bluuebunny/crossref_metadata_2025 huggingface dataset:
The Interplay Between Gray Matter and White Matter Neurodegeneration in Subjective Cognitive Decline
Authors: Cedres Nira , Diaz-Galvan Patricia , Diaz-Flores Lucio , Muehlboeck J-Sebastian , Molina Yaiza , Barroso Jose , Westman Eric , Ferreira Daniel
Published: October 2020

AIMS: To investigate the interplay between gray matter (GM) and white matter (WM) neurodegeneration in subjective cognitive decline (SCD), including thickness across the whole cortical mantle, hippocampal volume, and integrity across the whole WM. METHODS: We included 225 cognitively unimpaired individuals from a community-based cohort, of whom 123 endorsed one or more subjective cognitive complaints. GM neurodegeneration was assessed through measures of cortical thickness across the whole mantle and hippocampal volume. WM neurodegeneration was assessed through measures of mean diffusivity (MD) across the whole WM skeleton. Mediation analysis and multiple linear regression were conducted to investigate the interplay between the measures of GM and WM neurodegeneration.RESULTS: A higher number of complaints was associated with reduced hippocampal volume, cortical thinning in several frontal and temporal areas and the insula, and higher MD across the WM skeleton, with a tendency to spare the occipital lobe. SCD-related cortical thinning and increased MD were associated with each other and jointly contributed to the complaints, but the contribution of cortical thinning to SCD was stronger.CONCLUSIONS: Neurodegeneration processes affecting the GM and WM seem to be associated with each other in SCD and include brain areas other than those typically targeted by Alzheimer’s disease (AD). Our findings suggest that SCD may be a sensitive behavioral marker of heterogeneous brain pathologies in individuals recruited from the community.
A cytokine receptor-masked IL2 prodrug selectively activates tumor-infiltrating lymphocytes for potent antitumor therapy
Authors: Hsu Eric , Cao Xuezhi , Moon Benjamin , Bae joonbeom , Sun Zhichen , Liu Zhida , Fu Yang-Xin
Published: October 2020

Interleukin-2 (IL-2) is an FDA approved treatment for multiple metastatic cancers. However, while IL-2 is a potent activator of CD8 and NK cells, its clinical use is limited by short in vivo half-life, low potency, and severe in vivo toxicity. Current strategies of reducing IL-2 receptor alpha binding and increasing IL-2 receptor beta binding reduce efficacy or increase toxicity. Here, we address these issues by engineering a novel IL-2 prodrug (ProIL2). We mask the activity of a CD8 T cell-preferred IL-2 mutein/Fc fusion protein with IL2 receptor beta linked to a tumor-associated protease substrate. ProIL2 restores activity after cleavage by tumor-associated enzymes, and preferentially activates inside tumors, where it is efficiently cleaved and expands CD8 T cells. This significantly reduces IL-2 associated cytokine storm, body weight loss, and mortality without compromising antitumor efficacy. ProIL2 also overcomes resistance of cancers to immune checkpoint blockade. Lastly, neoadjuvant ProIL2 treatment can effectively eliminate metastatic cancer by inducing an abscopal effect. Taken together, our approach presents an effective tumor targeting therapy with reduced toxicity.
Analysis and Prediction of COVID-19 Outbreak by the Numerical Modelling 
Authors: Mohammed Dilshad Azad , Tawfeeq Hassan Mohammad , Ali Kameran Mohammed , Rostam Hassan Muhammad
Published: October 2020

Pandemic COVID-19 is a contagious disease affecting more than 200 countries, territories and regions. Recently, Iraq is one of the countries that has immensely suffered with this outbreak. The Kurdistan Region of Iraq (KRI) is also prone to the disease. Until now more than 23,000 confirmed cases have been recorded in the region. Since the onset of the COVID-19 in Wuhan, based on epidemiological modelling, researchers have used various models to predict the future of the epidemic and the time of peak, yielding a diverse number in different countries. This study aims to estimate the basic reproductive number (R0) for COVID-19 in KRI, using the standard SIR (Susceptible-Infected-Removed) epidemic model. A system of nonlinear differential equations is formulated and solved numerically by the 4th order Runge-Kutta method. Reproductive numbers R0 have been estimated by this method of fitting the curves between the actual daily data and numerical solution by applying the least square method. For the analysis, data were taken for the duration of 165 days from 1st of March to 12th August in a population of 5.2 million. It has been concluded that R0 is fluctuating during the outbreak with an average of 1.33, predicting that infected cases will reach their maximum value of around 540,000 on 5th of November 2020. Then the spread of the disease will die out since the number of susceptible will decrease to about 3.2 million. While the number of removed individuals will reach approximately to 1.5 million.
Kynurenine analog 3-HAA is a ligand for transcription factor YY1
Authors: Shi Zhaopeng , Gan Guifang , Xu Xiang , Zhang Jieying , Yuan Yuan , Bi Bo , Gao Xianfu , Xu Pengfei , Zeng Wenbin , Li Jixi , Ye Youqiong , Zhou Aiwu , Zhang Naixia , Liu Wen , Lin Shu-hai , Mi Jun
Published: October 2020

Kynurenine, a metabolite of tryptophan, promotes immune tolerance in development and tumor evasion by binding to the aryl hydrocarbon receptor (AHR). However, the IDO inhibitors, blocking kynurenine generation, fail in stage III of clinical trials in several tumors for unknown reasons. Here, we report that 3-hydroxyanthranilic acid (3-HAA) synergizes with IDO inhibitors by dramatically increasing the suppression of IDO inhibitors on HCC xenograft growth. The content of 3-HAA, a catabolite of kynurenine, is lower in tumor cells by downregulating its synthetic enzyme KMO/KYNU and/or upregulating its catalytic enzyme HAAO. Overexpression of KMO suppresses tumor formation and tumor growth by increasing endogenous 3-HAA while adding exogenous 3-HAA also inhibits tumor growth. Moreover, we found that 3-HAA directly binds transcription factor YY1 rather than AHR and increasing the PKCζ phosphorylation of YY1 at the Thr 398 in response to 3-HAA; YY1 phosphorylation at T398 increases the YY1 binding to chromatin. 3-HAA-induced Thr398 phosphorylation of YY1 upregulates the expression of dual-specificity phosphatase 6 (DUSP6), etc. DUSP6 overexpression induces apoptosis of hepatocellular carcinoma (HCC) cells and suppresses the HCC growth in vitro and in vivo. The T398 phosphorylation of YY1 is critical for the 3-HAA-induced apoptosis in tumors. These findings demonstrate that kynurenine analog 3-HAA is a functional metabolite associating YY1 as an endogenous ligand, downregulation of 3-HAA is necessary for the rapid growth of tumor cells, suggesting its promising approach in HCC therapy.
Prognostic Impact of Atherogenic Index of Plasma (AIP) In Type 2 Diabetes Mellitus Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention
Authors: Ma Xiaoteng , Sun Yan , Cheng Yujing , Shen Hua , Gao Fei , Qi Jing , Yang Lixia , Wang Zhijian , Shi Dongmei , Liu Yuyang , Liu Xiaoli , Zhou Yujie
Published: October 2020

Background: The association of atherogenic index of plasma (AIP), an emerging lipid index which can predict risk for cardiovascular (CV) disease, with adverse outcomes in type 2 diabetes mellitus (T2DM) patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) has been undetermined. Therefore, the aim of this study was to investigate whether AIP could independently predict adverse CV events in T2DM patients with ACS undergoing PCI.Methods: This study was a retrospective analysis of a single-centre prospective registry involving 826 consecutive T2DM patients who underwent primary or elective PCI for ACS at our CV center from June 2016 to November 2017. This study eventually included 798 patients (age, 61±10 years, male, 72.7%). AIP was calculated as the base 10 logarithm of the ratio of plasma concentration of triglycerides to high density lipoprotein-cholesterol (HDL-C). All patients were divided into 4 groups based on the AIP quartiles. The primary endpoint was a composite of all-cause death, non-fatal ischemic stroke, non-fatal myocardial infarction (MI), or unplanned repeat revascularization. The key secondary endpoint was a composite of cardiovascular death, non-fatal ischemic stroke, or non-fatal MI.Results: During a median follow-up period of 927 days, 198 patients developed at least one event. An unadjusted Kaplan–Meier analysis showed the incidence of the primary endpoint increased gradually with rising AIP quartiles (log-rank test, P =0.001). A multivariate Cox proportional hazards analysis revealed that compared with the lowest AIP quartile, the top AIP quartile was associated with significantly increased risk for the primary and key secondary endpoints (hazard ratio [HR]: 2.153; 95% confidence interval [CI]: 1.355 to 3.421; P =0.001, and HR: 2.613; 95% CI: 1.024 to 6.666; P =0.044, respectively). Inclusion of AIP quartiles in a baseline prediction model for the primary endpoint increased the Harrell’s C statistic from 0.697 to 0.707. More importantly, addition of AIP quartiles to the above model significantly improved the continuous net reclassification improvement (continuous NRI =19.1%, P <0.001).Conclusions: A higher AIP value on admission was independently and strongly associated with adverse CV events in T2DM patients with ACS undergoing PCI.
Pre-Hospital Critical Care Management of Severe Hypoxemia in Victims of Covid-19: A Case Series
Authors: Mæhlen Jens Otto , Hagemo Jostein , Rehn Marius , Heimdal Hans Julius , Mikalsen Roger , Ottestad William
Published: October 2020

Objective: Despite critical hypoxemia, Covid-19 patients may present without proportional signs of respiratory distress. In this case series we describe the pre-hospital management of three patients with critical respiratory failure due to Covid-19. All presented with severe hypoxemia refractory to supplemental oxygen. The specific cause of hypoxemia in these patients is a matter of speculation, and several mechanisms have been suggested. We discuss possible strategies for ventilatory support in the emergency pre-hospital setting. Methods: Three cases with similar clinical presentation were identified at two bases within the Norwegian national helicopter emergency medical service (HEMS) system. The HEMS units are manned by a consultant anesthesiologist, a HEMS crew member and a pilot. Patients´ next of kin and the Regional committee for medical and health research ethics have approved the publication of this report.Conclusion: Patients with Covid-19 and severe hypoxemia may pose a considerable challenge for the prehospital emergency services. Covid-19 patients with hypocapnic hypoxia and a high minute ventilation demand high oxygen flow rates in order to avoid dilution of oxygen with ambient air, which is difficult to achieve with non-rebreathers and disposable CPAP systems. Intubation may be associated with a high risk of complications in these patients and should be carried out with diligence when considered necessary.
Exosomal miR-186 Derived from BMSCs Promote Osteogenesis Through Hippo Signaling Pathway in Postmenopausal Osteoporosis
Authors: Li Lu , Zhou Xin , Zhang Jun-tao , Liu Ai-feng , Zhang Chao , Han Jin-chang , Zhang Xiao-qing , Wu Si , Zhang Xiao-yu , Lv Fu-quan
Published: October 2020

Background: Postmenopausal osteoporosis (PMO) that results from estrogen withdrawal is the most common primary osteoporosis among older women. However, little is known about the mechanism of PMO, and effective treatment of PMO is limited.Methods: We used qPCR, western blotting, and RNA pull down to investigate the relationship between miR-186 and Mob1. Also we investigated the effect of exosome in osteogenesis using ALP staining. And HE staining was used to verify the osteogenesis in PMO model.Results: Exosomal miR-186 plays an important role in bone formation. The results of miRNA-seq and q-PCR showed that miR-186 was upregulated in a PMO+Exo treatment group. Results of RNA-pull down and luciferase reporter assays verified interactions between miR-186 and Mob1. We also verified the Hippo signaling pathway plays an important role in osteogenesis.Conclusions: We concluded that exosomes derived from hBMSCs can transfer miR-186 to promote osteogenesis in ovariectomy (OVX) rats through the Hippo signaling pathway.
Arthroscopic-assisted Treatment of Popliteus Tendinitis
Authors: Chen Biao , Liu Hankun , Chen Haitao , Chen Liaobin , Wang Hua
Published: October 2020

Background: Popliteus tendinitis is an unusual factor to cause pain of the knee joint in its posterolateral compartment. There are few reports that the arthroscopy used for the treatment of refractory and symptomatic popliteus tendinitis. This study aimed to evaluate the effect of arthroscopic treatment of popliteus tendinitis via an auxiliary extreme lateral approach and to investigate the pathogenesis and treatment of popliteus tendinitis.Methods: From 2014 to 2018, arthroscopic popliteus tendon ablation was performed in 15 patients (15 knees) with popliteus tendinitis via an auxiliary extreme lateral approach. Clinical outcomes were assessed using the Lysholm knee scoring scale, the Tegner score, the International Knee Documentation Committee (IKDC) score and the visual analogue scale (VAS) pain score at the 24-month follow-up after surgery.Results: A total of 15 patients (mean age, 51.1 ± 7.1 years) were included; they had a mean body mass index of 23.8 ± 2.1. The minimum follow-up period was 24 months. Comparing the postoperative state to the preoperative state, the mean postoperative Lysholm score, Tegner score, and IKDC score improved significantly from 70.0 ± 5.0, 3.0 ± 0.9, and 62.3 ± 5.5 to 89.3 ± 4.2, 4.6 ± 0.61, and 80.5 ± 4.4, respectively (p < 0.01). The preoperative VAS score for pain improved from 4.3 ± 0.7 to 0.9 ± 0.6 (p < 0.01). No patients were lost to follow-up.Conclusion: Following arthroscopic-assisted treatment, all the patients with popliteus tendinitis achieved satisfactory clinical outcomes in terms of pain relief and improved function.
Anti-Diabetic, Anti-Inflammatory and Antioxidant Properties of Four Underutilized Ethnomedicinal Plants: An in Vitro Approach
Authors: Datta Sudeshna , Seal Tapan
Published: October 2020

Background : In the present study, antidiabetic, anti-inflammatory activities and antioxidant properties in four diverse dissolvable concentrates of four lesser known ethnomedicinal plants viz. Apluda mutica, Mikania micrantha, Kyllinga nemoralis and Cleome rutidosperma were investigated. Methods: The benzene, chloroform, methanol and 70% aqueous (aq.) ethanol extract of these plants were tried for antioxidant by various established in vitro systems like total phenolic content, DPPH free radical scavenging, ABTS radical cation scavenging, metal chelating activity. Anti-diabetic and anti-inflammatory activities were explored by quantifying α-amylase, α-glucosidase and protein denaturation inhibitory activities of the investigated plants. Results: Among the various solvents 70% aq. ethanol extract of M. micrantha had the highest total phenolic content (230.450 ± 0.12mg GAE/g extract), DPPH & ABTS radical scavenging activity, FRAP value (4.122± 0.004 μM Trolox equivalent/ g dry extract), anti-lipid peroxidation capacity, reducing power and metal chelating activity. The highest amount of total flavonoid was detected in the 70% aq. ethanol extract of C. rutidosprema (71.050 ± 0.058 mg RE /g extract. Similarly M. micrantha also exhibited significantly lower IC 50 values for the percentage inhibition of α-amylase (IC50 58.44 ± 0.012 µg/ml) and α-glucosidase (IC50 113.31 ± 0.010 µg/ml) compared to acarbose (IC50 = 53.8 ± 0.009 µg/ml ; IC50 = 79.48 ± 0.006 µg/ml respectively) (p ≤ 0.05). Anti-inflammatory activity was determined by using protein denaturation assay and M. micrantha showed significant lower IC50 value for the inhibition of protein denaturation (IC50= 89.27 ± 0.008 µg/ml) compared to other plants under investigation. Quantification of polyphenolics by HPLC showed the presence of different phenolic acids in varying amounts. Conclusion: Therefore, the results indicate that these plants were shown to contain a remarkable amount of different bio-active compounds, thus confirming their involvement in several biological activities and to serve as a potential antioxidative, anti-inflammatory and anti-diabetic agent in food and pharmaceutical industries.
Brain Stimulation in Attention Deficits after Traumatic Brain Injury: A Literature Review and Feasibility Study
Authors: Boissonnault Ève , Higgins Johanne , LaGarde Geneviève , Barthélemy Dorothy , Lamarre Céline , Dagher Jehane H.
Published: October 2020

Background: After a traumatic brain injury, disturbances in the attentional processes have a direct negative effect on functional recovery and on return to complex activities. To date, there is no good attention remediation treatment available. The primary objective of this review and pilot study is to get a comprehensive analysis and to evaluate the feasibility of implementing a tDCS protocol to improve attention disorders in patients with mild complicated to severe subacute TBI, hospitalized in an inpatient rehabilitation facility. Our secondary objective is to extract preliminary data and observational information on participants’ response to treatment. Methods: Participants were recruited from a consecutive series of patients admitted to the TBI unit of a subspecialized regional rehabilitation center. They received a 20-minute tDCS stimulation 3 times a week for 3 weeks. A neuropsychological evaluation was performed before and after the intervention. We collected participants’ socio-demographic and clinical characteristics as well as information about satisfaction, tolerability and adverse effects.Results: 164 patients were admitted between September 2018 and January 2020. 158 were excluded and 6 patients with presumed attentional deficits were enrolled. None completed the protocol as intended. No major side effects occurred. Conclusion: Non-invasive brain neurostimulation is promising to enhance attention deficits in patients with TBI. Implementation of a tDCS protocol to fulfill this purpose in an intensive inpatient rehabilitation center has its limitations. We made recommendations to facilitate the implementation of similar projects in the future. Trial registration: ISRCTN, ISRCTN55243064. Registered 14 October 2020 - Retrospectively registered, http://www.isrctn.com/ISRCTN55243064.
Electric Signals Counterbalanced Posterior vs Anterior PTEN Signaling in Directed Migration of Dictyostelium
Authors: Song Bing , Gu Yu , Jiang Wenkai , Li Ying , Ayre Wayne Nishio , Liu Zhipeng , Yin Tao , Janetopolous Christopher , Iijima Miho , Devreotes Peter , Zhao Min
Published: October 2020

Background: Cells show directed migration response to electric signals, namely electrotaxis or galvanotaxis. PI3K and PTEN jointly play counterbalancing roles in this event via a bilateral regulation of PIP3 signaling. PI3K has been proved essential in anterior signaling of electrotaxing cells, whilst the role of PTEN remains elusive.Methods: Dictyostelium cells with different genetic backgrounds were treated with direct current electric signals to investigate the genetic regulation of electrotaxis.Results: We demonstrated that electric signals promoted PTEN phosphatase activity and asymmetrical translocation to the posterior plasma membrane of the electrotaxing cells. Electric stimulation produced a similar but delayed rear redistribution of myosin II, immediately before electrotaxis started. Actin polymerization is required for the asymmetric membrane translocation of PTEN and myosin. PTEN signaling is also responsible for the asymmetric anterior redistribution of PIP3 / F-actin, and a biased redistribution of pseudopod protrusion in the forwarding direction of electrotaxing cells. Conclusions: PTEN controls electrotaxis by coordinately regulating asymmetric redistribution of myosin to the posterior, and PIP3/F-actin to the anterior region of the directed migration cells.
Development and validation of a scale evaluating pregnant women's breastfeeding competency in third trimester: Breastfeeding Competency Scale(BCS)
Authors: Wu Yu , Wang Ying , Hu Jiazhen , Dang Yan , Zhang Yuanyuan , Qi Xiumei , Tian Qingxiu , Wang Aihua , Li Yunfeng
Published: October 2020

Background: Breastfeeding plays an important role in the early stages of humans and throughout the development process. Breastfeeding competency is a self-assessment of pregnant women's overall competency to breastfeeding which could predict behaviors of pregnant women’ breastfeeding. However, a valid and reliable scale to assess the breastfeeding competency has not yet been developed and validated. This study was designed to develop and validate an assessment scale designed to assess the pregnant women's breastfeeding competency in third trimester: Breastfeeding Competency Scale(BCS).Methods: The BCS was developed and validated over three phases between September 2018–September 2019 which include item statistics, exploratory factor analysis(EFA), content validation, internal consistency assessment, split-half reliability and confirmatory factor analysis.Results: Item statistics and exploratory factor analysis resulted in 38 items, 4 factors that explained 66.489% of total variance. The Cronbach’s α coefficient in total scale and 4 factors were 0.970, 0.960, 0.940, 0.822, 0.931 respectively. The split-half reliability of BCS was 0.894, 0.890. Confirmatory factor analytic model showed the 4-factor model matching the data well.Conclusions: The BCS was a new instrument with certain validity and reliability for assessing the breastfeeding competency of pregnant women in third trimester.
Minimally invasive closure of transthoracic ventricular septal defect: postoperative complications and risk factors
Authors: Ren Chunnian , Wu Chun , Pan Zhengxia , Li Yonggang
Published: October 2020

ObjectivesTo summarize and analyze the clinical characteristics of postoperative complications after minimally invasive closure of transthoracic ventricular septal defect, and to explore the risk factors for its occurrence.MethodsRetrospectively analyzed the clinical data of 209 patients underwent transthoracic ventricular septal defect closure performed in the Department of Cardiothoracic Surgery, Children’s Hospital of Chongqing Medical University from January 2018 to January 2020, obtained relevant clinical data from the electronic medical record system and summarized their postoperative complications. And used univariate logistics regression and multivariate logistics regression to analyze the risk factors of its occurrence.ResultsThe postoperative hospital stay of 27 patients was longer than 9 days. Residual shunt occurred in 33 patients recently after operation. One patient underwent surgical treatment again because of mechanical hemolysis after the operation. Two patients were re-operated 1 month and 10 months after surgery because of persistent moderate to severe aortic regurgitation. After surgery, 3 patients underwent pericardiocentesis due to a large amount of pericardial effusion, and 2 patients developed a new atrioventricular block after the operation. No other serious adverse events occurred. Multivariate logistic regression analysis showed that the size of VSD defect (OR: 1.494, 95% Cl: 1.108-2.013, P value: 0.008) was related to long postoperative hospitalization. The residual shunt is related to the size of the occluder (OR: 1.452, 95%Cl: 1.164-1.810, P value: 0.001). In the univariate logistics regression analysis, no risk factors related to serious adverse events were found.ConclusionsThe minimally invasive closure of transthoracic ventricular septal defect is very effective, with no mortality and low incidence of serious adverse events after surgery. The size of the defect is related to the long postoperative hospitalization, and the size of the occluder is related to the residual shunt in the early postoperative period. No risk factors related to the occurrence of serious adverse events after the operation were found.
Meta-Analysis of Economic Evaluation Studies: Data Harmonisation and Methodological Issues
Authors: Bagepally Bhavani Shankara , Chaikledkaew Usa , Chaiyakunapruk Nathorn , Attia John , Thakkinstian Ammarin
Published: October 2020

In the context of ever-growing health expenditure and limited resources, economic evaluations aid in making evidence-informed policy decisions. Cost utility analyses (CUA) are often used in this context, but limitations include pairwise contrasts, missing contrasts, and different sources or quality of data. Synthesis of CUA data from multiple studies is therefore desirable to assist policy makers, but there are many challenging methodological issues including: inconsistent reporting of results using different economic parameters, and multiple sources of heterogeneity including: setting, time horizon, perspective, modelling approaches and assumptions, currency, willingness to pay (WTP) threshold, level of country income, and input parameters. In this paper, we provide a step by step description of the methods for data harmonisation and synthesis of aggregated data from CUA studies, as well as a framework for handling heterogeneity; we demonstrate these methods using the example of agents for type 2 diabetes. These meta-analytic methods for the synthesis of economic evidence synthesis should be useful for policy makers.
Adapting the Wheelchair Skills Program for Pediatric Rehabilitation: Recommendations from Key Stakeholders
Authors: Daoust Geneviève , Rushton Paula W. , Racine Marissa , Leduc Karolann , Assila Najoua , Demers Louise
Published: October 2020

Background: Backed by over 20 years of research development, the Wheelchair Skills Program (WSP) has proven to be a safe and effective program to improving wheelchair skills for adult wheelchair users. However, evidence is lacking for the pediatric population, which may help to explain the limited use of the WSP in pediatric settings. While additional evidence specific to the pediatric population is needed, concurrent implementation of the WSP into pediatric clinical practice is equally prudent to allow those users to benefit from the years of accumulated WSP evidence. To facilitate implementation of evidence-based programs into practice, adaptation is also often required to improve the fit between the program and the local context. Therefore, the objective of this study was to understand what adaptations, if any, are required for the Wheelchair Skills Program (WSP) to be implementable in a pediatric setting. Methods: A deductive qualitative descriptive study design was used, guided by the Consolidated Framework for Implementation Research (CFIR). Occupational Therapist (OTs) from a pediatric rehabilitation center and two specialized schools in Montreal, Canada were invited to participate in a 90-min focus group. The Framework Method was followed for the data analysis. Results: One focus group in each site (n=3) was conducted with a total of 19 participants. From the OTs’ perspectives, our analysis revealed benefits of WSP use and various issues (e.g. some skills seem unrealistic) affecting its uptake in relation to the constructs of the CFIR Intervention Characteristics domain. The results provided guidance for the recommendations of adaptations (e.g. addition of a caregiver assistance score) to enhance implementation of the WSP in pediatric rehabilitation settings and helped to identify the need for the production of new knowledge and knowledge translation (KT) tools.Conclusions: Implementation of the WSP with the adaptations and KT tools proposed could allow pediatric manual wheelchair users to improve their wheelchair skills.
Body Fat Distribution in Trunk and Legs Are Associated With Cardiometabolic Risk Clustering Among Chinese Adolescents Aged 10-18 Years Old
Authors: Yang Qingmei , Ma Ping , Zhang Hao , Cai Rongrong , Dong Yangyang , Ding Wenqing
Published: October 2020

Background: The association between total fat, body fat distribution and cardiometabolic risk factors are highly controversial among adolescents. The aim of the present study was to evaluate the association of body fat distribution with cardiometabolic risk factors clustering among Chinese adolescents.Methods: In this cross-sectional study a total of 1175 adolescents aged 10 to 18 years underwent a comprehensive assessment of cardimetabolic risk factors. Body fat analysis was performed with Bioelectrical impedance analysis. Results: Individuals with the CVRFs ≥1 or CVRFs ≥2 had higher indices of body fat distribution such as body fat mass(BFM) compared to those with normal CVRFs (all P<0.001). The prevalence of CVRFs ≥1, CVRFs ≥2 increased with increasing of the quartile of BFM, TBFM, ABFM, LBFM, PBF, VFL compared to normal subjects. After adjusted for age and sex, the study indicated an linear relationship between TBFM(β=0.693, 95%CI:0.363,1.023), LBFM(β=-1.471, 95%CI:-2.768,-0.175) and CVRFs z-score. Logistic regression models suggested TBFM was associated with CVRFs≥1 and CVRFs≥2 by higher odds. Lower odds of LBFM was associated with CVRFs≥2. Conclusions A significant association between body fat mass of trunk(TBFM), body fat mass of leg(LBFM) and cluster of cardiometabolic risk factors was showed in the study. It suggested to reduce body fat mass of trunk and increase body fat mass of leg were essential for adolescents to prevent cardiovascular risk factors clustering.
Factors Associated With Practice of Chemical Pesticide Use and Acute Poisoning Experienced by Farmers in Chitwan District, Nepal
Authors: KAFLE SIMRIN , Vaidya Abhinav , Pradhan Bandana , Jørs Erik , Onta Sharad
Published: October 2020

Background: Irrational use and unsafe handling of pesticides in agriculture farming is a serious public health concern in developing countries including Nepal. This study was conducted to assess the practice of chemical pesticide use and associated factors along with the acute health symptoms experienced by farmers in Chitwan District, Nepal.Methods: This was a descriptive cross-sectional study using quantitative methods with 790 farmers from Chitwan district, Nepal selected through systematic random sampling. Scores for knowledge, attitude/perception and practice were calculated by aggregating variables where each variable was scored 1 or 0 based on a right or wrong answer. Further, the practice variable was segregated into three groups namely practice during purchasing, practice during mixing and spraying and practice during storage and disposal. Statistical analysis was performed with X2 test, T-test and Multiple Logistic Regression. Confounder controls were made for age, sex and education.Results: Out of the 790 farmers, 663 (84.0%) were found to use exclusively chemical pesticide. Among them, 62% had no idea about its label. Farmers with better knowledge on pesticide handling were 8.3 times more likely to practice safe purchasing (95% CI=5.0-13.8), four times more likely to practice safe mixing and spraying (95% CI=2.5-5.9) and two times more likely to safe storage and disposal (95% CI=1.6-3.6). Similarly, perception/attitude of farmers about chemical pesticide policy and market management was significantly associated with the practice of farmers during purchasing (95% CI=1.1-2.8), mixing and spraying (95% CI=2.0-4.5) and storage and disposal (95% CI=1.1-2.5). Farmers with unsafe practice of pesticide handling were two times more likely to suffer from acute poisoning (AOR = 2.1, 95% CI = 1.3-3.3).Conclusion: There was a high use of pesticide in agriculture farming in Chitwan District. Improving knowledge of farmers on safe handling of pesticides and developing strategies for proper market management would promote the safe handling practices among farmers and reduce the acute pesticide poisoning in Nepal.
New Inside Into Clinical Heterogeneity and Inheritance Diversity of FBLN5-Related Cutis Laxa
Authors: Gharesouran Jalal , Hosseinzadeh Hassan , Ghafouri-Fard Soudeh , Moghadam Yalda Jabbari , Heris Javad Ahmadian , Jafari-Rouhi Amir Hossein , Taheri Mohammad , Rezazadeh Maryam
Published: October 2020

BackgroundFBLN5-related cutis laxa (CL) is a rare disorder that involves elastic ﬁber-enriched tissues and is characterized by lax skin and variable systemic involvement such as pulmonary emphysema, arterial involvement, inguinal hernias, hollow viscus diverticula and pyloric stenosis. This type of CL follows mostly autosomal recessive (AR) and less commonly autosomal dominant patterns of inheritance. ResultsIn this study, we detected a novel homozygous missense variant in exon 6 of FBLN5 gene (c.G544C, p.A182P) by using whole exome sequencing in a consanguineous Iranian family with two affected members. Our twin patients showed some of the clinical manifestation of FBLN5-related CL but they did not present pulmonary complications, gastrointestinal and genitourinary abnormalities. The notable thing about this monozygotic twin sisters is that only one of them showed ventricular septal defect (VSD), suggesting that this type of CL has intrafamilial variability. Co-segregation analysis showed the patients’ parents and relatives were heterozygous for detected variation suggesting AR form of the CL. In silico prediction tools showed that this mutation is pathogenic and 3D modeling of the normal and mutant protein revealed relative structural alteration of fibulin-5 suggesting that the A182P can contribute to the CL phenotype via the combined effect of lack of protein function and partly misfolding-associated toxicity.ConclusionWe underlined the probable roles and functions of the involved domain of fibulin-5 and proposed some possible mechanisms involved in AR form of FBLN5-related CL. However, further functional studies and subsequent clinical and molecular investigations are needed to confirm our findings.
Transpedicular Bi-vertebrae Wedge Osteotomy in Treatment of Post-tubercular Spinal Deformity: A Retrospective Study
Authors: HUANG Yi , HU Wenhao , LI Jing , WANG Tianhao , LIU Huawei , ZHENG Guoquan , ZHANG Xuesong , WANG Yan
Published: October 2020

Background: In the late stage of spinal tuberculosis, the bony destruction and vertebral collapse often leads to significant kyphosis, presenting clinically as a painful gibbus deformity, with increased instability, vertebral body translations and increased risk of neurologic involvement. Spinal osteotomy is thought to be suitable for most patients with severe rigid kyphosis. The aim of this study was to evaluate the efficacy of transpedicular bi-vertebrae osteotomy technique in the patients with Pott’s kyphosis and other post-tubercular spinal deformity.Methods: Between January 2012 and December 2015, 18 patients with post-tubercular spinal deformity underwent the transpedicular bi-vertebrae wedge osteotomy, with a minimum follow up of 27.0 months. Preoperative and postoperative kyphotic angle, sagittal plane parameters (T1-T12 angle for thoracic deformity, T10-L2 angle for thoracolumbar and L1-L5 angle for lumbar deformity) and sagittal vertical axis (SVA) were measured. Oswestry Disability Index (ODI), Visual analog scale (VAS) and modified American Spinal Injury Association grading(ASIA) of preoperative and final follow-up were documented. Results:The average operation time was 455 minutes (range, 200-260 minutes) with a mean intraoperative blood loss of 425 mL (range, 200-700 mL). The kyphotic angles decreased from 80.3° (range, 28.5°-130.8°) preoperatively to 26.1° (range, 7.0°-63.3°) at the final follow-up (P<0.01). The mean VAS score was reduced from preoperative 5.2(range, 2-9) to 0.9(range, 0-2, P<0.01) and the ODI improved from 55.3% (range, 46%-76%) to 6.3% (range, 2%-18%, P<0.01). At final follow-up, there was radiographic evidence of solid fusion at the osteotomy site and fixed segments in all patients. Neurological function improved from ASIA scale D to E in 7 patients, C to D in 3 patients.Conclusions:Our results suggest that transpedicular bi-vertebrae wedge osteotomy is a safe and effective treatment option for post-tubercular spinal deformity. This technique achieves satisfying correction and fusion rates with adequate decompression of neurological elements.
Tetracalcium Phosphate Treatment on Experimental Fracture Model in Rats
Authors: Kaymaz Burak , Yılmaz Onur , Taşova Ali Osman , Anapa Doğukan
Published: October 2020

The authors have requested that this preprint be removed from Research Square.
Neodymium-doping Concentration Induced Face-shared to Corner-shared Transition in Strontium Cobaltite
Authors: Huang Haoliang , Chen Zezhi , Xie Liang , Wang Jianlin , Peng Ranran , Fu Zhengping , Lu Yalin
Published: October 2020

The topotactic connection style of oxygen octahedron/tetrahedron in transition metal oxides (TMOs) is an important feature that modulates their corresponding physical properties. Using a simple chemical doping technique, we obtained Sr1-xNdxCoO3-δ with a crystal structure transition from face-shared octahedron to corner-shared octahedron/tetrahedron. The Rietveld analyses of the x-ray diffraction (XRD) patterns show that the crystal structure changes from rhombohedral to cubic and the connection style transforms from face-shared to corner-shared with the increase neodymium (Nd) content. During this process, the ferromagnetic behavior is greatly improved due to the larger amount of the corner-shared cubic SrCoO3-δ phase. The synchrotron radiation x-ray absorption spectroscopies of the Co L-edge and O K-edge show that Nd doping mainly affects the electronic structure of oxygen rather than the valence state of Co. Thereby, the Nd changes the connection style of oxygen octahedron/tetrahedron, which then alters the magnetic interactions.
WGCNA Co-Expression Network Analysis Reveals LncRNA LINC00313 Functions as A ceRNA to Regulate PTEN-Mediated PI3K/AKT Signaling Pathway by Sponging miR-19a-3p in Docetaxel-Resistant Prostate Cancer Cells
Authors: Chen Bin shen , Xu Kai , Zhang Yiming , Xu Peng , Li Chaoming , Liu Jun , Xu Yawen
Published: October 2020

Background: Docetaxel is the preferred chemotherapeutic agent for patients with hormone-refractory PCa. LncRNAs play important roles in the development of docetaxel resistance in patients with PCa. We evaluated the effects of the lncRNA LINC00313 on growth and metastasis in docetaxel-resistant PCa cells, and the molecular mechanisms underlying these effects.Methods: The mRNA dataset (GSE102124 and GSE55945) and lncRNA dataset (GSE115414) were downloaded from the GEO database. The DEGs were identified using the “R package limma”. WGCNA were performed to identify the modules and genes associated with PCa. A PPI network was constructed using the STRING database and visualized using Cytoscape. The Cytohubba plug-in was used to identify the hub genes and cytoNCA plug-in was used to identify the highest linkage hub genes. Based on lncRNA-miRNA pairs and miRNA-mRNA pairs using StarBase and TargetScan databases, a ceRNA network was constructed. Functional analysis was performed via GO, GSEA, and GSVA analysis. Cell proliferation, apoptosis, cell cycle progression, migration, and invasion were evaluated by CCK-8, colony formation, flow cytometry, transwell, and wound healing assays. RT-PCR, western blot, and immunohistochemistry were used to evaluate mRNA and protein expression. The oncogenicity of LINC00313 in docetaxel-resistant PCa cells was determined by tumor transplantation in nude mice. Luciferase reporter and RNA pull-down assays were used to evaluate interactions between LINC00313 and miR-19a-3p as well as between miR-19a-3p and PTEN.Results: LINC00313-miR-19a-3p-PTEN was a core network of ceRNA network. Cox regression analysis identified LINC00313 as an independent prognostic variable for OS in patients with PCa. LINC00313 overexpression in docetaxel-resistant PCa cells suppressed proliferation, invasion, and migration, and induced apoptosis and cell cycle arrested at the G1 phase. These changes were related to changes in cyclinD1, p27, Ki67, Bax, Bcl-2, caspase-3/9, E-cadherin, N-cadherin, Vimentin, and MMP-2 expression. Animal experiments showed that LINC00313 silencing promoted tumor formation. Co-transfection with LINC00313‐WT and miR-19a-3p mimic reduced luciferase activity, and co-transfection with PTEN‐WT and LINC00313 increased luciferase activity. The effects of LINC00313, including increased PTEN, decreased PIP3 expression, and the inhibition of proliferation and metastasis in docetaxel-resistant PC cells, were abolished by miR-19a-3p mimic.Conclusion: LINC00313 overexpression suppressed the proliferation and metastasis of docetaxel-resistant PC cells by competitively binding to miR-19a-3p to regulate PTEN expression and inhibit the activation of the PI3K/Akt signaling pathway.
Infrapatellar Fat Pad-derived Mesenchymal Stem Cell-based Spheroids Enhance Their Therapeutic Efficacy to Reverse Synovitis and Fat Pad Fibrosis
Authors: Kouroupis Dimitrios , Willman Melissa A , Best Thomas M , Kaplan Lee D , Correa Diego
Published: October 2020

Background: To investigate the in vitro and in vivo anti-inflammatory/anti-fibrotic capacity of IFP-MSC manufactured as 3D spheroids. According to our hypothesis, IFP-MSC do not require prior cell priming to acquire a robust immunomodulatory phenotype in vitro in order to efficiently reverse synovitis and IFP fibrosis and secondarily delay articular cartilage damage in vivo.Methods: Human IFP-MSC immunophenotype, tri-potentiality, and transcriptional profiles were assessed in 3D settings. Multiplex secretomes were assessed in IFP-MSC spheroids [Crude (non-immunoselected), CD146+ or CD146- immunoselected cells] and compared with 2D cultures with and without prior inflammatory/fibrotic cell priming. Functionally, immunopotency limiting human PBMCs proliferation and effect on stimulated synoviocytes with inflammation and fibrotic cues. Finally, spheroids were tested in vivo in a rat model of acute synovitis/fat pad fibrosis.Results: Spheroids enhanced IFP-MSC phenotypic, transcriptional and secretory immunomodulatory profiles compared to 2D cultures. Further, CD146+ IFP-MSC spheroids showed enhanced secretory and transcriptional profiles, however, not reflected in a superior capacity to suppress activated PBMC suggesting 3D environment sufficient to induce an immunomodulatory phenotype. Crude IFP-MSC spheroids modulated the molecular response of synoviocytes previously exposed to inflammatory cues. Therapeutically, IFP-MSC spheroids retained Substance P degradation potential in vivo, while effectively induced resolution of inflammation/fibrosis of synovium and fat pad, halting the articular cartilage degradation in a rat model of progressive synovitis, fat pad fibrosis and osteoarthritis.Conclusions: 3D spheroids confer IFP-MSC a reproducible and enhanced immunomodulatory effect in vitro and in vivo, circumventing the requirement of non-compliant cell priming or selection before administration, thus streamlining cell products manufacturing protocols.
Gene Engineered Mesenchymal Stem Cells: Greater Transgene Expression and Efficacy With Minicircle Vs. Plasmid DNA Vectors in a Mouse Model of Acute Lung Injury
Authors: Florian Maria , Wang Jia-Pey , Deng Yupu , Souza-Moreira Luciana , Stewart Duncan John , Mei Shirley Hsin-Ju
Published: October 2020

Background: Acute lung injury (ALI), and in its severe form the Acute respiratory distress syndrome (ARDS), results in increased pulmonary vascular inflammation and permeability, and is a major cause of mortality in many critically ill patients. Although cell-based therapies have shown promise in experimental ALI, strategies are needed to enhance potency of mesenchymal stem cells (MSC) to develop more effective treatments. Genetic modification of MSC has been demonstrated to significantly improve therapeutic benefits of these cells; however, the optimal vector for gene transfer is not clear. Given the acute nature of ARDS, transient transfection is desirable to avoid off target effects of long-term transgene expression, as well as the potential adverse consequences of genomic integration. Methods: Here, we explored whether a minicircle DNA (MC) DNA vector containing human angiopoietin 1 (MC-ANGPT-1) can provide more effective platform for gene-enhanced MSC therapy of ALI/ARDS. Results: At 24 hours after transfection, nuclear-targeted electroporation using a MC-ANGPT1 vector resulted in a 3,7 fold greater increase in human ANGPT1 protein in MSC conditioned media compared to the use of a plasmid ANGPT1 (pANGPT1) vector (2048±567pg/mL vs. 552.1±33.5pg/mL). In the lipopolysaccharide (LPS)-induced ALI model, administration of pANGPT1 transfected MSC significantly reduced bronchoalveolar lavage (BAL) neutrophil counts by 57%, while MC-ANGPT1 transfected MSC reduced it by 71% (p<0.001) by Holm-Sidak’s multiple comparison test. Moreover, compared to pANGPT1, the MC-ANGPT1 transfected MSC significantly reduced pulmonary inflammation, as observed in decreased levels of proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interferron gamma (IFN-γ), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2). pANGPT1 transfected MSC significantly reduced BAL albumin levels by 71% , while MC-ANGPT1 transfected MSC reduced it by 85%. Coclusions: Overall, using a minicircle vector, we demonstrated an efficient and sustained expression of the ANGPT1 transgene in MSC and enhanced therapeutic effect on ALI model compared to plasmid. These results support the potential benefits of the MC-ANGPT1 gene enhancement of MSC therapy to treat ARDS.
Screening of Potential Inhibitors of Covid-19 with Repurposing Approach Via Molecular Docking
Authors: Alizadehmohajer Negin , Sadeghi Bahman , Najafgholian Simin , Moradi Shabnam , Mohammadi Forogh , Nedaeinia Reza , javanmard Shaghayegh haghjooy , Sohrabi Ehsan , Salehi Rasoul , A.Ferns Gordon , Manian Mostafa , Nejad Asieh Emami
Published: October 2020

Background: 2019-nCoV (COVID-19) is a pandemic disease with a high infectivity and mortality. The prevention and treatment of COVID-19 have become urgent matters for consideration. It often takes several years to develop new drugs, or vaccines, based on the usual clinical trial process. This dwell-time can be shortened by repurposing previously approved drugs.Methods: We have designed and evaluated a bacterial biosensor expressing a luciferase We aimed to assess several available small-molecule; Abl kinase inhibitors, Janus kinase inhibitor, Dipeptidyl peptidase 4 inhibitors, RNA-dependent RNA polymerase inhibitors, and Papin-like Protease inhibitors, using binding simulation with proteins that might prove to be effective in inhibiting COVID-19 infection. The efficiency of inhibitors was evaluated based on docking scores using auto dock vina software.Results: Strong ligand-protein interactions were predicted among some of these drugs, such as Imatinib, Remdesivir, and Telaprevir, and this may render these compounds promising candidates. Some candidate drugs might be efficient in disease control (directly and indirectly) or in viral proteins attenuation. It is worth to highlight the powerful immunomodulatory role of Abivertinib that inhibits pro-inflammatory cytokine production that are associated with cytokine release syndrome (CRS) or cytokine storm and progression of COVID-19 infection.Conclusions: COVID-19 is similar to SARS-CoV, the potential role of Abl kinase inhibitors such as Imatinib in reducing SARS-CoV and MERS-CoV viral titers, immune regulatory function and the development of acute respiratory distress syndrome (ARDS) may indicate that these drugs may be useful for COVID-19. Moreover, Remdesivir, and Telaprevir have the most efficiency with their docked proteins in-silico as well although clinical trials are needed to confirm the effect of these drugs.