bluuebunny/crossref_metadata_2025_split huggingface dataset:
Azithromycin added to hydroxychloroquine for patients admitted to intensive care due to coronavirus disease 2019 (COVID-19)—protocol of randomised 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 , Le Roy Anne , Vymazal Tomáš , Řehořová Veronika , Černý Vladimír ,   on behalf of Czech Anaesthesia Clinical Trials and Audit Network
Published: July 2020

Abstract
Background
Novel coronavirus SARS-CoV-2 is known to be susceptible in vitro to exposure to hydroxychloroquine and its effect has been found to be potentiated by azithromycin. We hypothesise 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 h of admission to the 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, and pregnancy. Interventions: Patients will be randomised in 1:1:1 ratio to receive Hydroxychloroquine 800 mg orally in two doses followed by 400 mg 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 the 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, and 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 suggests 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 patient-centred outcomes, such as mechanical ventilation-free survival.

Trial registration
Clinical trials.gov: NCT04339816 (Registered on 9 April 2020, amended on 22 June 2020); Eudra CT number: 2020-001456-18 (Registered on 29 March 2020).
Multi-method genome- and epigenome-wide studies of inflammatory protein levels in healthy older adults
Authors: Hillary Robert F. , Trejo-Banos Daniel , Kousathanas Athanasios , McCartney Daniel L. , Harris Sarah E. , Stevenson Anna J. , Patxot Marion , Ojavee Sven Erik , Zhang Qian , Liewald David C. , Ritchie Craig W. , Evans Kathryn L. , Tucker-Drob Elliot M. , Wray Naomi R. , McRae Allan F. , Visscher Peter M. , Deary Ian J. , Robinson Matthew R. , Marioni Riccardo E. 
Published: July 2020

Abstract
Background
The molecular factors which control circulating levels of inflammatory proteins are not well understood. Furthermore, association studies between molecular probes and human traits are often performed by linear model-based methods which may fail to account for complex structure and interrelationships within molecular datasets.

Methods
In this study, we perform genome- and epigenome-wide association studies (GWAS/EWAS) on the levels of 70 plasma-derived inflammatory protein biomarkers in healthy older adults (Lothian Birth Cohort 1936; n = 876; Olink® inflammation panel). We employ a Bayesian framework (BayesR+) which can account for issues pertaining to data structure and unknown confounding variables (with sensitivity analyses using ordinary least squares- (OLS) and mixed model-based approaches).

Results
We identified 13 SNPs associated with 13 proteins (n = 1 SNP each) concordant across OLS and Bayesian methods. We identified 3 CpG sites spread across 3 proteins (n = 1 CpG each) that were concordant across OLS, mixed-model and Bayesian analyses. Tagged genetic variants accounted for up to 45% of variance in protein levels (for MCP2, 36% of variance alone attributable to 1 polymorphism). Methylation data accounted for up to 46% of variation in protein levels (for CXCL10). Up to 66% of variation in protein levels (for VEGFA) was explained using genetic and epigenetic data combined. We demonstrated putative causal relationships between CD6 and IL18R1 with inflammatory bowel disease and between IL12B and Crohn’s disease.

Conclusions
Our data may aid understanding of the molecular regulation of the circulating inflammatory proteome as well as causal relationships between inflammatory mediators and disease.
Potential roles of psychological and oxidative stress in insulin resistance: a cohort-based study
Authors: Janczura Miroslaw , Dropinski Jerzy , Gielicz Anna , Kotula-Horowitz Katarzyna , Iwaniec Teresa , Stanisz Andrzej , Rosa Rafal , Domagala Teresa B. 
Published: July 2020

AbstractBackgroundThe present study investigated the relationships between psychological stress indices and oxidative stress marker, also when combined with emergent insulin resistance (IR), in the non-diabetic, middle-aged subjects, exposed to frequent/chronic psychological stressors.MethodsCross-sectional data from a cohort of non-diabetic police officers (n = 234; 19F), aged 27–56 years, were used. Plasma inflammatory (CRP, TNF-α), oxidative stress (free 8-iso-prostaglandin F2α; 8-iso-PGF2α) markers, and insulin were measured. The value of homeostasis model assessment of IR index (HOMA-IR) was assumed the threshold value of IR, i.e. 2.04. Free cortisol in urine and perceived stress (psychological stress indices) were also measured.ResultsIn the IR subjects, most biochemical variables, inflammatory markers and urine cortisol were significantly higher, as compared to the non-IR ones. Psychological stress indices were associated with plasma 8-iso-PGF2α[B = 0.139, 95% CI (0.048, 0.230), p = 0.002, and B = 0.007, 95% CI (0.0006, 0.014), p = 0.03; for perceived stress level and cortisol, respectively]. Positive associations were established between plasma 8-iso-PGF2α[B = 0.069, 95% CI (0.016–0.120), p = 0.01] and urine cortisol [B = 0.003, 95% CI (0.0003, 0.005), p = 0.02] with HOMA-IR. Metabolic syndrome, as defined by IDF criteria, was established in 110 study subjects, whereas 136 of them were hypertensive. Waist circumference [B = 0.056, 95% CI (0.039, 0.074), p < 0.0001], and systolic blood pressure [B = 0.009, 95% CI (0.00003, 0.018), p = 0.04] were positively associated with HOMA-IR, whereas the association of HDL cholesterol [B = − 0.597, 95% CI (− 1.139, − 0.055), p = 0.03] was a negative one. Cortisol [OR = 1.007, 95% CI (1.002, 1.012), p = 0.006], and 8-iso-PGF2α[OR = 1.103, 95% CI (1.010, 1.201), p = 0.02] affected the incidence of IR. After adjustment for metabolic syndrome (or its components), age, sex, and current smoking, the effects became non-significant. Out of metabolic syndrome components, waist circumference [OR 4.966, 95% CI (2.29, 10.751), p = 0.00004] and hypertriglyceridemia [OR 1.993, 95% CI (1.063, 3.736), p = 0.03] increased the chance of IR incidence.ConclusionsBoth psychological stress indices were associated with oxidative stress, but only cortisol with HOMA-IR. In the subjects exposed to frequent/chronic psychological stressors, cortisol and oxidative stress marker affected IR incidence, being statistically attenuated, though, following adjustment for metabolic syndrome, or its components.
The MLH1 polymorphism rs1800734 and risk of endometrial cancer with microsatellite instability
Authors: Russell Holly , Kedzierska Katarzyna , Buchanan Daniel D. , Thomas Rachael , Tham Emma , Mints Miriam , Keränen Anne , Giles Graham G. , Southey Melissa C. , Milne Roger L. , Tomlinson Ian , Church David , Spurdle Amanda B. , O’Mara Tracy A. , Lewis Annabelle 
Published: July 2020

AbstractBoth colorectal (CRC, 15%) and endometrial cancers (EC, 30%) exhibit microsatellite instability (MSI) due to MLH1 hypermethylation and silencing. The MLH1 promoter polymorphism, rs1800734 is associated with MSI CRC risk, increased methylation and reduced MLH1 expression. In EC samples, we investigated rs1800734 risk using MSI and MSS cases and controls. We found no evidence that rs1800734 or other MLH1 SNPs were associated with the risk of MSI EC. We found the rs1800734 risk allele had no effect on MLH1 methylation or expression in ECs. We propose that MLH1 hypermethylation occurs by different mechanisms in CRC and EC.
Transient elevation of serum ferritin in a Sri Lankan with homozygosity for H63D mutation in the HFE gene: a case report
Authors: Wickramasinghe Wasanthi , Karunathilaka Chathurika , Jayasinghe Saroj , Gooneratne Lallindra 
Published: July 2020

Abstract
Introduction
Hereditary hemochromatosis is an inherited disorder of iron metabolism, characterized by excessive iron deposition in major organs of the body, leading to multi-organ dysfunction. It is a genetically heterogeneous disease caused by mutations in one or more different genes, the most common being mutations in the HFE gene. HFE hereditary hemochromatosis is mostly found in Europeans and is almost always a result of two mutations: C282Y and H63D. The H63D mutation is not as penetrant as the C282Y mutation, but there are rare reported cases of hereditary hemochromatosis with homozygous H63D genotype. While the C282Y mutation is primarily confined to persons of Northern European origin, the H63D mutation is spread worldwide. Other types of hereditary hemochromatosis are rare and broadly defined as non-HFE hereditary hemochromatosis and include mutations in the hemojuvelin gene, hepcidin (HAMP gene), transferrin receptor 2 gene, and ferroportin gene.
Hereditary hemochromatosis is commonly found in populations of European origin; in contrast, it is rare and less well understood in Asia. It can be masked by the presence of concurrent iron deficiency or secondary iron overload in thalassemias.

Case presentation
We report the case of a 42-year-old Sri Lankan man investigated for fatigue during a brief upper respiratory tract infection and found to have high liver transaminases and high serum ferritin, which persisted even after complete resolution of the infection. Homozygosity for H63D mutation in the HFE gene was detected. Liver enzymes, serum ferritin, and transferrin saturation normalized following venesections.

Conclusion
This case adds to the literature on the importance of being vigilant and investigating patients suspected for iron overload, including genetic studies for hereditary hemochromatosis, even though it is a rare clinical entity in Asians.
Pathogenic characteristics of a QX-like infectious bronchitis virus strain SD in chickens exposed at different ages and protective efficacy of combining live homologous and heterologous vaccination
Authors: Shao Lei , Zhao Jing , Li Lihua , Huang Xiuying , Yang Huiming , Cheng Jinlong , Liu Changqing , Zhang Guozhong 
Published: July 2020

AbstractContinued reports of infections with infectious bronchitis virus (IBV) variants have occurred since its first isolation in the 1930s. Currently, QX-like IBVs are the predominant circulating genotype around the world. Here, the pathogenicity of QX-like IBV strain SD was characterized in chickens at different ages of exposure to the virus, and the protection efficacy of available vaccine combinations against IBV was evaluated. The results revealed that QX-like IBV strain SD was severely pathogenic in chickens, causing respiratory, urinary and reproductive infections, irrespective of age, based on clinical observations, viral distribution in tissues and a ciliostasis study. Severe respiratory signs, tracheal cilia injury, nephritis and abnormal development of the oviduct and ovarian follicles were evident throughout the experiment. A challenge experiment demonstrated that the homologous QX vaccine showed superior protection efficacy compared with other available vaccines, confirming the importance of IBV vaccine seed homology against the circulating IBV strains. Our findings aid an understanding of the pathogenicity of QX-like IBVs that may help to further control the infection.
Innate immune responses to duck Tembusu virus infection
Authors: Li Ning , Zhao Jun , Yang Yudong , Zeng Yongqing , Liu Sidang 
Published: July 2020

AbstractThe disease caused by duck Tembusu virus (DTMUV) is characterized by severe egg-drop in laying ducks. Currently, the disease has spread to most duck-raising areas in China, leading to great economic losses in the duck industry. In the recent years, DTMUV has raised some concerns, because of its expanding host range and increasing pathogenicity, as well as the potential threat to public health. Innate immunity is crucial for defending against invading pathogens in the early stages of infection. Recently, studies on the interaction between DTMUV and host innate immune response have made great progress. In the review, we provide an overview of DTMUV and summarize current advances in our understanding of the interaction between DTMUV and innate immunity, including the host innate immune responses to DTMUV infection through pattern recognition receptors (PRRs), signaling transducer molecules, interferon-stimulated genes (ISGs), and the immune evasion strategies employed by DTMUV. The aim of the review is to gain an in-depth understanding of DTMUV pathogenesis to facilitate future studies.
A comprehensive descriptive assessment of obesity related chronic morbidity and estimated annual cost burden from a population-based electronic health record database
Authors: Reges Orna , Leibowitz Morton , Hirsch Avital , Dicker Dror , Finer Nick , Haase Christiane Lundegaard , Satylganova Altynai , Leventer-Roberts Maya , Feldman Becca 
Published: July 2020

Abstract
Background
The growing prevalence of obesity and its complications pose a huge burden on the individual and health care systems worldwide. This study presents the frequency of multiple prevalent co-morbidities and estimated annual cost burden by body mass index (BMI) groups, age, and sex among the Israeli adult population to provide policy makers with further evidence to appropriately target interventions.

Methods
This cross-sectional study utilized population-based electronic medical records from the largest payer-provider health fund in Israel. The population included individuals ≥25 years as of 01/01/2014. A new approach assessing body system-related morbidity (BSRM) prevalence was assessed along with estimated annual cost burden for the year 2015 and presented across BMI group, age, and sex via heat maps.

Results
Among 1,756,791 adults, 65% had an elevated BMI (BMI > 25 kg/m2). Heat map analysis demonstrated a higher multi-BSRM prevalence and relative estimated annual cost burden among participants with obesity in all age groups. There was a notably higher multi-BSRM prevalence among men and women aged 25–29 with class III obesity (26 and 30%, respectively) compared to the corresponding BMI groups between 18·5- < 25 kg/m2 (5 and 9%, respectively). Healthcare costs were 1·72 times higher among men aged 25–29 with class III obesity and 2·75 times among women aged 25–29 with class III obesity compared to those of healthy weight.

Conclusions
The detailed analysis describes the uneven distribution of burdens across BMI groups, age, and sex allowing policy makers to identify sub-populations for targeted interventions.
Comparison of the proximal and distal approaches for axillary vein catheterization under ultrasound guidance (PANDA) in cardiac surgery patients susceptible to bleeding: a randomized controlled trial
Authors: Su Ying , Hou Jun-yi , Ma Guo-guang , Hao Guang-wei , Luo Jing-chao , Yu Shen-ji , Liu Kai , Zheng Ji-li , Xue Yan , Luo Zhe , Tu Guo-wei 
Published: July 2020

Abstract
Background
The present study aimed at comparing the success rate and safety of proximal versus distal approach for ultrasound (US)-guided axillary vein catheterization (AVC) in cardiac surgery patients susceptible to bleeding.

Methods
In this single-center randomized controlled trial, cardiac surgery patients susceptible to bleeding and requiring AVC were randomized to either the proximal or distal approach group for US-guided AVC. Patients susceptible to bleeding were defined as those who received oral antiplatelet drugs or anticoagulants for at least 3 days. Success rate, catheterization time, number of attempts, and mechanical complications within 24 h were recorded for each procedure.

Results
A total of 198 patients underwent randomization: 99 patients each to the proximal and distal groups. The proximal group had the higher first puncture success rate (75.8% vs. 51.5%, p < 0.001) and site success rate (93.9% vs. 83.8%, p = 0.04) than the distal group. However, the overall success rates between the two groups were similar (99.0% vs. 99.0%; p = 1.00). Moreover, the proximal group had fewer average number of attempts (p < 0.01), less access time (p < 0.001), and less successful cannulation time (p < 0.001). There was no significant difference in complications between the two groups, such as major bleeding, minor bleeding, arterial puncture, pneumothorax, nerve injuries, and catheter misplacements.

Conclusions
For cardiac surgery patients susceptible to bleeding, both proximal and distal approaches for US-guided AVC can be considered as feasible and safe methods of central venous cannulation. In terms of the first puncture success rate and cannulation time, the proximal approach is superior to the distal approach. Trial registration Clinicaltrials.gov, NCT03395691. Registered January 10, 2018, https://clinicaltrials.gov/ct2/show/NCT03395691?cond=NCT03395691&draw=1&rank=1.
Fractional integral inequalities involving Marichev–Saigo–Maeda fractional integral operator
Authors: Tassaddiq Asifa , Khan Aftab , Rahman Gauhar , Nisar Kottakkaran Sooppy , Abouzaid Moheb Saad , Khan Ilyas 
Published: July 2020

AbstractThe aim of this present investigation is establishing Minkowski fractional integral inequalities and certain other fractional integral inequalities by employing the Marichev–Saigo–Maeda (MSM) fractional integral operator. The inequalities presented in this paper are more general than the existing classical inequalities cited.
Solvability and stability of a fractional dynamical system of the growth of COVID-19 with approximate solution by fractional Chebyshev polynomials
Authors: Hadid Samir B. , Ibrahim Rabha W. , Altulea Dania , Momani Shaher 
Published: July 2020

AbstractLately, many studies were offered to introduce the population dynamics of COVID-19. In this investigation, we extend different physical conditions of the growth by employing fractional calculus. We study a system of coupled differential equations, which describes the dynamics of the infection spreading between infected and asymptomatic styles. The healthy population properties are measured due to the social meeting. The result is associated with a macroscopic law for the population. This dynamic system is appropriate to describe the performance of growth rate of the infection and to verify if its control is appropriately employed. A unique solution, under self-mapping possessions, is investigated. Approximate solutions are presented by utilizing fractional integral of Chebyshev polynomials. Our methodology is based on the Atangana–Baleanu calculus, which provides various activity results in the simulation. We tested the suggested system by using live data. We found positive action in the graphs.
A novel privacy-preserving speech recognition framework using bidirectional LSTM
Authors: Wang Qingren , Feng Chuankai , Xu Yan , Zhong Hong , Sheng Victor S. 
Published: July 2020

AbstractUtilizing speech as the transmission medium in Internet of things (IoTs) is an effective way to reduce latency while improving the efficiency of human-machine interaction. In the field of speech recognition, Recurrent Neural Network (RNN) has significant advantages to achieve accuracy improvement on speech recognition. However, some of RNN-based intelligence speech recognition applications are insufficient in the privacy-preserving of speech data, and others with privacy-preserving are time-consuming, especially about model training and speech recognition. Therefore, in this paper we propose a novel Privacy-preserving Speech Recognition framework using Bidirectional Long short-term memory neural network, namely PSRBL. On the one hand, PSRBL designs new functions to construct security activation functions by combing with an additive secret sharing protocol, namely a secure piecewise-linear Sigmoid and a secure piecewise-linear Tanh respectively, to achieve privacy-preserving of speech data during speech recognition process running on edge servers. On the other hand, in order to reduce the time spent on both the training and the recognition of the speech model while keeping high accuracy during speech recognition process, PSRBL first utilizes secure activation functions to refit original activation functions in the bidirectional Long Short-Term Memory neural network (LSTM), and then makes full use of the left and the right context information of speech data by employing bidirectional LSTM. Experiments conducted on the speech dataset TIMIT show that our framework PSRBL performs well. Specifically compared with the state-of-the-art ones, PSRBL significantly reduces the time consumption on both the training and the recognition of the speech model under the premise that PSRBL and the comparisons are consistent in the privacy-preserving of speech data.
Using provider-focused education toolkits can aid enhanced recovery programs to further reduce patient exposure to opioids
Authors: Sarin Ankit , Lancaster Elizabeth , Chen Lee-lynn , Porten Sima , Chen Lee-may , Lager Jeanette , Wick Elizabeth 
Published: July 2020

Abstract
Background
Evidence-based perioperative analgesia is an important tactic for reducing patient exposure to opioids in the perioperative period and potentially preventing new persistent opioid use.

Study design
We assessed the impact of a multifaceted optimal analgesia program implemented in the setting of a mature surgical pathway program at an academic medical center. Using existing multidisciplinary workgroups established for continuous process improvement in three surgical pathway areas ((colorectal, gynecology, and urologic oncology (cystectomy)), we developed an educational toolkit focused on implementation strategies for multimodal analgesia and non-pharmacologic approaches for managing pain with the goal of reducing opioid exposure in hospitalized patients. We analyzed prospectively collected data from pathway patients before dissemination of the toolkit (July 2016–June 2017; n = 869) and after (July 2017–June 2018; n = 838). We evaluated the association between program implementation and use of oral morphine equivalents (OME), average pain scores, time to first ambulation after surgery, urinary catheter duration, time to solid food after surgery, length of stay, discharge opioid prescriptions, and readmission.

Results
Multivariate regression demonstrated that the program was associated with significant decreases in intraoperative OME (14.5 ± 2.4 mEQ (milliequivalents) reduction; p < 0.0001), day before discharge OME (18 ± 6.5 mEQ reduction; p < 0.005), day of discharge OME (9.6 ± 3.28 mEQ reduction; p < 0.003), and discharge prescription OME (156 ± 22 mEq reduction; p < 0.001). Reduction in OME was associated with earlier resumption of solid food (0.58 ± 0.15 days reduction; p < 0.0002).

Conclusion
Our multifaceted optimal analgesia program to manage perioperative pain in the hospital was effective and further improved analgesia in the setting of a mature enhanced recovery program.