bluuebunny/crossref_metadata_2025 huggingface dataset:
An Integrated Approach to Well Integrity Diagnostics Utilizing Next Generation Passive Acoustic Logging Technology
Authors: Atakishiyev Fuad , Ramazanov Rizvan , Allan Fergus , Zett Adrian , Graham Tom , Imrie Andrew , Tracadas Philip , Mirzayev Kamil
Published: October 2020

To ensure the continuation of safe and reliable well operations diagnosing well health issues becomes increasingly necessary. Having access to the right technology can provide greater confidence in diagnostics data; enabling more effective well management and risk mitigation. As a prudent operator, bp is proactive and rigorous in monitoring the health of its well stock and is continuously introducing new technology and methods to increase the effectiveness of its surveillance capabilities.

Traditionally, a combination of passive acoustics and temperature has been deployed in such investigations, but historically this has yielded limited success in offshore wells due to the combination of complex overprints. Whilst it is still acknowledged that passive acoustic logging does have limitations, chiefly due to their inability to characterize sporadic signals, next generation passive acoustics technology equipped with spectral sensor arrays have significantly enhanced abilities to measure subtle acoustic signals. This paper details an approach utilized offshore Azerbaijan for such diagnostics work, using these latest passive acoustic technologies, teamed with conventional temperature and distributed fibre optics.

As part of routine and ongoing data gathering, different tools were tested across a multi-well campaign in a variety of environments and different well states; static, active annular bleed and whilst applying pressure to annuli. Previous logging programs have deployed passive acoustic tools to confirm pre-existing notions of well issues. The logging programs described in this paper used higher sample densities and longer station intervals to enable a detailed and objective view of well health. There were thousands of stations acquired in more than 10 runs across production, water and gas injector wells. The acquired dataset generated a vast number of data points across different fluid types, completions and well conditions which allowed a more robust assessment of tool repeatability, sensitivity and spectral response. Highly sensitive hydrophones in modern spectral passive acoustic logging tools along with temperature and fibre measurements integrated with other information helped our understanding of the dynamics behind the casing, allowing us to make better informed decisions about wells operations.

As the datasets grew in size, quick-look processing methodology was developed to identify and characterize acoustic anomalies. The paper will demonstrate how the techniques developed have generated more confidence in passive acoustic technology. It will show how both acquisition procedures and data processing techniques were optimized to ensure the best quality answer products were delivered.
Numerical Calculation of the Pressure Drop and Saturation of Two-Phase Flow Through Porous Medium
Authors: Akasheva Zhibek , Assilbekov Bakhytzhan , Kudaikulov Aziz , Bolysbek Darezhat
Published: October 2020

Two-phase flow through a fibrous porous medium is numerically simulated. The goal of the study is to investigate the effect of numerical slip length on variation of pressure drop and saturation.

The simulation is based on the numerical solution of incompressible Navier-Stokes equations for two-phase flow around a circular cylinder with radii in the ranges from 0.1 to 0.4. Variations of pressure drop and saturation in time are numerically calculated on simple and snap meshes for different values of surface tension (σ), viscosity ratio (M = μnw/μw), and mesh sizes. Also, numerical results using simple and snap meshes are compared. Numerical calculations are performed using the interFoam solver in OpenFOAM® finite volume library.

The presented results show that solutions of saturation and pressure drop in time vary with mesh refinement, so the numerical slip length significantly affects the flow. For a coarser mesh the influence of numerical slip length is less than for a finer mesh, also as bigger the value of the viscosity ratio or surface tension as lower the influence of numerical slip length. The results show that the contact line motion significantly depends not only on the microstructure of the porous media, but also on the fluid properties (viscosity ratio, surface tension and etc.).
Pregnancy outcomes of Chinese women undergoing IVF with embryonic cryopreservation as compared to natural conception
Authors: Wang Jingxue , Liu Qiwei , Deng Boer , Chen Fang , Liu Xiaowei , Cheng Jiumei
Published: October 2020

Background: To examine differences in the maternal characteristics and pregnancy outcomes of Chinese women with various causes of infertility who underwent in vitro fertilization (IVF) with embryonic cryopreservation treatment.Methods: Cases were pregnancies after IVF-ET with embryonic cryopreservation; controls were spontaneously conceived pregnancies. Subgroup analysis was carried out according to etiology of infertility. The IVF treatment group was divided into 5 subgroups according to infertility etiology as follows: ovulation disorder, tubal disease, male infertility, endometriosis, and mixed infertility. Data on demographic characteristics, medical history, laboratory tests, and delivery were reviewed. Logistic regression analysis was performed for pregnancy and perinatal complications and neonatal outcomes. The multivariable model was adjusted for potential confounders.Results: Among singleton pregnancies, compared with spontaneous pregnancies, IVF pregnancies were associated with significant increases in the rates of the following: gestational diabetes mellitus (GDM) (aOR 1.76[95% CI 1.33-2.33]), preeclampsia (2.60[1.61-4.20]), preterm preeclampsia (4.52[2.03-10.06]), postpartum hemorrhage (1.57[1.04-2.36]), intrahepatic cholestasis of pregnancy (3.84[1.06-13.94]), preterm premature rupture of membranes (2.11[1.17-3.81]), preterm birth (1.95[CI 1.26-3.01]), low birthweight (1.90[1.13-3.20]), macrosomia (1.53[1.03-2.27]), and neonatal intensive care unit (NICU) admission (1.69[1.22-2.34]) in the ovulation disorder group; GDM (1.50[1.21-1.86]), placenta previa (2.70[1.59-4.59]), placenta accreta (1.78[1.10-2.89]), postpartum hemorrhage (1.61[1.19-2.18]), macrosomia (1.60[1.21-2.13]) and 5-minute Apgar score ≤7 (4.09[1.04-16.08]) in the tubal disease group; placenta previa (9.33[4.22-20.62]), small for gestational age (2.29[1.04-5.08]), macrosomia (2.00[1.02-3.95]) and NICU admission (2.35[1.35-4.09]) in the endometriosis group; placenta previa (4.14[2.23-7.68]) and placenta accreta (2.05[1.08-3.87]) in the male infertility group; and GDM (1.85[1.15-2.98]), placenta previa (4.73[1.83-12.21]), placental abruption (3.39[1.20-9.56]), chorioamnionitis (2.93[1.04-8.26]), preterm birth (2.69[1.41-5.15]), and 1-minute Apgar score ≤7 (4.68[1.62-13.51]) in the mixed infertility group. Among multiple pregnancies, most of the differences that were significant in singleton pregnancies were less extensive or had disappeared.Conclusions: Infertility etiology within the IVF population was found to affect maternal and neonatal outcomes among all births. During the perinatal period, infertility etiology appears to be an additional risk factor for abnormal pregnancy outcomes besides the use of IVF techniques compared with spontaneous pregnancies. Higher risk was found for ovulation disorders, and lower risk was found for male infertility.
Effects of social support, hope and resilience on depressive symptoms within 18 months after diagnosis of prostate cancer
Authors: Zhao Xinxin , Sun Ming , Yang Ye
Published: October 2020

Background: The prevalence of depression symptoms and related modifiable factors in prostate cancer (PCa) are not well evaluated. We aimed to assess the effects of perceived social support, hope and resilience on depressive symptoms within 18 months after diagnosis of PCa, and to evaluate the role of hope and resilience as mediators of that relationship.Method: A cross-sectional study was analyzed in consecutive inpatients with PCa during the months of January 2018 and August 2019. A questionnaire was administered to 667 patients. All registered patients were all volunteers and anonymous. Depressive symptoms, perceived social support, hope and resilience were measured anonymously. Out of 667 patients, a total of 564 effective respondents (< 30% missing data) became our subjects. Hierarchical linear regression was used to identify the factors associated with depressive symptoms. Asymptotic and resampling strategies were used to conduct the mediating effects of hope and resilienceResults: The prevalence of depressive symptoms was 65.9% in PCa patients. Hierarchical regression analyses indicated that perceived social support, hope, and resilience together accounted for 27.5% variance of depressive symptoms. Support from family, hope, and resilience significantly associated with depressive symptoms, respectively. Hope (a*b = -0.0783, BCa95% CI:-0.134 to -0.0319, p < 0.05), and resilience (a*b = -0.1315, BCa95% CI:-0.1894 to -0.0783, p < 0.05) significantly mediated the association between perceived social support and depressive symptoms.Conclusions: The high prevalence of depressive symptoms among PCa patients should receive more attention. Perceived social support, hope and resilience could be positive resources for combating depressive symptoms, and hope and resilience mediated the association between perceived social support and depressive symptoms. Enhancing social support, particularly the support form family, and improving patients’ outlook and resilience may be potential targets for future psychosocial interventions aimed at reducing depressive symptoms.
Co-relation with novel phosphorylation sites of IκBα and necroptosis in breast cancer cells
Authors: Choi Sung Hoon , Chung Young Ho , Yoon Hee-sub , Yoo Shin-ae , Yun Sung Ho , Park Joo-Hee , Han Eun Hee , Chi Sung-Gil
Published: October 2020

Background: Phosphorylation of NF-kappaB inhibitor alpha (IκBα) is key to regulation of NF-κB transcription factor activity in the cell. Several sites of IκBα phosphorylation by members of the IκB kinase family have been identified, but phosphorylation of the protein by other kinases remains poorly understood. We investigated a new phosphorylation site on IκBα and identified its biological function in breast cancer cells.Methods: Previously, we observed that aurora kinase (AURK) binds IκBα in the cell. To identify the domains of IκBα essential for phosphorylation by AURK, we performed kinase assays with a series of IκBα truncation mutants. AURK significantly promoted activation of IκBα at serine 32 but not serine 36; by contrast, IκB kinase (IKK) family proteins activated both of these residues. We also confirmed phosphorylation of IκBα by matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF MS) and nano-liquid chromatography hybrid quadrupole orbitrap mass spectrometer (nanoLC-MS/MS; Q-Exactive).Results: We identified two novel sites of serine phosphorylation, S63 and S262. Alanine substitution of S63 and S262 (S63A and S262A) of IκBα inhibited proliferation and suppressed p65 transcription activity. In addition, S63A and/or S262A of IκBα regulated apoptotic and necroptotic effects in breast cancer cells.Conclusions: Phosphorylation of IκBα by AURK at novel sites is related to the apoptosis and necroptosis pathways in breast cancer cells.
Bone Marrow Mesenchymal Stem Cell-derived Exosomes Promote Plasminogen Activator Inhibitor 1 Expression in Vascular Cells in the Local Microenvironment During Rabbit Osteonecrosis of the Femoral Head
Authors: Li Lu , Wang Yikai , Yu Xiaobing , Bao Yongming , An Lijia , Wei Xiaowei , Yu Weiting , Liu Baoyi , Li Junlei , Yang Jiahui , Xia Yan , Liu Ge , Cao Fang , Zhang Xiuzhi , Zhao Dewei
Published: October 2020

Background: Nontraumatic osteonecrosis of the femoral head (NONFH) is a highly disabling orthopedic disease in young individuals. Plasminogen activator inhibitor 1 (PAI-1) has been reported to be positively associated with NONFH. We aimed to investigate the dysregulating PAI-1 in bone marrow mesenchymal stem cells (BMMSCs) and vascular cells in rabbit steroid-induced NONFH. Methods: To verify the hypothesis that BMMSCs could promote thrombus formation in a paracrine manner, we collected exosomes from glucocorticoid-treated BMMSCs (GB-Exo) to determine their regulatory effects on vascular cells. microRNA sequencing was conducted to find potential regulators in GB-Exo. Utilizing gain-of-function and knockdown approaches, we testified regulatory effect of microRNA in exosomes.Results: The expression of PAI-1 was significantly increased in local microenvironment of the femoral head in ONFH model. GB-Exo promoted PAI-1 expression in vascular smooth muscle cells and vascular endothelial cells. We also revealed that miR-451-5p in GB-Exo plays a crucial role for the elevated PAI-1. Moreover, we identified miR-133b-3p and tested its role as a potential inhibitor of PAI-1. Conclusions: This study provided considerable evidence for BMMSC exosomal miR-mediated upregulation of the fibrinolytic regulators PAI-1 in vascular cells. The disruption of coagulation and low fibrinolysis in the femoral head will eventually lead to a disturbance in microcirculation of NONFH. We believe that our findings could be of great significance for guiding clinical trials in the future.
Prevalence and antimicrobial susceptibility pattern of Staphylococcus Aureus isolated from clinical specimens at the Mater Hospital Nairobi, Kenya.
Authors: Okello Christina , Achieng Loice , Mwachari Christina , Otieno Davies , Otieno Frederick , Omonge Enoch
Published: October 2020

Staphylococcus aureus is a leading cause of hospital and community acquired infections globally. Surveillance of prevalence and antibiotic susceptibility patterns is important to ensure appropriate antibiotic prescription. The aim of this study was to determine the prevalence and susceptibility patterns of Staphylococcus aureus isolated from clinical specimens in a tertiary referral and training hospital.A retrospective study was conducted at the Mater Misericordiae Hospital, Nairobi.It involved analyzing records of specimens analyzed between January 2014 and December 2018. Strains phenotypically resistant to <3 non β-lactam antimicrobial categories were defined as non-multidrug-resistant MRSA (nmMRSA) and strains that were resistant to ≥3 non-β-lactam antimicrobial groups were defined as multidrug-resistant MRSA (mMRSA). A specimen was categorized as Penicillin susceptible (PSSA) if susceptible to Penicillin and Oxacillin, MSSA if resistant to Penicillin and susceptible to Oxacillin, and MRSA if resistant to Oxacillin and Penicillin.ResultsPSSA accounted for 60.85%, (401/659)of S.aureus cultured.The prevalence of MSSA was 38.54%(254/659).MRSA was the least prevalent.(0.61%,4/659).No multi-drug Methicillin resistant S. aureus were isolated in the five-year period.PSSA accounted for 60.85%(401/659)of all S.aureus isolates.100% of MRSA isolated was sensitive to Vancomycin, Linezolid, Tigecycline, Tetracycline and Rifampicin. MRSA was resistant to Clindamycin and Erythromycin.Conclusion;The prevalence of MRSA was low compared to previous studies.All strains isolated were non-multidrug resistant.There was no resistance to Vancomycin detected.Penicillins are still a viable option in the treatment of majority of S.aureus infections in our setting.
Clinical outcomes and prognostic factors in bloodstream infections due to extended-spectrum β-lactamase-producing Enterobacteriaceae among patients with malignancy: a meta-analysis
Authors: Jiang Ai-Min , Liu Na , Zhao Rui , Zheng Hao-Ran , Chen Xue , Fan Chao-Xin , Zhang Rui , Zheng Xiao-Qiang , Fu Xiao , Yao Yu , Tian Tao
Published: October 2020

Background: The colonization of Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) in bloodstream infections (BSIs) has been increased dramatically worldwide, and it was associated with worse clinical outcomes in patients with malignancy. We performed the meta-analysis to investigate the prognosis and risk factors in BSIs caused by ESBL-PE in oncological patients.Methods: PubMed, EMBASE, and Cochrane Library were searched for related studies. All-cause mortality was considered as the primary outcome. Subgroup analyses, meta-regression analyses, and sensitivity analysis were used to investigate heterogeneity and reliability in results.Results: 6,729 patients from 25 studies were eligible. Six studies enrolled oncological patients with BSIs caused by ESBL-PE only, while 19 studies both enrolled ESBL-PE and non-ESBL-PE infections. The results showed that BSIs caused by ESBL-PE in patients with malignancy was associated with higher mortality than non-ESBL-PE infections (RR = 2.21, 95 % CI: 1.60–3.06, P < 0.001), with a significant between-study heterogeneity (I2 = 78.3%, P < 0.001). Subgroup analyses showed that children (RR = 2.80, 95 % CI: 2.29–3.43, P < 0.001) and hematological malignancy (RR =3.20, 95 % CI: 2.54–4.03, P < 0.001) were associated with a higher mortality. Severe sepsis/ septic shock, pneumonia, and ICU admission were the most common predictors of mortality.Conclusions: Our study identified that BSIs caused by ESBL-PE in patients with malignancy were associated with worse clinical outcomes compared with non-ESBL-PE infections. Furthermore, children and hematological malignancy were associated with higher mortality. Severe sepsis/ septic shock, pneumonia, and ICU admission were the most common predictors of mortality.
Ferulic acid attenuates microglia-mediated neuroinflammation in retinal degeneration
Authors: Sun Xiaowei , Sun Peng , Liu Limei , Jiang Pengfei , LI YUANBIN
Published: October 2020

Background: Retinal degeneration is often accompanied by microglia-mediated neuroinflammation. Ferulic acid (FA), an active ingredient of traditional Chinese medicines (TCMs), has been reported to have anti-inflammatory effects. This study explores the impact of FA on microglia-mediated neuroinflammation and associated retinal degeneration in rd10 mice.Methods: Rd10 mice received different concentrations of FA every day from postnatal day (P)4 to P24. On P25, the visual function of the mice was evaluated by electroretinogram, and retinae were collected for further investigation. Microglial activation and the expression of relevant cytokines in the retina were evaluated by qPCR, western blotting and immunofluorescence staining. Retinal structure was assessed by haematoxylin and eosin(HE) staining. Results: supplementation with 50 mg/kg FA provided optimal protection against retinal degeneration, with treated mice exhibiting more photoreceptor nuclei as well as greater wave amplitude amplification on electroretinogram than untreated mice. FA suppressed microglial activation both in vivo and in vitro, and inhibited the expression of pro-inflammatory factors Tnfα, IL1β, and Ccl2 in the retinae of rd10 mice. Furthermore, FA suppressed the activation of STAT1 and subsequently inhibited IRF8 expression, potentially highlighting a role for these pathways in FA-mediated immunomodulatory activity. Conclusions: Attenuation of neuroinflammation by FA may be beneficial for retarding retinal degeneration.
Effects of Propofol on Intracranial Pressure and Prognosis in Patients with Severe Neuropathy Undergoing Endotracheal Suctioning
Authors: Wu Menghang , Yin Xiaorong , Chen Maojun , Liu Yan , Zhang Xia , Li Tingting , Long Yujuan , Wu Xiaomei , Pu Lihui , Zhang Maojie , Hu Zhi , ye ling
Published: October 2020

Background To investigate whether the administration of intravenous propofol before endotracheal suctioning (ES) in patients with severe neuropathy can reduce the sputum suction response, improve prognosis, and accelerate recovery.Methods A total of 208 severe neuropathy patients after craniocerebral surgery were enrolled in the study. The subjects were randomly assigned to the experimental group (n=104) and the control group (n=104). The experimental group was given intravenous propofol (10ml propofol with 1ml 2% lidocaine), 0.5-1 mg/kg, before ES, while the control group was subjected to ES only. Changes in vital signs, sputum suction effect, the fluctuation range of intracranial pressure (ICP) before and after ES, choking cough response, short-term complications, length of stay, and hospitalization cost were evaluated. Additionally, the Glasgow Outcome Scale (GOS) prognosis score was obtained at six months after the operation.Results At the baseline, the characteristics of the two groups were comparable (P>0.05). The increase of systolic blood pressure after ES was higher in the control group than in the experimental group (P < 0.05). The average peak value of ICP in the experimental group during the suctioning (15.57 ± 12.31 mmHg) was lower than in the control group (18.24 ± 8.99 mmHg; P < 0.05). The percentage of patients experiencing cough reaction and pain during suctioning in the experimental group was lower than in the control group (P < 0.05), and the fluctuation range of ICP was increased (P < 0.0001). The effect of ES was achieved in both groups. The incidence of short-term complications in the two groups was comparable (P > 0.05). At 6 months after the surgery, the GOS scores were significantly higher in the experimental than in the control group (4-5 points, 51.54% vs. 32.64%; 1-3 points, 48.46% vs. 67.36%; P<0.05). There was no significant difference in the length of stay and hospitalization cost between the two groups.Conclusions Propofol sedation before ES couldreduce choking cough response, painful experience, and intracranial hypertension response. The use of propofol was safe and improves long-term prognosis.The study was registered in the Chinese Clinical Trial Registry on May 16, 2015 (ChiCTR-IOR-15006441).
Localization of Epileptic Seizure Focus by Computerized Analysis of fMRI Recordings
Authors: hekmati rasoul , Azencott Robert , Zhang Wei , Zili Chu , Paldino Michael
Published: October 2020

By computerized analysis of cortical activity recorded via fMRI for pediatric epilepsy patients, we implement algorithmic localization of epileptic seizure focus within one of eight cortical lobes. Our innovative machine learning techniques involve intensive analysis of large matrices of mutual information coefficients between pairs of anatomically identified cortical regions. Drastic selection of pairs of regions with biologically significant inter-connectivity provides efficient inputs for our Multi-Layer Perceptron (MLP) classifier. By imposing rigorous parameter parsimony to avoid overfitting we construct a small size MLP with very good percentages of successful classification.
Outcomes of 42 pregnancies in 14 women with cartilage-hair hypoplasia: a retrospective cohort study
Authors: Holopainen Elina , Vakkilainen Svetlana , Mäkitie Outi
Published: October 2020

Background: Cartilage-hair hypoplasia (CHH) is a rare skeletal dysplasia characterized by disproportionate short stature, immunodeficiency, anemia and risk of malignancies. All theses features can affect pregnancy and predispose to maternal and fetal complications. This study aimed to evaluate obstetric history and maternal and fetal outcomes in women with CHH. Methods: Among 47 Finnish women with CHH, we identified 14 women with ICD codes related to pregnancies, childbirth and puerperium in the National Hospital Discharge Registry and obtained detailed data on gynecologic and obstetric history with a questionnaire. Offspring birth length and weight were collected and compared with population-based normal values. Results: There were altogether 42 pregnancies in 14 women (median height 124 cm, range 105-139 cm; 4'1'', range 3'5''-4'7''). Twenty-six pregnancies (62%), including one twin pregnancy, led to a delivery. Miscarriages, induced abortions and ectopic pregnancies complicated 9, 5 and 2 pregnancies, respectively. Severe pregnancy-related complications were rare. All women with CHH delivered by cesarean section, mostly due to evident cephalo-pelvic disproportion, and in 25/26 cases at full-term. In the majority, the birth length (median 48 cm, range 45.5-50 cm; 1'7'', range 1'6''-1'8'') and weight (3010 g, range 2100-3320 g; 6.6 lb, range 4.6-7.3 lb) of the offspring in full-term singelton pregnancies was normal. Conclusions: Despite CHH mothers' significant short stature and other potential CHH-related effects on pregnancy outcome, most pregnancies lead to a term cesarean section delivery. Since fetal growth was generally unaffected, cephalo-pelvic disproportion was evident and planned cesarean section should be planned in term pregnancies.
Evaluation of Preventive, Supportive and Awareness Building Measures among International Students in China in Response to COVID-19: A Structural Equation Modeling Approach
Authors: Sarker Tanwne , Sarkar Apurbo , Rabbany Md. Ghulam , Barmon Milon , Roy Rana , Rahman Md. Ashfikur , Hossain Kh Zulfikar , Hoque Fazlul , Asaduzzaman Muhammad
Published: October 2020

Background:Public awareness campaigns and behavioral change campaigns are a necessary basis to facilitate and motivate the use of preventive measures. During this COVID-19 pandemic, how the Chinese government handled this vulnerable situation through enhancing behavior change communication among international students is a research interest. The objective of this current study is to evaluate the preventive, supportive and awareness building measures adopted among international students in China in response to this deadly pandemic.Method and methodology:In this study, we have evaluated how the level of awareness, satisfaction, and trust in authorities (i.e., government, local authorities, and institutions) shapes the behavior and close interconnection each other. Simple bivariate statistics was used to describe the background characteristics of the respondents along with adoption of the partial least squares-structural equation modeling (PLS-SEM) as the final model to show the association between the variables.ResultsOur study findings showed the great impact of preventive and supportive measures in the development of students’ satisfaction. The satisfied students possessed a strong influence which eventually helped in building sufficient trust on their institutions. Moreover, present study provides insight views of the selected latent variables by counteracting the interaction among them.Conclusions:The worldwide student group is one of the most affected and vulnerable communities in this situation. So there is a profound ground of research on how different states or authorities handle such situation. In this study we have depicted the types and magnitude of care taken by Chinese government and educational institutions towards international students to relieve the panic of pandemic situation. Further research and such initiatives should be taken in to consideration for future emerging conditions.
Weighted Gene Co-Expression Network Analysis revealed key biomarkers associated with the diagnosis of hypertrophic cardiomyopathy
Authors: Li Xin , Wang Chenxin , Zhang Xiaoqing , Liu Jiali , Wang Yu , Li Chunpu , Guo Dongmei
Published: October 2020

Objective: To reveal the molecular mechanism underlying the pathogenesis of HCM and find new effective therapeutic strategies using a systematic biological approach.Methods: The WGCNA algorithm was applied to building the co-expression network of HCM samples. A sample cluster analysis was performed using the hclust tool and a co-expression module was constructed. The WGCNA algorithm was used to study the interactive connection between co-expression modules and draw a heat map to show the strength of interactions between modules. The genetic information of the respective modules was mapped to the associated GO terms and KEGG pathways, and the Hub Genes with the highest connectivity in each module were identified. The Wilcoxon test was used to verify the expression level of hub genes between HCM and normal samples, and the "pROC" R package was used to verify the possibility of hub genes as biomarkers. Finally, the potential functions of hub genes were analyzed by GSEA software. Results: Seven co-expression modules were constructed using sample clustering analysis. GO and KEGG enrichment analysis judged that the turquoise module is an important module. The hub genes of each module are RPL35A for module Black, FH for module Blue, PREI3 for module Brown, CREB1 for module Green, LOC641848 for module Pink, MYH7 for module Turquoise and MYL6 for module Yellow. The results of the differential expression analysis indicate that MYH7 and FH are considered true hub genes. In addition, the ROC curves revealed their high diagnostic value as biomarkers for HCM. Finally, in the results of the GSEA analysis, MYH7 and FH highly expressed genes were enriched with the "proteasome" and a "PPAR signaling pathway," respectively.Conclusions: The MYH7 and FH genes may be the true hub genes of HCM. Their respective enriched pathways, namely the "proteasome" and the "PPAR signaling pathway," may play an important role in the development of HCM.
Comparison of the central human and mouse platelet signaling cascade by systems biological analysis
Authors: Balkenhol Johannes , Kaltdorf Kristin V. , Mammadova-Bach Elmina , Braun Attila , Nieswandt Bernhard , Dittrich Marcus , Dandekar Thomas
Published: October 2020

Background: Understanding the molecular mechanisms of platelet activation and aggregation is of high interest for basic and clinical hemostasis and thrombosis research. The central platelet protein interaction network is involved in major responses to exogenous factors. This is defined by systemsbiological pathway analysis as the central regulating signaling cascade of platelets (CC). Results: The CC is systematically compared here between mouse and human and major differences were found. Genetic differences were analysed comparing orthologous human and mouse genes. We next analyzed different expression levels of mRNAs. Considering 4 mouse and 7 human high quality proteome data sets, we identified then those major mRNA expression differences (81%) which were supported by proteome data. CC is conserved regarding genetic completeness, but we observed major differences in mRNA and protein levels between both species. Looking at central interactors, human PLCB2, MMP9, BDNF, ITPR3 and SLC25A6 (always uniprot notation) show absence in all murine datasets. CC interactors GNG12, PRKCE and ADCY9 occur only in mice. Looking at the common proteins, TLN1, CALM3, PRKCB, APP, SOD2 and TIMP1 are higher abundant in human, whereas RASGRP2, ITGB2, MYL9, EIF4EBP1, ADAM17, ARRB2, CD9 and ZYX are higher abundant in mouse. Pivotal kinase SRC shows different regulation on mRNA and protein level as well as ADP receptor P2RY12.Conclusions: Our results highlight species-specific differences in platelet signaling and points of specific fine-tuning in human platelets as well as murine-specific signaling differences.
Costs and its Drivers for Diabetes Mellitus Type 2 Patients in France and Germany: A Systematic Review of economic studies
Authors: Stegbauer Constance , Falivena Camilla , Moreno Ariadna , Hentschel Anna , Rosenmöller Magda , Heise Tim , Szecsenyi Joachim , Schliess Freimut
Published: October 2020

Background: Type 2 diabetes represents an increasingly critical challenge for health policy worldwide. It absorbs massive resources from both patients and national economies to sustain direct costs of the treatment of type 2 diabetes and its complications and indirect costs related to work loss and wages. More recently, there are innovations based on remote control and personalised programs that promise a more cost-effective diabetes management while reducing diabetes-related complications. In this context, this work attempts to update cost analysis reviews on type 2 diabetes, focusing on France and Germany, in order to explore most significant cost drivers and cost-saving opportunities through innovations in diabetes care. Although both countries approach care delivery differently, France and Germany represent the primary European markets for diabetes technologies.Methods: A systematic review of the literature listed in MEDLINE, Embase and EconLit has been carried out. It covered interventional, observational and modelling studies on expenditures for type 2 diabetes management in France or Germany published since 2012. Included articles were analysed for annual direct, associated and indirect costs of type 2 diabetes patients. An appraisal of study quality was performed. Results: were summarised narratively. Results From 1.260 records, the final sample was composed of 24 papers selected according to predefined inclusion/exclusion criteria. Both France and Germany revealed a predominant focus on direct costs. Comparability was limited due to different study populations and cost categories used. Indirect costs were only available in Germany. According to prior literature, reported cost drivers are hospitalisation, prescriptions, higher HbA1c and BMI, treatment with insulin and complications, all indicators of disease severity. The diversity of available data and included costs limits the results and may explain the differences found. Conclusions: Complication prevention and glycaemic control are widely recognized as the most effective ways to control diabetes treatment costs. The value propositions of self-based supports, such as hybrid closed-loop metabolic systems, already implemented in type 1 diabetes management, are the key points for further debates and policymaking, which should involve the perspectives of caregivers, patients and payers.
A Randomised Clinical Trial of a Theory-Based Fentanyl Overdose Education and Fentanyl Test Strip Distribution Intervention to Reduce Rates of Opioid Overdose: Study Protocol for A Randomized Controlled Trial
Authors: Jacka Brendan , Goldman Jacqueline E , Yedinak Jesse , Bernstein Edward , Hadland Scott E , Buxton Jane A , Sherman Susan G , Biello Katie , Marshall Brandon DL
Published: October 2020

Background: Opioid overdose deaths involving synthetic opioids, particularly illicitly manufactured fentanyl, remain a substantial public health concern in North America. Responses to overdose events (e.g. administration of naloxone and rescue breathing) are effective at reducing mortality; however, more interventions are needed to prevent overdoses involving illicitly manufactured fentanyl. This study protocol aims to evaluate the effectiveness of a behaviour change intervention that incorporates individual counseling, practical training in fentanyl test strip use, and distribution of fentanyl test strips for take home use among people who use drugs.Methods: Residents of Rhode Island aged 18–65 years who report recent substance use (including prescription pills obtained from the street; heroin, powder cocaine, crack cocaine, methamphetamine; or any drug by injection) (n=500) will be recruited through advertisements and targeted street-based outreach into a two-arm randomised clinical trial with 12 months of post-randomisation follow-up. Eligible participants will be randomised (1:1) to receive either the RAPIDS intervention (i.e. fentanyl-specific overdose education, behaviour change motivational interviewing (MI) sessions focused on using fentanyl test strips to reduce overdose risk, fentanyl test strip training, and distribution of fentanyl test strips for personal use), or standard overdose education as control. Participants will attend MI booster sessions (intervention) or attention-matched control sessions at 1, 2, and 3 months post-randomisation. All participants will be offered naloxone at enrolment. The primary outcome is a composite measure of self-reported overdose in the previous month at six- and/or 12-month follow-up visit. Secondary outcome measures include administratively linked data regarding fatal (post-mortem investigation) and non-fatal (hospitalisation or emergency medical service utilisation) overdoses.Discussion: If the RAPIDS intervention is found to be effective, its brief MI and fentanyl test strip training components could be easily incorporated into existing community-based overdose prevention programming to help reduce the rates of fentanyl-related opioid overdose. Trial Registration: clinicaltrials.gov: NCT04372238; 01 May 2020
A randomized, multicentre, open-label phase II proof-of-concept trial investigating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19: the Donated Antibodies Working against nCoV (DAWn-Plasma) trial.
Authors: Devos Timothy , Geukens Tatjana , Schauwvlieghe Alexander , Ariën Kevin K , Barbezange Cyril , Cleeren Myriam , Compernolle Veerle , Dauby Nicolas , Desmecht Daniël , Grimaldi David , Lambrecht Bart N , Luyten Anne , Maes Piet , Moutschen Michel , Romano Marta , Seyler Lucie , Nevessignsky Michel Toungouz , Vandenberghe Katleen , Griensven Johan van , Verbeke Geert , Vlieghe Erika , Yombi Jean Cyr , Liesenborghs Laurens , Verhamme Peter , Meyfroidt Geert
Published: October 2020

Background:The COVID-19 pandemic has imposed an enormous burden on health care systems around the world. In the past, the administration of convalescent plasma of patients having recovered from SARS and severe influenza to patients actively having the disease, showed promising effects on mortality and appeared safe. Whether or not this also holds true for the novel SARS-CoV-2 virus is currently unknown.Methods:DAWn-Plasma is a multicentre nation-wide, randomized, open-label, phase II proof-of-concept clinical trial, evaluating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19 in Belgium. Patients hospitalized with a confirmed diagnosis of COVID-19 are eligible when they are symptomatic (i.e. clinical or radiological signs) and have been diagnosed with COVID-19 in the 72 hours before study inclusion through a PCR (nasal/nasopharyngeal swab or bronchoalveolar lavage) or a chest-CT scan showing features compatible with COVID-19 in the absence of an alternative diagnosis. Patients are randomized in a 2:1 ratio to either standard of care and convalescent plasma (active treatment group) or standard of care only. The active treatment group receives 2 units of 200 to 250 mL of convalescent plasma within 12 hours after randomization, with a second administration of 2 units 24 to 36 hours after ending the first administration. The trial aims to include 483 patients and will recruit from 25 centres across Belgium. The primary endpoint is the proportion of patients that require mechanical ventilation or have died at day 15. The main secondary endpoints are clinical status on day 15 and day 30 after randomization, as defined by the WHO Progression 10-point ordinal scale, and safety of the administration of convalescent plasma.Discussion:This trial will either provide support or discourage the use of convalescent plasma as early intervention for the treatment of hospitalized patients with COVID-19 infection.Trial registration: Clinicaltrials.gov, Identifier: NCT04429854. Registered 12 June 2020 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04429854.
An endoscopic dilation method using the rendezvous approach for the treatment of severe anastomotic stenosis after rectal cancer surgery: A case report
Authors: Nakashima Takuya , Matsuhahshi Nobuhisa , Suetsugu Tomonari , Iwata Yoshinori , Kiyama Shigeru , Takahashi Takao , Fukada Masahiro , Yasufuku Itaru , Sato Yuta , Imai Takeharu , Tanaka Yoshihiro , Okumura Naoki , Kubota Masaya , Ibuka Takashi , Shimizu Masato , Yoshida Kazuhiro
Published: October 2020

Background: Postoperative anastomotic stenosis is a common complication in colorectal cancer patients (3-30%). Complete anastomotic stenosis is rare; however, when it occurs, almost all cases require surgical treatment. We herein report a case in which endoscopic dilation was effective for treating complete anastomotic stenosis after high anterior resection in a rectal cancer patient.Case presentation: The patient was a 67-year-old man who underwent laparoscopic high anterior resection for rectal cancer (RS,　 T4a, N0, M0, Stage IIB (TNM Classification of Malignant Tumors)) in May 2018. The postoperative course was good and the patient was discharged on the 12th postoperative day. Subsequently adjuvant chemotherapy was initiated with oral uracil and tegafur plus leucovorin (UFT/LV); however, he complained of frequent defecation and melena after completion of the first course of chemotherapy. Thus, colonoscopy was performed, which revealed anastomotic stenosis. Endoscopic dilation was initially attempted, but failed. Thus, low anterior resection was performed with diverting colostomy. Four additional courses of chemotherapy were administered for one month after surgery. At six months after the second surgery, colonoscopy was performed, and complete anastomotic stenosis was pointed out again. The patient was successfully treated by endoscopic dilation using the rendezvous method. After this treatment, the lumen of the anastomotic site was observed to have narrowed again and endoscopic dilatation to treat anastomotic stenosis was repeated. In addition, he received local injection of steroids in anastomotic stenosis site. The lumen of anastomotic stenosis remained after the local injection of steroids and closure of colostomy was performed nine months after the second operation.Conclusions: Endoscopic dilation using the rendezvous method was effective for treating anastomotic stenosis after colorectal surgery.
Effect of Pyrolytic Carbon Interphase on Mechanical Properties of mini T800-C/SiC Composites
Authors: Zhao Donglin , Guo Tong , Fan X.M. , Chen Chao , Ma Yue
Published: October 2020

The effect of pyrolytic carbon (PyC) thickness on the tensile property of mini T800-carbon fiber reinforced SiC matrix composites (mini-C/SiC) was studied in this work. PyC interphase was prepared by chemical vapor infiltration (CVI) process using C3H6-Ar as gas source, and the PyC thickness was adjusted from 0 to 400 nm, then the SiC matrix was prepared by CVI process using methyltrichlorosilane (MTS)-H2-Ar as precursor and gas source. The results showed that the tensile strength of mini-C/SiC increased first and then decreased with the increase of the PyC thickness. When the thickness of PyC was 100 nm, the average strength reached the maximum value of 393±70 MPa. The Weibull modulus increased from 2.0 to 8.06 with the increase of PyC thickness, the larger the Weibull modulus, the smaller the dispersion, which indicated that the regulation of PyC thickness is conducive to improve tensile properties.
RASSF1A regulates the abnormal cell proliferation in psoriasis via inhibition of YAP
Authors: Jia Jinjing , Wang Ning , Zheng Yan , Mo Xiumei , Zhang Yu , Ye Siqi , Liu Junfeng , Yan Fenggen , Li Hongyi , Chen Dacan
Published: October 2020

Background: Psoriasis is a chronic, inflammatory skin disease with high incidence, treatment resistance, and high recurrence. Currently, the exact etiology and pathogenesis of psoriasis are unclear. The goal of this study was to characterize the effect of the upstream negative regulator RAS-association domain family 1A (RASSF1A) on Yes-associated protein (YAP) in psoriasis. Methods: Skin lesions of 22 patients with psoriasis and 19 controls with normal skin tissue were used. Human epidermal keratinocytes were stimulated with M5 (IL-1 α, IL-17, IL-22, TNF-α, oncostatin M) to establish the psoriatic cell model. Methylation inhibitor 5-Aza-CdR was prepared at different concentrations (5, 10, 20 μmol/L). Cells were infected with lentivirus vector overexpressing RASSF1A. Twenty-five 6–8-week-old female BALB/c mice were used to establish the psoriatic mouse model. Mice were randomly divided into five groups: control (Vaseline applied daily), psoriasis (imiquimod applied daily), and the three different 5-Aza-CdR concentrations (applied daily with imiquimod). Methylation-specific PCR (MSP) was used to detect RASSF1A methylation and immunohistochemistry was used to detect RASSF1A expression in skin lesions. After adding 5-Aza-CdR or lentivirus vector overexpressing RASSF1A, YAP expression, cell proliferation, cell cycle, apoptosis, inflammatory cytokines, and related signal pathway activity were investigated. Results: As RASSF1A methylation level increased, its expression in patients with psoriasis and mice with skin lesions decreased. Addition of 5-Aza-CdR or lentivirus vector overexpressing RASSF1A increased the expression of RASSF1A, reduced the expression of YAP and inflammatory cytokines, cell proliferation, as well as AKT, ERK, STAT3, and NF-κB signaling pathway activities, induced cell cycle arrest in G0/G1 phase, increased apoptosis, and improved skin lesions. Conclusions: RASSF1A inhibited the proliferation of psoriatic cells, induced apoptosis, and reduced the expression of inflammatory factors by inhibiting YAP expression. Based on our findings, targeted drugs that can inhibit RASSF1A methylation and increase its expression may be useful in the treatment of psoriasis.
Study on Suitable Analysis Method for HIV-1 Non-catalytic Integrase Inhibitor
Authors: Park Ki Hoon , Kim Minjee , Bae Seoung Eun , Lee Hee Jung , Kim Kyung-Chang , Choi Byeong Sun , Kim Young Bong
Published: October 2020

Background: Integrase (IN) is an essential protein for HIV replication that catalyzes insertion of the reverse-transcribed viral genome into the host chromosome during the early steps of viral infection. Highly active anti-retroviral therapy (HAART) is a HIV/AIDS treatment method that combines three or more antiviral drugs often formulated from compounds that inhibit the activities of viral reverse transcriptase and protease enzymes. Early IN inhibitors (INIs) mainly serve as integrase strand transfer inhibitors (INSTI) that disrupt strand transfer by binding the catalytic core domain (CCD) of IN. However, mutations of IN can confer resistance to INSTI. Therefore, non-catalytic integrase inhibitors (NCINI) have been developed as next-generation INIs. Methods: In this study, we evaluated and compared the activity of INSTI and NCINI according to the analysis method. Antiviral activity was compared using p24 ELISA with MT2 cell and TZM-bl luciferase system with TZM-bl cell. Each drug was serially diluted and treated to MT2 and TZM-b1 cells, infected with HIV-1 AD8 strain and incubated for 5 and 2 days, respectively. Additionally, to analyze properties of INSTI and NCINI, transfer inhibition assay and 3'-processing inhibition assay were performed. Results: During screening of INIs using the p24 ELISA and TZM-bl luciferase systems, we found an inconsistent result with INSTI and NCINI drugs. Following infection of MT2 and TZM-bl cells with T-tropic HIV-1 strain, both INSTI and NCINI treatments induced significant p24 reduction in MT2 cells. However, NCINI showed no antiviral activity in the TZM-bl luciferase system, indicating that this widely used and convenient antiretroviral assay is not suitable for screening of NCINI compounds that target the second round of HIV-1 replication. Conclusion: Accordingly, we recommend application of other assay procedures, such as p24 ELISA or reverse transcription activity, in lieu of the TZM-bl luciferase system for preliminary NCINI drug screening. Utilization of appropriate analytical methods based on underlying mechanisms is necessary for accurate assessment of drug efficacy.