bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of visit-to-visit blood pressure variability on cardiovascular events in populations with different body mass indexes: a prospective cohort study
Authors: Chen Haojia , Chen Youren , Wu Weiqiang , Huang Jianhuan , Chen Zekai , Chen Zhichao , Yan Xiuzhu , Wu Shouling
Published: September 2020

Objective

This study was performed to explore the effects of visit-to-visit blood pressure variability (BPV) on cardiovascular events (CVEs) in people with various body mass indexes (BMIs).

Design

Prospective cohort study.

Setting

The average real variability of systolic blood pressure (ARVSBP) was the indicator for visit-to-visit BPV. The participants were divided into three groups: normal weight, overweight and obesity. We further divided these groups into four subgroups based on the ARVSBP. A Cox regression model was used to calculate the HRs of the ARVSBP on CVEs in the same and different BMI groups. Additionally, a competitive risk model was used to calculate the HRs of the ARVSBP on CVEs in the same BMI group.

Participants

In total, 41 043 individuals met the inclusion criteria (no historical CVEs or tumours, no incidence of CVEs or tumours and no death during the four examinations) and had complete systolic blood pressure and BMI data.

Results

A total of 868 CVEs occurred. The cumulative incidence of CVEs increased as ARVSBP rose in both the normal weight and overweight groups. In same BMI groups, the risk of CVEs significantly increased as ARVSBP increased only in the normal weight group (highest quartiles of ARVSBP: HR (95% CI) 2.20 (1.46–3.31)). In the different BMI groups, the risk of CVEs in the ARVSBP subgroup in each BMI group was higher than that the least quintile of ARVSBP in the normal weight group (highest quartiles of ARVSBP in obesity: HR (95% CI) 2.28 (1.47–3.55)). The result of the competitive risk model did not change.

Conclusions

As BMI and ARVSBP increase, the risk of CVEs increases. However, the risk of visit-to-visit BPV on CVEs varies in different BMI groups, especially in people of normal weight.

Trial registration number

CHiCTR-TNC1100 1489.
Voluntary disclosures of payments from pharmaceutical companies to healthcare professionals in Germany: a descriptive study of disclosures in 2015 and 2016
Authors: Stoll Marlene , Hubenschmid Lara , Koch Cora , Lieb Klaus
Published: September 2020

Objective

To analyse voluntary payment reports of pharmaceutical companies to German healthcare professionals (HCPs) in 2015 and 2016 based on an industry-self-regulating transparency codex.

Design and participants

Cohort study of all German HCPs who voluntarily agreed that at least one payment they received in 2015 and 2016 from pharmaceutical companies is disclosed.

Main outcome measures

Number of HCPs who disclosed at least one payment in the database; separated by year of disclosure and whether they disclosed once or repeatedly. Amount of disclosed payments and distribution parameters of disclosed annual payment sums per person; separated by year of disclosure und whether they disclosed once or repeatedly.

Results

28 230 HCPs agreed to the disclosure of at least one payment in the database. In 2015, 19 905 HCPs agreed to the disclosure, decreasing to 15 782 HCPs in 2016. Whereas 7457 disclosed payments in both years, 12 448 disclosed only in 2015 and 8325 only in 2016. Payments of €32 426 721 in 2015 and €23 289 343 in 2016 were disclosed, that is, 27% and 23% of the total amounts spent on HCPs, respectively. Distribution of annual payments was skewed: the top 1% of HCPs disclosed annual payment sums between €17 049 and €200 194, while the median disclosed annual payment sum per person was €536 (IQR €1092). Disclosed payments were higher in male physicians and in physicians with higher academic degree.

Conclusions

If voluntary, disclosure rates of payments are low and therefore only provide a fragmented picture of interactions between HCPs and pharmaceutical companies. Efforts must be intensified to ensure obligatory disclosure of all payments worldwide.
Evaluation of outcome relevance of quality indicators in the emergency department (ENQuIRE): study protocol for a prospective multicentre cohort study
Authors: Drynda Susanne , Schindler Wencke , Slagman Anna , Pollmanns Johannes , Horenkamp-Sonntag Dirk , Schirrmeister Wiebke , Otto Ronny , Bienzeisler Jonas , Greiner Felix , Drösler Saskia , Lefering Rolf , Hitzek Jennifer , Möckel Martin , Röhrig Rainer , Swart Enno , Walcher Felix
Published: September 2020

Introduction

Quality of emergency department (ED) care affects patient outcomes substantially. Quality indicators (QIs) for ED care are a major challenge due to the heterogeneity of patient populations, health care structures and processes in Germany. Although a number of quality measures are already in use, there is a paucity of data on the importance of these QIs on medium-term and long-term outcomes. The evaluation of outcome relevance of quality indicators in the emergency department study (ENQuIRE) aims to identify and investigate the relevance of QIs in the ED on patient outcomes in a 12-month follow-up.

Methods and analysis

The study is a prospective non-interventional multicentre cohort study conducted in 15 EDs throughout Germany. Included are all patients in 2019, who were ≥18 years of age, insured at the Techniker Krankenkasse (statutory health insurance (SHI)) and gave their written informed consent to the study.

The primary objective of the study is to assess the effect of selected quality measures on patient outcome. The data collected for this purpose comprise medical records from the ED treatment, discharge (claims) data from hospitalised patients, a patient questionnaire to be answered 6–8 weeks after emergency admission, and outcome measures in a 12-month follow-up obtained as claims data from the SHI.

Descriptive and analytical statistics will be applied to provide summaries about the characteristics of QIs and associations between quality measures and patient outcomes.

Ethics and dissemination

Approval of the leading ethics committee at the Medical Faculty of the University of Magdeburg (reference number 163/18 from 19 November 2018) has been obtained and adapted by responsible local ethics committees.

The findings of this work will be disseminated by publication of peer-reviewed manuscripts and presentations as conference contributions (abstracts, poster or oral presentations).

Moreover, results will be discussed with clinical experts and medical associations before being proposed for implementation into the quality management of EDs.

Trial registration number

German Clinical Trials Registry (DRKS00015203); Pre-results.
Impact of hearing loss and vestibular decline on cognition in Alzheimer’s disease: a prospective longitudinal study protocol (Gehoor, Evenwicht en Cognitie, GECkO)
Authors: Bosmans Joyce , Jorissen Cathérine , Cras Patrick , Van Ombergen Angelique , Engelborghs Sebastiaan , Gilles Annick , Princen Eline , Moyaert Julie , Mertens Griet , Van Rompaey Vincent
Published: September 2020

Introduction

Dementia is a prevalent disease affecting a growing number of the ageing population. Alzheimer’s disease (AD) is the most common cause of dementia. Previous research investigated the link between hearing loss and cognition, and the effect of vestibular dysfunction on cognition. Hearing loss and, to a lesser extent, vestibular decline both result in a decreasing cognitive function. However, their interaction should not be underestimated. The aim of this study is to assess the effect of hearing loss, vestibular decline and their interaction on cognition in people suffering from mild cognitive impairment (MCI) and dementia due to AD (ADD).

Methods and analysis

We designed a prospective longitudinal study to assess the effect of hearing loss and vestibular decline on cognition. A total of 100 cognitively impaired elderly (between 55 and 84 years of age), consisting of 60 patients with MCI due to AD and 40 patients with ADD will be included. The control group will consist of individuals with preserved cognition group-matched based on age, hearing level and vestibular function. A comprehensive assessment is performed at baseline, 12-month and 24-month follow-ups. The primary outcome measure is the change in the Repeatable Battery for the Assessment of Neuropsychological Status adjusted for Hearing-impaired individuals total score, a cognitive test battery assessing different cognitive domains. Secondary outcome measures include additional neuropsychological assessments, cortical auditory-evoked potentials, and evaluation of general and disease-specific health-related quality of life. Variables include cognitive, audiological and vestibular evaluation. Variance analyses will assess the effect of hearing loss and vestibular decline on cognition. More precisely, the link between hearing loss and non-spatial cognitive functioning, the effect of vestibular decline on spatial cognition and the impact of both factors on the rate of conversion from MCI due to AD to ADD will be investigated.

Ethics and dissemination

The study protocol was approved by the ethical committee of the Antwerp University Hospital on 4 February 2019 with protocol number B300201938949. The findings will be disseminated through peer-reviewed publications and conference presentations.

Trial registration number

ClinicalTrials.gov Registry (NCT04385225).
Characteristics of COVID-19 clinical trials registered with ClinicalTrials.gov: cross-sectional analysis
Authors: Jones Christopher W , Woodford Ashley L , Platts-Mills Timothy F
Published: September 2020

Objectives

To characterise current COVID-19-related research activities.

Design

Cross-sectional analysis.

Setting

Clinical trials registered with ClinicalTrials.gov testing interventions relevant to COVID-19.

Data sources

ClinicalTrials.gov was searched for COVID-19 and related terms to identify trials registered between 1 December 2019 and 1 May 2020 that test interventions related to the COVID-19 pandemic.

Main outcome measures

We classified trials according to intervention type, and report key trial characteristics including recruitment status, location, funder type, target enrolment number, intervention model (single group, randomised or sequential assignment) and projected completion date.

Results

Of the 630 identified clinical trials related to COVID-19, 509 (81%) involved the study of drugs or biological agents. Of these trials of drugs and biologics, 305 (60%) use an open-label design, 43 (8%) are single blinded (participant only) and 161 (32%) are double blinded (participant and investigator). 94 (18%) of the drug/biological trials are non-randomised. Either hydroxychloroquine or chloroquine is administered as part of the study protocol in 152 (30%) of the drug/biological trials. The total planned enrolment for these hydroxychloroquine/chloroquine trials is over 200 000 participants, which represents 65% of the total planned enrolment for all registered trials of drugs or biologics. There are also at least 25 registered trials of azithromycin (n=53), convalescent plasma (n=38), lopinavir/ritonavir (n=30), stem cell treatments (n=29) and tocilizumab (n=25). 142 trials were registered in the first 3 months of 2020, and 488 trials were registered between 1 April and 1 May 2020.

Conclusions

These findings demonstrate a robust research response to the COVID-19 pandemic, though many of the currently planned and ongoing trials focus on a small number of potential therapies, and many also lack essential design features and power necessary to provide accurate treatment effect estimates.
Differential gene expression of tumor-infiltrating CD8+T cells in advanced versus early-stage colorectal cancer and identification of a gene signature of poor prognosis
Authors: Saleh Reem , Sasidharan Nair Varun , Toor Salman M , Taha Rowaida Z , Murshed Khaled , Al-Dhaheri Mahmood , Khawar Mahwish , Petkar Mahir Abdulla , Abu Nada Mohamed , Al-Ejeh Fares , Elkord Eyad
Published: September 2020

Background

Cytotoxic CD8+T cell-mediated response is the most important arm of adaptive immunity, which dictates the capacity of the host immune response in eradicating tumor cells. Due to tumor intrinsic and/or extrinsic factors, the density and function of CD8+tumor-infiltrating lymphocytes (TILs) could be compromised, leading to poor prognosis and survival.

Methods

Using RNA-Seq, transcriptomes of sorted CD3+CD8+TILs from treatment-naïve colorectal cancer (CRC) patients at advanced stages (III and IV) were compared with those from patients with early stages (I and II). A signature referred to as ‘poor prognosis CD8 gene signature (ppCD8sig)’ was identified and analyzed in The Cancer Genome Atlas CRC dataset. Scores for the ppCD8sig were calculated and classified as high, intermediate and low, and its prognostic significance was assessed using multivariate analysis and Cox proportional hazard model. Densities of CD3+and CD8+T cell infiltration in tumors from patients with high and low ppCD8sig scores were assessed by flow cytometry and immunostaining.

Results

Genes related to epigenetic regulation and response to hypoxia were upregulated in CD8+TILs from patients with advanced stages, while genes related to T cell activation, cell proliferation and cell cycle were downregulated. Patients with high ppCD8sig score had poorer disease-specific survival (DSS) and shorter progression-free interval (PFI). The ppCD8sig was an independent prognostic indicator for DSS (HR 1.83, 95% CI 1.40 to 2.38, p<0.0001) and PFI (HR 1.42, 95% CI 1.04 to 1.93, p=0.026). Additionally, patients with high ppCD8sig score were more likely to have advanced stages (χ2p<0.0001) and residual disease after primary therapy (χ2p=0.046). Patients with high ppCD8sig score had reduced levels of CD3+and CD8+TILs and low Immunoscores (IS), compared to patients with low ppCD8sig score.

Conclusions

Our data provided insights into the altered regulation of biological mechanisms and signaling pathways in CD8+TILs during CRC progression, and revealed a gene signature as an independent prognostic indicator. Patients with high ppCD8sig score had lower levels of TILs and low IS. These data further confirm the prognostic value of the identified ppCD8sig and potentially highlight its clinical relevance.
Effects of feeding ISA brown and Shaver white layer breeders with sources of n-3 fatty acids on hatching egg profiles, apparent embryonic uptake of egg components, and body composition of day-old chicks
Authors: Akbari Moghaddam Kakhki Reza , Kiarie Elijah G.
Published: September 2020

Effects of feeding ISA brown and Shaver white breeders sources of n-3 fatty acids (FA) on egg components, apparent embryonic uptake (AEU) of egg components, and hatching body composition were examined. A total of 240 females and 30 males per each strain were fed either: (1) control (CON); (2) CON + 1% of dried microalgae (DMA), as a source of docosahexaenoic acid; or (3) CON + 2.60% of dry extruded product consisting of full-fat flaxseed (FFF), as a source of α-linolenic acid for 30 d. Eggs were incubated and the residual yolks (RY) sampled at hatch for AEU of dry matter (DM), minerals, and organic matter (OM). Feeding n-3 FA sources reduced the AEU of OM and minerals resulting in a higher ratio of RY to body weight (P = 0.002). Feeding FFF increased body fat and decreased lean in Shaver white hatchlings compared with CON (P < 0.05). The body mineral was reduced by feeding DMA compared with other treatments (P < 0.05). The change in body composition in response to feeding of n-3 sources was associated with the change in AEU of DM, OM, and minerals, not the concentration of these components in the yolk.
Numerical analysis of blockage effects on the flow between parallel plates by using lattice Boltzmann method
Authors: Islam Shams-Ul , Ullah Naqib , Zhou Chao Ying
Published: September 2020

In this study the two-dimensional flow over a square cylinder placed in between parallel plates is simulated numerically by using the lattice Boltzmann method (LBM) at low Reynolds numbers. Both the plates are obstructed by solid rectangular blocks of variable length. The fluid was allowed to flow between the parallel plates for Reynolds number (Re) from 75 to 150, and blockage ratio (g*) from 1 to 3. The numerical investigation does not simply yield the predictable primary region of recirculating flow connected to the obstructions; it also shows supplementary regions of the flow downstream of the single cylinder placed in a computational domain. These supplementary separation zones were not already described in the research. The numerical analysis shows that the flow downstream of obstructions and the single cylinder remained two-dimensional for Re varied from 75 to 150. Results available in previous research are reported and compared with both of the available experimental and numerical results for code validation with a single cylinder. Furthermore, the effects of various Re and blockage ratio on the lift forces and drag coefficient is analyzed. Under these circumstances, good agreement between experimental and numerical results are obtained. The hydrodynamic forces of the cylinder are strongly influenced by the spacing ratios.
Cramér-type moderate deviations for the likelihood ratio process of Ornstein–Uhlenbeck process with shift
Authors: Jiang Hui , Liu Hui
Published: September 2020

For the Ornstein–Uhlenbeck process in stationary and explosive cases, this paper studies Cramér-type moderate deviations for the log-likelihood ratio process. As an application, we give the negative regions of drift testing problem, and also obtain the decay rates of the error probabilities. The main methods of this paper consist of mod-[Formula: see text] convergence approach, deviation inequalities for multiple Wiener–Itô integrals and asymptotic analysis techniques.
DISRUPTIVE AND PARADOXICAL ROLES IN THE SHARING ECONOMIES
Authors: ÖBERG CHRISTINA
Published: September 2020

The sharing economy could be said to disrupt who does what in exchanges. This paper categorises the roles played by users, providers, and platforms in different interpretations of the sharing economy. It asks: What different roles do the users, providers, and platforms play in the sharing economy? And: How do the roles differ in various interpretations of the sharing economy? The paper classifies the different interpretations based on their market/non-market logic and concludes that roles are more extensive for users and providers in non-market logic interpretations, while market logic suggests that the platform acts more roles. The user is, despite the peer-to-peer connotation of the sharing economy, often quite passive. Contributions are made to the emerging literature on the sharing economy through highlighting its many different interpretations, where roles help to systematise these. The paper furthermore contributes to the literature on roles through highlighting them as transitory and expanding beyond expectations related to digitalisation. Practically, the systematisation of roles helps to navigate among various business model designs and makes informed decisions when launching platforms in the sharing economy. Additionally, the focus on roles raises important questions on risk sharing, resource provisions, and the creation of value for each participating party.
The temperature of Britain's coalfields
Authors: Farr G. , Busby J. , Wyatt L. , Crooks J. , Schofield D.I. , Holden A.
Published: September 2020

Low-temperature heat recovery, cooling and storage schemes, using abandoned flooded mine workings, are a viable option for low-carbon heating solutions within many abandoned British coalfields. The temperature of mine water is a useful parameter, coupled with depth to water, sustainable yield and recharge potential, to identify suitable locations and calculate the likely performance of heat recovery schemes. This paper aims to provide the first mapping and synthesis of the temperature of Britain's coalfields to support this emerging technology. Using the best available evidence, a median geothermal gradient of 24.1°C km
−1
was calculated for the British coalfields. However, geothermal gradients between separate coalfields can vary from 17.3 to 34.3°C km
−1
. The North East, Cumbria and Yorkshire coalfields all have mean geothermal gradients generally >30°C km
−1
, whereas geothermal gradients of generally <23°C km
−1
are measured in the Warwickshire, South Wales, Staffordshire, Douglas and Fife coalfields. Active dewatering schemes are shown to locally increase the apparent measured geothermal gradient by ingress and mixing of deeper water into the pumping shafts. This baseline spatial mapping and synthesis of coalfield temperatures offers significant benefit to those planning, designing and regulating heat recovery and storage in Britain's abandoned coalfields.
Upregulation of serum and glucocorticoid-regulated kinase 1 exacerbates brain injury and neurological deficits after cardiac arrest
Authors: Lee Reggie Hui-Chao , Grames Mychal S. , Wu Celeste Yin-Chieh , Lien Chih-Feng , Couto e Silva Alexandre , Possoit HarLee E. , Clemons Garrett A. , Citadin Cristiane T. , Neumann Jake T. , Pastore Donatella , Lauro Davide , Della-Morte David , Lin Hung Wen
Published: September 2020

Upregulation of SGK1 exacerbates brain injury during cerebral ischemia. Inhibition of SGK1 affords neuroprotection against cardiac arrest-induced hypoperfusion, neuroinflammation, neuronal cell death, and neurological deficits.
Proarrhythmic electrophysiological and structural remodeling in rheumatoid arthritis
Authors: Patel Kiran Haresh Kumar , Jones Timothy Nicholas , Sattler Susanne , Mason Justin C. , Ng Fu Siong
Published: September 2020

Chronic inflammatory disorders, including rheumatoid arthritis (RA), are associated with a twofold increase in the incidence of sudden cardiac death (SCD) compared with the healthy population. Although this is partly explained by an increased prevalence of coronary artery disease, growing evidence suggests that ischemia alone cannot completely account for the increased risk. The present review explores the mechanisms of cardiac electrophysiological remodeling in response to chronic inflammation in RA. In particular, it focuses on the roles of nonischemic structural remodeling, altered cardiac ionic currents, and autonomic nervous system dysfunction in ventricular arrhythmogenesis and SCD. It also explores whether common genetic elements predispose to both RA and SCD. Finally, it evaluates the potential dual effects of disease-modifying therapy in both diminishing and promoting the risk of ventricular arrhythmias and SCD.
Identification of Power Transformer Currents by Using Random Forest and Boosting Techniques
Authors: Khatib Tamer , Arar Gazi
Published: September 2020

In this research, a differential protection technique for a power transformer is proposed by using random forest and boosting learning machines. The proposed learning machines aim to provide a protection expert system that distinguishes between different transformer status which are normal, inrush, overexcitation, CT saturation, or internal fault. Data for 20 different transformers with 5 operating cases are used in this research. The utilized random forest and boosting techniques are trained using these data. Meanwhile, the proposed models are validated by other measures such as out-of-bag error and confusion matrix. In addition, variable importance analysis that shows signal’s component importance inside a transformer at different instances is provided. According to the result, the proposed random forest model successfully identifies all of the current cases (100% accuracy for the conducted experiment). Meanwhile, it is found that it is less accurate as a conditional monitoring element with accuracy in the range of 97%–98%. On the other hand, the proposed boosting model identifies all of the currents for both cases (100% accuracy for the conducted experiment). In addition to that, a comparison is conducted between the proposed models and other AI-based models. Based on this comparison, the proposed boosting model is the simplest and the most accurate model as compared to other models.
Research on Credit Risk Measurement of Small and Micro Enterprises Based on the Integrated Algorithm of Improved GSO and ELM
Authors: Jingming Li , Xuhui Li , Daoming Dai , Sumei Ruan , Xuhui Zhu
Published: September 2020

Small and micro enterprises play a very important role in economic growth, technological innovation, employment and social stability etc. Due to the lack of credible financial statements and reliable business records of small and micro enterprises, they are facing financing difficulties, which has become an important factor hindering the development of small and micro enterprises. Therefore, a credit risk measurement model based on the integrated algorithm of improved GSO (Glowworm Swarm Optimization) and ELM (Extreme Learning Machine) is proposed in this paper. First of all, according to the growth and development characteristics of small and micro enterprises in the big data environment, the formation mechanism of credit risk of small and micro enterprises is analyzed from the perspective of granularity scaling, cross-border association and global view driven by big data, and the index system of credit comprehensive measurement is established by summarizing and analyzing the factors that affect the credit evaluation index. Secondly, a new algorithm based on the parallel integration of the good point set adaptive glowworm swarm optimization algorithm and the Extreme learning machine is built. Finally, the integrated algorithm based on improved GSO and ELM is applied to the credit risk measurement modeling of small and micro enterprises, and some sample data of small and micro enterprises in China are collected, and simulation experiments are carried out with the help of MATLAB software tools. The experimental results show that the model is effective, feasible, and accurate. The research results of this paper provide a reference for solving the credit risk measurement problem of small and micro enterprises and also lay a solid foundation for the theoretical research of credit risk management.
Efficacy of Lianhua Qingwen Compared with Conventional Drugs in the Treatment of Common Pneumonia and COVID‐19 Pneumonia: A Meta‐Analysis
Authors: Hu Caiyun , Liang Mingming , Gong Fengfeng , He Bin , Zhao Dongdong , Zhang Guoliang
Published: September 2020

Background and Objectives. Lianhua Qingwen is a traditional Chinese medicine, which has been reported to be effective in the treatment of pneumonia. However, no consensus has been reached; therefore, we aimed to provide reliable assessments of common pneumonia and COVID‐19 pneumonia. Methods. Seven English and Chinese databases were used to search for qualified experimental studies as of July 27, 2020. All data were extracted directly from the included studies, and no special conversion formula was used. The weighted mean difference (WMD), 95% confidence interval (CI), and odds ratio (OR) were used for evaluation. Results. Forty‐two studies involving 3793 subjects met the qualification criteria. For common pneumonia, a short duration of flu‐like symptoms (WMD = −1.81, 95% CI = −2.12 to −1.50, P < 0.001), sputum (WMD = −1.10, 95% CI = −1.50 to −0.70, P < 0.001), pulmonary rale (WMD = −2.03, 95% CI = −2.74 to −1.31, P < 0.001), pulmonary imaging improvement (WMD = −1.88, 95% CI = −2.28 to −1.47, P < 0.001), curative effect (OR = 3.65, 95% CI = 2.81 to 4.76, P < 0.001), and healing period (WMD = −1.68, 95% CI = −2.62 to −0.74, P < 0.001) were associated with the Lianhua Qingwen group; subgroup analysis based on flu‐like symptoms showed statistically significant improvements in fever and cough. For COVID‐19 pneumonia, improvements in flu‐like symptoms (OR = 3.18, 95% CI = 2.36 to 4.29, P < 0.001), shortness of breath (OR = 10.62, 95% CI = 3.71 to 30.40, P < 0.001), curative effect (OR = 2.49, 95% CI = 1.76 to 3.53, P < 0.001), healing period (WMD = −2.06, 95% CI = −3.36 to −0.75, P = 0.002), and conversion of severe cases (OR = 0.46, 95% CI = 0.27 to 0.77, P = 0.003) were associated with the Lianhua Qingwen group; subgroup analysis indicated statistically significant improvements of fever, cough, fatigue, and muscle pain in the Lianhua Qingwen group compared to the conventional drug group. Regarding adverse reactions, no significant difference was detected for common pneumonia (OR = 0.75, 95% CI = 0.54 to 1.05, P = 0.097). Conclusions. Lianhua Qingwen combined with conventional drugs may be a promising therapy for treating common pneumonia and COVID‐19 pneumonia.
Fuzzy Energy Management Scheme for a Hybrid Power Sources of High-Altitude Pseudosatellite
Authors: Corcau J. I. , Dinca L.
Published: September 2020

HAPS (high-altitude pseudosatellites) are flight machines, airplane type, generally without pilot which fly in a definite zone at 18-22 km altitude, providing communication and surveillance services. These flight machines do not leave the atmosphere, and their purpose is to maintain a constant flight level for as long time as possible in the interest zone (e.g., five years) to fulfill their mission. HAPS energetic system proposed in this paper has to feed the electric propulsion system of HAPS (12.5 kW) and also to feed on-board equipment (navigation, data links, scientific equipment, etc.). On-board energy sources have to maintain HAPS in the interest zone for long periods. For this reason, it is used in the present solar power sources. A part of the generated energy is consumed on board; the rest is stored daytime and consumed nighttime. So, the system is provided with energy generation systems and also with storage and management systems. HAPS energetic system is a hybrid type, with two or more power sources. In this case, power sources are photovoltaic panels are used daytime and fuel cell are used nighttime, and also, a battery and/or a supercapacitor is used in transition periods from day to night and in peak load periods. In this paper, an electric power system used nighttime is designed and analysed. In this situation, the primary power source is the fuel cell and the secondary power sources are battery and/or supercapacitor. There are used numerical simulations models, developed in Matlab/Simulink, for all hybrid power source components: fuel cell stack, battery system, supercapacitors, conversion system, and fuzzy logic power management system. For a part of these components, there are used existing simulation models in Matlab/Simulink, adapted to these simulation requirements, and for others, there are designed and implemented simulation schemes according to these simulation requirements. An important component of the hybrid power source is the power conversion system which adapts the power sources parameters to consumer input requirements. A fuzzy logic power management system is designed.
Polymyxin B-Induced Skin Hyperpigmentation
Authors: Wen Xueke , Luo Chunliu , Lyu Weitao
Published: September 2020

Polymyxin B-induced skin hyperpigmentation is a rare adverse drug reaction (ADR). In this report, we present the case of a patient who underwent an abscess resection with right epididymitis, in which a multidrug-resistant Klebsiella pneumoniae infection (KPI) is formed. The patient was treated with polymyxin B and subsequently developed skin hyperpigmentation and desquamation. The desquamation improved and the pigmentation gradually returned to normal after sixty days after the withdrawal of polymyxin B.
Clinical Significance of the Interleukin 24 mRNA Level in Head and Neck Squamous Cell Carcinoma and Its Subgroups: An In Silico Investigation
Authors: Qiu Lan-Lan , Zhang Xiao-Guohui , Chen Gang , Dang Yi-Wu , Huang Zhi-Guang , Li Ming-Xuan , Liang Yao , Huang Su-Ning , Tang Xiao-Zhun , Chen Xiao-Xia , Wei Hong-Yu , Wu Hua-Yu
Published: September 2020

IL24 mRNA is known to have an apoptotic effect on cancer cells but not on noncancer cells. However, the expression level of the IL24 mRNA in head and neck squamous cell carcinoma (HNSCC) and its subgroups is rarely studied. In this study, the clinical implication of IL24 mRNA was evaluated in the common subgroups of HNSCC, including oral squamous cell carcinoma (OSCC), nasopharyngeal carcinoma (NPC), and laryngeal squamous cell carcinoma (LSCC) for analysis. Substantial IL24 mRNA expression data were calculated from several databases, such as the Gene Expression Omnibus (GEO), ArrayExpress, Sequence Read Archive (SRA), ONCOMINE, and The Cancer Genome Atlas (TCGA) databases. We ultimately collected a total of 41 microarrays and RNA-seq including 1,564 HNSCC and 603 noncancer tissue samples. IL24 mRNA was highly expressed in OSCC, LSCC, and NPC as shown by the separated standard mean difference (SMD), as well as HNSCC as a whole part (SMD = 1.47, 95% confdence interval (CI) = 1.24−1.70, P<0.0001). In all subgroups, the IL24 mRNA upregulation had the ability to distinguish cancer from noncancer tissue with area under the curves (AUCs) of the summary receiver operating characteristic (sROC) higher than 0.85. In conclusion, IL24 mRNA may be used as a potential marker for cancer screening, and its clinical diagnostic value needs to be further studied. It also provides a new idea for the treatment of the IL24 gene in HNSCC and its subgroups in the future.
Effect of PKC/NF-κB on the Regulation of P2X3 Receptor in Dorsal Root Ganglion in Rats with Sciatic Nerve Injury
Authors: Li Xue , Yuan Jie , Yu Xuan , Zhang Qin , Qin Bangyong
Published: September 2020

Background. Protein kinase C (PKC), nuclear factor-kappa B p65 (NF-κB p65), and P2X3 receptor (P2X3R) play significant roles in the sensitization and transduction of nociceptive signals, which are considered as potential targets for the treatment of neuropathic pain. However, the mechanisms and relationships among them have not been clearly clarified. Methods. 80 rats were randomized and divided into 10 groups (n = 8). Sciatic chronic constriction injury (CCI) rats were intrathecally administered with bisindolylmaleimide I (GF109203X), a PKC-selective antagonist once a day, or pyrrolidine dithiocarbamate (PDTC), an NF-κB inhibitor twice a day. Sham-operated rats were intrathecally administered with saline. Thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were evaluated in all the groups before CCI operation (baseline) and on the 1st, 3rd, 7th, 10th, and 14th day after CCI operation. Protein levels of p-PKCα, p-NF-κB p65, and P2X3R were analyzed in the CCI ipsilateral L4–6 dorsal root ganglions (DRGs). Results. Intrathecal injection of GF109203X or PDTC alleviated the TWL and MWT in the following 2 weeks after CCI surgery. The protein levels of p-PKCα, p-NF-κB p65, and P2X3R in the ipsilateral DRGs significantly increased after CCI operation, which could be partly reversed by intrathecal administration of GF109203X or PDTC. Conclusion. The upregulation of p-PKCα, p-NF-κB p65, and P2X3R expression in the DRGs of CCI rats was involved in the occurrence and development of neuropathic pain. Phosphorylated PKCα and phosphorylated NF-κB p65 regulated with each other. Phosphorylated NF-κB p65 and PKCα have a mutual regulation relationship with P2X3R, respectively, while the specific regulatory mechanism needs further research.
Type I Fracture Toughness Test of Rock‐like Materials Based on the Particle Flow Method
Authors: Yue Ling , Yu Bangyong , Zhao Chengxi , Guo Fei , Huang Fei
Published: September 2020

In order to investigate the feasibility and reliability of the three‐dimensional particle flow method in simulating the type I fracture toughness test, four types of numerical samples were established by particle flow code PFC3D: straight crack three‐point bending (SC3PB), edge cracked flattened semicircular disc (ECFSD), cracked chevron notched Brazilian disc (CCNBD), and edge cracked flattened ring (ECFR). Three models with different strength parameters (group A, group B, and group C) were established for each type, in which group A parameters are obtained from the concrete model, group B parameters are applied for simulating marble, and group C parameters are for granite. The type I fracture toughness and the failure form of each model are obtained by conducting the numerical test, and the curves of load versus displacement of loading point are recorded. The numerical test results show that, with the same strength parameter, the maximum difference in test results of each specimen type is 0.39 MPa·m1/2. The KIC of ECFR specimen is 0.13–0.28 MPa·m1/2 smaller than that of CCNBD specimen, and the KIC of ECFSD specimen is slightly higher than that of CCNBD sample. The KIC of SC3PB specimen is 0.06–0.21 MPa·m1/2 smaller than that of the CCNBD sample. When the loading rate is less than 0.01 m/s, the effect of loading rate on fracture toughness can be reduced to less than 0.1 MPa·m1/2.
Data-Driven Analysis of the Chaotic Characteristics of Air Traffic Flow
Authors: Zhang Zhaoyue , Zhang An , Sun Cong , Xiang Shuaida , Li Shanmei
Published: September 2020

Understanding the chaos of air traffic flow is significant to the achievement of advanced air traffic management, and trajectory data are the basic material for studying the chaotic characteristics. However, at present, there are two main obstacles to this task, namely, large amounts of noise in the measured data and the tedium of existing data processing methods. This paper improves the incorrect trajectory processing method based on ADS-B trajectory data and proposes a method by which to quickly extract the traffic flow through a certain waypoint. Currently, the commonly used theoretical analysis tools for nonlinear complex systems include the classical nonlinear dynamics analysis method and the newly developed complex network-based analysis method. The latter is currently in an exploratory stage because it has just been introduced into the study of air traffic flow. From these two perspectives, the chaotic characteristics of air traffic flow are studied in the present work. From the perspective of nonlinear dynamics, the improved C-C method is used to calculate the reliability parameters, namely, the time delay τ and embedding dimension m, of phase-space reconstruction, and the maximum Lyapunov index is calculated by using the small data volume method to prove the existence of chaos in the system. From the perspective of complex networks, the construction of a visibility graph and horizontal visibility graph is used to prove the existence of chaos in the system, and the goodness-of-fit parameters of the degree distributions of two fitting methods under different time scales are evaluated, which provides support for the air traffic flow theory.
Influencing Factor Analysis on the Anomalously Low‐Friction Effect in the Block Rock Mass
Authors: Li Liping , Wu Jinpeng , Pan Yishan , Tang Jupeng
Published: September 2020

According to the instability failure of the deep rock mass, a superposition block model of anomalously low‐friction effect was established. The numerical results were compared with the previous experiment, which verifies the feasibility and effectiveness of the simulation. A vertical impact and confining pressure were applied to the superimposed block model, and a horizontal static force was applied to the working block (the third block). This study aimed to determine the influence rules of vertical impact energy, confining pressure, and block lithology on the horizontal displacement of the working block and normal force on the contact surface. The results show that, with the increase of the vertical impact energy, the horizontal residual displacement of the working block increases linearly, and the horizontal displacement amplitude increases by the exponential function. The minimum normal force on the contact surface decreases linearly. As the confining pressure increases, the horizontal residual displacement of the working block decreases logarithmically, and the horizontal displacement amplitude decreases linearly. The minimum normal force on the contact surface increases linearly. The horizontal residual displacement and displacement amplitude of the working block in the coal‐rock combination are 1.51 times and 1.63 times of the rock mass, and the minimum normal force of the former is 0.84 times of the latter. Coal‐rock combination is more prone to the anomalously low‐friction effect than the rock mass.
When a Dead Patient Is Not Really Dead: Lazarus Phenomenon
Authors: Sharma Munish , Chandna Megha , Nguyen Thang , Vakil Abhay , Franco Rene , Ratnani Iqbal , Varon Joseph , Surani Salim
Published: September 2020

Lazarus phenomenon refers to autoresuscitation of a patient declared dead after cessation of cardiopulmonary resuscitation (CPR). The Lazarus phenomenon is rarely encountered and pathophysiology is not very well understood, but physicians need to be aware of this phenomenon. It is prudent that a physician leading a CPR effort waits for some time and monitors the patient further using blood pressure and electrocardiogram before confirming that a patient is actually dead.
Differentiation Potential of Early- and Late-Passage Adipose-Derived Mesenchymal Stem Cells Cultured under Hypoxia and Normoxia
Authors: Zhao Ashley G. , Shah Kiran , Freitag Julien , Cromer Brett , Sumer Huseyin
Published: September 2020

With an increasing focus on the large-scale expansion of mesenchymal stem cells (MSCs) required for clinical applications for the treatment of joint and bone diseases such as osteoarthritis, the optimisation of conditions for in vitro MSC expansion requires careful consideration to maintain native MSC characteristics. Physiological parameters such as oxygen concentration, media constituents, and passage numbers influence the properties of MSCs and may have major impact on their therapeutic potential. Cells grown under hypoxic conditions have been widely documented in clinical use. Culturing MSCs on large scale requires bioreactor culture; however, it is challenging to maintain low oxygen and other physiological parameters over several passages in large bioreactor vessels. The necessity to scale up the production of cells in vitro under normoxia may affect important attributes of MSCs. For these reasons, our study investigated the effects of normoxic and hypoxic culture condition on early- and late-passage adipose-derived MSCs. We examined effect of each condition on the expression of key stem cell marker genes POU5F1, NANOG, and KLF4, as well as differentiation genes RUNX2, COL1A1, SOX9, COL2A1, and PPARG. We found that expression levels of stem cell marker genes and osteogenic and chondrogenic genes were higher in normoxia compared to hypoxia. Furthermore, expression of these genes reduced with passage number, with the exception of PPARG, an adipose differentiation marker, possibly due to the adipose origin of the MSCs. We confirmed by flow cytometry the presence of cell surface markers CD105, CD73, and CD90 and lack of expression of CD45, CD34, CD14, and CD19 across all conditions. Furthermore, in vitro differentiation confirmed that both early- and late-passage adipose-derived MSCs grown in hypoxia or normoxia could differentiate into chondrogenic and osteogenic cell types. Our results demonstrate that the minimal standard criteria to define MSCs as suitable for laboratory-based and preclinical studies can be maintained in early- or late-passage MSCs cultured in hypoxia or normoxia. Therefore, any of these culture conditions could be used when scaling up MSCs in bioreactors for allogeneic clinical applications or tissue engineering for the treatment of joint and bone diseases such as osteoarthritis.
Methylated DNA Markers of Esophageal Squamous Cancer and Dysplasia: An International Study
Authors: Qin Yi , Taylor William , Bamlet William R. , Ravindran Adharsh , Buglioni Alessia , Cao Xiaoming , Foote Patrick H. , Slettedahl Seth W. , Mahoney Douglas W. , Albert Paul S. , Kim Sungduk , Hu Nan , Taylor Philip R. , Etemadi Arash , Sotoudeh Masoud , Malekzadeh Reza , Abnet Christian C. , Smyrk Thomas C. , Katzka David , Topazian Mark D. , Dawsey Sanford M. , Ahlquist David , Kisiel John B. , Iyer Prasad G.
Published: September 2020

Background:

Discovery of methylated DNA markers (MDM) of esophageal squamous cell carcinoma (ESCC) has sparked interest in assessing these markers in tissue. We evaluated MDMs in ESCC from three geographically and ethnically distinct populations, and explored the feasibility of assaying MDMs from DNA obtained by swallowed balloon devices.

Methods:

MDMs were assayed in ESCC and normal tissues obtained from the populations of United States, Iran, and China, and from exfoliative cytology specimens obtained by balloons in a Chinese population. Areas under the receiver operating curve (AUC) of MDMs discriminating ESCC from normal tissues were calculated. Random forest prediction models were built, trained on U.S. cases and controls, and calibrated to U.S.-only controls (model 1) and three-country controls (model 2). Statistical tests were used to assess the relationship between dysplasia and MDM levels in balloons.

Results:

Extracted DNA from 333 ESCC and 322 normal tissues was analyzed, in addition to archival DNA from 98 balloons. For ESCC, model 1 validated in Iranian and Chinese tissues with AUCs of 0.90 and 0.87, and model 2 yielded AUCs of 0.99, 0.96, and 0.94 in tissues from the United States, Iran, and China, respectively. In Chinese balloons, MDMs showed a statistically significant trend of increasing levels with increasing grades of dysplasia (P < 0.004).

Conclusions:

MDMs accurately discriminate ESCC from normal esophagus in tissues obtained from high- and low-incidence countries. Preliminary data suggest that levels of MDMs assayed in DNA from swallowed balloon devices increase with dysplasia grade. Larger studies are needed to validate these results.

Impact:

MDMs coupled with minimally invasive collection methods have the potential for worldwide application in ESCC screening.
Dual Mechanisms of Novel CD73-Targeted Antibody and Antibody–Drug Conjugate in Inhibiting Lung Tumor Growth and Promoting Antitumor Immune-Effector Function
Authors: Jin Rui , Liu Liang , Xing Yun , Meng Tao , Ma Lanping , Pei Jinpeng , Cong Ying , Zhang Xuesai , Ren Zhiqiang , Wang Xin , Shen Jingkang , Yu Ker
Published: September 2020

Although tyrosine kinase inhibitor therapy and immunotherapy have significantly improved lung cancer management, many patients do not benefit or become resistant to treatment, highlighting the need for novel treatments. We found elevated CD73 expression to be prevalent in non–small cell lung cancer (NSCLC) including those harboring the RAS- or RTK (EGFR, EML4-ALK) oncogenes. CD73 expression is enriched closely with the transcriptome signature of epithelial–mesenchymal transition and the immune-tolerant tumor microenvironment, which are increasingly relevant for disease progression and therapy resistance. We developed two novel series of CD73 antibody, Ab001/Ab002 and humanized version Hu001/Hu002, which demonstrated high CD73 binding affinity, potent enzyme inhibition, and efficiently protected effector T lymphocyte function from adenosine/cancer-imposed toxicity. Hu001/Hu002 inhibited growth of RAS-mutant NSCLC tumors in mice via enhanced antibody-dependent cell-mediated cytotoxicity and multifaceted remodeling of the tumor immune environment, reflecting diminished levels of tumor-associated macrophages, myeloid-derived suppressor cells, and tumor vasculature. A novel MMAE-conjugated CD73-ADC (Hu001–MMAE) elicited potent cytotoxicity against CD73-high expressing tumor cells (IC50<0.1 nmol/L) and suppressed in vivo growth of multiple NSCLC and glioma tumors, including the RAS-mutant models [minimum effective dose <1 mg/kg]. Treatment with CD73–ADC triggered a robust intratumoral accumulation of proinflammatory macrophages and activated dendritic cells (DC), which were not observed with naked CD73 antibody or standard chemotherapy. Studies with human PBMC-derived systems confirmed CD73-ADC as fully functional in protecting effector T cells and stimulating DCs thus providing dual benefits in killing CD73-high tumors and improving cancer immunity response. These results warrant clinical investigation of CD73-targeted antibody and ADC for treating advanced lung cancer.