bluuebunny/crossref_metadata_2025 huggingface dataset:
A COVID-19 Spread Model of the Discrete Grid to Assess the Potential of Non-pharmaceutical Interventions
Authors: Cao Wen , Dai Haoran , Tong Xiaochong , Zhu Jingwen , Tian Yuzhen , Peng Feilin
Published: January 2021

Background: The outbreak of COVID-19 posed a serious threat to human health, economic development, and social stability worldwide, and many countries had taken different interventions to control the deterioration of the epidemic. Although many studies have evaluated the effectiveness of these interventions, there were few reasonable explanations for the practical geographic significance of the model parameters. Our aim was to evaluate the potential of different interventions to mitigate the spread of the epidemic, including discussion about the different time and intensity of implementation, and map parameters of model to the practical application meanings of the special interventions.Methods: In this study, a COVID-19 spread model based on the discrete grid was proposed from perspective of geography. A multi-level grid was introduced to describe the quarantine status and intensity in different spaces, which also combined with the model of medical reception-cured and self-protection, and the spatiotemporal evolution process of early COVID-19 spread was simulated based on the spatial correlation, finally, the effect of interventions was quantitatively analyzed by the dynamic transmission model of COVID-19.Results: Quarantine measure were the most effective interventions, which could effectively reduce the peak value of infection, advance the arrival time of the peak, and shorten the duration of the epidemic, but it only played a role under sufficient intensity; the medical reception-cured and self-protection measure could effectively fatten the infection curve and slowed the spread of the epidemic in the early stage, which could provide more buffer time for the relevant government departments, but the practical effect was not obvious because of the limitation of actually invested resources. The role of the medical reception-cured measure was more reflected in the reduction of the number of deaths, and the effect of the self-protection measure could be reduced in strict quarantine measure.Conclusions: Results of the study indicated that the quarantine, medical reception-cured and self-protection measures were effective, and mitigating the spread of COVID-19 by achieving strong interventions was necessary. Strict quarantine should be implementing as soon as possible in countries with serious development of COVID-19.
Serum urate and lung cancer: a cohort study and Mendelian randomization using UK Biobank
Authors: Horsfall Laura J , Hall Ian P , Nazareth Irwin
Published: January 2021

Background

Serum urate is the most abundant small molecule with antioxidant properties found in blood and the epithelial lining fluid of the respiratory system. Moderately raised serum urate is associated with lower rates of lung cancer and COPD in smokers but whether these relationships reflect antioxidant properties or residual confounding is unknown.
Methods

We investigated the observational and potentially causal associations between serum urate and lung cancer incidence using one-sample Mendelian randomization (MR) and the UK Biobank resource. We instrumented serum urate level using genetic variants that explain ~ 5% of population-level variability. Incident lung cancer events were identified from national cancer registries. Observational and genetically instrumented incidence rate ratios (IRRs) and risk differences per 10,000 person-years (PYs) by smoking status were estimated.
Results

The analysis included 359,192 participants and 1,924 lung cancer events. The relationships between observed urate levels and lung cancer were generally U-shaped but varied by sex at birth with the strongest associations in current smoking men. After adjustment for confounding variables, current smoking men with low serum urate (100 µmol/L) had the highest predicted lung cancer incidence at 125/10,000PY (95%CI: 56–170/10,000PY) compared with 45/10,000PY (95%CI: 38–47/10,000PY) for those with the median level (300 µmol/L). The associations were weaker for women.
Conclusions

We found no strong evidence to support a causal association between genetically predicted serum urate and lung cancer or FEV1. Although low serum urate levels might be useful for identifying male smokers at highest risk, we found no evidence that urate is a modifiable risk factor for lung cancer.
Analysis of Predictors of Adherent Perinephric fat and its Impact on Perioperative Outcomes in Laparoscopic Partial Nephrectomy: A Retrospective Case-control Study
Authors: Fang Lu , Li Huan , Zhang Tao , Liu Rui , Zhang Taotao , Bi Liangkuan , Xie Dongdong , Wang Yi , Yu Dexin
Published: January 2021

Background: Adherent perinephric fat (APF), characterized by inflammatory fat surrounding the kidney, can limit the isolation of renal tumors and increase the operative difficulty in laparoscopic partial nephrectomy (LPN). The aim of this study was to investigate the predictors of APF and its impact on perioperative outcomes during LPN.Methods: A total of 215 consecutive patients undergoing LPN for renal cell carcinoma (RCC) from January 2016 to June 2019 at our institute were included. We divided these patients into two groups according to the presence of APF. Radiographic data were retrospectively collected from preoperative cross-sectional imaging. The perioperative clinical parameters were compared between the two groups. Univariate and multivariate analyses were performed to evaluate the predictive factors of APF. Results: APF was observed in 41 patients (19.1%) at the time of LPN. Univariate analysis demonstrated that APF was significantly correlated with male gender (P = 0.001), higher body mass index (P = 0.002), lower preoperative estimated glomerular filtration rate (P = 0.004), greater posterior perinephric fat thickness (P < 0.001), greater perinephric stranding (P < 0.001) and higher Mayo Adhesive Probability (MAP) score (P < 0.001). The MAP score (P < 0.001) was the only variable that remained an independent predictor for APF in multivariate analysis. We found that patients with APF had longer operative times (P < 0.001), warm ischemia times (P = 0.001), and greater estimated blood loss (P = 0.003) than those without APF. However, there were no significant differences in surgical approach, transfusion rate, length of postoperative stay, complication rate or surgical margin between the two groups.Conclusions: Several specific clinical and radiographic factors including the MAP score can predict APF. The presence of APF is associated with an increased operative time, and warm ischemia time and greater estimated blood loss but has no impact on other perioperative outcomes in LPN.
Association between Respiratory and Heart Rate Fluctuations and Death Occurrence in Dying Cancer Patients: Continuous Measurement with a Non-wearable Monitor
Authors: Fukui Sakiko , Ikuta Kasumi , Maeda Isseki , Hattori Satoshi , Hatano Yutaka , Yamakawa Miyae , Utsumi Momoe
Published: January 2021

Background: The cancer deaths at home and in care facilities are increasing worldly. If we can identify imminent death using a monitoring device and inform it to family members and care staff, it will help them, even in the absence of healthcare professionals at all times. We examined the association between impending death and continual changes in respiratory and heart rates measured by a non-wearable monitor every minute for the final 2 weeks of dying cancer patients. In this longitudinal study, we enrolled patients in a palliative-care-unit and continuously measured their respiratory/heart rates by a monitor, capturing their other vital signs and clinical status from medical records.Result: A dataset was created with 240 patient-days from every minute data to death (345,600 data) among 24 patients for 3-14 days to death. We analyzed this 240 patient-day data. After confirming the associations between the value of death day (n=24) or other days (2–14 days before death, n=216) and the mean, maximum, minimum, and variance of respiratory and heart rates every 24 hours by univariate analyses, we conducted a repeated measures logistic regression analysis using a generalized estimating equation. Finally, the maximum respiratory rate and mean heart rate were significantly associated with death at 24, 48, and 72 hours later, other than the respiratory rate of the last 24 hours.Conclusion: The maximum respiratory rate and mean heart rate measured every minute by a monitor can warn imminent death during the last days of life among dying patients. Our findings can help for caregivers to aware imminent death among dying patients at home or in facilities, in collaboration with palliative care professionals.
Untargeted Metabolomic Approach to Study the Serum Metabolites in Women with Polycystic Ovary Syndrome
Authors: YU Ying , TAN PANLI , ZHUANG ZHENCHAO , WANG ZHEJIONG , ZHU LINCHAO , QIU RUYI , XU HUAXI
Published: January 2021

Background: Polycystic ovary syndrome (PCOS) is a kind of common endocrine syndrome as well as metabolic disorder, which harms the reproductive system and the overall body metabolism of the patients. This study, we aimed to investigate the difference of serum metabolic profiles of the patients with PCOS compared to the healthy controls.Material and methods: a total of 62 study subjects including 31 PCOS patients and 31 matched healthy female controls were recruited, the clinical characteristics data were recorded at the time of recruitment, the laboratory biochemical data were detected. Then, we utilized metabolomics approach by UPLC-HRMS technology to study the metabolic changes between PCOS and controls.Results: The metabolomics analysis showed that there were 68 were downregulated and 78 were upregulated metabolites in PCOS patients serum compared to the controls. These metabolites mainly belong to Triacylglycerols, Glycerophosphocholines, Acylcarnitines, Diacylglycerols, Peptides, Amino acids, Glycerophosphoethanolamines and fatty acid. Pathway analysis showed that these metabolites were enriched in pathways including Glycerophospholipid metabolism, Fatty acid degradation, Fatty acid biosynthesis, Ether lipid metabolism etc. Diagnosis value assessment by ROC analysis showed that the changed metabolites including Leu-Ala/Ile-Ala, 3-(4-Hydroxyphenyl) propionic acid, Ile-Val/Leu-Val, Gly-Val/Val-Gly, aspartic acid, DG(34:2)_DG(16:0/18:2), DG(34:1)_DG(16:0/18:1), Phe-Trp, DG(36:1)_DG(18:0/18:1), Leu-Leu/Leu-Ile had higher AUC values, indicated significant role in PCOS.Conclusion: The present study characterized the difference of metabolic and related pathway profiles in PCOS patients, this finding hope to provide potential metabolic marker for the prognosis and diagnosis of this disease.
An Experimental Method for Estimating the Tearing Energy in Rubber-like Materials Using the True Stored Energy
Authors: Elmukashfi Elsiddig
Published: January 2021

A method for determining the critical tearing energy in rubber-like materials is proposed. In this method, the energy required for crack propagation in a rubber-like material is determined by the change of the recovered elastic energy. Hence, the dissipated energy due to different inelastic processes is deducted from the total strain energy applied to the system. Therefore, the classical method proposed by Rivlin and Thomas using the pure shear tear test is modified using the actual stored elastic energy. The elastically stored energy in a pure shear is determined experimentally using cyclic loading under quasi-static loading rate of 0.01 s-1 for different unloading rates, i.e. 0.01, 0.1 and 1.0 s-1. The experimental results show that the classical method overestimates the critical tearing energy by approximately 18% and the unloading rate is minimal which suggests that the dissipation depends only on the loading path.
Clinical and Demographic Features among Patients with Type 1 Diabetes Mellitus in Henan, China
Authors: Yang Liguo , Yang Guangxing , Li Xialian
Published: January 2021

BackgroundThe hallmark of type 1 diabetes (T1D) is the failure of islet cell. However, many studies showed a tendency to heterogeneity in TID. We aimed to investigate the demographic and clinical characteristics in T1D and the differences in young-onset and adult-onset patients.MethodsThis retrospective study was conducted among 1917 patients with T1D. Medical records on patients’ demographics, anthropometric measurements, and clinical manifestation were collected. According to the age at onset, it was divided into the young-onset group (<18 years, 234 patients, mean age 11 years) and adult-onset group (≥18 years, 219 patients, mean age 27 years). ResultsThe median age of patients at disease onset was 22 yd. The median duration of patients was 3 years. The overall median HbA1c value was 10.3%. Seventeen percent of patients were overweight or obesity. The frequency of overall dyslipidemia was 37.8%. The most frequent dyslipidemia was low high-density lipoprotein-cholesterol (HDL) (29%). The proportion of patients with anti-glutamic acid decarboxylase (GADA), insulin antibody (IAA) and islet cell antibody (ICA) were 28.0%, 6.4% and 21.6%, respectively. Compared with young-onset T1D, adult-onset patients comprised better islet function and glycemic control, higher prevalence of diabetes condition in the male gender (64.4% VS. 51.3%), higher proportion of obesity or overweight (24.6% VS. 9.5%), higher frequency of GADA (33.7% VS. 23.3%), and lower frequency of HDL (8.8% VS. 16.6%). Increasing or decreasing trends of overweight and obesity in this population during the period 2012 to 2018 was not found.ConclusionThis population was characterized by poor overall blood glucose control, high prevalence of dyslipidemia and low prevalence of GADA, IAA, ICA. Adult-onset patients with T1D are not uncommon and have better clinical manifestations than young-onset patients.
Modeling the Cost of Management Options for small benign non-functional adrenal incidentaloma: A Decision Tree Analysis
Authors: Ni Wenjun , Chen Xingxing , Ye Xiao , Pang Guofu , Liu Yan , Yuan Xiaoxu
Published: January 2021

Background Adrenal incidentaloma (AI) is the term for any unsuspected lesion of the adrenal gland found by radiologic imaging, usually done for other indications. Although it is consistently recommended that hyper-functional tumor and suspicious malignancy need surgery, the management of patients with small benign non-functional adrenal incidentaloma remains controversial. Here we develop a detailed mathematical decision analysis model comparing the projected management costs for small benign non-functional adrenal incidentaloma.Methods A detailed model was developed that integrates projected costs for a few possible treatment outcomes. Starting values and probabilities were derived from a comprehensive meta-analysis of 1298 patients. Hypothesis testing was performed using sensitivity analysis.Results The model predicts a cost premium for follow-up compared with surgery. The tornado analysis identify the cost of follow-up for once as the most important variables for our model. One-way sensitivity analysis demonstrated that cost equivalence could be met with ¥4359.5 for once follow-up, keeping other factors constant.Conclusion Our models of treatment for small benign non-functional adrenal incidentaloma showed significant cost differences for follow-up vs immediate surgery. The cost of follow-up for once featured threshold values.
Nomogram for Perinatal Prediction of Intrapartum Fever: A Case-control Study
Authors: Jiang Zhenfei , Hu Xiaoyi , Zeng Huabei , Wang Xinghe , Tan Cheng , Ni Chunyan , Dai Lingyun , Liu Su
Published: January 2021

Objective: To explore the risk factors of intrapartum fever and develop a nomogram to predict the incidence of intrapartum fever.Methods: The general demographic characteristics and perinatal factors of 696 parturient who underwent vaginal delivery in the Affiliated Hospital of Xuzhou Medical University from May 2019 to April 2020 were retrospectively analyzed. 487 patients collected from May 2019 to October 2019 were formed into a training cohort. A multivariate logistic regression model was used to identify the independent risk factors associated with intrapartum fever during vaginal delivery, then a nomogram was developed to predict the occurrence. 209 cases collected from January 2020 to April 2020 were formed into a validation cohort to verify the nomogram.Results: Intrapartum fever was found in 72 of 487 parturient (14.78%) in the training cohort, and the incidence of intrapartum fever in the validation cohort was 14.83% (31/209). Multivariate logistic regression analysis showed that primiparas (Odds Ratio [OR]2.433; 95% confidence interval [CI]1.149-5.150), epidural labor analgesia (OR2.890; 95%CI 1.225-6.818), premature rupture of membranes (OR2.366; 95%CI 1.130-4.954), second stage of labor ≥120min (OR4.363; 95%CI 1.419-13.410), amniotic fluid pollution Ⅲ degree (OR10.391; 95%CI 3.299-32.729), fetal weight ≥4000g (OR7.492; 95%CI 2.115-26.542) were significantly related to intrapartum fever. According to clinical experience and previous studies, the duration of epidural labor analgesia also seemed to be a meaningful factor for intrapartum fever, so these 7 variables were incorporated to develop a nomogram, which achieved good area under ROC curve of 0.855 in the training cohort and 0.808 in the validation cohort, and it had a well-fitted calibration curve, which showed an excellent diagnostic performance.Conclusion: We constructed a model to predict the occurrence of fever during childbirth and developed an accessible nomogram. The nomogram can help doctors assess the risk of fever during childbirth, so as to lead to reasonable treatment measures.Clinical Trial Registration: (www.chictr.org.cn ChiCTR2000035593)
The Association between BMI, Smoking, Drinking and Thyroid Disease: A Cross-sectional Study in Wuhan, China
Authors: Chen Xiao , Wang Juanjuan , Yu Li , Wang Hanyu , Sun Hui
Published: January 2021

Background: There is no clear conclusion on the relationship between thyroid disease and obesity and living habits such as smoking and drinking. In this study, a cross-sectional survey of urban residents in central China was conducted to analyze the association of body mass index (BMI), smoking and drinking with subclinical hypothyroidism (SHO) and thyroid nodules (TNs), and to discuss the potential mechanism between these risk or protective factors and the two diseases.Methods: This study included 1279 participants in 2011 and 2012. Questionnaire survey, laboratory examination and ultrasonic diagnosis were conducted on these participants. Binary logistics regression analysis was used to analyze these factors.Results: Overweight (BMI ≥25kg/m2) was closely related to subclinical hypothyroidism and thyroid nodules in univariate and multivariate logistics regression analysis. Smoking had protective effect on subclinical hypothyroidism and thyroid nodules in univariate logistics regression, while drinking had protective effect on thyroid nodules in univariate logistics regression, but there was no significant difference between smoking and drinking and two kinds of thyroid diseases in multivariate logistics regression analysis. In subgroup analysis, BMI ≥ 25kg/m2 was significantly associated with subclinical hypothyroidism in people with positive thyroid antibodies (OR= 2.221, 95%CI: 1.168-4.184, P=0.015) and smokers (OR= 2.179, 95%CI: 1.041-4.561, P=0.039). Thyroid nodules were significantly associated with thyroid nodules in people over 60 years old (OR= 2.069, 95%CI: 1.149-3.724, P=0.015) and drinkers (OR=3.065, 95%CI: 1.413-6.648, P=0.005). Drinking alcohol has a protective effect on thyroid nodules in smokers (OR=0.456, 95%CI: 0.240-0.865, P=0.016) and people with BMI ≥ 25kg/m2 (OR=0.467, 95%CI: 0.236-0.925, P=0.029). No statistical association was found between smoking and the two thyroid diseases in different subgroups.Conclusion: Obesity is a risk factor for thyroid disease, especially in the elderly and people with positive thyroid autoantibodies. Obesity and metabolic syndrome may be more associated with thyroid nodules than subclinical hypothyroidism. Smoking may be a protective factor for thyroid disease, while drinking is a protective factor for thyroid nodules.
A Secure and Privacy Preserving Authentication Protocol for Wireless Sensor Networks in Smart City
Authors: Xie Qi , Li Keheng , Tan Xiao , Han Lidong , Tang Wen , Hu Bin
Published: January 2021

Smart city can improve the efficiency of managing assets and resources, optimize urban services, and improve the quality of citizens’ life. Wireless sensor networks (WSN) can solve many problems in smart city, such as smart transportation, smart healthcare, smart energy, and so on. However, security and privacy are the biggest challenges for WSN. Recently, Banerjee et al. proposed a security enhanced authentication and key agreement scheme for WSN, but their scheme can't resist off-line password guessing attack, impersonation attack, and does not achieve session key secrecy, identity unlinkability and perfect forward secrecy. In order to fix these flaws, a secure and privacy preserving authentication protocol for WSN in smart city is proposed. We prove the security of the proposed protocol by using applied pi calculus based formal verification tool ProVerif, and show that it has high computational efficiency by comparison with some related schemes.
Environmental Factors Shape the Epiphytic Bacterial Communities of Gracilariopsis Lemaneiformis
Authors: Pei Pengbing , Du Hong , Aslam Muhammad , Liang Honghao , Wang Hui , Liu Xiaojuan , Chen Weizhou
Published: January 2021

Macroalgae host variety of symbionts on their surface which play critical role in their growth and development processes. Nevertheless, the complete understanding of this interaction of epiphytic bacteria and host algae is still in its infancy. This study comprehensively analyses epiphytic bacterial communities composition of red macroalga Gracilariopsis lemaneiformis and environmental factors such as nitrogen and phosphorus which shape the composition of epiphytic bacterial communities of G. lemaneiformis and variation of epiphytic bacterial communities composition at different geographical location. The composition and structure of epiphytic bacterial communities were characterized using high throughput sequencing data of the V3-V4 hypervariable region of 16S rRNA gene amplicon sequencing. The epiphytic bacterial communities composition data revealed that epiphytic bacteria varied significantly among three different geographic locations i) Nan’ao Island (NA) (ii) Lianjiang County (LJ) and iii) Nanri Island (NR) in China. Redundancy analysis (RDA) showed that the relative abundance of Bacteroidetes, Firmicutes, Verrucomicrobia and Epsilonbacteraeota at NR were strongly positively correlated with total nitrogen (TN), total phosphorus (TP), nitrate nitrogen (NO3-N), and dissolved inorganic nitrogen (DIN), whereas negatively correlated with nitrite nitrogen (NO2-N). In addition, the relative abundance of cyanobacteria at NA and LJ were strongly positively correlated with NO2-N, whereas negatively correlated with TN, TP, NO3-N, and DIN. Furthermore, the results of Mantel test indicated that the epiphytic bacterial communities composition is significantly correlated with these environmental factors, which are also proved by Pearson correlation analysis. In conclusion, it is proposed that environmental factors such as NO3-N and DIN play key role in the communities composition of epiphytic bacteria in G. lemaneiformis. Our study provides important baseline knowledge for the communities composition of epiphytic bacteria in G. lemaneiformis and their correlation among themselves as well as with their surrounding environmental factors.
Cryptic U2-dependent Pre-mRNASplice Site Usage Induced by Splice Switching Antisense Oligonucleotides
Authors: Ham Kristin , Keegan Niall , McIntosh Craig , Aung-Htut May , Zaw Khine , Greer Kane , Fletcher Sue , Wilton Stephen
Published: January 2021

Antisense oligomers (AOs) are increasingly being used for modulating RNA splicing in live cells, both for research and for therapeutic purposes. While the most common intended effect of these AOs is to induce skipping of whole exons, rare examples are emerging of AOs that induce skipping of only part of an exon, through activation of an internal cryptic splice site. In this report, we examined seven such examples of AO-induced cryptic splice site activation – five new examples from our own experiments and three from reports published by others. We modelled the predicted effects that AO binding would have on the secondary structure of each of the RNA targets, and how these alterations would in turn affect the accessibility of the RNA to splice factors. We observed that a common predicted effect of AO binding was a disruption to the exon definition signal within the exon’s excluded segment.
Sleep Disorders and Gout in Australian Adults 
Authors: New-Tolley Julia , Reynolds Amy , Appleton Sarah , Gill Tiffany , Lester Susan , Adams Robert , Hill Catherine
Published: January 2021

BACKGROUND: The aims of our study were two-fold. Firstly, to determine if there is an association between gout and OSA in a representative Australian adult population. Secondly, to explore associations between gout and patient reported sleep outcomes. METHODS: A cross-sectional national online survey of a representative sample of Australian adults > 18 years assessed self-reported doctor-diagnosed OSA, insomnia and patient reported sleep outcomes. Possible undiagnosed OSA was estimated using self-reported frequent loud snoring and witnessed apnoeas. Participants self-reported physician-diagnosed gout and other health conditions. Multivariable logistic regression analyses were performed for both objectives. Odds ratios with 95% confidence intervals were reported.RESULTS: There were 1948 participants of whom 126 (6.5%) had gout and 124 (6.4%) had diagnosed sleep apnoea. After adjusting for age, body mass index (BMI), sex, alcohol intake and the presence of arthritis, those with obstructive sleep apnoea diagnosed on polysomnography were twice as likely to report having gout compared to those without. (OR=2.6, 95% CI 1.5 - 4.6). Additionally, participants with symptoms suggestive of sleep apnoea were also twice as likely to have gout compared to those without (OR=2.8, 95%CI 1.6 - 5.1). There was also a higher likelihood of restless legs syndrome, insomnia and worry about sleep in patients with gout. CONCLUSION: Diagnosed and suspected OSA are associated with higher likelihood of gout. Participants with gout are also more likely to report suffering from restless legs syndrome, insomnia and worry about their sleep. Given the morbidity associated with sleep problems, we should be vigilant regarding sleep health in our patients with gout.
Construction of K+ ions gradient in crystalline carbon nitride to accelerate charge separation for efficient visible light H2 production
Authors: Zhang Guoqiang , Xu Yangsen , He Chuan-Xin , Li Yongliang , Ren Xiangzhong , Zhang Peixin , Mi Hongwei
Published: January 2021

Like most of the recent reported semiconductor photocatalysts, the sluggish dynamic charges transfer and separation caused by weak driving force still restricts the further improvement of photocatalytic performance in crystalline carbon nitride (CCN). Here, we successfully prepared a series of heptazine-based K+ implanted CCN (KCN) for the first time, where the K+ ions concentration was gradiently inserted through controlling its diffusion from the surface to bulk in carbon nitride (CN). As a powerful driving force, the built-in electric field (BIEF) induced by this concentration gradient, greatly accelerates the drift movement and the transport from bulk to the surface, as well as the separation of photogenerated carriers. Consequently, the KCN with optimized BIEF displays a ～34 times promotion than original CN for visible-light H2 evolution. Such a high activity enhancement factor is at a relatively good level in reported CCN. Our proposed strategy to induce BIEF production by constructing concentration gradients through thermodynamically feasible diffusion controlled solid-state reaction, can be adopted to build other efficient photocatalytic systems.
Virtual Screening of Potential AEC2 Inhibitors for COVID-19 from Traditional Chinese Medicine
Authors: He Xiang , WANG JUNYI , Zhang Lei , Ran Qin , Xiong Anying , Liu Shengbin , Wu Dehong , Niu Bin , Xiong Ying , Li Guoping
Published: January 2021

Background: Angiotensin-converting enzyme 2 (ACE2), a negative regulator of the renin-angiotensin system and the severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-CoV-2 receptor, plays an important role in viral genome replication and immune response. ACE2 has been proposed as a potential therapeutic target. Traditional Chinese medicine (TCM) could be considered as a promising complementary therapeutic option in the management of COVID-19. However, the active components and action mechanisms that account for its therapeutic effects remain controversial. Methods: ACE2 was employed as a target related to COVID-19 to explore the active ingredients from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. And the PharmMapper database and TCMSP database were used to predict the targets of the compounds. Moreover, the potential therapeutic targets of COVID-19 were acquired by intersection among genes differentially expressed in COVID-19 patients, genes screened from five public databases and genes targeted by active compounds. Finally, molecular docking verification and function analysis were performed.Results: In this study, puerarin, the common active compound for targeting ACE2 across the five TCMs (Radix Cyathulae, Flos Puerariac, Radix Bupleuri, Radix Puerariac and Radix Hemerocallis), was found. Due to the comprehensive analysis, we revealed that puerarin might prevent the entrance of SARS-CoV-2 entry into cells by blocking ACE2, chiefly modulated the T cell immunity and regulate pro-inflammatory cytokine response by affecting TNF, STAT1 and RNASE3. Conclusion: Taken together, the present study found that puerarin might have a therapeutic effect on COVID-19 through regulation of the immune system, inhibition of inflammation and prevention of virus entry into cells.
Frequent POLE-Driven Hypermutation in Ovarian Endometrioid Cancer Revealed by Mutational Signatures in RNA Sequencing
Authors: Davila Jaime , Chanana Pritha , Sarangi Vivekananda , Fogarty Zach , Weroha John , Guo Ruifeng , Ellen Goode , Huang Yajue , Chen Wang
Published: January 2021

Background: DNA polymerase epsilon (POLE) is encoded by the POLE gene, and POLE-driven tumors are characterized by high mutational rates. POLE-driven tumors are relatively common in endometrial and colorectal cancer, and their presence is increasingly recognized in ovarian cancer (OC) of endometrioid type. POLE-driven cases possess an abundance of TCT>TAT and TCG>TTG somatic mutations characterized by mutational signature 10 from the Catalog of Somatic Mutations in Cancer (COSMIC). By quantifying the contribution of COSMIC mutational signature 10 in RNA sequencing (RNA-seq) we set out to identify POLE-driven tumors in a set of unselected Mayo Clinic OC. Methods: Mutational profiles were calculated using expressed single-nucleotide variants (eSNV) in the Mayo Clinic OC tumors (n=195), The Cancer Genome Atlas (TCGA) OC tumors (n=419), and the Genotype-Tissue Expression (GTEx) normal ovarian tissues (n=84). Non-negative Matrix Factorization (NMF) of the mutational profiles inferred the contribution per sample of four distinct mutational signatures, one of which corresponds to COSMIC mutational signature 10. Results: In the Mayo Clinic OC cohort we identified six tumors with a predicted contribution from COSMIC mutational signature 10 of over five mutations per megabase. These six cases harbored known POLE hotspot mutations (P286R, S297F, V411L, and A456P) and were of endometrioid histotype (P=5e-04). These six tumors were hypermutated with a higher tumor mutation load (mean, 54.02 mutations per megabase) compared to non-POLE endometrioid OC cases (mean, 7.69 mutations per megabase; P=5e-04), and had an early onset (average age of patients at onset, 48.33 years) when compared to non-POLE endometrioid OC cohort (average age at onset, 60.13 years; P=.008). Samples from TCGA and GTEx had a low COSMIC signature 10 contribution (median 0.16 mutations per megabase; maximum 1.78 mutations per megabase) and carried no POLE hotspot mutations.Conclusions: From the largest cohort of RNA-seq from endometrioid OC to date (n=53), we identified six hypermutated samples likely driven by POLE (frequency, 11%). Our result suggests the clinical need to screen for POLE driver mutations in endometrioid OC, which can guide enrollment in immunotherapy clinical trials.
Oral Health and Risk Indicators of Early Adolescents in Shandong Province, China: A Cross-sectional Oral Health Survey
Authors: Zhang Meng , Lan Jing , Zhang Tiantian , Sun Wenshuang , Liu Panpan , Wang Zhifeng
Published: January 2021

Objective: We aimed to analyse the oral health status of adolescents in Shandong province, including dental caries and gingivitis, and the relevant risk indicators.Methods: Adolescents aged 12-15-years in Shandong province were recruited. Caries and gingival status were assessed following the World Health Organisation diagnostic criteria. Information including the sociodemographic, oral hygiene knowledge, attitudes and practices were collected through the questionnaire. Chi-square test and multivariate logistic regression analysis were used to investigate the independent risk indicators.Results: In total, 3,868 students (50.2% males) were enrolled. Of these, 39.9% of the participants experienced caries, and 81.7% and 31.3% had calculus and bleeding gums, respectively. Multivariate logistic regression analysis revealed that there was an association between an increased risk of caries with toothaches, dental visits and sleeping troubles caused by oral problems (P < 0.024). A low-frequency of brushing, high sugar consumption and no flossing increased the risk of calculus formation and gum bleeding (P < 0.008).Conclusion: Compared to caries, worse gingival condition was more prevalent among adolescents in Shandong province and was not taken seriously. Brushing behaviour is associated with gingivitis, while dental visits and toothaches are associated with caries. Hence, prevention-oriented dental visits and oral hygiene training are strongly recommended to improve oral health status.Trial registration: Not applicable.
4-Methylumbelliferone Administration Enhances Radiosensitivity of Human Fibrosarcoma by Intercellular Communication
Authors: Saga Ryo , Matsuya Yusuke , Takahashi Rei , Hasegawa Kazuki , Date Hiroyuki , Hosokawa Yoichiro
Published: January 2021

Hyaluronan synthesis inhibitor 4-methylumbelliferone (4-MU) is a candidate of radiosensitizers which enables both anti-tumour and anti-metastasis effects in X-ray therapy. The curative effects under such 4-MU administration have been investigated in vitro; however, the radiosensitizing mechanisms remain unclear. Here, we investigated the radiosensitizing effects under 4-MU treatment from cell experiments and model estimations. We generated experimental surviving fractions of human fibrosarcoma cells (HT1080) after 4-MU treatment combined with X-ray irradiation. Meanwhilst, we also modelled the pharmacological effects of 4-MU treatment and theoretically analyzed the synergetic effects between 4-MU treatment and X-ray irradiation. The results show that the enhancement of cell killing by 4-MU treatment is the greatest in the intermediate dose range of around 4 Gy, which can be reproduced by considering intercellular communication (so called non-targeted effects) through the model analysis. As supposed to be the involvement of intercellular communication in radiosensitization, the oxidative stress level associated with reactive oxygen species (ROS), which leads to DNA damage induction, is significantly higher by the combination of 4-MU treatment and irradiation than only by X-ray irradiation, and the radiosensitization by 4-MU can be suppressed by the ROS inhibitors. These findings suggest that the synergetic effects between 4-MU treatment and irradiation are predominantly attributed to intercellular communication and provide more efficient tumour control than conventional X-ray therapy.
Associations of community, family and early individual factors with body mass index trajectories among children aged 1-18：a longitudinal study in China
Authors: Liang Jing , Zheng Si , Wang Peigang
Published: January 2021

Recently born children are increasing in height and weight, but no studies have analyzed changes in BMI trajectories and the heterogeneity in China. We aimed to examine the developmental trajectories of BMI among Chinese children and the potential determinants including early individual factors, family and community factors. Data came from the China Family Panel Studies (CFPS 2010, 2012, 2014, 2016, and 2018), and group-based trajectory modeling (GBTM) was employed to identify BMI trajectories from 1 to 18 years. Multivariate logistic regression was conducted to determine the association between early individual, family, community factors and child BMI trajectory. We identified three distinct BMI trajectories among boys and girls: low-increasing, medium-increasing, and high-increasing, and found that early individual factors, family and community factors were associated with different trajectories of BMI. There were heterogeneous BMI trajectories from children to adolescents in the recent Chinese birth cohort. Targeted interventions at early individual, family, community levels are essential.
Intimal Thickening and Disruption of The Media Occur in The Arterial Walls of Coronary Arteries Not Associated With Coronary Arterial Aneurysms in Patients With Kawasaki Disease
Authors: Tsuchihashi Tomoya , Kakimoto Nobuyuki , Takeuchi Takashi , Suenaga Tomohiro , Suzuki Takayuki , Shibuta Shoichi , Ino Yasushi , Kubo Takashi , Akasaka Takashi , Suzuki Hiroyuki
Published: January 2021

Background Coronary artery aneurysm (CAA) is an important complication of Kawasaki disease (KD) that is associated with arterial structure damage. However, few studies have examined structural changes in coronary arteries not associated with CAA.Methods We examined coronary arteries in KD patients with CAAs who underwent follow-up coronary angiography (CAG) and optical coherence tomography (OCT). Coronary arterial branches with no abnormal findings on most recent CAG were classified into two groups. Arteries with an acute-phase CAA that later regressed were classified as group R and arteries with no abnormal findings on either acute or convalescent phase CAG were classified as group N. Coronary arterial wall structural changes were compared between groups using OCT.ResultsFifty-seven coronary arterial branches in 23 patients were evaluated by OCT. Thirty-six branches showed no abnormality on most recent CAG. Both groups R and N comprised 18 branches. Maximum intimal thickness in groups R and N was 475 and 355 µm, respectively (p = 0.007). The incidence of disruption of the media was 100% and 67%, respectively (p = 0.02). Calcification, macrophage accumulation, and thrombus were not found in either group.ConclusionsIntimal thickening and disruption of the media occur not only in coronary arteries with acute phase CAAs that later regress in the convalescent phase, but also in arteries with normal CAG findings in the acute and convalescent phases.
Dynamic Monitor of CT Scan Within Short Interval in Invasive Pulmonary Aspergillosis for Nonneutropenic Patients
Authors: Chen Fei , Zhong Yonghong , Li Na , Wang Huijie , Tan Yanbin , Zhang Hao , Hua Wen , Mao Yanxiong , Huang Huaqiong
Published: January 2021

Background: In nonneutropenic patients with underlying respiratory diseases (URD), invasive pulmonary aspergillosis (IPA) is a life-threatening disease. Yet establishing early diagnosis in those patients remains quite a challenge. Methods :A retrospective series of nonneutropenic patients with probable or proven IPA were reviewed from January 2014 to May 2018 in Department of Respiratory Medicine of two Chinese hospitals. Refer to the relevant diagnostic criteria in the 《American Society of Infectious Diseases Guidelines for Invasive Aspergillus 2008》1. Those patients were suspected of IPA and underwent lung computed tomography (CT) scans twice within 5-21 days. The items required for IPA diagnosis were assessed by their host factors, mycological findings and CT scans according to EORTC/ MSG criteria. Results: Together with the risk factors, mycological findings and nonspecific radiological signs on first CT, ten patients were suspected of IPA. With the appearance of cavities on second CT scan in following days, all patients met the criteria of probable or possible IPA. Except one patient who refused antifungal treatment, nine patients received timely antifungal treatment and recovered well. One of the nine treated IPA cases was further confirmed by pathology, one was confirmed by biopys. Conclusions: Dynamic monitor of CT scan provided specific image evidences for IPA diagnosis. This novel finding might provide a noninvasive and efficient strategy in IPA diagnosis with URD.
COVID-19 and the Impact of Cash Transfers on Health Care Use in Togo
Authors: TOSSOU Yaovi
Published: January 2021

Background: Cash transfer program during pandemics provide a social protection mechanism to improve the health of the most vulnerable households. This article analysis the impact of cash transfers on household demand for health care during Covid-19.Methods: Using data from the survey conducted from 8 to 17 July 2020 covering all 44 districts in the 6 health regions of Togo under the direction of the United Nations Office for Project Services (UNOPS), we used propensity score matching and the ESR model. These models allow us to analysis the impact of cash transfers on health care use during Covid-19. Results: Analysis of the results shows a positive impact of cash transfers on the use of health care services in Togo for beneficiary households. In addition, the health insurance promotes the use of health care among households' socio-economic factors. Conclusion: This cash transfer program is an effective approach to improving access to health care services for the most vulnerable households, particularly in the most disadvantaged settings. Thus, policy makers need to extend these cash transfers to a large part of the population during this Covid-19 health crisis as it has a positive impact on the demand for health care.
Risk Factors for Poor Health-related Quality of Life in Patients With Colon Cancer Include Stoma and Smoking Habits
Authors: Tiselius Catarina , Rosenblad Andreas , Strand Eva , Smedh Kenneth
Published: January 2021

Objectives: Studies have shown that poor Health-related quality of life (HRQoL) might worsen the cancer-related prognosis. The aim of this study was to investigate risk factors for poor HRQoL in patients with colon cancer.Method: This was a prospective population-based study of patients with colon cancer included between 2012 and 2016. HRQoL was measured using the cancer-specific European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30. Multiple linear regression analysis adjusted for age, sex, body mass index, smoking habits, American Society of Anesthesiologists physical status classification, emergency/elective surgery, resection with/without a stoma and tumour stage was used.Results: A total of 67% (376/561) of all incident patients with colon cancer (196 [52.1%] females) was included. Mean (range) age was 73 (30–96) years. Patients with more comorbidity (American Society of Anesthesiologists status 3 and 4), those with higher body mass index, smokers and patients who were planned to be operated on with a stoma were at a higher risk for poor QoL than the other included patients at baseline and at 6 months of follow-up.Conclusion: These findings may be used to provide more individualized attention to patients who need more support from health care.ClinicalTrials.gov (NCT 03910894)
Failed Etonogestrel Implant (Nexplanon) in a Woman on anti-TB  Medications: A Case Report
Authors: Tufa Tesfaye H. , Fessehaye Abraham , Abubeker Ferid A.
Published: January 2021

BackgroundA new form of implantable subdermal contraceptive device (Nexplanon) is available in the market since 2001 and provides 99% effective contraception. However, similar to other hormonal contraception, its effectiveness is compromised with the use of cytochrome P450 inducing drugs resulting in an unplanned pregnancy. Despite this theoretical risk, little is known on the outcome of concomitant use of anti-tuberculosis medications and Implants.Case presentationA 26 years old GIII PII who has been using Nexplanon for the past 2 years and 7 months presented to the family planning referral clinic with the diagnosis of failed implant and second-trimester pregnancy at gestational age of 19 weeks. She was initiated on rifampicin based anti-tuberculosis 8 months prior to her presentation for the diagnosis of tuberculosis of the lymph nodes.ConclusionAll health professionals should be aware of the possible reduced effectiveness of certain hormonal contraceptives due to concomitant use of hepatic cytochrome P450 enzyme-inducing medications. Women should be given detailed counseling about the potential for drug interaction. The discussion should include the use of other alternative methods. A multidisciplinary approach with consultation or referral to reproductive health specialists is crucial for optimal management of women who are at increased risk of contraceptive failure and unintended pregnancy.
The Analytical Contribution to the Theory of Solar-induced Earthquakes: the Croatian December 2020 M=6.4 Case Study
Authors: Toman Ivan , Brčić David , Kos Serdjo
Published: January 2021

Solar-induced earthquakes are a relatively new field of research of possible connection between events originating from Sun, and the Earth's lithosphere dynamics. This is a theory that tries to explain the temporal correlation between the solar activity increase, particularly measured using proton density values, and occurrence of the strongest earthquakes on Earth. In this paper, the case study of Croatian major earthquake in December 2020 was investigated. The increase in proton density as measured by STEREO satellite, by +4.2 standard deviations from the monthly mean value, preceded the main shock of M=6.4 by 16 hours. Such proton density increases, within one day before major earthquake, agrees with previous research where strong temporal correlation of those two events was found.