bluuebunny/crossref_metadata_2025_split huggingface dataset:
Azithromycin added to Hydroxychloroquine in Patients Admitted to Intensive Care due to Coronavirus Disease 2019 (COVID-19) – Protocol of Randomized Controlled Trial AZIQUINE-ICU
Authors: Duška František , Waldauf Petr , Halačová Milada , Zvoníček Václav , Bala Jakub , Balík Martin , Beneš Jan , Klementová Olga , Kozáková Irena , Kubricht Viktor , Roy Anne Le , Vymazal Tomáš , Řehořová Veronika , Černý Vladimír 
Published: April 2020

Abstract
Background: Novel coronavirus SARS-CoV-2 is known to be susceptible in vitro to exposure to hydroxychloroquine and its effect have been found to be potentiated by azithromycin. We hypothesize, that early administration of hydroxychloroquine alone or in combination with azithromycin can prevent respiratory deterioration in patients admitted to intensive care due to rapidly progressive COVID-19 infection. Methods: Design: Prospective, multi-centre, double blind, randomised, controlled trial (RCT). Participants: Adult (>18 years) within 24 hours of admission to intensive care unit with proven or suspected COVID-19 infection, whether or not mechanically ventilated. Exclusion criteria include duration symptoms of febrile disease for ≥1 week, treatment limitations in place or moribund patients, allergy or intolerance of any study treatment, pregnancy. Interventions: Patients will be randomized in 1:1:1 ratio to receive Hydroxychloroquine 800mg orally in two doses followed by 400mg daily in two doses and Azithromycin 500 mg orally in one dose followed by 250 mg in one dose for a total of 5 days (HC-A group) or Hydroxychloroquine+ placebo (HC group) or placebo + placebo (C-group) in addition to best standard of care, which may evolve during the trial period but will not differ between groups. Primary outcome is the composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14. Secondary outcomes: The percentage of patients who were prevented from needing intubation until day 14; ICU length of stay; mortality (in hospital) at day 28 and 90.Discussion: Although both investigational drugs are often administered off label to patients with severe COVID-19, at present, there is no data from RCTs on their safety and efficacy. In vitro and observational trial suggest their potential to limit viral replication and the damage to lungs as the most common reason for ICU admission. Therefore, patients most likely to benefit from the treatment are those with severe, but early disease. This trial is designed and powered to investigate whether the treatment in this cohort of patients leads to improved clinical patients-centered outcomes, such as mechanical ventilation-free survival.Trial registration: Clinical trials.gov: NCT04339816 (Registered on 9th April 2020); Eudra CT number: 2020-001456-18 (Registered on 29th March 2020)
Scanning Electron Microscopic Observation of the In Vitro Cultured Protozoan, Perkinsus olseni, Isolated from the Manila Clam, Ruditapes philippinarum
Authors: Gajamange Dinesh , Kim Seung-Hyeon , Choi Kwang-Sik , Azevedo Carlos , Park Kyungil 
Published: April 2020

Abstract
Background
Perkinsosis is a major disease affecting the commercially important marine mollusk Ruditapes philippinarum (Manila clam) in Asian waters. In this study, we investigated the morphological characteristics of Perkinsus olseni, the causative agent of perkinsosis, cultured under laboratory conditions at different stages of its life cycle by using a scanning electron microscope (SEM).
Results
Prezoosporangia that formed following induction with Ray’s fluid thioglycollate medium developed into zoosporangia. During this process, a discharge tube formed a porous sponge-like structure that detached before the zoospores were released; thus, this organelle operated as a bung. Liberated zoospores gradually transformed into immature trophozoites, during which detachment of the anterior flagella occurred but loss of the posterior flagella was not clearly observed in the present study. Mature trophozoites underwent schizogony by cleaving the cell forming a number of merozoites in schizonts, which were released by the rupturing of the cellular membrane of the schizont within a few days.
Conclusions
Our morphological and ultrastructural studies contribute new information on the life cycle and propagation of P. olseni.
Three-dimensional random walk models of individual animal movement and their application to trap counts modelling
Authors: Ahmed Danish Ali , Benhamou Simon , Bonsall Michael , Petrovskii Sergei 
Published: April 2020

Abstract
Background: Random walks (RWs) have proved to be a powerful modelling tool in ecology, particularly in the study of animal movement. An application of RW concerns trapping which is the predominant sampling method to date in insect ecology, invasive species, and agricultural pest management. A lot of research effort has been directed towards modelling ground-dwelling insects by simulating their movement in 2D, and computing pitfall trap counts, but comparatively very little for flying insects with 3D elevated traps. Methods: We introduce the mathematics behind 3D RWs and present key metrics such as the mean squared displacement (MSD) and path sinuosity, which are already well known in 2D. We develop the mathematical theory behind the 3D correlated random walk (CRW) which involves short-term directional persistence and the 3D Biased random walk (BRW) which introduces a long-term directional bias in the movement so that there is an overall preferred movement direction. In this study, we consider three types of shape of 3D traps, which are commonly used in ecological field studies; a spheroidal trap, a cylindrical trap and a rectangular cuboidal trap. By simulating movement in 3D space, we investigated the effect of 3D trap shapes and sizes and of movement diffusion on trapping efficiency. Results: We found that there is a non-linear dependence of trap counts on the trap surface area or volume, but the effect of volume appeared to be a simple consequence of changes in area. Nevertheless, there is a slight but clear hierarchy of trap shapes in terms of capture efficiency, with the spheroidal trap retaining more counts than a cylinder, followed by the cuboidal type for a given area. We also showed that there is no effect of short-term persistence when diffusion is kept constant, but trap counts significantly decrease with increasing diffusion. Conclusion: Our results provide a better understanding of the interplay between the movement pattern, trap geometry and impacts on trapping efficiency, which leads to improved trap count interpretations, and more broadly, has implications for spatial ecology and population dynamics.
A retrospective cohort study of clinical characteristics, treatment patterns, and disease outcomes of chronic kidney disease in patients with diabetes using a Japanese claims database
Authors: Yamazaki Toru , Yoshihara Nariaki , Yi Jingbo , Tanimura Yoko , Bruce Crawford 
Published: April 2020

Abstract
Objectives: The primary objective of this study was to characterize the clinical characteristics, treatment patterns, and clinical outcomes of chronic kidney disease (CKD) patients with diabetes, using a Japanese claims database and focusing on the use of mineralocorticoid receptor antagonists (MRAs) in this population in the real-world setting.Methods: This retrospective cohort study used the Medical Data Vision database, a large, electronic health records-based claims database in Japan. The observation period was a maximum of 8 years (from 1st April 2008 to 31st August 2016). The inclusion criteria were a claim with a diagnosis of diabetes (ICD-10: E10-E14), eGFR less than 60 mL/min/1.73 m2 at the index date, and use of any antiglycemic medications within 6 months prior to the index date or during the index month. Patients who had a claim for an MRA drug after the index date were identified as the MRA subcohort. This exploratory study investigated the burden of disease in patients with CKD and diabetes, including demographics, treatments, safety, and time-to-event analysis for renal and cardiovascular-related endpoints.Results: A total of 19,582 patients were included in the analysis, and 2,295 MRA patients were included in the subcohort. Renin-angiotensin-aldosterone system inhibitors were used at baseline by 52.3% in the overall cohort and 58.8% in the MRA subcohort. Cumulative incidences of hyperkalemia were 5.19% in the overall cohort and 7.63% in the MRA subcohort. Cox models showed that the 30–44 mL/min/1.73 m2 eGFR group had a significantly higher hazard of composite cardiovascular outcomes compared to the 45–59 mL/min/1.73 m2 group (HR, 1.22; 95% CI, 1.09–1.36).Conclusion: There are residual risks for hyperkalemia and renal and cardiovascular-related events in diabetic patients with CKD in the real-world setting in Japan, even after starting treatment with steroidal MRA drugs. The unmet needs and burden of disease should be considered in future treatments for CKD patients with diabetes.
Single cell transcriptomics of human nephritis reveal the cellular origin of kidney disease associated genes
Authors: chen zhejun , zhang ting , wang qin , li zhenyuan , xie yuanyuan , yuan xiaodong , ying liang , zhang ming , mou shan 
Published: April 2020

Abstract
Background Single cell RNA sequencing (scRNA-seq) have become a powerful tool in discovering a novel cell type and pinpointing cellular specific gene within tissues. However, in diseased kidneys, especially caused by glomerulonephritis, there have few study focusing on revealing gene expression changes at the cellular level. Methods To reveal cellular gene expression profiles of glomerulonephritis, we performed scRNA-seq of 2 human kidney transplantation donor samples, 4 human glomerulonephritis samples, 1 human malignant hypertension sample and 1 human chronic interstitial nephritis sample, all tissues were taken from biopsy. Results Upon disease occur, immune cells infiltrate which can be proved by our dataset. In the cluster of podocyte, two glomerulonephritis related genes named FXYD5 and CD74 were found, and interferon alpha/beta signalling pathway and antigen processing and presentation was enriched in podocyte of LN and IgAN comparing with other samples, thus inhibiting these signalling pathway may alleviate the symptom of these disease. Conclusions Cellular origin of kidney disease associated genes and the activated signaling pathways the genes involved in can be found by scRNA-seq.
Mitochondrial Accumulation of Apurinic/Apyrimidinic Endonuclease 1 Protein in Early Stages of Hepatocellular Carcinoma Enhances mtDNA Repairing Rate Contributing to Cell Proliferation and Mitochondrial Functionality.
Authors: Bazzani Veronica , Barchiesi Arianna , Radecka Dorota , Pravisani Riccardo , Guadagno Antonio , Loreto Carla Di , Baccarani Umberto , Vascotto Carlo 
Published: April 2020

Abstract
Background Hepatocellular carcinoma (HCC) is the leading cause of primary liver cancers. Surveillance of individuals at specific risk of developing HCC, early diagnostic markers, and new therapeutic approaches are essential to obtain a reduction in disease-related mortality. Apurinic/apyrimidinic endonuclease 1 (APE1) expression levels and its cytoplasmic localization have been reported to correlate with a lower degree of differentiation and shorter survival rate. The aim of this study is to fully investigate, for the first time, the role of the mitochondrial form of APE1 in HCC.Methods As a study model, we analyzed samples from a cohort of patients diagnosed with HCC who underwent surgical resection. Mitochondrial APE1 content, expression levels of the mitochondrial import protein Mia40, and mtDNA damage of tumor tissue and distal non-tumor liver of each patient were analyzed. In parallel, we generated a stable HeLa clone for inducible silencing of endogenous APE1 and re-expression of the recombinant shRNA resistant mitochondrially targeted APE1 form (MTS-APE1). We evaluated mtDNA damage, cell growth, and mitochondrial respiration.Results APE1’s cytoplasmic positivity in Grades 1 and 2 HCC patients showed a significantly higher expression of mitochondrial APE1, which accounted for lower levels of mtDNA damage observed in the tumor tissue with respect to the distal area. In the contrast, the cytoplasmic positivity in Grade 3 was not associated with APE1’s mitochondrial accumulation even when accounting for the higher number of mtDNA lesions measured. Loss of APE1 expression negatively affected mitochondrial respiration, cell viability, and proliferation as well as levels of mtDNA damage. Remarkably, the phenotype was efficiently rescued in MTS-APE1 clone, where APE1 is present only within the mitochondrial matrix.Conclusions Our study confirms the prominent role of the mitochondrial form of APE1 in the early stages of HCC development and the relevance of the non-nuclear fraction of APE1 in the disease progression. We have also confirmed overexpression of Mia40 and the role of the MIA pathway in the APE1 import process. Based on our data, inhibition of the APE1 transport by blocking the MIA pathway could represent a new therapeutic approach for reducing mitochondrial metabolism by preventing the efficient repair of mtDNA.
Elevated serum iron level is a predictor of prognosis in severe patients with acute kidney injury
Authors: Shu Jie , HU Yufeng , Yu Xueshu , Chen Jiaxiu , Xu Wenwei , Pan Jingye 
Published: April 2020

Abstract
Background: Accumulation of iron is associated with oxidative stress (OS), inflammation and regulated cell death. The above three reactions contribute to the development of acute kidney injury (AKI). Here we aimed to investigate the association between the serum iron level and prognosis in severe patients with AKI.Methods: A total of 483 patients with AKI defined by Kidney Disease: Improving Global Guidelines (KIDGO) were included in this retrospective study. The data was extracted from the single-center Medical Information Mart for Intensive Care Ⅲ (MIMIC-Ⅲ) database. The max serum iron concentration measured after Intensive Care Unit (ICU) admission was defined as the serum iron in the study and divided into three groups (Low group, Middle group, High group). We plotted boxplots and Kaplan–Meier curves and used cox regression analysis to analyze data.Results: In univariable Cox regression analysis, serum iron levels were significantly correlated to the prognosis of AKI patients. After adjusting for confounding variables, higher serum iron level was remained to associate with the increase in 90-day mortality in the multivariable Cox regression analysis. Moreover, the risk of 90-day mortality stepwise increased as the groups of serum iron levels increased in AKI patients.Conclusions: From our study, we investigated that high serum iron level was associated with the increased mortality in severe patients with AKI. Serum iron levels on admission can be a predictor for predicting the prognosis of AKI patients.
The impact of scrubber washwater on inland waters
Authors: Teuchies Johannes , Cox Tom J.S. , Itterbeeck Katrien Van , Me Filip J.R. , Blust Ronny 
Published: April 2020

Abstract
Background : The International Maritime Organization (IMO) has set limits on sulphur content in fuels for marine transport. However, vessels continue to use these residual high sulphur fuels in combination with exhaust gas cleaning systems (EGCS or scrubbers). Next to high sulphur, combustion of these fuels also results in higher emissions of contaminants including metals and PAHs. In scrubbers, exhaust gases are sprayed with water in order to remove SOx, resulting in acidic washwater with elevated contaminant concentrations discharged in the aquatic ecosystem. The number of vessels with scrubbers is increasing rapidly, but knowledge on washwater quality and impact are limited. Results : The scrubber washwater is found to be acidic with elevated concentrations of e.g. zinc, vanadium, copper, nickel, phenanthrene, naphthalene, fluorene and fluoranthene. Model calculations on the effects of scrubber (20% of vessels) discharge on aquatic systems showed a decrease in pH of 0.015 units and an increase in surface water concentrations for e.g. naphthalene (110% increase) and vanadium (17% increase). Conclusions : The IMO established sulphur regulations to mitigate the impact of high sulphur emissions of the maritime sector. However, the use of open loop scrubbers as an abatement technology will not reduce their contribution to the acidification. In addition, different types of scrubbers discharge washwater that is acute toxic for aquatic organisms. However, washwater is diluted and the compounds for which a large increase in surface water concentrations was calculated (Naphthalene > Phenanthrene > Fluorene > Acenaphthene > Vanadium) were not the compounds that already exceed their respective Water Quality Standards (WQS). Nevertheless, existing WQS exceedances of ‘priority hazardous substances’ (Water Framework Directive) that are also identified in the washwater indicate that coastal waters and estuaries, often with large ecological value, are already under pressure. In these areas the discharge of scrubber washwater should be discouraged.
Effects Of Non-periodized And Linear Periodized Combined Exercise Training On Insulin Resistance Indicators In Adults With Obesity: A Randomized Controlled Trial
Authors: Streb Anne Ribeiro , Leonel Larissa dos Santos , Delevetti Rodrigo Sudatti , Cavaglieri Claúdia Regina , Duca Giovani Firpo Del 
Published: April 2020

Abstract
Background
The aim was to verify the effect of non-periodized and linear periodized combined (aerobic more resistance) exercise training on insulin resistance markers in adults with obesity.
Methods
Was conducted a blinded randomized controlled trial with three groups of individuals with obesity (BMI, 30–39.9 kg/m²): control group (CG, n = 23), non-periodized group (NG, n = 23), and periodized group (PG, n = 23). The NG and PG performed aerobic and resistance exercises in the same session in aerobic-resistance order for 16 weeks. Both intervention groups trained three sessions weekly, with total duration of 60 minutes each. The aerobic training of the NG had duration of 30 min always between 50–59% of the reserve heart rate (HRres), while resistance part was compost of 6 exercise, performed always in 2 × 10–12 maximum repetitions (RM). The PG progressed the aerobic and resistance training from 40–49% to 60–69% (HRres) and from 2 × 12–14 to 2 × 8–10 RM, respectively, along intervention period. The evaluated indicators of insulin resistance included fasting glucose, fasting insulin, and homeostasis model assessment-estimated insulin resistance (HOMA-IR) collected pre and post intervention. The analyses to verify the exercise training effect were performed using generalized estimating equations.
Results
After 16 weeks of training, per protocol analysis (n = 39) showed significant reductions in HOMA-IR only in the training groups (NG: ∆=-1.6, PG: ∆=-0.6; p = 0.094). Intention-to-treat analysis demonstrated significant reductions in fasting insulin levels (NG: ∆=-1.4, PG: ∆=-1.0; p = 0.004) and HOMA-IR (NG: ∆=-5.5, PG: ∆=-3.8; p = 0.002).
Conclusion
Periodized and non-periodized combined exercise training reduces similarly insulin resistance markers in adults with obesity.
Homologous Overexpression of Genes in Cordyceps militaris Improves the Production of Polysaccharide
Authors: Yang Xi , Wang Yifeng , Chen Ping , Fan Linglu , Yang Shengli , Zhang Hui 
Published: April 2020

Abstract
Background Cordyceps polysaccharides have been used around the globe for its bioactivity for millennia. However, the study and medicinal of Cordyceps militaris polysaccharides has been hampered by the low in natural abundances. Recently, the genetic engineered C. militaris developed for production of exopolysaccharides (EPS) had received extensive attention.Results In this study, based on the biosynthetic pathway and metabolization mechanism of exopolysaccharides, the crucial biosynthetic genes of Cordyceps polysaccharides were introduced by Agrobacterium transformation to provide a high flux of EPS. 21 mutants of C. militaris were identified through antibiotic screening and DNA sequencing. The maximum yield of EPS produced by mutant CM-pgm-H was 4.63 ± 0.23 g/L, while the yield of wild-type strain was 3.43 ± 0.26 g/L. And the data obtained in the present study indicated that the yield of EPS produced by the engineered strain treated with co-overexpression of phosphoglucomutase and UDP-glucose 6-dehydrogenase genes achieved 6.11 ± 0.21 g/L, which was increased by 78.13% compared with the wild-type strain.Conclusions CM-pgm-H obtained the highest EPS content than that of mutants glucokinase, UDP-glucose pyrophosphorylase, UDP-glucose 6-dehydrogenase. It indicated that the content of protein phosphoglucomutase was the most critical influencing factor on the CP production in C.militaris. Furthermore, the EPS production of CM-ugdh-pgm-M was significantly improved 1.78-fold by co-overexpression. It anticipated that our engineering strategies will play an important role in the development of C. militaris for sustainable production of Cordyceps polysaccharides.
Effectiveness of Community-Based Interventions for Patients with Schizophrenia: A Study Protocol for a Systematic Review
Authors: Kim Soo-yeon , Kim Ah Rim 
Published: April 2020

Abstract
Background Schizophrenia requires a community-based intervention approach combined with standard treatment to prevent relapses. A literature review is required to understand the effectiveness of community-based interventions and to enhance quality in countries where they have not been fully established. This is a protocol for a systematic review of the effectiveness of community-based interventions for patients with schizophrenia. Methods Only randomized and non-randomized controlled trials and cohort studies will be considered. Studies from September 2009 to September 2019 will be searched on five databases, with the primary words: “schizophrenia” and “community mental health services.” Studies on community-based interventions for patients with schizophrenia that originated from governmental programs will be considered. To assess bias, randomized and non-randomized trials will be analyzed via the Cochrane RoB 2.0 and the ROBINS-I, respectively. Results will be descriptively synthesized and statistically analyzed, and will be structured according to patients’ characteristics, intervention type and exposure, and outcome type. Discrete variables will be calculated via odds ratio, and continuous variables will be calculated via standardized mean difference using RevMan 5.3 software. Discussion We will provide a summary of the available evidence on the effectiveness of community-based interventions and specific guidelines to improve their outcomes. Systematic review registration CRD42019145660