bluuebunny/crossref_metadata_2025 huggingface dataset:
Adverse effects of nicotine on endometrium receptivity markers: and protective effect of caffeic acid phenyl ester
Authors: NAMDARI AMIN , MOHAMMADIAN FARIDEH , KHAJEH Fatemeh , KAVOUSIPOUR SOUDABEH , miladpour behnoosh
Published: July 2020

Background

nicotine adversely affects the female reproductive system and changes the methylation pattern of some genes in the placenta. In contrast, caffeic acid phenylethyl ester) CAPE (, as a potent antioxidant, has protective effects against the harmful effects of oxygen free radical molecules, methotrexate, and pesticides on the reproductive system. To find the effect of nicotine on the endometrium, we investigated three markers of endometrium receptivity including fibroblast growth factor 2, vascular endothelial growth factors A, and C-X-C motif chemokine ligand 12 and also changes in methylation levels of CXCL-12 gene promoter. In addition, we evaluated the protective effect of CAPE against nicotine.
Methods

the appropriate treatment dose was selected based on the literature, the endometrial stromal cells were divided into 4 groups, including control, treated with nicotine, CAPE, and nicotine followed by CAPE. Finally, the quantitative polymerase chain reaction and Methylation-Specific PCR were carried out.
Results

The results showed that treatment of endometrial stromal cells with nicotine (10− 6 µM) for 24 h significantly reduced expression of CXCL-12, FGF, and VEGFA genes. However, a decrease in CXCL-12 expression was not associated with increased methylation levels in the studied promoter region. In contrast, endometrial stromal cells treated with CAPE (4 µg/ml) for 24 h adverse significantly nicotine-induced reduction of CXCL-12, FGF, and VEGFA genes expression.
Conclusion

Exposure to nicotine has negative effects on uterine receptivity, implantation, and fertility, via reducing the expression of VEGFA, CXCL-12, and FGF2 genes. In contrast, CAPE has a protective effects and improves these genes expression.
Pregnancy Outcomes of Patients with Takayasu’s Arteritis -- A Retrospective Clinical Analysis
Authors: Liu Simiao , Liu Juntao , Gao Jinsong , Yingna Song
Published: July 2020

Background: Takayasu’s arteritis (TA) often occurs in women of reproductive age and affect gestational outcomes. However, TA is a rare disease, and the number of reports addressing the effect of TA on pregnancy in Chinese women is small. We aimed to analyse the influence of TA on gestational outcomes and explore related factors.Methods: We studied the medical records of 28 pregnancies among 27 women with TA. Patient characteristics, TA activity and classification, treatment, laboratory test results, delivery mode, obstetrical complications, medical complications during pregnancy and pregnancy outcomes were evaluated and compared.Results: The mean age of all patients at delivery was 30.28±4.54 years. The live birth rate was 96.4%, and the gestational age at delivery was 36.5±2.78 weeks. Gestational complications included preeclampsia (22.2%), foetal distress (14.8%), intrauterine growth restriction (22.2%) and premature delivery (37.0%). Medical complications during pregnancy included heart failure (11.1%), pulmonary hypertension (3.7%), and Sjogren syndrome (3.7%). The TA status in ten pregnancies was active, and compared with those of pregnancies with inactive TA, the rates of obstetrical complications and medical complications were higher (P=0.014 and P=0.047, respectively). The rate of seeking standard treatment and follow-up was lower among patients with active disease (P=0.021). Among all patients, the Kerr scores and severity scores during pregnancy were similar to those before pregnancy (P=0.664 and P=0.134, respectively).Conclusions: Active TA may increase the risk of pregnancy complications and medical complications. When treated in a timely and appropriate manner, the gestational outcome is good.
Amlexanox Enhances Temozolomide-Induced Anti-Tumor Effects In Human Glioblastoma Cells By Inhibiting Ikbke And The Akt-mtor Signaling Pathway
Authors: Xiong Jinbiao , Guo Gaochao , Guo Lianmei , Wang Zengguang , Chen Zhijuan , Nan Yang , Cao Yiyao , Li Ruilong , Yang Xuejun , Dong Jun , Jin Xun , Yang Weidong , Huang Qiang
Published: July 2020

Background: Temozolomide (TMZ), as the first-line chemotherapeutic agent for the treatment of glioblastoma multiforme (GBM), often fails to improve the prognosis of GBM patients due to the quick development of resistance. The need for more effective management of GBM is urgent. The aim of this study is to evaluate the efficacy of combined therapy with TMZ and amlexanox, a selective inhibitor of inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKBKE), for GBM.Methods: in vitro, cell viability assay, apoptosis analysis, western blot, migration and invasion assay were used. In vivo, intracranial tumor models were constructed and the immunohistochemistry were used. Results: We found that combined treatment resulted in significant induction of cellular apoptosis and the inhibition of cell viability, migration and invasion in primary glioma cell and in the human glioma cell line, U87 MG. TMZ enhanced expression of phosphoration of adenosine 5‘-monophosphate-activated protein kinase (p-AMPK) and amlexanox led to reduction of IKBKE, with no impact on p-AMPK. Furthermore, we demonstrated that, compared to other groups treated with each component alone, TMZ combined with amlexanox effectively inhibited phosphorylation of protein kinase B (AKT) and mammalian target of rapamycin (mTOR). In addition, the combination treatment also clearly reduced in vivo tumor volume and prolonged median survival time in the xenograft mouse model. Conclusion: These results suggest that amlexanox sensitized primary glioma cell and U87 MG cell to TMZ at least partially though the suppression of IKBKE activation and the attenuation of AKT activation. Overall, combined treatment with TMZ and amlexanox may provide a promising possibility for improving the prognosis of glioblastoma patients in clinical practice.
miR-129-5p Inhibits Clear Cell Renal Cell Carcinoma Cell Proliferation, Migration and Invasion by Targeting SPN
Authors: Gao Bin , Wang Lijuan , Zhang Yubo , Zhang Na , Han Miaomiao , Liu Huancai , Sun Dongli , Wu Xiaotang , Xiao Xiaolong , Liu Yifei
Published: July 2020

Objective: Our study aims to investigate the mechanism of the miR-129-5p/SPN axis in clear cell renal cell carcinoma (ccRCC), providing a novel direction for the targeted therapy of ccRCC. Methods: Bioinformatics methods were implemented to find the differentially expressed genes (DEGs) associated with ccRCC from TCGA database. qRT-PCR was performed to detect miR-129-5p and SPN mRNA expression, while western bot was carried out for the detection of protein expression of SPN. Bioinformatics analysis was used to predict the binding sites of miR-129-5p on SPN 3’UTR, while dual-luciferase assay was conducted to verify their binding relationship. CCK-8 assay, colony formation assay, wound healing assay and Transwell assay were employed to measure ccRCC cell proliferative ability, cell formation ability, cell migratory and invasive abilities.Results: miR-129-5p exhibited a significantly down-regulated expression level in ccRCC, while SPN showed a remarkably up-regulated expression level. Overexpressed miR-129-5p inhibited ccRCC cell proliferative, invasive and migratory capacities. Dual-luciferase assay confirmed that there was a binding relationship between miR-129-5p and SPN. Additionally, overexpressing miR-129-5p markedly reduced SPN expression in tumor cells, and attenuated the promoting effect of SPN on cell proliferation, migration and invasion.Conclusion: Our study proves the regulatory effect of the miR-129-5p/SPN axis in ccRCC, and provides a novel potential target for precise treatment of patients with ccRCC.
Association between Sense of Loneliness, Social support, Quality of Life and Multimorbidity in Elderly Patients
Authors: Vespa Anna , Spatuzzi Roberta , Gattafoni Pisana , Fabbietti Paolo , Giulietti Maria Velia
Published: July 2020

Multi-morbidity has been associated with adverse health outcomes, such as reduced physical function, poor quality-of-life(QoL), poor self-rated health. The adverse impact of multi-morbidity on other health domains is further exacerbated by other factors. In this study the association between quality of life, social support, sense of loneliness and sex, age in elderly patients affected by two or more chronic diseases (multi- morbidity) was evaluated. Patients n. 216 affected by tumors hypertension, cardiovascolar diseases, ictus, diabetes, all self-sufficient and living with family members. Tests: MMSE-Mini-Mental-State-Examination; ADL-Activities of Daily Living; Social-Schedule: demographic variables; Loneliness Scale -de Jong Gierveld; Quality-of-Life - FACT-G; WHOQOL-BRIEF social relationships. Statistical analysis: Multivariate Regression Analysis. The patients with three or more diseases have worse dimensions of QoL Physical-well-being(p = .003), Social well-being (p = .003), Emotional-well-being(p = .012), Functional-well-being(p < .001), than those with two. Multiple linear regression. QoL: PWB, SWB, EWB,FWB as dependent variables.In the presence of multi-morbidity with an increase in the patient's age PWB (B = − .131, p = .014), SWB (B = − .170, p = .009) EWB (B = − .457, p < .000), FWB (B=-.139,p = .013), decreases by an average of 0.1, and as the sense of solitude increases PWB (B=-.425, p < .000), SWB(B=-.464,p < .000),EWB(B=-.457,p < .000),FWB(B=-468,p < .000) decrease by 0.4. The sense of loneliness and increasing age are associated with bad quality-of life in self-sufficient elderly patients with multi-morbidity. Demonstrating that loneliness, also in presence of interpersonal relations, predicted worse quality of life helps identify people most at risk for common symptoms and lays the groundwork for research about diagnosis and treatment.
Optimization of Energy Consumption and Analysis of the Emission of Greenhouse Gases in the Production of Rice (Case Study of Mazandaran Province)”
Authors: Vahedi adel , yousefi zahra
Published: July 2020

The present study has been done with the aim of investigating the energy consumption pattern, the economic analysis of production and assessing the greenhouse gas emissions (GHG) resulting from the production of rice in the Mazandaran province. The input and output energies were calculated and energy indices were determined. The efficiency of the rice farms and the optimization of energy consumption were estimated by using Data Envelopment Analysis (DEA) method and the amount of greenhouse gas emissions was determined after improving the consumption of inputs. According to the results, the total energies of consumed inputs and outputs for the production of paddy were calculated to be 91,061.5 and 100,967.95 MJ ha-1, respectively. The energy input of diesel fuel, machinery and chemical fertilizers were determined to be 41.27%, 19.63% and 19.58% out of the total energy inputs, representing the most highly consumed energy inputs in the production of paddy.
Prevalence of malnutrition in COVID-19 inpatients: the Nutricov study
Authors: Rouget Antoine , Vardon-Bounes Fanny , Lorber Pierre , Vavasseur Adrien , Marion Olivier , Marcheix Bertrand , Lairez Olivier , Balardy Laurent , Fourcade Olivier , Conil Jean-Marie , Minville Vincent
Published: July 2020

Background: Recent ESPEN guidelines highlighted the interest of prevention, diagnosis and treatment of malnutrition in the management of coronavirus disease 19 (COVID-19) patients. The aim of our study was to evaluate the prevalence of malnutrition in patients hospitalized for COVID-19. Methods: Prospective observational cohort study on COVID-19 inpatients admitted to a tertiary hospital. Malnutrition was diagnosed according to the Global Leadership Initiative on Malnutrition two-step approach. Patients were divided in two groups according to the diagnosis of malnutrition. Covariate selection for the multivariate analysis was based on P value <0.2 in univariate analysis, with a logistic regression model and a backward elimination procedure. A partitioning of the population was represented using a Classification and Regression Tree analysis.Results: 80 patients were prospectively enrolled in the study. Thirty patients (37.5%) had criteria for malnutrition. The need for ICU admission (n=46, 57.5%) was similar in the two groups. Three patients who died (3.75%) were malnourished. Multivariate analysis exhibited that low BMI (OR=0.83, 95% CI [0.73-0.96], p=0.0083), dyslipidemia (OR=29.45, 95% CI [3.12-277.73], p=0.0031), oral intakes reduction <50% (OR=3.169, 95% CI [1.04-9.64], p=0.0422) and GFR (CKD-EPI) at admission (OR=0.979, 95% CI [0.96-0.998], p=0.0297) were associated with the occurrence of malnutrition in COVID-19 inpatients.Conclusions: We demonstrate the existence of a high prevalence of malnutrition (37.5%) in a general cohort of COVID-19 inpatients according to GLIM criteria. Considering this high prevalence, nutritional support in COVID-19 care seems an essential element. Trial registration: Ethical Committee No 2020-A01237-32)(RC31/20/0165 NUTRI-COV
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

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

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

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

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

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

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

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 >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

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

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

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.
LINC00886, as a Biomarker Indicative of Thyroid Cancer Dedifferentiation, Negatively Regulates the Malignancy in Anaplastic Thyroid Cancer
Authors: Ma Ben , Luo Yi , Xu Weibo , Han Litao , Liu Wanlin , Jiang Hongyi , Wang Xiao , Wen Shishuai , Liao Tian , Wei Wenjun , Ji Qinghai , Wang Yu
Published: July 2020

Backgroud: Anaplastic thyroid cancer (ATC) is the most aggressive type of thyroid cancer. This study aimed to identify a long non-cdoing RNA (lncRNA) as a specific biomarker associated with ATC, and further investigated its biological function and molecular mechanism underlying regulation of malignancy in ATC.Methods: We searched for lncRNAs associated with dedifferentiation and screened out specific lncRNAs significantly deregulated in ATC by using transcriptome data of dedifferentiation cancers from Fudan University Shanghai Cancer Center (FUSCC) and the Gene Expression Omnibus (GEO) database. The above lncRNAs were analyzed to identify a useful biomarker in thyroid cancer patients from the FUSCC, GEO and The Cancer Genome Atlas, which was further investigated for its functional roles and molecular mechanism in ATC in vitro.Results: The clinicopathological association analyses revealed that LINC00886 was correlated with thyroid cancer dedifferentiation and significantly suppressed in ATC. In vitro, LINC00886 was confirmed to negatively regulate cell proliferation, colony formation and cell migration and invasion of ATC. LINC00886 physically interacted with protein kinase R (PKR) and affected its stability through ubiquitin/proteasome-dependent degradation pathway in the ATC cell. Decreased PKR caused by LINC00886 downregulation, enhanced the activity of eukaryotic initiation factor 2α (eIF2α) via reducing the phosphorylation of eIF2α and thus promoted protein synthesis to maintain the ATC malignancy. Conclusions: Our findings identify LINC00886 as a novel biomarker of thyroid cancer and suggest that the LINC00886/PKR/eIF2α signaling axis is a potential therapeutic target in ATC.
Knowledge and attitudes among medical students toward the clinical usage of e-cigarettes: A cross-sectional study in a university hospital in Saudi Arabia
Authors: Alzahrani Sami , Almutairi Ahmed Mabruk , Alghamdi Ali Ahmed , Aljuhani Abdullah Abdulwahab , ALbalawi Abdulrahman Hamed
Published: July 2020

Background

To assess knowledge and attitudes about e-smoking among undergraduate medical students, specifically focused on favorable view of therapeutic ecigarette use for smoking cessation or harm reduction.
Methods

This cross-sectional study included medical students at King Abdulaziz University, Saudi Arabia. A six-item subscale was used to explore knowledge and attitudes about the therapeutic use of e-cigarettes, measuring participants’ likelihood of favoring such use. A four-item questionnaire measured confidence and importance of being educated about smoking and e-smoking, in addition to sources of knowledge about e-cigarettes.
Results

A total of 399 students participated. Smoking history included current smokers (19.8%) and ex-smokers (6.5%), while e-cigarettes were tried by 36.6% and are currently used by 11.5%. A minority (13.5%) believed that e-cigarettes are FDA-approved for smoking cessation, while approximately one-third believed e-smoking lowers cancer risks (31.1%) and could help with smoking cessation (31.1%). Further, 35.9% agreed or strongly agreed that e-cigarettes are better for patients than tobacco products, and 17.5% were likely to recommend e-smoking to their patients for smoking cessation. Reliability of the six-item scale showed Cronbach’s alpha = 0.676, which was enhanced to 0.746 after deletion of one item about addictiveness. Using the corrected five-item scale, 23.6% of the participants would favor therapeutic use of e-cigarettes.
Conclusion

We observed several misconceptions about addictiveness and inadequate awareness about e-cigarettes’ harmful effects, leading to non-scientific opinions about its therapeutic use for harm reduction or in smoking cessation. Academic programs around this topic should be updated in accordance with majority expert recommendations.
Multi-Locational Evaluation of Medium-Staple Cotton Genotypes for Seed-Cotton Yield under the Middleveld Agro-Ecological Zone of Zimbabwe.
Authors: Mare Marco , Chapepa Blessing , Mubvekeri Washington
Published: July 2020

Background The Zimbabwe national cotton breeding programme has the mandate to develop superior cotton (Gossypium Hirsutum) varieties with good field performance and high fibre properties. Cotton productivity in Zimbabwe has remained very low, with national average seed cotton yield record of 650 kg/ha (AMA Report, 2019) compared to the potential 2000 kg/ha. Though this is a result of many biotic and abiotic factors, field experiments laid in a Randomized Complete Block Design were conducted on ten genotypes (seven test genotypes and three check varieties) from 2012 to 2019 across 13 diverse locations in Zimbabwe to evaluate cotton yield performance, stability and adaptability by Analysis of Variance (ANOVA) and Genotype and Genotype by Environment Interaction (GGE) Biplot methods.Results The Analysis of Variance indicated significant (P < .001) effects of Genotype (G), Environment (E) and their Interaction (GE). The highest percentage of variation was explained by E/G/GE (60.34%) while G/E + GE together explained the rest of the variation (< 40%). Joint effects of G and GE were partitioned using the GGE biplot analysis explaining total of 59.08% (PC1 = 36.96% and PC2 = 22.12%) of the GGE sum of squares. The biplot analysis revealed that candidates 917-05-7, TN96-05-9, 912-05-1 and GN 96 (b)-05-8 were the ideal and stable genotypes. The candidate variety 917-05-7 significantly (P < .001) showed superior yield performance over checks CRI-MS1 and CRI-MS2 recording 5% and 5.5% yield increase respectively. Candidate 917-05-7 recorded a higher earliness index (78.11%) over checks CRI-MS1 and CRI-MS2 (77 and 76% respectively) thus indicating potential attributes for good cotton production with more pick-able bolls earlier than the current commercial varieties.Conclusion Candidate 917-05-7 has been identified as the ideal genotype in terms of high yielding potential, and stability hence recommended for commercial release and use as breeding parent for future breeding programs.
Adverse Impact of Climate Change on Mambioko Community Dependent Forest and Local Perception on Vulnerabilities and Responses-Centre Region of Cameroon
Authors: Nghogekeh Tieminie Robinson , Eugene Chia Loh , Mandiefe Piabuo Serge , Mayiadieh Nghobuoche Frankline
Published: July 2020

This study was undertaken to identify and assess climate change vulnerabilities and impacts on the livelihoods of forest dependent communities in Mambioko community forest in the Centre Region of Cameroon. Primary data was collected from 120 households; key informants, focus group discussions and was supplemented with secondary data from desk review of relevant literature. Forest resources were generally perceived by forest dependent communities as declining. Climate Change was observed to have impacted on their major livelihood’s activities/resources of forest dependent communities by way of prolonged drought, erratic rainfall pattern, and variability in rainfall intensity. These trends have consequently led to drying of rivers and streams, shift in cropping season, reduced yield, frequent and extreme warm conditions among others. Use of irrigation, crop diversification, household income diversification through alternative livelihood activities and increase in size of cultivated farms are among the different measures being adopted by communities to cope up with the effects of climate change. Using socio-economic indicators, the bimodal agro ecological zone is vulnerable to climate change impact. The zone has relatively higher dependency on climate sensitive livelihood activities/resources, limited diversified income sources and moderate access to climate change information. In an attempt to help forest dependent communities cope up with climate change impacts, fundamental issues such as non-climate dependent alternative livelihood activities, access to climate, sustainable agricultural practices and sustainable forest resources management are key areas for various multidisciplinary intervention.
The Sulfatide/Myb/MEF2C Axis Controls the Malignant Behaviors of Hepatocellular Carcinoma Cells by Modulating lncAY Expression
Authors: Chen Mei Hua , Qi Bing , Cai Qian Qian , Sun Jia Wen , Fu Li Sheng , Kang Chun Lan , Ma Ming Zhe , Wu Xing Zhong
Published: July 2020

The authors have requested that this preprint be removed from Research Square.
Evaluation of Implementation and Effectiveness of a Pilot Multi-Domain Program for Older Adults at Risk of Cognitive Impairment at Neighborhood Senior Centres – A Randomized Controlled Trial
Authors: Ng Pei Ern Mary , Nicholas Sean Olivia , Wee Shiou-Liang , Yau Teng Yan , Chan Alvin , Chng Isaiah , Yap Lin Kiat Philip , Ng Tze Pin
Published: July 2020

Background The efficacy of multi-domain interventions for dementia prevention has been investigated in a few large randomized controlled trials (RCT). To link research to community action, we evaluated the implementation and effectiveness of a community-based multi-domain program for older adults at risk of cognitive impairment. Methods Three enterprises implemented a 24-week, bi-weekly, multi-domain program for older adults at risk of cognitive impairment through neighborhood senior centres (SCs). The program comprised a combination of dual-task group physical exercise, pen-and-paper cognitive games, computerised cognitive training, and mobile application-based personalized nutritional guidance. An effectiveness-implementation hybrid design using a RCT design and informed by the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework was adopted to evaluate the program. Cognition and quality of life were assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and EuroQol EQ-5D-5L (EQ-5D) respectively, at baseline and 24-weeks. Blood lipid panel and physical assessments were also conducted. Questionnaires on implementation outcomes were administered at the participants-, provider- and community-levels to participants, implementers, and SC managers. Program schedules and attendance were obtained from implementers and the research team conducted unannounced, random and non-intrusive observations of the program. Results The intervention program reached almost 50% of eligible participants, had an attrition rate of 22%, and was adopted by 8.7% of the SCs approached. The intervention was implemented as intended, except the nutritional component that was re-designed due to participants’ unfamiliarity with the application. There were no between-group differences in cognition, quality of life, and blood lipid panel, though there was a reduction in quality of life in the control group and improved physical function in the intervention group at 24-weeks. Intervention group participants reported improvement in their physical and cognitive functions. The program was well-received by participants and centre managers, who wanted the intervention to continue post-study. Conclusions A six-month multi-domain program for older adults at risk of cognitive impairment can be implemented through neighborhood SCs and elicit improvement in physical but not cognitive performance. Implementation evaluation highlight areas to improve on the uptake of such community-based interventions. Trial registration Trial registration: ClinicalTrials.gov NCT04440969. Registered 22 June 2020 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04440969
Characteristics of mandibular third molars that have greater risk to cause pathologies
Authors: Ye Zhouxi , Qian Wenhao , Yang Chi , Wu Yubo , Sun Bing , Li Zhiyao , Ling Feng , Xiang Fei , Zhang Yu , Zhu Minwen , Li Hongquan
Published: July 2020

Background

To evaluate the associations of impaction patterns of mandibular third molars (M3Ms) with pathologies caused by them.
Methods

In this study, 262 patients with 432 impacted M3Ms were included. The pathologies include pericoronitis, mandibular second molar (M2M) caries, and M2M distal periodontal pathology. The impaction patterns of M3Ms and the pathologies were examined, and the M2Ms outcomes after the surgeries were evaluated. χ2 test was used to analyze the data and a P value of < 0.05 was considered statistically significant.
Results

Pericoronitis was the major symptom in all patients, whereas the propensities of M2M distal caries and periodontal pathologies increased in older patients. Soft tissue impacted and vertically angulated teeth were more associated with the pericoronitis (p < 0.05); Mesio-angular impacted teeth in less deep positions had greater risks of M2Ms distal caries (p < 0.05); Mesio-angular and horizontal impacted teeth in relative deep positions were more likely to cause M2Ms distal periodontal pathologies (p < 0.05).
Conclusions

Extractions of soft tissue impacted teeth in vertical angulations should be considered. While removals of mesially and horizontally angulated or bony impacted teeth could be delayed.