bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Method for Correcting Shale High-Pressure Adsorption Curves Based on Instantaneous Adsorption Capacity
Authors: Duan Xianggang , Hu Zhiming , Cai Changhong , Li Wuguang , Chang Jin , Shen Rui , Qian Cao
Published: September 2020

A high-pressure isothermal adsorption curve is the basis of calculating the amount of gas adsorbed in a shale reservoir. Although shale gas adsorption measurements report an excess adsorption amount as a function of pressure, this leads to a widely known effect in which adsorption measurements show a decrease in the excess adsorption amount at high pressure. Therefore, it is not appropriate to use the excess adsorption amount to calculate the amount of gas adsorbed. Understanding adsorption mechanics and correcting the high-pressure adsorption curve of shale is critical for accurate assessments of adsorbed shale gas. This study uses a high-pressure (more than 50 MPa) experimental setup addressing this effect in the context of hydrocarbon gas (methane) in shales. By observing the change in adsorption amount between two pressure measurement points, the instantaneous adsorption capacity (IAC) is defined to calculate the cumulative adsorption capacity (CAC). Based on an analysis of the adsorption mechanism and measurements, a new method is proposed to correct the adsorption curves and obtain absolute adsorption values. The results show that the IAC is lower than zero when the testing pressure is higher than 15 MPa. This is because the commonly used volumetric method for calculating adsorption capacity does not consider the volume of the adsorption phase. Based on the assumption that the IAC is not less than zero, the volume of the adsorbed phase at different pressures is calculated by defining the equivalent diameter of the adsorbed molecules. The corrected results show that the calculated equivalent diameter of an adsorbed methane molecule is 0.58 to 0.65 nm. Based on the modified instantaneous adsorption curve, a high-pressure adsorption model is established to fit and predict the CAC. This model provides a simpler and more practical method for obtaining the accurate amount of shale gas adsorbed.
Efficient Preparation of Nano-Starch Particles and Its Mechanism of Enhanced Oil Recovery in Low-Permeability Oil Reservoirs
Authors: Zhang Lei , Jing Cheng , Khan Nasir , He Yanlong , Gu Xiaoyu , Zheng Liming
Published: September 2020

As development of low-permeability oil reservoirs continues to increase, it urgently needs an efficient enhanced oil recovery (EOR) technology to adapt to the new situation and requirement of oilfield exploitation. Although the application of nanomaterials for the EOR of low-permeability oil reservoirs has initially obtained good results, the types of currently used nanomaterials in the field of EOR are limited, and the mechanism of EOR is still unclear.

In this paper, a type of nanosized starch particle is efficiently prepared using the method of precipitation with the help of ultrasonic oscillation. Under ultrasonic oscillation, the viscosity of starch paste can be significantly decreased, which is beneficial for the precipitation of starch nanoparticles. After ultrasonic oscillation, the size of the developed nanoparticles is smaller and controlled during the precipitation of starch paste using ethanol as the precipitating agent. The developed nanosized starch particles are suitable for the low-permeability oil reservoirs with low-salinity water.

Subsequently, the mechanism of EOR of the developed nanosized starch particles is systematically studied through laboratory experiments. In addition to changing the wettability of rock surface and decreasing oil/water interfacial tension (IFT), the nanosized starch particles can effectively change the motion state of water molecules and cause the change of the structure of water molecules. In the low-permeability core, the displacement front of the nanosized starch solution is uniform, and the sweep volume of the nanosized starch solution flooding is large. Because of a higher sweep volume and a smaller adsorption loss, nanosized starch solution flooding can achieve a better effect of oil recovery than surfactant flooding in 30 m of low-permeability porous medium. The conclusions can provide a new guidance for EOR technology to support the efficient development of low-permeability oil reservoirs.
Demographic and cardiovascular risk factors associated with drug use in truck drivers in the state of Sao Paulo, Brazil: A cross-sectional study.
Authors: Pereira Mariana Moura , Mansur Antonio Padua , Takada Julio Yoshio , Leyton Vilma
Published: September 2020

Background: The irregular routine of truck drivers favors the development of chronic noncommunicable diseases (NCDs), especially cardiovascular diseases (CVDs), which can be exacerbated by the use of illicit drugs. Methods: A cross-sectional study was carried out with data from 2,071 truck drivers who traveled through the state of São Paulo between 2010 and 2016. Socioeconomic and occupational variables, risk factors for CVD, use of illicit drugs were analyzed. Clinical and toxicological tests were also carried out. Results: The average age of the truck drivers was 42.27 ± 11.07 years, and the use of illicit drugs, at least once while working, was reported or detected in 388 (18.7%) drivers. Compared to non-users, drug users were younger (37.25 ± 9.45 vs. 43.43 ± 11.1 years; p <0.001) and single (43.3% vs. 28.4%; p <0.001). The independent variables age [OR = 0.93 (95% CI: 0.91 - 0.95; p<0.001)], smoking [OR = 2.18 (95% CI: 1.39 - 3.44; p = 0.001)], alcohol consumption [OR = 1.626 (95% CI: 1.06 - 2.49; p = 0.026)] and hours of driving per day [OR = 1.08 (95% CI: 1.01 - 1.15; p = 0.012)] were also associated with the use of illicit drugs. Conclusion: The use of illicit drugs was higher in young and single drivers and was associated with a higher prevalence of smoking, alcohol consumption and more driving hours, which are risk factors for NCDs, CVD and traffic accidents.
MISIRoot: A Robotic Minimum Invasion in Situ Imaging System for Plant Root Phenotyping
Authors: Song Zhihang , Qiu Wei , Jin Jian
Published: September 2020

The authors have withdrawn this preprint due to erroneous posting.
The Epidemiological and Economic Impact of a Cell-Based Quadrivalent Influenza Vaccine in an Adult Population in the US: A Dynamic Modeling Approach
Authors: Nguyen Van Hung , Hilsky Yvonne , Mould-Quevedo Joaquin
Published: September 2020

Background: Mutations of the H3N2 vaccine strain during the egg-based vaccine manufacturing process seem to partly explain the suboptimal effectiveness of traditional seasonal influenza vaccine. Cell-based influenza vaccines avoid such egg-adaptation, thereby improving antigenic match and vaccine effectiveness. The objective of this study was to evaluate the public health and economic impact of a cell-based quadrivalent influenza vaccine (QIVc) in adult population (18-64 years) compared to the standard egg-based quadrivalent influenza vaccine (QIVe), in the US. Methods: The impact of QIVc over QIVe in terms of public health and costs outcomes was estimated using a dynamic SEIR transmission model. The model is age-structured and accounts for 4 circulating influenza strains (A/H1N1pdm9, A/H3N2, B(Victoria), and B(Yamagata)). It was calibrated on US attack rate and strain circulation for the influenza seasons 2013-2018. US specific absolute vaccine effectiveness for QIVe, specific hospitalization rate, mortality rate, Quality-Adjusted Life Years (QALYs) and costs were extracted from published literature. Relative vaccine effectiveness of QIVc over QIVe for subjects 18-64 years of age was obtained from a US retrospective cohort study. Robustness of the results was assessed in univariate and probabilistic sensitivity analyses.Results: Switching from QIVe to QIVc in the 18-64 year-old population may prevent 5.7 M symptomatic cases, 1.8 M outpatient visits; 50K hospitalizations and 5,453 deaths annually. The switch could save 128 K QALYs and US$ 845M in direct costs, resulting in a cost-saving alternative in a 3-year time horizon analysis. Probabilistic sensitivity analyses confirmed the robustness of the cost-saving result.Conclusions: The analysis shows that QIVc is expected to prevent a substantial number of hospitalizations and deaths, and would result in substantial savings in health care costs.
Mediation of the salicylic acid pathway by ROS1 in response to abiotic stresses
Authors: Yang Liping , Jin Taicheng , Wu Yanju , Lang Chenjing , Meng Dawei , Wang Yue , Zhou Xiaofu
Published: September 2020

Background: DNA methylation plays an important role in the growth and development of plants in response to various abiotic stresses. Salicylic acid (SA) is an important signaling molecule that is synthesized by plants and induces the expression of defense genes. Results: In this paper, we investigated the molecular mechanisms by which an upstream regulator (ACD6) in the SA pathway, an ABA pathway-related gene (ACO3), and a stress resistance gene (GSTF14) were induced by various abiotic stresses. The results demonstrated that abiotic stresses, including drought, cold, and salt stresses, induced the demethylation of the repeats in the promoters of ACD6, ACO3, and GSTF14 and transcriptionally activated their expression. Furthermore, our results revealed that ROS1-mediated DNA demethylation plays an important role in the process of transcriptional activation of ACD6 and GSTF14 when Arabidopsis plants were under cold stress. Conclusion: Our results confirmed that ROS1 plays an important role in the process of defense genes in the SA pathway and stress resistance gene GSTF14 in response to abiotic stresses.
Leadership Perspectives on Learning Health Systems: a qualitative interview study
Authors: Enticott Joanne , Braaf Sandy , Johnson Alison , Jones Angela , Teede Helena
Published: September 2020

Background: Integrated utilisation of digital health data has the power to transform healthcare to deliver more efficient and effective services, and the learning health system (LHS) is emerging as a model to achieve this. The LHS uses routine data from service delivery and patient care to generate knowledge to continuously improve healthcare. The aim of this project was to explore key features of a successful and sustainable LHS to inform implementation in an Academic Health Science Centre context.Methods: We purposively identified and conducted semi-structured qualitative interviews with leaders, experienced in supporting or developing data driven innovations in healthcare. A thematic analysis using NVivo was undertaken.Results: Analysis of 26 interviews revealed five themes thought to be integral in an effective, sustainable LHS: (1) Systematic approaches and iterative, continuous learning with implementation into healthcare contributing to new best-practice care; (2) Broad stakeholder, clinician and academic engagement, with collective vision, leadership, governance and a culture of trust, transparency and co-design; (3) Skilled workforce, capability and capacity building; (4) Resources with sustained investment over time and; (5) Data access, systems and processes being integral to a sustainable LHS. Conclusions: This qualitative study provides insights into the elements of a sustainable LHS across a range of leaders in data-driven healthcare improvement. Fundamentally, an LHS requires continuous learning with implementation of new evidence back into frontline care to improve outcomes. Structure, governance, trust, culture, vision and leadership were all seen as important along with a skilled workforce and sustained investment. Processes and systems to optimise access to quality data were also seen as vital in an effective, sustainable LHS. These findings will inform a co-designed framework for implementing a sustainable LHS within the Australian healthcare and Academic Health Science Centre context. It is anticipated that application of these findings will assist to embed and accelerate the use of routine health data to continuously generate new knowledge and ongoing improvement in healthcare delivery and health outcomes.
iTRAQ-based comparative proteomic analysis of differences in the protein profiles of stems and leaves from two alfalfa genotypes
Authors: Sun Hao , Yu Jie , Zhang Fan , Kang Junmei , Li Mingna , Wang Zhen , Liu Wenwen , Zhang Jiaju , Yang Qingchuan , Long Ruicai
Published: September 2020

Background: To explore the molecular regulatory mechanisms of early stem and leaf development, proteomic analysis was performed on leaves and stems of F genotype alfalfa, with thin stems and small leaves, and M genotype alfalfa, with thick stems and large leaves.Results: Based on fold-change thresholds of >1.20 or <0.83 (p<0.05), a large number of proteins were identified as being differentially enriched between the M and F genotypes: 249 downregulated and 139 upregulated in stems and 164 downregulated and 134 upregulated in leaves. The differentially expressed proteins in stems were mainly involved in amino acid biosynthesis, phenylpropanoid biosynthesis, carbon fixation, and phenylalanine metabolism. The differentially enriched proteins in leaves were mainly involved in porphyrin and chlorophyll metabolism, phenylpropanoid biosynthesis, starch and sucrose metabolism, and carbon fixation in photosynthetic organisms. Six differentially enriched proteins were mapped onto the porphyrin and chlorophyll metabolism pathway in leaves of the M genotype, including five upregulated proteins involved in chlorophyll biosynthesis and one downregulated protein involved in chlorophyll degradation. Eleven differentially enriched proteins were mapped onto the phenylpropanoid pathway in stems of the M genotype, including two upregulated proteins and nine downregulated proteins.Conclusion: Enhanced chlorophyll synthesis and decreased lignin synthesis provided a reasonable explanation for the larger leaves and lower levels of stem lignification in M genotype alfalfa. This proteomic study aimed to classify the functions of differentially enriched proteins and to provide information on the molecular regulatory networks involved in stem and leaf development.
Haemodynamic activity characterization of Resting State Networks by Fractal Analysis and thalamocortical morphofunctional integrity in chronic migraine
Authors: Porcaro Camillo , Renzo Antonio Di , Tinelli Emanuele , Lorenzo Giorgio Di , Parisi Vincenzo , Caramia Francesca , Fiorelli Marco , Piero Vittorio Di , Pierelli Francesco , Coppola Gianluca
Published: September 2020

Background

Chronic migraine (CM) can be associated with aberrant long-range connectivity of MRI-derived resting-state networks (RSNs). Here, we investigated how the fractal dimension (FD) of blood oxygenation level dependent (BOLD) activity may be used to estimate the complexity of RSNs, reflecting flexibility and/or efficiency in information processing in CM patients respect to healthy controls (HC).

Methods

Resting-state MRI data were collected from 20 untreated CM without history of medication overuse and 20 HC. On both groups, we estimated the Higuchi’s FD. On the same subjects, fractional anisotropy (FA) and mean diffusivity (MD) values of bilateral thalami were retrieved from diffusion tensor imaging and correlated with the FD values.

Results

CM showed higher FD values within dorsal attention system (DAS) and the anterior part of default-mode network (DMN), and lower FD values within the posterior DMN compared to HC. Although FA and MD were within the range of normality, both correlated with the FD values of DAS.

Conclusions

FD of DAS and DMN may reflect disruption of cognitive control of pain in CM. Since the normal microstructure of the thalamus and its positive connectivity with the cortical networking found in our CM patients reminds similar results obtained assessing the same structures but with the methods of neurophysiology, in episodic migraine during an attack, this may be yet another evidence in supporting CM as a never-ending migraine attack.
Colossal Permittivity and Multiple Effects in (Zn + Ta) co-doped TiO2 Ceramics
Authors: Fan Jiangtao , Yang TianTian , Cao Zhenzhu
Published: September 2020

The authors have withdrawn this preprint due to erroneous posting.
Evaluation of the disease burden of sporadic Creutzfeldt-Jacob disease with the surveillance data from 2013 to 2017 in China
Authors: Gao Chen , Zhang Lina , Xiao Kang , Zhou Wei , Wang Yuan , Chen Cao , Shi Qi , Dong Xiao-Ping
Published: September 2020

Background Sporadic Creutzfeldt-Jacob disease (sCJD) is the commonest type of human prion disease and cause 100% fatality. The morbidity of sCJD is about 1 to 2 cases/million/year worldwide.Methods In this study, the disease burden of sCJD in China was evaluated based on the data of Chinese National CJD Surveillance from 2013 to 2017.Results The Disability-Adjusted Life Year (DALY) of sCJD was measured with 753 probable sCJD patients. The total DALY of 753 sCJD cases in the past five surveillance years was 16202.62 person-years. The Years of Life Lost (YLL) was the predominant component for DALY reaching to more than 95%, while the Years Lost due to Disability (YLD) accounted for less than 5% only. The highest DALY was noticed in the group of 45-50 year-old (6541.49), followed by the groups of 60-69 year-old (6311.25). Furthermore, the indirect economic burdens of 753 sCJD patients were estimated with the official capital data. Total indirect economic burden for five years was 372.08 million RMB (1US $=6.9 RMB), with the average of 494,133 RMB per case. The patients aged 45-59 years old were the predominant population that accounted for approximate 73% of total indirect economic burden. Although still lacking the exact annual incidence of sCJD in China, the DALY intensity of sCJD in China could be estimated and predicted as 2.2 to 4.4 person-years /100,000 with the global morbidity of sCJD.Conclusion This is the first disease burden assay for sCJD in China, which will supply fundamental evidence for further development of medical strategy.
Flow of Antarctic Bottom Water from the Vema Channel
Authors: Morozov Eugene G , Frey Dmitry I. , Tarakanov Roman Y.
Published: September 2020

We analyze measurements of bottom currents and thermohaline properties of water north of the Vema Channel with the goal to find pathway continuations of Antarctic Bottom Water flow from the Vema Channel into the Brazil Basin. The analysis is based on CTD/LADCP casts north of the Vema Channel. The flow in the deep Vema Channel consists of two branches. The deepest current flows along the bottom in the center of the channel and the other branch flows above the western wall of the channel. We found two smaller channels of the northern continuation of the deeper bottom flow. These flows become weak and almost disappear at a latitude of 25°30’S. The upper current flows at a depth of 4100-4200 m along the continental slope. We traced this current up to 24°S over a distance exceeding 250 km. This branch transports bottom water that eventually fills the deep basins of the North Atlantic. Key words: Vema Channel; abyssal currents; Antarctic Bottom Water; CTD/LADCP profiles; bottom layer
miR-548j-5p Regulates Angiogenesis in Peripheral Artery Disease
Authors: Lee Chiu-Yang , Lin Shing-Jong , Wu Tao-Cheng
Published: September 2020

Background: Peripheral artery disease (PAD) is a vascular disease involving diffuse atherosclerosis, which is associated with increased cardiovascular mortality and morbidity. Critical limb ischemia is the most severe complication of PAD. In addition to medical and interventional treatment, therapeutic angiogenesis is a novel therapy for PAD. Circulating microRNAs (miRNAs) are considered to be key regulators of gene expression, but their role in ischemic-induced angiogenesis is poorly characterized. There is little knowledge of specific miRNAs associated with PAD. Methods: To determine the regulation of miRNAs, we obtained miRNA profiles using RNA isolated from patients with PAD and a control group. The effect of the specific miRNA in angiogenesis were evaluated by in vitro angiogenic function of endothelial progenitor cells (EPCs), in vivo angiogenesis assay and a hind-limb ischemic model. Results: Circulating miR-548j-5p was significantly reduced in patients with PAD compared with the controls. miR-548j-5p promoted EPC angiogenesis by enhancing migration and tube formation. The endothelial nitric oxide synthase and stromal cell-derived factor (SDF)-1 signaling pathways appeared to be potential targets for miR-548j-5p. Furthermore, a directed in vivo angiogenesis assay of EPCs and a hind-limb ischemia mouse model demonstrated that miR-548j-5p enhanced capillary density and blood flow recovery in hind-limb ischemia. Conclusion: Taken together, our data indicates that up-regulation of miR-548j-5p promotes angiogenesis in ischemic tissue and might be a novel therapeutic approach for PAD.
Effectiveness of Oral Health Education Intervention Strategies Among 12-15-Year-Old School Children in Dharan, Nepal: A Randomized Controlled Trial
Authors: Subedi Krishna , Shrestha Ashish , Bhagat Tarakant , Baral Dharanidhar
Published: September 2020

Background: School aged adolescents are in particular need of preventive program to ensure positive long-term oral health and hygiene. However, due to lack of health education and insufficient preventive measures, the oral health status of these students is not always good resulting in high morbidity. The objective of this study was to assess the effectiveness of an oral health education intervention on oral hygiene knowledge, attitude and practices (KAP), plaque control and gingival health among 12-15 years old school children in Dharan sub-metropolitan city, Nepal.Methods: A randomized controlled trial was conducted with parallel study groups, comprising 12-15-year-old school children, 120 in each group (experimental and control group). Interview of the participants were done using a 23-item questionnaire for assessment of oral hygiene knowledge, attitude and practices (KAP). Oral examination was done using mouth mirror and WHO probe to record Turesky-Gilmore-Glickman modification of the Quigley-Hein plaque index (1970), Gingival index (Loe H and Silness J 1963) and Dentition status and treatment needs at baseline and third and sixth months of the study period. Analysis was done using chi-square test for categorical data and Independent t test, repeated ANOVA, Kruskal-Wallis test, Friedman test, Mann-Whitney U test for quantitative data. The level of significance was set at p<0.05.Results: There was 54.58% improvement in overall oral hygiene KAP in experimental group (p=0.001) whereas no improvement was seen in control group after 6 months of intervention. The mean plaque score was improved by 57.67% (p=0.001) in experimental group in comparison to 4.56% in control group. Gingival index was improved by 49.90% (p=0.001) in experimental group in comparison to 0.7% (p=0.05) in control group. Caries experience was increased in both groups but no significant difference was seen.Conclusions: The study concluded that oral health education was effective in improving oral hygiene KAP, plaque control and gingival health.Trial registration: The trial was retrospectively registered with Clinical Trial Registry India (CTRI) with identifier no. CTRI/2018/05/013985, registered on 05/21/2018. (http://www.ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=23651&EncHid=&modid=&compid=%27,%2723651det%27). Institutional Review Committee, B. P. Koirala Institute of Health Sciences (BPKIHS), Dharan, Nepal provided the ethical approval (Ref. No.: 292/074/075-IRC).
Cardiovascular and Renal Outcomes with SGLT-2 Inhibitors Versus GLP-1 Receptor Agonists in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease: A Systematic Review and Network Meta-Analysis
Authors: Yamada Takayuki , Bhalla Abhinav , Wakabayashi Mako , Chopra Nitin , Miyashita Hirotaka , Mikami Takahisa , Ueyama Hiroki , Fujisaki Tomohiro , Saigusa Yusuke , Yamaji Takahiro , Azushima Kengo , Urate Shingo , Suzuki Toru , Abe Eriko , Wakui Hiromichi , Tamura Kouichi
Published: September 2020

BackgroundBoth sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are known to reduce cardiovascular and renal events in type 2 diabetes mellitus (DM) patients. However, no study to date has compared the effect of SGLT-2 inhibitors with that of GLP-1 RAs in type 2 DM patients with chronic kidney disease (CKD). We herein investigated the benefits of SGLT-2 inhibitors and GLP-1 RAs in CKD patients.MethodsWe performed a systematic literature search through July 2020. We selected randomized control trials that compared the risk of major adverse cardiovascular events (MACE) and a composite of renal outcomes. We performed a network meta-analysis to compare SGLT-2 inhibitors with GLP-1 RA indirectly. Risk ratios (RRs) with corresponding 95 % confidence interval (CI) were synthesized.ResultsFifteen studies were selected with a total of 20,947 patients. SGLT-2 inhibitors led to a risk reduction in MACE (RR [95 % CI]; 0.80 [0.70-0.91]) , but GLP-1 RAs did not (RR 0.89 [0.78-1.00]). Compared to GLP-1 RAs, SGLT-2 inhibitors did not demonstrate a significant difference (RR 0.90 [0.75-1.08]). Similarly, SGLT-2 inhibitors significantly decreased renal events (RR 0.66 [0.58-0.75]), but GLP-1 RAs did not (RR 0.80 [0.90-1.00]). SGLT-2 inhibitors were also associated with a lower risk of renal events compared to GLP-1 RAs (RR 0.73 [0.62-0.87]).ConclusionsIn patients with type 2 DM and CKD, SGLT-2 inhibitors were associated with a decreased risk of cardiovascular and renal events, but GLP-1 RA were not. SGLT-2 inhibitors significantly decreased the risk of renal events compared to GLP-1 RAs.
Dynamic stability of complex networks
Authors: Barzel Baruch , Meena Chandrakala , Hens Chittaranjan , Haber Simi , Stefano Boccaletti
Published: September 2020

Will a large complex system be stable? This question, first posed by May in 1972, captures a long standing challenge, fueled by a seeming contradiction between theory and practice. While empirical reality answers with an astounding yes, the mathematical analysis, based on linear stability theory, seems to suggest the contrary - hence, the diversity-stability paradox. Here we settle this dichotomy, by considering the interplay between topology and dynamics. We show that this interplay leads to the emergence of non-random patterns in the system's stability matrix, leading us to relinquish the prevailing random matrix-based paradigm. Instead, we offer a new matrix ensemble, which captures the dynamic stability of real-world systems. This ensemble helps us analytically identify the relevant control parameters that predict a system's stability, exposing three broad dynamic classes: In the asymptotically unstable class, diversity, indeed, leads to instability a la May's paradox. However, we also expose an asymptotically stable class, the class in which most real systems reside, in which diversity not only does not prohibit, but, in fact, enhances dynamic stability. Finally, in the sensitively stable class diversity plays no role, and hence stability is driven by the system's microscopic parameters. Together, our theory uncovers the naturally emerging rules of complex system stability, helping us reconcile the paradox that has eluded us for decades.
Defining the Features of Registry Based Randomised Controlled Trials (rRCT): A Systematic Review
Authors: Shea Niamh O , Eustace Joseph , Shiely Frances
Published: September 2020

Background: Registry Based Randomised Controlled Trials have been described as pragmatic studies utilising patient data embedded in large scale registries, to facilitate key clinical trial procedures such as case report completion, randomisation and follow up data. While the practice of utilising registries to support the conduct of randomised trials is increasing, the reporting of how a registry is used within a trial can vary, causing difficulty in identifying registry based randomised trials and interpreting their exact definition. Methods: The databases PubMed, Embase, Cinahl Plus, Scopus and the Cochrane Central Register of Controlled Trials will be searched using a combination of subject headings, MeSH and free text terms. Search terms will be adapted accordingly for each database, with English language articles included and no other filters applied. Also, grey literature and reference lists will be searched, contacting trial authors for clarification when necessary. Two independent reviewers will complete study screening, selection and quality assessment. A preliminary synthesis will be conducted tabulating the relevant evidence into separate data extraction tables. A narrative synthesis approach will be adopted based on the Guidance on the Conduct of Narrative Synthesis in Systematic Reviews.Results: The present study will synthesise existing registry based randomised trial literature and define their key features.Conclusions: It is essential that trialists and researchers can review published trials and endeavour to duplicate trial designs. There is a lack of consensus in terms of the reporting of registry based randomised trials, making replication of this emerging trial design difficult. This review will clearly summarise and define the key features of these randomised trials, to allow researchers understand and reproduce the novel registry based randomised controlled trial methodology. Systematic Review Registration: PROPSERO CRD42020192419
Effects of Immediate and Delayed Loading Protocols on Marginal Bone Loss Around Implants in Unsplinted Mandibular Implant-Retained Overdentures: A Systematic Review and Meta-Analysis
Authors: Liu Wei , Cai He , Zhang Junjiang , Wang Jian , Sui Lei
Published: September 2020

Background: Immediate loading has recently been introduced into unsplinted mandibular implant-retained overdentures for the management of edentulous patients due to their increasing demand on immediate aesthetics and function. However, there is still a scarcity of meta-analytical evidence on the efficacy of immediate loading compared to delayed loading in unsplinted mandibular implant-retained overdentures. The purpose of this study was to compare the marginal bone loss (MBL) around implants between immediate and delayed loading of unsplinted mandibular implant-retained overdentures.Methods: Randomized controlled trials (RCTs), controlled clinical trials (CCTs), and cohort studies quantitatively comparing the MBL around implants between immediate loading protocol (ILP) and delayed loading protocol (DLP) of unsplinted mandibular overdentures were included. A systematic search was carried out in PubMed, EMBASE, and CENTRAL databases on April 28, 2020. “Grey” literature was also searched. A meta-analysis was conducted to compare the pooled MBL of two different loading protocols of unsplinted mandibular overdentures through weighted mean differences (WMDs) with 95% confidence intervals (95% CIs). The subgroup analysis was performed between different attachment types (i.e. Locator attachment vs. ball anchor). The risk of bias within and across studies were assessed using the Cochrane Collaboration’s tool, the Newcastle-Ottawa scale, and Egger’s test. Results: Of 305 records, five RCTs and two cohort studies were included and evaluated, which totally contained 191 participants with a follow-up of no less than 12 months. The MBL of ILP group showed no significant difference with that of DLP group (WMD 0.04, CI -0.13 to 0.21, P > .05). The subgroup analysis revealed similar results between the two different loading groups restored with Locator attachments or ball anchors (P > .05). Apart from one RCT (20%) with a high risk of bias, four RCTs (80%) showed a moderate risk of bias. Two prospective cohort studies were proved with acceptable quality. Furthermore, the Egger’s test indicated no significant bias among seven included studies (P > .05). Conclusions: For unsplinted mandibular implant-retained overdentures, the MBL around implants after ILP seems comparable to that of implants after DLP. Immediate loading may be a promising alternative to delayed loading for the management of unsplinted mandibular implant-retained overdentures. PROSPERO registration number: CRD42020159124
Phenotypic and Molecular Characterization of the Capsular Serotypes of Pasteurella Multocida Isolates From Bovine Respiratory Disease Cases in Ethiopia
Authors: Yilma Mirtneh Akalu , Vemulapati Murthy Bhadra , Tefera Takele Abayneh , Yami Martha , Negi Teferi Degefa , Belay Alebachew , Derese Getaw , Leykun Esayas Gelaye
Published: September 2020

Background: Pasteurella multocida is a heterogeneous species and opportunistic pathogen that causes bovine respiratory disease. This disease is one of an economically important disease in Ethiopia. Losses due to mortality and associated expenses are estimated to be higher in the country. Studies revealed that limited information is available regarding the capsular types, genotypes, and antimicrobial sensitivity of P. multocida isolates circulating in the country. This suggests, further molecular advances to understand the etiological diversity of the pathogens representing severe threats to the cattle population. Results: Bacteriological analysis of nasopharyngeal swab and pneumonic lung tissue samples collected from a total of 400 samples revealed isolation of 61 (15.25%) P. multocida subspecies multocida. 35 (20.59%) were isolated from calves and 26 (11.30%) from adult cattle. Molecular analysis using PCR assay targeting KMT1 gene (~460 bp) amplification was shown in all presumptive isolates. Capsular typing also confirmed the presence of serogroup A (hyaD-hyaC) gene (~1044 bp) and serogroup D (dcbF) gene (~657 bp) from 56 (91.80%) and 5 (8.20%) isolates, respectively. The biovar typing identified 48 (78.69%) isolates of biovar 3. Phylogenetic analysis based on the hyaD-hyaC gene nucleotide sequences showed that P. multocida serogroup A are genetically closely related to the different P. multocida isolates retrieved from the GenBank. Antibiogram of isolates revealed high sensitivity towards chloramphenicol (100%), amoxicillin (95.08%), and amikacin (90.16%). Resistance was observed in cloxacillin (88.52%) and Penicillin-G (77.05%). Conclusions: In the present study, P. multocida capsular type A biovar 3 was predominantly isolated from pneumonic cases in cattle in the study areas. The finding provides useful information for further research and choice of antimicrobials for treatment. Hence, further comprehensive molecular epidemiological investigation is proposed covering wider areas of the country to identify pathogens associated with BRD for an effective control strategy.
Diagnostic and Prognostic Value of the Electrocardiogram in Stable Outpatients With Type 2 Diabetes
Authors: Gregers Mads Christian Tofte , Schou Morten , Jensen Magnus T. , Jensen Jesper , Petrie Mark C. , Vilsbøll Tina , Goetze Jens Peter , Rossing Peter , Jørgensen Peter G.
Published: September 2020

Background: The 2019 European Society of Cardiology (ESC) guidelines on diabetes and cardiovascular disease (CVD) recommend an electrocardiogram (ECG) in patients with diabetes and hypertension or with suspected CVD, including heart failure (HF). The objective was to investigate whether ECG abnormalities can be used as a diagnostic and prognostic marker of HF in patients with type-2 diabetes (T2D) in secondary care diabetes-clinics. Methods: A total of 722 patients with T2D in sinus rhythm were prospectively included. The ESC definition of HF with reduced and preserved ejection fraction (HFrEF and HFpEF) was used. An abnormal ECG was defined as having Q-waves, bundle-branch-block, left ventricular hypertrophy, or ST-T deviations. The composite endpoint was incident CVD and cardiovascular death.Results: Overall, 24% patients had ECG abnormalities. A total of 13% had HF (2.5% HFrEF and 11% HFpEF) whereof 51% had ECG abnormalities. A normal ECG had a 99.2% negative predictive value (NPV) of ruling out HFrEF. The ECG was less efficient in ruling out HFpEF (NPV of 92%). In a multivariable analysis, the hazard-ratio (HR) of incident cardiovascular disease or death in patients with HFrEF or HFpEF and a normal ECG compared to patients without HF was 1.88 [1.00-3.53], p=0.05, while an abnormal ECG increased the HR to 3.62 [2.18-6.00], p<0.001.Conclusion: HFrEF was rare and HFpEF was frequent in this T2D population. A normal ECG could safely rule out HFrEF but not HFpEF. The ECG carried prognostic information and an abnormal ECG increased the HR for incident cardiovascular event or cardiovascular death.
Time driven activity-based costing as a strategy to increase value: a case from cardiac interventional procedure
Authors: Etges Ana Paula Beck da Silva , Cruz Luciane N , Schlatter Rosane , Neyeloff Jeruza , Carodso Ricardo B , Kopittke Luciane , Nunes Altacilio , Neto José Alburquerque , Nogueira José , Assis Renata de , Tobias Joilma , Marin-Neto José , Moreira Leila , Polanczyk Carisi Anne
Published: September 2020

BackgroundAdopting value-based health care management strategies requires monitoring of real costs and care delivered to patients. In unified health systems, recognizing institutions that provide high-quality services, demands understanding their processes of care and costs. This study aimed to evaluate processes and costs of interventional coronary procedures performed in public academic hospitals of a middle-income country.MethodsData from 90 patients submitted to the coronary angioplasties were evaluated in five hospitals in Brazil. Time-driven activity-based costing (TDABC) was used to assess real-world costs and time spent over the care pathway. Descriptive cost analyses were followed by a labor cost-saving estimate potentially achieved by the redesign of the ICP pathway, considering the benchmark of patient care cycle identified in the sample of hospitals studied.ResultsThe mean cost per patient of interventional angioplasties was $1,677 (SD $881). The procedure phase duration per patient was similar between the hospitals, while the post procedure presented the highest length of time variation. However, it was possible to demonstrate that the highest direct cost saving opportunities are concentrated in the procedure phase, due to the way that labor and non-labor resources are consumed. The physician involvement redesign can account for a 51% ICP cost decrease. ConclusionThis study demonstrated how the level of detailing provided by microcosting methods such as TDABC can contribute to driving health care management to value. In a public health system, turning transparent how resources are allocated in an individual level basis along an entire episode of care might allow managers to identify cost-saving opportunities and ways to improve the health service delivery.
Chronic cough in children: the etiology and medical history of 420 cases in Shanghai
Authors: Jiang Yonghong , Jiang Zhiyan , Yang Zhoujian , Li Junxia , Mao Liming , Gu Jingwen , Chen Yiliu , Wang Shuqin , Jang Sunguk , Xiao Zhen
Published: September 2020

Background

Chronic cough is one of the most common and frequently-occurring diseases in children. We investigated the etiologies and clinical features of children with chronic cough (CC), in order to improve the diagnostic and treatment of the disease by pediatricians.
Methods

The clinical data of 420 cases of children, aged 1–14 years old, from 5 hospitals’ Outpatient Department in different regions of Shanghai, who suffered from chronic cough between the period of September 2017 and July 2019 were prospectively analyzed. Children with chronic cough were enrolled to identify the specific cause and clinical information based on a questionnaire survey. All the data were collected and statistically analyzed by Chi-square test to identify the constituent ratio of each cause.
Results

The etiology component ratio showed that 146 cases (34.8%) had post-infection cough (PIC); 96 cases (22.9%) had upper airway cough syndrome (UACS); 90 cases (21.4%) had cough variant asthma (CVA); 75 cases (17.9%) had allergic (atopic) cough (AC); 11 cases (2.6%) had tourette cough (TS); 2 cases (0.5%) had gastroesophageal reflux cough (GERD). For the children with CC, the mainly age of onset is 3–6 years (54.05%). The mainly cough character is wet cough (65.7%). 67.1% of children with chronic cough were prescribed antibiotics, of which 41.7% were azithromycin. Various cough drops, antihistamines, aerosolized inhalation, montelukast, etc. were often used in the treatment of children's chronic cough.
Conclusion

The leading 3 causes of chronic cough in children were PIC, UACS and CVA. The mainly age of onset is 3–6 years; mainly cough character is wet cough. Antibiotics are the mainly treatment, often combined with cough medicine and atomization.
PD-L1 chimeric costimulatory receptor improves the efficacy of CAR-T cells for PD-L1-positive solid tumors and reduces toxicity in vivo
Authors: Liao Qibin , Mao Yunyu , He Huan , Ding Xiangqing , Zhang Xiaoyan , Xu Jianqing
Published: September 2020

Background: On-target off-tumor toxicity impedes the clinical application of chimeric antigen receptor-modified T cells (CAR-T cells) in the treatment of solid tumors. The combinatorial antigen recognition strategy can improve the therapeutic safety of CAR-T cells by targeting two different tumor-associated antigens (TAAs) using a CAR and a chimeric costimulatory receptor (CCR). Although programmed death-ligand 1 (PD-L1, also known as B7-H1) is expressed on multiple tumors, the potential of PD-L1 as a universal target for designing CCR remains unknown.Methods: A first-generation CD19 or HER2 CAR and a PD-L1 CCR containing the CD28 signaling domain were constructed and delivered into Jurkat T cells or primary T cells by a pseudotyped lentivirus. The release of cytokines, including IL-2, IFN-γ and TNF-α, was quantified using enzyme-linked immunosorbent assay (ELISA) kits or a cytometric bead array (CBA). The in vitro cytotoxicity of CAR-T cells was detected with a luciferase-based killing assay. The in vitro proliferation of CAR-T cells was assessed by flow cytometry. The therapeutic safety and efficacy of CAR-T cells was evaluated using a subcutaneous dual-tumor model in vivo.Results: Jurkat T cells or primary T cells expressing both the CD19/HER2 CAR and PD-L1 CCR produced higher levels of cytokines in the presence of CD19/HER2 and PD-L1 than in the presence of HER2/CD19. Compared to HER2-z-engineered T cells, HER2-z-PD-L1-28-engineered T cells had higher in vitro cytotoxicity potential against PD-L1-positive tumor cells. CD19/HER2-z-PD-L1-28-engineered T cells showed higher proliferation potential in the presence of CD19/HER2 and PD-L1 than in the absence of PD-L1. CD19/HER2-z-PD-L1-28-engineered T cells preferably destroyed xenograft tumors expressing CD19/HER2 and PD-L1 in vivo and did not significantly affect CD19/HER2-expressing tumors. The PD-L1 CCR improved the antitumor efficacy of low-affinity HER2 CAR-T cells against PD-L1-positive tumors expressing high levels of HER2.Conclusion: Our findings confirmed that PD-L1 can be used as a universal target antigen for designing CCR, improving the efficacy of CAR-T cells in the treatment of PD-L1-positive solid tumors but reducing toxicity within PD-L1-negative normal tissues expressing low levels of TAA in vivo.
A Universal Approach to Target Various HBB Gene Mutations in Hematopoietic Stem/Progenitor Cells for Beta-Thalassemia Gene Therapy by CRISPR/Cas9 and the rAAV6 Vector
Authors: He Li-Na , Yang Yi , Cheng Yi , Wu Han , Lin Shou-Heng , Song Bing , Liu Neng-Qing , Chen Di-Yu , Lu Dian , Yang Ying-Hong , Zeng Juan , Fan Yong , Xiaofang Sun
Published: September 2020

Background

Engineered nuclease-mediated gene targeting through homology-directed repair (HDR) in autologous hematopoietic stem and progenitor cells (HSPCs) has the potential to cure β-thalassemia (β-thal). Although previous studies have precisely corrected site-specific HBB mutations by HDR in vitro and in vivo, targeting the various HBB mutations in β-thal is still challenging. Here, we devised a universal strategy to achieve repaired most types of HBB mutations through the CRISPR/Cas9 and the rAAV6 donor.
Methods

Using cord blood-derived HSPCs from health donors, we tested the strategy to achieved highly efficient targeted integration by optimizing design and delivery parameters of a ribonucleoprotein (RNP) complex comprising Cas9 protein and modified single guide RNA, together with a rAAV6 donor. We assessed the edited HSPCs function in vitro by methylcellulose colonies assay, CFU assay, differentiation experiment and Wright-Giemsa staining. Edited HSPCs transplanted into NSI mice to assess the long-term reconstitution in vivo. Whole-genome sequencing was used to analysis the off-target mutagenesis of edited HSPCs.
Results

Edited HSPCs exhibited normal multilineage formation and erythroid differentiation abilities without off-target mutagenesis and retained the ability to engraft. Moreover, we used the strategy to efficiently correct the β-CD41/42 mutation of patient-derived HSPCs, erythrocytes differentiation from which expressed more HBB mRNA than uncorrected cells.
Conclusion

This strategy demonstrated a universal approach to correct most types of HBB gene mutations in β-thal.
A Simplified Method to Isolate Rice Mitochondria
Authors: Xu Yanghong , Li Xiaoyi , Huang Jishuai , Peng Leilei , Luo Dinghui , Zhang Qiannan , Dan Zhiwu , Xiao Haijun , Yang Fang , Hu Jun
Published: September 2020

Background: Mitochondria play critical roles in plant growth, development and stress tolerance. Numerous researchers participate in the studies of plant mitochondrial genome structure, mitochondrial metabolism and nuclear-cytoplasmic interactions. However, traditional plant mitochondria extraction methods are time-consuming and complicated operation of ultra-centrifuge with the expensive reagent. To develop a more rapid and convenient method for isolation of plant mitochondria, in this study we established a simplified method to isolate rice mitochondria efficiently for further study.Results: To isolate rice mitochondria, the cell wall was first dispelled by enzymolysis to obtain the protoplast which is similar to the animal cell. Then the rice mitochondria were isolated with a modified method basing on the animal mitochondria isolation protocol. The extracted mitochondria were next detected on DNA level and protein level to rule out the contamination of nucleus and chloroplasts. Furthermore, we examined the physiological status and characters of the isolated mitochondria, including the integrity of mitochondria, mitochondrial membrane potential, and the activity of inner membrane complexes. Our results demonstrated that the extracted mitochondria were remained intact for further studies.Conclusion：The combination of plant protoplasts isolation and animal mitochondria extraction methods facilitates the extraction of plant mitochondria without ultracentrifugation. Consequently, this improved method is cheap and time-saving with good operability, and can be broadly applied in the researches on plant mitochondria.