bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating metabolites from the choline pathway and acute coronary syndromes in a Chinese case-control study
Authors: Dai Yuxiang , Tian Qianqian , Si Jing , Sun Zhonghan , Shali Shalaimaiti , Xu Lili , Ren Daoyuan , Chang Shufu , Dong Xin , Zhao Hongxia , Mei Zhengdong , Zheng Yan , Ge Junbo
Published: May 2020

Background: Accumulating evidence shows that circulating levels of trimethylamine N-oxide, which is generated from the metabolism of dietary choline, may predict cardiovascular disease among Caucasians. Acute coronary syndrome (ACS), one common presentation of cardiovascular disease, is a spectrum of signs and symptoms due to acute decreased blood flow in the coronary arteries. The relationship between the metabolites from choline pathway and ACS remains unclear. We aimed to assess the associations of circulating metabolites from the choline pathway with ACS among a Chinese population, who consume a different dietary pattern than their Western counterparts. Methods: We recruited 501 participants who were admitted to the Department of Cardiology, Zhongshan Hospital,Shanghai China between March 2017 and June 2018, including 254 ACS cases and 247 controls. Liquid chromatography-tandem mass spectrometry was used to measure circulating concentrations of metabolites in the choline pathway, including betaine, choline, trimethylamine, and trimethylamine N-oxide. A composite metabolite score using a weighted sum of these four metabolites, and the betaine/choline ratio were calculated. Multivariable logistic regressions were applied to estimate the association of metabolites with ACS, with adjustment of age, sex, body mass index, smoking index, history of diseases, and kidney function. Results : After adjusting for traditional risk factors, per 1-standard deviation (SD) increment in choline was positively associated with the odds of ACS [odds ratio (OR), 95% confidence interval (CI), 1.77(1.44-2.18)], and the other metabolites were not associated with ACS at a statistical significance level. Compared with participants in the lowest quartile of the metabolite score, those in the highest quartile had higher odds of ACS [OR (95% CI), 3.18(1.85-5.54), p <0.001 for trend]. Per 1-SD increment in metabolite score was positively associated with higher odds of ACS [OR (95% CI), 1.80 (1.37-2.40)], and per 1-SD increment inthebetaine/choline ratio was inversely associated with the odds of ACS [OR (95% CI), 0.49 (0.39-0.60)]. Conclusions: Among our Chinese participants, trimethylamine N-oxide was not associated with ACS, while a composite metabolite score of metabolites from the choline pathway was associated with increased odds of ACS. The choline pathway metabolites may be related to the pathophysiology of ACS among Chinese.
Novel insights into the Thaumarchaeota in the deepest oceans: their metabolism and potential adaptation mechanisms
Authors: Zhong Haohui , Lehtovirta-Morley Laura , Liu Jiwen , Zheng Yanfen , Lin Heyu , Song Delei , Todd Jonathan D. , Tian Jiwei , Zhang Xiao-Hua
Published: May 2020

Background: Marine Group I (MGI) Thaumarchaeota, which play key roles in the global biogeochemical cycling of nitrogen and carbon (ammonia oxidizers), thrive in the aphotic deep sea with massive populations. Recent studies have revealed that MGI Thaumarchaeota were present in the deepest part of oceans - the hadal zone (depth > 6,000 m, consisting almost entirely of trenches), with the predominant phylotype being distinct from that in the “shallower” deep sea. However, little is known about the metabolism and distribution of these ammonia oxidizers in the hadal water.Results: In this study, metagenomic data were obtained from 0-10,500 m deep seawater samples from the Mariana Trench. The distribution patterns of Thaumarchaeota derived from metagenomics and 16S rRNA gene sequencing were in line with that reported in previous studies: abundance of Thaumarchaeota peaked in bathypelagic zone (depth 1,000 – 4,000 m) and the predominant clade shifted in the hadal zone. Several metagenome-assembled thaumarchaeotal genomes were recovered, including a near-complete one representing the dominant hadal phylotype of MGI. Using comparative genomics we predict that unexpected genes involved in bioenergetics, including two distinct ATP synthase genes (predicted to be coupled with H+ and Na+ respectively), and genes horizontally transferred from other extremophiles, such as those encoding putative di-myo-inositol-phosphate (DIP) synthases, might significantly contribute to the success of this hadal clade under the extreme condition. We also found that hadal MGI have the genetic potential to import a far higher range of organic compounds than their shallower water counterparts. Despite this trait, hadal MDI ammonia oxidation and carbon fixation genes are highly transcribed providing evidence they are likely autotrophic, contributing to the primary production in the aphotic deep sea.Conclusions: Our study reveals potentially novel adaptation mechanisms of deep-sea thaumarchaeotal clades and suggests key functions of deep-sea Thaumarchaeota in carbon and nitrogen cycling.
First month of the epidemic caused by COVID-19 in Italy: current status and real-time outbreak development forecast
Authors: Megna Rosario
Published: May 2020

Background : The first outbreaks of COVID-19 in Italy occurred during the second half of February 2020 in some areas in the North of the country. Due to the high contagiousness of the infection, further spread by asymptomatic people, Italy has become in a few weeks the country with the greatest number of infected people in the World. The large number of severe cases among infected people in Italy led to the hospitalization of thousands of patients, with a heavy burden on the National Health Service. Methods: We analyzed data provided daily by Italian Authorities for the period from 24 February 2020 to 30 March 2020. Considering such information, we developed a forecast model in real-time, based on the cumulative logistic distribution. We then produced an estimate of the overall number of potentially infected individuals and epidemic duration at a national and Regional level, for the most affected Regions. Results: A total of 101,739 infected individuals was confirmed until 30 March 2020, of which 75,528 active cases, 14,620 recovered or discharged, and 11,591 deaths. Until the same date patients quarantined at home were 43,752, whereas hospitalized patients were 31,776, of which 3,981 in intensive care. The forecast model estimated a number of infected persons for Italy of 130,000 about, and a duration of the epidemic greater than 2 months. Conclusions : Once month after the first outbreaks there seems to be the first signs of a decrease in the number of infections, showing that we could be now facing the descending phase of the epidemic. The forecast obtained thanks to our model could be used by decision-makers to implement coordinative and collaborative efforts in order to control the epidemic. The pandemic due to novel Coronavirus must be a warning for all countries worldwide, regarding a rapid and complete dissemination of information, surveillance, health organization, and cooperation among the states.
Artificial Immune Network Clustering Based on a Cultural Algorithm
Authors: Deng Liyuan , Yang Ping , Liu Weidong
Published: May 2020

There are some problems in evolutionary immune network clustering, such as the lack of guidance in the clustering process, the sensitivity of the fuzzy boundary and the difficulty in determining parameters. To solve these problems, an artificial immune network clustering algorithm based on a cultural algorithm is proposed. Three kinds of knowledge are constructed: normative knowledge is used to standardize the spatial scope of population initialization, avoiding blindness; state knowledge is used to distinguish antigens and take immune defense measures to prevent noise and unclear network structure caused by boundary; topology knowledge is used to guide the optimal antibody search. The clone mutation operation of the traditional method is improved, and a compression threshold adaptive determination method is proposed based on the shadow sets theory. The experimental results show that the proposed method can effectively overcome the above problems, and the clustering performance on a synthetic dataset and an actual dataset is satisfactory.
Efficacy of Dual Antiplatelet Treatment in Minor stroke or TIA Patients with Multiple Acute Infarctions and Lower Level of Stress Hyperglycemic Marker – A Post-hoc Analysis of a Randomized Control Trial
Authors: Suo Yue , Jing Jing , Wang Anxin , Zhang Yijun , Zhou Hongyu , Chen Weiqi , Pan Yuesong , Li Hao , Liu Liping , Zhao Xingquan , Wang Yilong , Meng Xia , Wang Yong-Jun
Published: May 2020

Background We intended to investigate how the interaction between glycemic status and infarction pattern affected the efficacy and safety of dual antiplatelet treatment in minor stroke or transient ischemic attack (TIA) patients.Methods This post-hoc analysis of the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) study included 797 patients with complete data of stress hyperglycemia markers (fasting plasma glucose (FPG)/glycated albumin (GA) ratio) and Magnetic Resonance Imaging work-up. The primary outcome is a 90-day new stroke (ischemic or hemorrhagic). Other endpoints included combined vascular events and bleeding events at 90 days. We used multivariable Cox regression models to evaluate the influence of stress hyperglycemia status × infarction pattern (Multiple acute infarctions (MAI), Single acute infarction (SAI) and No acute infarction (NAI)) on the efficacy and safety of clopidogrel plus aspirin treatment.Results Among 797 patients, the median age was 63.1 years, and 64.9% of the patients were male. Within the 90-day after randomization, 73 (9.2%) new strokes 75 (9.4%) combined vascular events, and 17 (2.1%) bleeding events occurred. Dual antiplatelet treatment significantly reduced new stroke and combined vascular events in patients with lower FPG/GA ratio (lower than the median of FPG/GA ratio) and multiple acute infarctions, after adjusted for all potential confounders (11.9% vs. 23.3%, adjusted HR(95% confidence interval, CI): 0.240(0.080–0.713)). No significant reductions of recurrence or occurrence of combined vascular events were seen in the other three groups (NAI or SAI with lower FPG/GA ratio; NAI or SAI with higher FPG/GA ratio and MA with higher FPG/GA ratio). The proportion of bleeding events was similar among treatment groups regardless of the FPG/GA ratio or infarction pattern.Conclusions Clopidogrel plus aspirin treatment was associated with reduced 90-day new stroke or combined vascular events in patients with multiple acute infarctions and lower FPG/GA ratio, without increasing the risk of bleeding events.
Willingness to join and pay for Social Health Insurance among Public Servants in Arba Minch town, Gammo Zone, Southern Ethiopia
Authors: Mulatu Bahiru , Mekuria Aleme , Tassew Berhane
Published: May 2020

Background Ethiopia plans to introduce social health insurance scheme for the formal sector. The scheme contribution will be collected as 3% of an employee’s monthly gross salary from both employee and employer. The scheme is expected to enhance access to health care, however, there is a concern that majority of civil servants were not willing to join and pay for it. Therefore, this study aims to assess willingness to join and pay for the newly proposed social health insurance among public servants in Arba Minch town, Southern Ethiopia.Methods Institution based, Cross-sectional study design was used among 713 randomly selected public servants in Arba Minch town. Multi-stage stratified random sampling technique was used to select participants. Data were collected by using a pre-tested, self-administered, structured questionnaire and then it was cleaned, coded, entered in to Epidata v.3.2 and exported to SPSS version 25 statistical package for analysis. Multivariate logistic regression was used to identify the predictors of willingness to join and pay for Social Health Insurance. Odds ratio less than 0.05 was used as cut-off point and 95% CI was used to report the finding. Open question contingent valuation method was also used to analyze willingness to pay for the scheme.Result Among the total of 692 respondents, 254 (36.7%) were willing to join the scheme. Out of those who were willing to join 171 (24.7%) respondents were willing to pay less than 1% and 41(5.9%) respondents were willing to pay 2–3% of their gross monthly salary. Interest to join the scheme was found to be affected by an awareness of the scheme, household size, regularly listening for health information and participation in the social network.Conclusion There is limited knowledge and awareness about the design of health issuance. Majority of the respondents were not willing to join and pay the proposed amount for the scheme. Provision of health information on mass media could be used as one strategy to enhance the understanding of health insurance and to change perception on social health insurance scheme.
Serodiagnosis of toxoplasmosis in pregnant women using dot-immunogold-silver staining with recombinant Toxoplasma gondii peroxiredoxin protein
Authors: liu zhuan-zhuan , Li Xue-yan , Fu Lin-lin , Yuan Fei , Tang Ren-xian , Liu Yi-sheng , Zheng Kui-yang
Published: May 2020

Background
Toxoplasma gondii infection endangers human health and affects animal husbandry. Serological detection is the main method used for epidemiological investigations and diagnosis of toxoplasmosis. The key to effective diagnosis of toxoplasmosis is the use of a standardized antigen and a specific and sensitive detection method. Peroxiredoxin is an antigenic protein and vaccine candidate antigen of T. gondii that has not yet been exploited for diagnostic application.
Methods
In this study, recombinant T. gondii peroxiredoxin protein (rTgPrx) was prepared and used in dot-immunogold-silver staining (Dot-IGSS) to detect IgG antibodies in serum from mice and pregnant women. The rTgPrx-Dot-IGSS method was established and optimized using mouse serum. Furthermore, serum samples from pregnant women were analyzed by rTgPrx-Dot-IGSS.
Results
Forty serum samples from mice infected with T. gondii and twenty negative serum samples were analyzed. The sensitivity and specificity of rTgPrx-Dot-IGSS were 97.5% and 100%, respectively, equivalent to those of a commercial ELISA kit for anti-Toxoplasma IgG antibody. Furthermore, 540 serum samples from pregnant women were screened with a commercial ELISA kit. Eighty-three positive and 60 negative serum samples were analyzed by rTgPrx-Dot-IGSS. The positive rate was 95.18%, comparable to that obtained with the commercial ELISA kit.
Conclusions
The Dot-IGSS method with rTgPrx as an antigen might be useful for diagnosing T. gondii infection in individuals.
Thrombolysis Implementation Intervention and Clinical Outcome: A Secondary Analysis of a Cluster Randomized Trial.
Authors: Hasnain Md Golam , Paul Christine L , Attia John R , Ryan Annika , Kerr Erin , Oldmeadow Christopher , D’Este Catherine A , Bivard Andrew , Hubbard Isobel J , Milton Abul Hasnat , Levi Christopher R
Published: May 2020

Background Multiple studies have attempted to increase the rate of intravenous thrombolysis for ischemic stroke using interventions to promote adherence to guidelines. Still, many of them did not measure individual-level impact. This study aimed to make a posthoc comparison of the clinical outcomes of patients in the “Thrombolysis ImPlementation in Stroke (TIPS)” study, which aimed to improve rates of intravenous thrombolysis in Australia.Methods A posthoc analysis was conducted using individual-level patient data. Excellent and poor clinical outcome and parenchymal haematoma were the three main outcomes, and a mixed logistic regression model was used to assess the difference between the intervention and control groups.Results There was a non-significantly higher odds of having an excellent clinical outcome of 57% (odds ratio: 1.57; 95% CI: 0.73–3.39) and 33% (odds ratio: 1.33; 95% CI: 0.73–2.44) during the active-and post-intervention period respectively, for the intervention compared to the control group. A non-significantly lower odds of having a poor clinical outcome was also found in the intervention, relative to control group of 4% (odds ratio: 0.96; 95% CI: 0.56–2.07) and higher odds of having poor outcome of 44% (odds ratio: 1.44 95% CI: 0.61–3.41) during both active and post-intervention period respectively. Similarly, a non-significant lower odds of parenchymal haematoma was also found for the intervention group during the both active- (odds ratio: 0.53; 95% CI: 0.21–1.32) and post-intervention period (odds ratio: 0.96; 95% CI: 0.36–2.52).Conclusion The TIPS multi-component implementation approach was not effective in reducing the odds of post-treatment severe disability at 90 days, or post-thrombolysis hemorrhage.Trial registration Clinical Trial Registration-URL: http://www.anzctr.org.au/ Unique Identifier: ACTRN12613000939796.
Indoor temperature and respiratory disease–related emergency department visits: a study of cumulative effects among older adults in Taiwan
Authors: Jung Chien-Cheng , Hsia Ying-Fang , Hsu Nai-Yun , Wang Yu-Chun , Su Huey-Jen
Published: May 2020

Background

Studies have demonstrated that exposure to extreme outdoor temperatures increases respiratory diseases related mortality and morbidity, especially in older adults. However, older adults spend over 80% of their time indoors, and the cumulative effects of exposure to indoor temperature on the risk of respiratory diseases have not been investigated. The objective of this study was to study the cumulative effect of indoor temperature exposure on emergency department visit due to respiratory diseases among older adults.
Methods

Participant data were collected from the Longitudinal Health Insurance Database from 2000 to 2014 in Taiwan. The cumulative degree hour was used to reflect the cumulative effect of indoor temperature exposure. A distributed lag nonlinear model was used to analyze the association between cumulative degree hour and emergency department visit due to respiratory diseases.
Results

Our findings revealed a significant risk of emergency department visits due to respiratory diseases at 27, 28, 29, 30, and 31 °C when cooling cumulative degree hours exceeded 60, 30, 19, 1, and 1, respectively, during the hot season (May to October) and at 19, 20, 21, 22, and 23 °C when heating cumulative degree hours exceeded 1, 1, 1, 39, and 49, respectively, during the cold season (November to April).
Conclusions

We conclude that the cumulative effects of indoor temperature exposure should be considered to reduce respiratory disease risk under climate change.
UBR-Box Containing Protein, UBR5, is Over-Expressed in Human Lung Adenocarcinoma and is a Potential Therapeutic Target
Authors: Saurabh Kumar , Shah Parag P , Doll Mark , Siskind Leah J , Beverly Levi J.
Published: May 2020

Background:N-end rule ubiquitination pathway is known to be disrupted in many diseases, including cancer. UBR5, an E3 ubiquitin ligase, is mutated and/or overexpressed in human lung cancer cells suggesting its pathological role in cancer. Methods: We determined expression of UBR5 protein in multiple lung cancer cell lines and human patient samples.Using immunoprecipitation followed by mass spectrometry we determined the UBR5 interacting proteins. The impact of loss of UBR5 for lung adenocarcinoma cell lines was analyzed using cell viability, clonogenic assays and in vivo xenograft models in nude mice. Additional Western blot analysis was performed to assess the loss of UBR5 on downstream signaling. Statistical analysis was done by one-way ANOVA for in vitro studies and Wilcoxon paired t-test for tumor volumes in vivo.Results:We show variability of UBR5 expression levels in lung adenocarcinoma cell lines and in primary human patient samples.To gain better insight into the role that UBR5 may play in lung cancer progression we performed unbiased interactome analyses for UBR5. Dataindicate that UBR5 has a wide range of interacting protein partners that are known to be involved in critical cellular processes such as DNA damage, proliferation and cell cycle regulation. We have demonstrated thatshRNA-mediated lossof UBR5 decreases cell viabilityand clonogenic potential of lung adenocarcinoma cell lines.In addition, we founddecreased levels of activatedAKT signaling after the loss of UBR5 in lung adenocarcinoma cell lines using multiple means of UBR5 knockdown/knockout. Furthermore, we demonstrated that loss of UBR5 in lung adenocarcinoma cells results in significant reduction of tumor volume in nude mice. Conclusions:These findings demonstrate that deregulation of the N-end rule ubiquitination pathway plays a crucial role in the etiology of some human cancers, and blocking this pathway via UBR5-specific inhibitors, may represent a unique therapeutic target for human cancers.
PD-L1, an Important Immune Checkpoint Regulator, Is Suppressed by miR-34a in Head and Neck Squamous Cell Carcinoma
Authors: Higashi Kenjiro , Ogawa Takenori , Saiki Yuriko , Ishikawa Tomohiko , Kobayashi Yuta , Ohkoshi Akira , Nakanome Ayako , Katori Yukio , Horii Akira
Published: May 2020

Background: Key molecules regulating the immune checkpoint have shed light on the efforts to control several cancers. Recently, immune checkpoint inhibitors for cancer therapy such as antibodies against programmed cell death 1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), and cytotoxic T-lymphocyte associated protein 4 (CTLA4) have been developed. In head and neck squamous cell carcinomas (HNSCCs), such immune checkpoint inhibitors have come into clinical use and are expected to improve patients’ prognoses. Recently, miR-34a has been shown to be a downstream micro RNA of TP53 that regulates PD-L1 in several types of cancer. To reveal the correlations between miR-34a and PD-L1 in HNSCCs in terms of clinical significance, we analyzed 19 HNSCC cell lines.Methods: We measured the expression levels of miR-34a and PD-L1 in 10 HNSCC cell lines as well as in 9 of their derived acquired cisplatin (CDDP) resistant cell lines by qRT-PCR and Western blotting. Results were further analyzed by their TP53 statuses. We also investigated the changes in PD-L1 expression levels after miR-34a precursor- or inhibitor-mediated forced expression or suppression in HNSCC cell lines. Results: We observed inverse correlations between both mRNA and protein expression levels of miR-34a and PD-L1. No significant differences in miR-34a levels were observed with regard to TP53 status. Forced expression of miR-34a decreased PD-L1 expression, and suppression of miR-34a increased PD-L1 expression. Conclusion: Our present results suggest that miR-34a negatively regulates PD-L1 expression, possibly in a TP53 independent manner in HNSCC.
Asymmetrical Cortical Vein Sign Predicts Early Neurological Deterioration in Acute Ischemic Stroke Patients with Severe Intracranial Arterial Stenosis or Occlusion
Authors: Li Wei , Xiao Wei-Min , Luo Gen-Pei , Liu Yong-Lin , Qu Jian-feng , Fang Xue-Wen , Wang Fang , Chen Yang-Kun
Published: May 2020

Background: Susceptibility weighted imaging (SWI) provides a rough assessment of tissue perfusion with the prominent hypointense cortical veins in the ischemic territory due to increased concentration of deoxyhemoglobin. We aimed to evaluate whether asymmetrical prominent cortical vein sign (APCVS) on SWI can predict early neurological deterioration (END) in acute ischemic stroke patients with severe intracranial arterial stenosis or occlusion (SIASO).Results: One hundred and nine acute ischemic stroke patients with SIASO who underwent SWI were retrospectively recruited. END was defined as a National Institutes of Health Stroke Scale (NIHSS) increasement≧2 points despite standard treatment in the first 72h after admission. APCVS was defined as more and/or large vessels with greater signal loss than those in the opposite hemisphere on SWI. Thirty out of the 109 (27.5%) patients developed END. Sixty (55.0%) patients presented with APCVS on SWI. APCVS occurred in 24 (80%) patients with END, whereas it only occurred in 36 (45.6%) patients without END (P=0.001). Patient with APCVS were more likely to have END (40.0%, vs. 12.2%, P=0.001), in comparation with those without END. Multivariate logistic regression indicated that APCVS (OR=4.349, 95% C.I.=1.580-11.970, P=0.004) was a significant predictor of END in acute ischemic stroke patients with SIASO, adjusted for previous stroke history and acute infarct volume.Conclusions: In acute ischemic stroke patients with SIASO, APCVS might be a useful neuroimaging marker for predicting END, suggesting the importance of evaluation of perfusion status.
Stroke Occurring on the Left or Right Side of the Brain Can Be Identified by the Analysis of Retinal Images: A Case Control Study
Authors: Zhuo Yuanyuan , Lin Jiaye , Wu Jiaman , Qu Yimin , Lee Jock-Wai , Huang Xingxian , Yu Haibo , Zhang Jinwen , Yang Zhuoxin , Zee Benny Chung-Ying
Published: May 2020

Background: The burden of stroke in China has increased dramatically in the past 30 years. Specifying the treatment according to the side of stroke in the brain might be an effective way to reduce the burden. Current imaging tools to identify the side of brain stroke, such as magnetic resonance imaging (MRI), are expensive and time-consuming. Hence, there is a great need for a rapid and inexpensive assessment. In this case, retinal image analysis is a possible approach for stroke side identification. This study aimed at determining the association between retinal characteristics and the stroke side and to establish a predictive model for further investigation.Methods: A total of 168 patients (89 left-sided stroke patients and 79 right-sided stroke patients) were recruited from the Shenzhen Traditional Chinese Medicine Hospital in the study. Retinal characteristics were analysed using an automated retinal image analysis (ARIA) system. Multivariable logistic regression was used to identify and develop predictive models.Results: Each unit increase in the right eye bifurcation coefficient of arterioles increased the risk of right-side stroke by 7.523 times (95% CI, 1.823–31.044). Additionally, an elevated bifurcation coefficient of venules in the right eye also increased the risk of stroke in the right side of the brain, with an odds ratio (OR) of 7.377 (95% CI, 1.771–30.724). A complex retinal composite score was also associated with a higher risk of right-side stroke (OR, 4.955; 95% CI, 3.061–8.022).Conclusions: This study demonstrated that retinal images can provide useful information for stroke side identification, and specific retinal characteristics may help predict the occurrence of stroke.Trial registration: Acupuncture Clinical Trail Redistry, ChiCTR1800019647, Registered 01 November 2018, AMCTR-OPC-18000228.
Worldwide Patterns in Alzheimer’s Disease and other Dementias Prevalence from 1990 to 2017: A Growth Mixture Models Approach
Authors: Borumandnia Nasrin , Majd Hamid Alavi , Khadembashi Naghmeh , Olazadeh Keyvan , Alaii Hojat
Published: May 2020

Background This study was designed to monitor the longitudinal trends of Alzheimer’s disease and other dementias (ADD) prevalence among world countries, as well as classifying them into clusters in which countries within each cluster have similar trends over time.Methods The ADD prevalence in 195 countries during 1990–2017 were extracted from the Global Burden of Disease study’s database. The Latent Growth Models (LGMs) and also Latent Growth Mixture models (LGMM) were applied for trend analysis.Results The highest and the lowest increase in ADD were observed in Europe and Africa, respectively. Increase in ADD was higher in women. LGMM allocated Nordic Countries in the class with a downward trend with a downward trend, with rate of -11.5 in 100000 person in every 2 years. Japan alone entered a class with a dramatically sharp increase with rate of 185 in 100000 person in every 2 years, the highest rank in ADD trend. Most European and American countries were entered into classes with higher increasing trend, rate between 20.4 and 53.6 in 100000 person in every 2 years, relative to the most of Asian countries which were less likely to have the increase of ADD, with rate of 6.45 in 100000 person in every 2 years.Conclusion A substantial difference was observed in ADD trend among the countries: the decline in Nordic countries, which could be due to "Health Care of the elderly in the Nordic Countries" program, and the highly differentiated ascending trend in Japan, which is not necessarily due to the aging population; none of other countries, which have elderly population too, witnessed such sharp increase in their ADD. The clarification of the cause of the last finding calls for more epidemiological studies.
Comparative transcriptome analysis of astaxanthin accumulation difference between non-motile cells and akinetes of Haematococcus pluvialis
Authors: Fang Lei , Zhang Jingkui , Fei Zhongnan , Wan Minxi
Published: May 2020

Background: Nature astaxanthin is mainly derived from Haematococcus pluvialis. H. pluvialis has four kinds of cell morphology. Based on sequential heterotrophy-dilution-photoinduction (SHDP) technology, photoinduction using non-motile cells as seeds could result in a higher astaxanthin production than that of using brown akinetes as photoinduction seeds. To have a comprehensive understanding of this phenomenon, transcriptome analysis was conducted in this study.Results: Though most of photosynthesis genes expression were down-regulated during the SHDP culture process. Comparing with the group using brown akinetes as photoinduction seeds, the genes expression involved in astaxanthin biosynthesis, lipid biosynthesis and photosynthesis were up-regulated in the non-motile cells group. Especially, chyb gene improving the conversion of β-carotene into astaxanthin was up-regulated by 2.6-fold. The acaca gene enhancing the carboxylation of acetyl-CoA to malonyl-CoA was up-regulated by 1.4-fold.Conclusions: Astaxanthin synthesis mechanism of non-motile cells with higher astaxanthin accumulation ability than brown akinetes was attributed to the up-regulation of astaxanthin metabolism, lipid metabolism and photosynthesis-related genes expression. The results are expected to guide the optimization of astaxanthin production in H. pluvialis by improving lipid content or photosynthesis.
Rutin trihydrate attenuated cisplatin- induced cardiac toxicity in isolated perfused rat’s hearts
Authors: Bukhari Ishfaq , Mohamed Osama Yousif , Lateef Rahmathunnisa , Fatima Sabiha , Vohra Fahim , Afzal Sibtain
Published: May 2020

Background

The present study aims to investigate the protective effect of rutin against cisplatin induced toxic effects on the mechanical performance of the myocardium, histopathology, and oxidative stress in isolated perfused rat hearts.
Methods

Cardiotoxicity of cisplatin was assessed at three dosage levels (1, 7, and 14 mg/l) in the isolated perfused rat hearts. The toxic effect of cisplarin was assessed on left ventricular pressure (LVP), heart rate (HR), dp/dt(max), dp/dt (min), perfusion pressure, pressure-time index, contractility index and duration of diastole. Measurements were carried out one minute before perfusion of cisplatin and 60 minutes after perfusion.
Results

Cisplatin reduced significantly (p < 0.05) in a dose-dependent manner LVP, dp/dt(max), dp/dt(min) and pressure- time index. Perfusion of rutin trihydrate (1 µM/l), 10 minutes before administration of cisplatin and throughout the experiment significantly (p < 0.05) attenuated the detrimental effects of cisplatin on cardiac parameters. Cisplatin caused degeneration and necrosis of cardiac muscle cells, while rutin reduced these changes and restored normal heart histology. Moreover, cisplatin reduced the myocardium concentration of reduced glutathione and increased the level of malondialdehyde, whereas rutin almost reversed these changes.
Conclusion

Cisplatin-induced dose-dependent impairment of several parameters of cardiac function and produced histopathological alterations in isolated rat hearts. These harmful effects of cisplatin were ameliorated by rutin trihydrate. These findings suggest the potential protective effects of rutin trihydrate against cisplatin-induced cardiotoxicity.
Detection of Several Carbapenems Resistant and Virulence Genes in Classical and Hyper-virulent Strains of Klebsiella pneumoniae Isolated from Hospitalized Neonates and Adults in Khartoum
Authors: Albasha Aalaa Mahgoub , Osman Esraa Hassan , Alhalim Saga Abd , Alshaib Elianz , Al-Hassan Leena , Altayb Hisham N
Published: May 2020

Background
Carbapenems resistant hypervirulent strains of Klebsiella pneumoniae are one of the most critical organisms that cause fatal nosocomial infections. This study aimed to detect and characterize K. pneumoniae virulence genes (mrkD, entB, rmpA, K2, kfu, and magA) and carbapenem resistant (blaNDM, blaIMP, blaOXA−48, and blaKPC) genes
Methods
Sixty K. pneumoniae strains were isolated from urine, blood, wound swab, and sputum samples, in two age groups: neonates and adults. String test was used to detect hypervirulent strains. Susceptibility testing for a wide range of antibiotics was performed on all isolates. DNA was extracted by the guanidine chloride method, then multiplex PCR was used for the detection of carbapenem-resistance and virulence genes.
Results
Seventy percent of the isolates were resistant to ceftazidime and 8% to imipenem, 35% were multi-drug resistant, and 7% extensively drug-resistant, all neonatal blood isolates (n = 15) were resistant to ceftazidime. entB was the most predominant virulence gene (93.3%), followed by mrkD (78.3%), kfu (60%), K2 (51.7%), magA (18.3%) and rmpA (5%). blaOXA−48 was the most predominant carbapenem-resistant gene (68.3%), followed by blaNDM (10%), blaKPC (8.3%), and blaIMP (3.3%). Eight hyper-virulent strains were positive for blaOXA−48 and two for blaNDM genes. The study concluded that there is a high rate of carbapenems resistant genes in hyper-virulent strains of K. pneumoniae isolated from hospitalized patients.
Conclusion
The study reported for the first time in Sudan presence of carbapenems resistant genes in hyper-virulent strains of K. pneumoniae isolated from hospitalized patients. Presence of MDR and XDR strains of K. pneumoniae in neonatal ward in some Sudanese hospitals.
Adsorption of Lead(II), Manganese(II), and Copper(II) onto biochar in landfill leachate: implication of non-linear regression analysis
Authors: Zand Ali Daryabeigi , Abyaneh Maryam Rabiee
Published: May 2020

The feasibility of using wood-derived biochar (BC) to remove Pb, Mn, and Cu from landfill leachate was investigated and modeled in this study. The effect of contact time, biochar dosage and particle size on adsorption of the heavy metals onto BC was examined. BC was used in two form i.e. pulverized (PWB) and crushed (CWB) to evaluate the effect of BC particle size on adsorption characteristics. Biochar was produced under the pyrolytic temperature of 740 °C. The kinetics of Pb, Mn, and Cu adsorption onto PWB and CWB were assessed using the pseudo second-order and Elovich models, where both applied models could well describe the adsorption kinetics. Equilibrium adsorption capacity of the heavy metals onto BC in leachate system was evaluated using the Langmuir, non-linearized Freundlich, linearized Freundlich, and Temkin isotherms and found to have the following order for PWB: Non-linearized Freundlich>Temkin>Langmuir>Linearized Freundlich. The Langmuir and linearized Freundlich models could not adequately represent adsorption of the heavy metals onto biochar, especially for CWB. Using the non-linearized Freundlich isotherm significantly reduced adsorption prediction error. The adsorption affinity of PWB for Pb, Mn, and Cu was greater than CWB in all treatments. Wood-derived biochar is suggested to be used for the removal of heavy metals from landfill leachate as an economical adsorbent.
Asthma Control According to the Community Pharmacists: Evidence and Potential Implications from an Italian Cross-Sectional Study
Authors: Caminati Marco , Cegolon Luca , Bacchini Marco , Segala Nadia , Dama Annarita , Bovo Chiara , Olivieri Bianca , Furci Fabiana , Senna Gianenrico
Published: May 2020

Background. Asthma control and monitoring still represents a challenge worldwide. Although the international guidelines suggest the interplay with primary care as an effective strategy, the community pharmacies’are rarely involved in asthma management.The present cross-sectional study aimed at providing a picture of the relationship between asthma severity and control according to the community pharmacies’ perspective of the health district of Verona (North-Eastern Italy).Methods. A call for participation was launched through the Pharmacists’ Association of Verona.Patients referring to the participating pharmacies with an anti-asthmatic drug medical prescription and an asthma exemption code were asked to completethe Asthma Control Testand a brief questionnaire collecting information on their age, sex, smoking status, aerobic physical exercise and usual asthma therapy, which also defined the severity level of asthma.A multinomial logistic regression model was fitted to investigate the risk of uncontrolled as well as poorly controlled vs. controlled asthma (base). Results were expressed as relative risk ratios (RRR) with 95% confidence interval (95%CI).Results.57 community pharmacies accepted to participate and 584 asthmatic patients (54% females; mean-age: 51 ± 19 years) were recruited. According to the ACT score 50.5% patients hada controlled asthma, 22.3% a poorly controlled and 27.2% uncontrolled. A variable proportion patients with uncontrolled asthma was observed at every level of severity, although more frequently in mild persistent form of disease. Most patients (92%) reported regular compliance with therapy. At multinomial regression analysis, patients under regular asthma treatment course (RRR=0.33; 95%CI: 0.15; 0.77) were less likely to have an ACT<16 compared to those not taking medications regularly.Conclusions.Overall, our findings highlighted an unsatisfactory asthma control from the pharmacists’ perspective, independently of the asthma severity level. The relevance of community pharmacies as a first line interface suggest their involvement inan effective asthma management plan, from disease control and treatment compliance assessment to referral of asthmatic patients to medical consultancies.
MiR-381 enhances the sensitivity of non-small cell lung cancer to radiotherapy by targeting ROCK2 to regulate NF-κB signaling pathway
Authors: Huang Jiuning , Zeng Jing , Zhang Shuping , Cai Jundong , Wang Wulong , Zhao Kaikai , Wang Xuelei , Pang Qingsong , Wang Ping
Published: May 2020

BackgroundWe investigated the effect of miR-381 on the sensitivity of non-small cell lung cancer (NSCLC) to radiotherapy, and examined its possible mechanism.MethodsNSCLC A549 cells and miR-381 overexpression and gene silencing cell lines were treated with radiotherapy. The cell proliferation was tested by CCK-8 assay and colony formation. Flow cytometry and TUNEL were used to detect the cell apoptosis. The expression of nuclear factor kappa B (NF-κB) signaling pathway related proteins were detected by western blot. NF-κB signaling pathway activator and inhibitor cell lines were further constructed and the above experiments were repeated. Double luciferase assay was used to verify the target of miR-381. Furthermore, a nude mouse xenograft model was constructed and treated with radiotherapy. The tumor volume and tumor weight were measured. The expression of PCNA protein in tumor tissues was observed by immunohistochemistry. The apoptosis related proteins in tumor tissues were detected by western blot.ResultsThe mRNA expression of miR-381 was increased after radiotherapy treatment. Radiotherapy treatment also can inhibit the proliferation and promote apoptosis of A549 cells. Compared with radiotherapy group, cell proliferation was significantly decreased and apoptosis was significantly increased in miR-381 overexpression group (p < 0.05). Moreover, ROCK2 is a target of miR-381, and overexpression of miR-381 can down-regulate the expression of ROCK2 protein. In nude mice, miR-381 mimic interference can reduce cell tumorigenicity and proliferation, and increase the apoptosis. However, the indicators above were contrary in miR-381 silencing group. Verification experiments further verify that NF-κB signaling pathway activator can reverse the role of miR-381.ConclusionMiR-381 overexpression could enhance the sensitivity of NSCLC to radiotherapy by targeting ROCK2 to inhibit NF-κB signaling pathway.
Recombinant tandem epitope vaccination provides cross protection against Actinobacillus pleuropneumoniae challenge in mice
Authors: Xiao Jiameng , Liu Jianfang , Bao Chuntong , Zhu Rining , Gu Jingmin , Sun Changjiang , Feng Xin , Du Chongtao , Han Wenyu , Li Yang , Lei Liancheng
Published: May 2020

Actinobacillus pleuropneumoniae (A. pleuropneumoniae/APP) is the pathogen that causes porcine contagious pleuropneumonia. Actinobacillus pleuropneumoniae is divided into 18 serovars, and the cross protection efficacy of epitopes is debatable, which has resulted in the slow development of a vaccine. Consequently, epitope-based vaccines conferring Actinobacillus pleuropneumoniae cross protection have rarely been reported. In this study, B cell epitopes in the head domain of trimeric autotransporter adhesin were predicted, and 6 epitopes were selected. Then, the predicted epitopes (Ba1, Bb5, C1, PH1 and PH2) were connected by linkers to construct a recombinant tandem antigen (rta) gene. The RTA protein encoded by the recombinant rta gene was expressed, and finally the ICR mice were immunized with the RTA protein with or without inactivated Actinobacillus pleuropneumoniae (serovars 1 and 5b) and challenged with Actinobacillus pleuropneumoniae to evaluate the protective effect of the epitope-based vaccine and combined vaccine.The mice in the RTA-immunized group and RTA plus inactivated Actinobacillus pleuropneumoniae vaccine group had a significant improvement in clinical symptoms and a higher level of antibody in the serum than those in the control group. The RTA immune group had a 40% survival rate after Actinobacillus pleuropneumoniae infection, whereas the combination of RTA and inactivated Actinobacillus pleuropneumoniae produced very strong cross immune protection in mice, at least 50% (RTA IB1+ C5) and at most 100% (RTA IB5 + C1), whereas no cross immunoprotection was found in the solo Actinobacillus pleuropneumoniae immune group. Overall, the combination of the RTA protein and inactivated bacteria significantly enhanced the cross protection effects. This implies that RTA protein in combination with a suitable inactivated Actinobacillus pleuropneumoniae strain could be a candidate vaccine for porcine contagious pleuropneumonia.
Dysbiosis of urine microbiota in obstructive urinary retention patients revealed by next-generation sequencing
Authors: Jiang Shan , Lu Saisai , Chen Xiaomin , Li Fengxia , Zhu Chengwei , Zheng Yuancai , Xu Shihao , Wang Xiaobing
Published: May 2020

Background
Urinary retention (UR) is a common urinary system disease can be caused by urinary tract obstruction with numerous reasons, however, the role of urine microbes in these disorders is still poorly understood. The aim of this study was to identify the urine microbial features of two common types of obstructive UR, caused by urinary stones or urinary tract tumors, with comparison to healthy controls.
Methods
Urine samples were collected from a cohort of 32 individuals with stone UR, 25 subjects with tumor UR and 25 healthy controls. The urine microbiome of all samples was analyzed using high-throughput 16S rRNA (16S ribosomal RNA) gene sequencing.
Results
We observed dramatically increased urine microbial richness and diversity in both obstructive UR groups compared to healthy controls. Despite different origins of UR, bacteria such as Pseudomonas, Acinetobacter and Sphingomonas were enriched, while Lactobacillus, Streptococcus, Gardnerella, Prevotella and Atopobium were decreased in both UR groups in comparison with healthy controls, exhibited an approximate urine microbial community and functional characteristics of two types of obstructive UR. Furthermore, disease classifiers were constructed using specific enriched genera in UR, which can distinguish stone UR or tumor UR patients from healthy controls with an accuracy of 92.29% and 97.96%, respectively.
Conclusion
We presented comprehensive microbial landscapes of two common types of obstructive urinary retention and demonstrated that urine microbial features of these patients are significantly different from that of healthy people. The urine microbial signatures would shed light on the pathogenesis of these types of urinary retention and might be used as potential classification tools in the future.
Immunological and clinicopathological characteristics of C1RL in 2143 glioma patients
Authors: Wang Junyou , Tong Luqing , Lin Gaojun , Wang Hui , Yang Xuejun
Published: May 2020

Glioma is a deadly and immunosuppressive brain tumor. Complement C1r Subcomponent Like (C1RL), as a prognostic biomarker in several kinds of tumors, has attracted increasing attention from oncologists. However, the role of C1RL in glioma remains unclear.
Through 2143 glioma patients from 5 public datasets, the relationships between C1RL expression and clinicopathological characteristics were analyzed. Furthermore, the C1RL associated genes were screened and GO analysis was conducted to investigate their biological process enrichment. In addition, tumor purity, leukocytes infiltration and overall survival were calculated based on C1RL expression.
We found that C1RL expression was upregulated in glioblastoma (GBM), especially mesenchymal GBM and primary GBM. Increased C1RL accompanied IDH1 wt both in lower grade glioma (LGG) and GBM. C1RL associated genes were mainly enriched in biological processes which are related to immune response. C1RL expression was also correlated with less tumor purity and more M2 macrophage infiltration. Higher C1RL expression predicted unfavorable survival for patients with glioma and therapeutic resistance in GBM.
Our results implied that C1RL is involved in immunological activities and is an independent unfavorable prognostic biomarker for patients with glioma. C1RL is a potential immunotherapeutic target for glioma in future clinical practice.