both intravenous administration and intra-articular injection can reduce intra-articular hemarthrosis, joint pain and swelling. No significant difference in the efficacies of reducing hemarthrosis, joint pain and swelling was found between intravenous administration and intra-articular injection.
Trial registration:

The study was registered by the Chinese Clinical Trial Registry (ChiCTR-INR-17012217, 1 August 2017)
Prognostic value of bedside lung ultrasound-score in patients with COVID-19
Authors: Ji Li , Cao Chunyan , Gao Ying , Zhang Wen , Xie Yuji , Duan Yilian , Kong Shuangshuang , You Manjie , Ma Rong , Jiang Lili , Liu Jie , Sun Zhenxing , Zhang Ziming , Wang Jing , Yang Yali , Lv Qing , Zhang Li , Zhang Jinxiang , Li Yuman , Xie Mingxing 
Published: July 2020

Abstract
BackgroundBedside lung ultrasound (LUS) has emerged as a useful and non-invasive tool to detect lung involvement and monitor changes in patients with coronavirus disease 2019(COVID-19). While the clinical significance of LUS-score in patients with COVID-19 remains unknown. We aimed to investigate the prognostic value of LUS-score in patients with COVID-19.MethodsLUS protocol consisted of 12 scanning zones and was performed in 280 consecutive patients with COVID-19. LUS-score based on B-lines, pleural line abnormalities and lung consolidation was evaluated. The primary outcome was a combination of severe acute respiratory distress syndrome (ARDS), and mortality.ResultsCompared with patients in the lowest LUS-score group, those in the highest LUS-score group were more likely to have a lower lymphocyte%, higher levels of D-dimer, C-reactive protein, hypersensitive troponin I and creatine kinase muscle-brain, more invasive mechanical ventilation therapy, higher incidence of ARDS, and higher mortality. After a median follow-up of 14 days, 37 patients progressed to the poor outcome. Compared with event-free survivors, patients with adverse event presented higher rate of bilateral involved, more involved zones and B-lines, pleural lines abnormalities and consolidation, and higher LUS-score. The Cox models adding LUS-score as a continuous variable (hazard ratio [HR]: 1.05, 95% confidence intervals [CI]: 1.02~1.08; P < 0.001; Akaike Information Criterion [AIC] =272; C-index = 0.903) or as a categorical variable (HR: 10.76, 95% CI: 2.75~42.05; P = 0.001; AIC =272; C-index = 0.902) were found to predict poor outcome more accurately than the basic model (AIC =286; C-index = 0.866). LUS-score cutoff >12 would predict adverse events with specificity and sensitivity of 90.5% and 91.9%, respectively.ConclusionsLUS-score is a powerful predictor of adverse events in patients with COVID-19, and is important for risk stratification in COVID-19 patients.
Effectiveness Of The Quadrivalent HPV Vaccine Against Anal ≥HSILs In A Spanish Population Of HIV+ MSM Aged &gt;26 Years
Authors: Hidalgo-Tenorio Carmen , Ramirez-Taboada Jessica , Omar-Mohamed Mohamed , Sampedro Antonio , Lopez-Ruz Miguel Angel , Hidalgo Javier Lopez , Pasquau Juan 
Published: July 2020

Abstract
Background: Anal squamous cell carcinoma is the most frequent virus-related non-AIDS-defining neoplasia among HIV-infected individuals, especially MSM. The objectives of this study were: to analyze the effectiveness of the quadrivalent HPV (qHPV) vaccine to prevent anal ≥ high-grade squamous intraepithelial lesions (≥HSILs), external ano-genital lesions (EAGLs), and infection by qHPV vaccine genotypes in HIV+ MSM; and to study the immunogenicity of the vaccine and risk factors for ≥HSILsMethods: This study is nested within a randomized, double-blind, placebo-controlled trial of the qHPV vaccine, which enrolled participants between May 2012 and May 2014, with a 48-month follow-up. Vaccine or placebo was administered at 0, 2, and 6 months, and vaccine antibody titers were evaluated at 7, 12, 24, 36, and 48 months. Data were gathered at 12, 24, 36, and 48 months on sexual habits, CD4/CD8 cell/counts, HIV viral load, and the results of cytology (Thin Prep® Pap Test), HPV PCR genotyping (Linear Array HPV Genotyping Test), and high-resolution anoscopy (Zeiss 150 fc© colposcope).Results: The study included 129 patients, 66 (51.2%) in vaccine arm and 63 (48.4%) in placebo arm. The vaccine and placebo groups did not differ in ≥ HSILs (14.1 vs. 13.1%, respectively, p=0.98) or EAGL (14.3 vs. 13.6%, p=0.98) rates during follow-up; however, a protective effect against HPV 6 was observed during the first year of follow-up in the vaccine versus placebo group (7.5% vs. 23.4%; p=0.047). A between-arm difference (p=0.0001) in antibody formation was observed at 7 months (76.9% in vaccine arm vs. 30.2% in placebo arm), 12 months (68.1% vs. 26.5%), 24 months (75% vs. 32.5%), 36 months (90% vs. 24.4%), and 48 months (87.2% vs. 30%). Finally, receipt of the full vaccine 6 months earlier was a risk factor for ≥ HSIL (82.4% vs. 17.6%, OR 0.869 [95% CI 0.825-0.917]).Conclusions: Vaccine and placebo arms did not significantly differ in ≥HSIL or EAGL rates or in protection against infection by HPV genotype vaccine except for HPV6 at 12 months after the first dose. A long-lasting immune response was observed in almost all of the vaccinated men. The main protective factor against ≥ HSIL was to have completed the vaccination regimen more than 6 months earlier.Clinical trial registration: ISRCTN14732216 (http://www.isrctn.com/ISRCTN14732216)
Fidelity of primary care nurses’ delivery of a behaviour change intervention to enhance physical activity in chronic patients
Authors: Westland Heleen , Trappenburg Jaap CA , Schuurmans Marieke J , Zonneveld Michelle , Schröder Carin D 
Published: July 2020

Abstract
Background

The effectiveness of a nurse-led intervention to enhance physical activity, the Activate intervention, was evaluated in primary care patients at risk for cardiovascular diseases in a cluster-randomised controlled trial (n = 195 patients, 31 general practices). To contribute to an accurate interpretation of the trial results, understanding of how the intervention works and enabling reproducibility, this study aimed to evaluate the fidelity of delivery of the Activate intervention by assessing: 1. self-reported fidelity of delivery; 2. observed fidelity of delivery; 3. quality of nurses’ delivery of the Activate intervention and 4. nurses’ beliefs about their capability, motivation, confidence and effectiveness towards delivering the Activate intervention, including behaviour change techniques.
Methods

An observational study was conducted. Nurses’ self-reported fidelity was evaluated using checklists (n = 279), and the observed fidelity and quality of delivery were examined using audio-recordings of intervention consultations (n = 44). Nurses’ beliefs towards delivering the intervention were assessed using questionnaires (n = 72).
Results

The self-reported fidelity was 87.6% and observed fidelity was 85.6%, representing high fidelity. The observed fidelity of applied behaviour change techniques was moderate (76.8%). The observed quality of delivery was sufficient and varied among nurses (mean 2.9; SD 4.4; range 0–4). Nurses’ beliefs about their capability, motivation, confidence and effectiveness towards delivering the intervention increased during the trial.
Conclusions

Nurses delivered most intervention components as intended with sufficient quality. Nurses believed they were capable, motivated and confident to deliver the intervention. They believed the intervention was effective to increase patients’ physical activity level. Despite the high fidelity and moderate fidelity of applied behaviour change techniques, the varying quality of delivery within and across nurses might have diluted the effectiveness of the Activate intervention.
Trial registration:

ClinicalTrials.gov NCT02725203 registered 31 March, 2016, https://clinicaltrials.gov/ct2/show/NCT02725203.
Two updates on adenocarcinoma of gastroesophageal junction from the fifth WHO classification of tumors of the digestive system: alteration of gastroesophageal junction definition and the emphasis on HER2 test.
Authors: Li Yunzhu , Li Jiayu , Li Manji 
Published: July 2020

Abstract
Background: The incidence of gastroesophageal junction (GEJ) adenocarcinoma has increased rapidly but remains controversial over the last decades. There are two crucial updates of the fifth WHO classification including the alteration of GEJ location and the emphasize on human epidermal growth factor receptor 2 (HER2) test.Methods: We retrospectively analyzed the clinicopathological features of 566 patients suffered from gastric adenocarcinoma. We comprehensively compared the clinicopathological features among GEJ and non-GEJ tumors, GEJ and proximal and distal gastric tumors with fourth and fifth edition, respectively. Besides, we discussed the correlation of the HER2 expression with clinicopathological features according to the fifth WHO classification.Results: The results showed that the difference was mainly between GEJ and distal adenocarcinoma in the fourth edition, but some were between proximal and distal adenocarcinoma in the fifth edition. Tumors with longer invasion of the oesophagus were still mainly concentrated in GEJ tumors. The expression of HER2 in GEJ and proximal gastric adenocarcinoma was still higher than that in gastric body and distal site, which was basically consistent with the conclusion of the fourth edition classification.Conclusions: The clinicopathological parameters of the GEJ tumors partly changed with the narrowing scope of the GEJ adenocarcinoma. The proximal gastric tumors rather than GEJ tumors tended to be more invasive. But the GEJ tumors with longer oesophageal invasion required additional management. The HER2-expression of GEJ adenocarcinoma is still higher than that of other gastric sites. The classification of the fifth edition is reasonable and worthy of recommendation.