bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome-based analysis of the effects of salicylic acid and high light on lipid and astaxanthin accumulation in Haematococcus pluvialis
Authors: Hu Qunju , Huang Danqiong , Li Anguo , Hu Zhangli , Gao Zhengquan , Yang Yongli , Wang Chaogang
Published: November 2020

Background: The fresh water unicellular alga Haematococcus pluvialis has achieved considerable interests for its capacity to accumulate large amounts of triacylglycerol and astaxanthin under various environmental stresses. To our knowledge, works focusing on transcriptome research of H. pluvialis under exogenous hormones together with physical stresses is rare.Results: In the present study, the change patterns at transcriptome level were analyzed to distinguish the multiple defensive systems of astaxanthin and fatty acid metabolism against exogenous salicylic acid and high light (SAHL) stresses. Based on RNA-seq data, a total of 112,463 unigenes and 61,191 genes were annotated in six databases, including NR, KEGG, Swiss-Prot, PFAM, COG and GO. The top five categorized GO terms based on these genes were “catalytic activity”, “binding”, “cellular process”, “cell” and “cell part”. Furthermore, 705 unigenes predicted as putative transcription factors (TFs) were identified and assigned to 25 families. The top five most abundant TFs families were C3H, MYB, Nin-like, MTB_related and ERF, which were likely to be associated with the biosynthesis of astaxanthin and fatty acid in H. pluvialis upon exposure to the SAHL stresses. Analysis of differentially expressed genes (DEGs) in KEGG identified many transcripts that associated with the biosynthesis of primary and secondary metabolites, photosynthesis, and immune system responses. Additionally, fifteen key genes that involved in astaxanthin and fatty acid biosynthesis pathways presented the same transcriptional pattern in response to the SAHL stresses, and positive correlations were observed among them by Pearson Correlation (PC) analysis, indicating the coordination between astaxanthin and fatty acid biosynthesis. Furthermore, protein–protein interaction (PPI) network analysis also demonstrated that this coordination might be at transcriptional level.Conclusion: The results demonstrated in this study provide valuable information to illustrate the molecular mechanisms of coordinate relations between astaxanthin and fatty acid biosynthesis, which may play a role in both genetic and metabolic engineering efforts to improve astaxanthin and fatty acid production by H. pluvialis.
An in silico approach to target SARS-CoV-2 RNA dependent RNA polymerase of COVID-19 with naturally occurring phytochemicals
Authors: Mahrosh Hafiza Salaha , Mustafa Ghulam
Published: November 2020

The novel coronavirus disease 2019 (COVID-19) was firstly reported from Wuhan city of China found as highly contagious, transmittable and pathogenic viral infection. The World Health Organization declared COVID-19 as a pandemic since its emergence from China. The RNA dependent RNA polymerase (nsp-12) is a complex with nsp-7 and nsp-8 cofactors major constituent of viral replication and RNA synthesis machinery. In current study, the RdRp of virus was selected as a receptor protein for computational drug discovery. Computational homology modelling was done in order to find the hidden secondary structures and structural assessment of viral protein to target them via antiviral drugs. The study based on docking of different phytochemicals to check potential of different plant metabolites against viral replicative proteins. Out of 200 ligands used in this study from different plants the best ten were selected based on drug discovery parameters such as S-score, ligand interactions, hydrophobic interactions and drug likeness. The ten best selected ligands were Verbenalin, Epigallocatechin, Swertisin, Nobiletin, Pinoresinol, Caftaric acid, Hesperetin, Islandicin, Neochlorogenic acid and Sesamin that exploit the potency as antagonist of viral protein. Among binding interactions of all ligands Arg339 centred as the main interacting residue among almost all the ligands. Till now many antiviral agents have shown potency in only mild cases of SARS-CoV-2 but no effective drug has been found for critical pulmonary cases. In clinical trials many broad-spectrum antiviral agents have been still in trail periods of testing against SARS-CoV-2. Till date no effective drug or vaccine has been validated with significant efficacy and potency against the SARS-CoV-2 therefore there is an urgent need to design effective vaccine against nCoV-19 infections.
Transcriptome and metabolome analyses of cold and darkness-induced pellicle cysts of Scrippsiella trochoidea
Authors: Guo Xin , Wang Zhaohui , Liu Lei , Li Yang
Published: November 2020

Background: Dinoflagellates are a group of unicellular organisms that are a major component of aquatic eukaryotes and important contributors to marine primary production. Nevertheless, many dinoflagellates are considered harmful algal bloom (HAB) species due to their detrimental environmental and human health impacts. Cyst formation is widely perceived as an adaptive strategy of cyst-forming dinoflagellates in response to adverse environmental conditions. Dinoflagellate cysts play critical roles in bloom dynamics. However, our insight into the underlying molecular basis of encystment is still limited. To investigate the molecular processes regulating encystment in dinoflagellates, transcriptome and metabolome investigations were performed on cold and darkness-induced pellicle cysts of Scrippsiella trochoidea.Results: No significant transcriptional response was observed at 2 h; however, massive transcriptome and metabolome reprogramming occurred at 5 h and in pellicle cysts. The gene-to-metabolite network demonstrated that the initial transformation from vegetative cells into pellicle cysts was highly energy demanding through the activation of catabolism, including glycolysis, β-oxidation, TCA cycle and oxidative phosphorylation, to cope with cold-darkness-induced stress. However, after transformation into pellicle cysts, the metabolism was greatly reduced, and various sugars, polyunsaturated fatty acids and amino acids accumulated to prolong survival. The identification of 56 differentially expressed genes (DEGs) related to signal transduction indicated that S. trochoidea received a cold-darkness signal that activated multiple signal transduction pathways, leading to encystment. The elevated expression of genes encoding enzymes involved in ROS stress suggested that pellicle cysts respond to increased oxidative stress. Several cell cycle-related genes were repressed. Intriguingly, 11 DEGs associated with sexual reproduction suggested that pellicle cysts (or some portion thereof) may be a product of sexual reproduction. Conclusions: This study provides the first transcriptome and metabolome analyses conducted during the encystment of S. trochoidea, an event that requires complex regulatory mechanisms and impacts on population dynamics. The results reveal comprehensive molecular regulatory processes underlying life cycle regulation in dinoflagellates involving signal transduction, gene expression and metabolite profile, which will improve our ability to understand and monitor dinoflagellate blooms.
Genotyping and lipid profiling of 601 cultivated sunflower lines reveals novel genetic determinants of oil fatty acid content
Authors: Chernova Alina , Gubaev Rim , Singh Anupam , Sherbina Katrina , Goryunova Svetlana , Martynova Elena , Goryunov Denis , Boldyrev Stepan , Vanyushkina Anna , Anikanov Nikolay , Stekolshchikova Elena , Yushina Ekaterina , Demurin Yakov , Mukhina Zhanna , Gavrilova Vera , Anisimova Irina , Karabitsina Yulia , Alpatieva Natalia , Chang Peter L , Khaitovich Philipp , Mazin Pavel , Nuzhdin Sergey
Published: November 2020

Background: Sunflower is an important oilseed crop domesticated in North America approximately 4000 years ago. During the last century, oil content in sunflower was under strong selection. Further improvement of the oil properties achieved by modulating its fatty acid composition is one of the main directions in modern oilseed crop breeding. Results: We searched for the genetic basis of fatty acid content variation by genotyping 601 inbred sunflower lines and assessing their lipid and fatty acid composition. Our genome-wide association analysis based on the genotypes of 15,483 SNPs and the concentrations of 23 fatty acids, including minor fatty acids, revealed significant genetic associations for eleven of them. Identified genomic regions included novel loci on chromosomes 3 and 14 cumulatively, explaining up to 34.5% of the total variation of docosanoic acid (22:0) in sunflower oil.Conclusions: This is the first large scale implementation of high-throughput lipidomic profiling on sunflower germplasm characterization. This study contributes to the genetic characterization of Russian collections, which made a substantial contribution to the development of a sunflower as the oilseed crop worldwide and provides new insights into the genetic control of oil composition that can be implemented in future studies.
Molecular dominance investigation for large-sized parents of Chinese Mitten Crab ( Eriocheir sinensis ) based on ovarian transcriptome
Authors: Xuan Fujun , Fu Longlong , Wang Kun , Hua Zonglin , Xiong Xinxin , Zhang Jianguang , Pan Jianlin , Tang Boping , Guan Weibing , Cheng Yongxu
Published: November 2020

Background: Germplasm degradation is one of the important issues for the healthy development of Chinese Mitten Crab (Eriocheir sinensis) industry. Nowadays, nursery units and crab farmers have realized the seedling superiority of large-sized parents (≥200g male, ≥150g female), but the underlying molecular mechanisms remain unclear. Here we investigated the advantage of breeding with large-sized parents based on ovarian transcriptome.Results: RNA isolation and transcriptome sequencing were performed using ovarian tissue obtained from three large-sized female E. sinensis and three medium-sized female E. sinensis. The differentially expressed genes (DEGs) were investigated between two groups, followed by the exploration of common DEGs (co-DEGs) among the DEGs in the current study and published genes for growth, reproduction, and immune response pathways. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to validate all co-DEGs. Finally, a pathway enrichment analysis was performed to investigate the potential pathways associated with the validated co-DEGs. A total of 5,307 up-regulated genes and 3,465 down-regulated genes were investigated between the two groups, of which 43 co-DEGs were explored when all the DEGs in the current study were integrated with 338 genes in 15 reproductive, immune, and growth pathways. A total of nine co-DEGs, including TRINITY_DN13931_c0_g1, TRINITY_DN1908_c0_g2, and TRINITY_DN6686_c0_g1, were enrolled for further study after qRT-PCR validation. These validated co-DEGs were mainly enriched in pathways such as apoptosis, insulin signaling, and mTOR signaling. Conclusion: Our original work might lay an important molecular foundation for further exploring the advantages of using large-sized parents for E. sinensis breeding in the future. Based on the comparative analysis of gene expression, the advantages of breeding large-sized female E. sinensis parents at the molecular level, such as growth, reproduction, and immunity, were analyzed for the first time. The apoptosis pathways, insulin signaling pathways, and mTOR signaling pathway might be involved in the advantage of breeding large-sized female E. sinensis parents.
Genome-wide identification of sucrose nonfermenting-1-related protein kinase (SnRK) genes in barley and RNA-seq analyses of their expression in response to ABA treatment
Authors: Chen Zhiwei , Zhou Longhua , Jiang Panpan , Lu Ruiju , Halford Nigel G. , Liu Chenghong
Published: November 2020

Background: Sucrose nonfermenting-1 (SNF1)-related protein kinases (SnRKs) play important roles in regulating metabolism and stress responses in plants, providing a conduit for crosstalk between metabolic and stress signalling, in some cases involving the stress hormone, abscisic acid (ABA). The burgeoning and divergence of the plant gene family has led to the evolution of three subfamilies, SnRK1, SnRK2 and SnRK3, of which SnRK2 and SnRK3 are unique to plants. Therefore, the study of SnRKs in crops may lead to the development of strategies for breeding crop varieties that are more resilient under stress conditions. In the present study we describe the SnRK gene family of barley (Hordeum vulgare), the widespread cultivation of which can be attributed to its good adaptation to different environmentsResults: The barley HvSnRK gene family was elucidated in its entirety from publicly-available genome data and found to comprise 50 genes. Phylogenetic analyses assigned six of the genes to the HvSnRK1 subfamily, 10 to HvSnRK2 and 34 to HvSnRK3. The search was validated by applying it to Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa) genome data, identifying 50 SnRK genes in rice (four OsSnRK1, 11 OsSnRK2 and 35 OsSnRK3) and 39 in Arabidopsis (three AtSnRK1, 10 AtSnRK2 and 26 AtSnRK3). Specific motifs were identified in the encoded barley proteins, and multiple putative regulatory elements were found in the gene promoters, with light-regulated elements (LRE), ABA response elements (ABRE) and methyl jasmonate response elements (MeJa) the most common. RNA-seq analysis of the roots of seedlings grown with and without ABA treatment showed that many of the genes responded to ABA, some positively, some negatively and some with complex time-dependent responses.Conclusions: The barley HvSnRK gene family is large, comprising 50 members, subdivided into HvSnRK1 (6 members), HvSnRK2 (10 members) and SnRK3 (34 members), showing differential positive and negative responses to ABA.
Carrageenan nasal spray may double the rate of recovery from coronavirus and influenza virus infections: re-analysis of randomized trial data
Authors: Hemilä Harri , Chalker Elizabeth
Published: November 2020

Carrageenan is a sulfated polysaccharide that has been extensively used in food products. Since the 1980s, carrageenan has been shown to prevent infections due to several viruses in cell cultures, including rhinoviruses which cause the common cold. In animal studies it prevented mortality caused by influenza A. Carrageenan is generally regarded as safe by the FDA. This individual patient data meta-analysis examined the datasets of two randomized placebo-controlled trials which investigated the effect of carrageenan separately on children and adults. In both trials, iota-carrageenan was administered nasally 3 times per day for 7 days for patients with the common cold and follow-up lasted for 21 days. Nasal carrageenan increased the recovery rate from all colds by 54% (95% CI 15% to 105%; P = 0.003). The increase in recovery rate was 140% in coronavirus infections, 119% in influenza A infections, and 70% in rhinovirus infections. We used quantile regression to calculate the effect of carrageenan on colds of differing lengths, by dividing the distribution into 5 quintiles. The mean duration of colds in the placebo groups of the first four quintiles were 4.0, 6.8, 8.8 and 13.7 days, respectively. The fifth quintile contained patients with censored data. The 13.7-day colds were shortened by 3.8 days (28% reduction), and 8.8-day colds by 1.3 days (15% reduction). Carrageenan had no meaningful effect on shorter colds. In the placebo group, 21 patients had colds that lasted over 20 days, compared with 6 patients in the carrageenan group. This corresponds to a 71% (P = 0.003) reduction in the risk of longer colds. Finally, in the placebo group, 37 patients had recurring cold symptoms after first being cured, compared with 16 in the carrageenan group. This corresponds to a 56% (P = 0.002) reduction in the risk of recurring symptoms. Given that carrageenan has an effect on diverse virus groups, and its demonstrated effects on two old coronaviruses, it seems plausible that nasal carrageenan may also have an effect on the new coronavirus SARS-CoV-2. Further research on nasal iota-carrageenan is warranted.
Efficacy and Safety of Atropine to Control Myopia Progression: A Systematic Review and Meta-analysis
Authors: Zhao Congling , Cai Chunyan , Ding Qiang , Dai Hongbin
Published: November 2020

Background: The effect and safety of atropine on delaying the progression of myopia has been extensively studied, but its optimal effect dose is still unclear. Therefore, the purpose of this meta-analysis is to systematically evaluate the safety and effectiveness of atropine in controlling the progression of myopia, and to explore the relationship between the dose of atropine and the effect of controlling the progression of myopia. Methods: This work was done through the data search from PubMed, MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. The Cochrane Handbook was also used to evaluate the quality of these included studies. In addition, a meta-analysis was performed using Revman5.3 software. Results: A total of 10 randomized controlled trials (RCTs) were included. Myopia progression was mitigated greater in the atropine treatment group than the control group, with MD = -0.80, 95% CI (-0.94, -0.66) during the whole observation period. There was a statistical difference between 0.05%, 0.5%, and 1.0% atropine (P = 0.004). In addition, less axial elongation was showed, with MD = -0.26, 95% CI (-0.33, -0.18) during the whole observation period. Conclusion: The effect of atropine in controlling the progression of myopia was dose related. A 0.05% atropine was likely to be the optimal dose.
Prevalence of Metabolic Syndrome among Breast Cancer Survivors in East Coast of Peninsular Malaysia
Authors: Shahril Mohd Razif , Amirfaiz Syed , Lua Pei Lin , Nurnazahiah Ali , Zakarai Nor Syamimi , Kow Ving Lok , Ahmad Aryati , Sulaiman Suhaina
Published: November 2020

To date, limited data are available on metabolic syndrome prevalence among breast cancer survivors in Malaysia. Therefore, this study was conducted to determine the prevalence of metabolic syndrome and abnormal metabolic syndrome components among breast cancer survivors in East Coast of Peninsular Malaysia. This cross-sectional study included 95 breast cancer survivors (age 53.7±7.6 years) who have completed main cancer treatments for ≥6 months. Cancer survivors were recruited from two main government hospitals in Kelantan and Terengganu using a purposive sampling method. According to the Harmonized criteria, the metabolic syndrome prevalence was 50.5%. Among those with metabolic syndrome, the most prevalent abnormal metabolic components were triglycerides (91.2%), fasting blood glucose (79.6%) and HDL-c level (78.4%). Except for total cholesterol and LDL-c, all other metabolic syndrome components were significantly different (p<0.05) between those with and without metabolic syndrome. Significant differences between metabolic syndrome and non-metabolic syndrome groups were found for weight, BMI, waist circumference, body fat percentage and cancer stages (p<0.05). However, no significant relationship was reported between sociodemographic, clinical parameters and metabolic syndrome among breast cancer survivors in this study. In conclusion, metabolic syndrome was highly prevalent among breast cancer survivors. It is recommended for health care professionals to closely monitor and improve the triglycerides, blood glucose and HDL-c level of the breast cancer survivors under their care to control the detrimental effect of metabolic syndrome.
The prevalence of depression, stress and anxiety symptoms in patients with chronic heart failure 
Authors: Tsabedze Nqoba , Kinsey Jamie-Leigh , Mpanya Dineo , Mogashoa Vanessa , Klug Eric , Manga Pravin
Published: November 2020

Background: Mental health illnesses are associated with frequent rehospitalisation and an increased risk of all-cause mortality. Despite the high prevalence of depression in patients with chronic heart failure (CHF), there is a paucity of data on this subject from low and middle-income countries (LMIC). This study aimed to determine the prevalence of depression, anxiety and stress symptoms in patients attending a dedicated chronic heart failure clinic. Methods: A prospective study was conducted at an outpatient heart failure clinic in a tertiary academic centre. The study participants completed a Depression, Anxiety and Stress (DASS-21) questionnaire to screen for the presence and severity of depression, anxiety and stress symptoms. Furthermore, the Minnesota Living with Heart Failure Questionnaire (MLHFQ) was completed and used to evaluate the impact of CHF on health-related quality of life. Descriptive statistics were used to describe patients' characteristics and logistic regression analysis to identify predictors of symptoms of depression.Results: The study population comprised of 103 patients, predominantly female (62.1%) with a median age of 53 (interquartile range 38 – 61) years. Symptoms of depression were reported by 52.4%, with 11.7% reporting symptoms suggestive of extremely severe depression. Anxiety was diagnosed in 53.4% of patients and extremely severe anxiety reported by 18.4% of patients. Fifty patients were classified as stressed, and only 7.7% had extremely severe stress. More than half of the patients (54.4%) were in New York Heart Association (NYHA) functional class I with a mean (SD) left ventricular ejection fraction (LVEF) of 30.5% (11.1). In the multivariable logistic regression model, permanent employment [odds ratio (OR) -1.22, 95% CI:-0.01– -0.00, p=0.012], the six-minute walk test [OR -0.07, 95% CI: 0.02 – 0.06, p=0.001] and orthopnoea [OR 1.89, 95% CI: -0.01 – -0.00, p=0.012] were identified as independent predictors of depression.Conclusion: Depression and anxiety symptoms were found in over half of patients attending the chronic heart failure clinic. We recommend that mental health screening should be routinely performed in patients with chronic heart failure. Prospective, adequately powered, multicentre studies from LMIC investigating the impact of depression, anxiety and stress on CHF hospitalisation and mortality are required.
Estimated glomerular filtration rate and postoperative mortality in patients undergoing non-cardiac and non-neuron surgery: a single-center retrospective study
Authors: Luo Xueying , Zheng Sujing , Liu Baoer , Yang Liping , Li Ya , Li Feng , Gao Rui , Hu Haofei , He Jinsong
Published: November 2020

Background：There is limited evidence to clarify the specific relationship between preoperative estimated glomerular filtration rate (preop-eGFR) and postoperative thirty-day mortality in Asian patients undergoing non-cardiac and non-neuron surgery. We aimed to investigate details of this relationship.Methods：We reanalyzed a retrospective analysis of the clinical records of 90,785 surgical patients at the Singapore General Hospital from January 1, 2012 to October 31, 2016. The main outcome was postoperative thirty-day mortality.Results ：The average age of these recruited patients was 53.96 ± 16.88 years, of which approximately 51.64% were female. The mean of preop-eGFR distribution was 84.45 ± 38.56mL/min/1.73m2. Multivariate logistic regression analysis indicated that preop-eGFR was independently associated with thirty-day mortality (adjusted odds ratio: 0.992; 95% confidence interval [CI]: 0.990-0.995; P < 0.001). A U-shaped relationship was detected between preop-eGFR and thirty-day mortality with an inflection point of 98.688(P for log likelihood ratio test <0.001). The effect sizes and confidence intervals on the right and left sides of the inflection point were 1.013 (1.007 to 1.019) [P < 0.0001] and 0.984 (0.981 to 0.987) [P < 0.0001], respectively. Preoperative comorbidities such as congestive heart failure (CHF), type 1 diabetes, ischemic heart disease (IHD),and anemia were associated with the odds ratio of preop-eGFR to thirty-day mortality (interaction P < 0.05).Discussion：The relationship between preop-eGFR and thirty-day mortality is U-shaped. The recommended preop-eGFR at which the rate of the thirty-day mortality was lowest was 98.688mL/min/1.73m2.
Effect of Biomechanical Properties on Myopia: a Study of New Corneal Biomechanical Parameters
Authors: Han Fang , Li Mengdi , Wei Pinghui , Ma Jiaonan , Jhanji Vishal , Wang Yan
Published: November 2020

Background: To investigate assess the corneal stress-strain index (SSI), which is a marker for material stiffness and corneal biomechanical parameters , in myopic eyes. Methods: A total of 105 4 6 myopic patients were included in this study. Corneal v isuali s ation Scheimpflug t echnology Corvis ST was used to measure the SSI. Corneal biomechanics w ere as evaluated assessed using the first and second applanation time s (A1- time and A2-time s ), maximum deflection amplitude (DefAmax), deflection area (HCDefArea) , and peak distance at highest concavity peak distance (HC-PD), HC-time, HC-DefA, and HC-PD), integrated radius (IR) , whole eye movement (WEM), stiffness parameter (SP), biomechanically corrected intraocular pressure (BIOP) , and Corvis b iomechanical i ndex (CBI). Scheimpflug tomography was used to obtain the mean keratometery (Km) and central corneal thickness (CCT). All participants were divided into two groups according to the spherical equivalent (SE) (low myopia: SE ≤ 3.00D and high myopia: SE ≥ 6.00D). Results: The mean SSI value was 0.854±0.004. The SSI ha d a positive correlation with A1-time ((r=0.272), HC-time (r=0.218), WEM (r=0.288), SP (r=0.316) , CBI (r=0.199 ) , CCT (r=0.125), BIOP (r=0.230) , and SE (r=0.313) (all p - values＜0.01) . The SSI had a negative correlation with HCDefA (r=-0.721), HCDefArea (r=-0.665), HC-PD(r=-0.597), IR (r=-0.555), DefAmax (r=-0.564) , and Km (r=-0.103) (all p - values＜0.01). There were significant differences in SSI (t=8.960, p＜0.01) and IR (t=-3.509, p＜0.01) between the low and high myopia groups group and high myopia group . Conclusions: In different grades of myopia, the SSI values were lower in eyes with higher SE spherical equivalent s . It indicates that the mechanical strength of the cornea may be compromise d in high myopia. The SSI was positively correlated with the spherical equivalent , and it It may provide a new way to study the mechanism of myopia.
The Potential Role of Local Pharmacies to Assess Asthma Control: 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: November 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 to control the disease, community pharmacies’ are seldom involved in asthma control assessment. The present cross-sectional study aimed at providing a picture of the relationship between asthma severity and control in community pharmacies of the health district of the city of Verona (Veneto Region, 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 complete the Asthma Control Test (ACT) and a brief questionnaire collecting information on their age, sex, smoking status, aerobic physical exercise and usual asthma therapy, which also defined asthma severity. 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 consecutively recruited from 1st January to 30th June 2018 (6 months). Based upon ACT score 50.5% patients had a controlled asthma, 22.3% a poorly controlled and 27.2% uncontrolled. A variable proportion of patients with uncontrolled asthma were observed for every level of severity, although more frequently with mild persistent form of asthma. 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 in the general population, independently of the severity level of the disease. Community pharmacies could be a useful frontline interface between patients and the health care services, supporting an effective asthma management plan, from disease assessment and monitoring treatment compliance to referral of patients to specialist medical consultancies.
Improvement of Parent’s Awareness, Knowledge, Perception, and Acceptability of HPV Vaccination After a Structured-educational Intervention
Authors: Sitaresmi Mei Neni , Rozanti Nisrina Maulida , Simangunsong Lamria Besty , Wahab Abdul
Published: November 2020

Background: Regardless of the disease burden of human papillomavirus (HPV), the vaccine has not been included in the Indonesia National Immunization Program. Since 2017 there was a demonstration program of the HPV vaccination in Yogyakarta Province. This vaccine was given free to female primary school students in the 5th and 6th grades (11-13 years old). This study aimed to assess whether a structured-educational intervention focus on HPV increases the parental awareness, knowledge, and perceptions toward HPV and the vaccine acceptability.Methods: We conducted a pre-post structured-educational intervention study from July to August 2017 before the implementation of the HPV vaccination demonstration program, in Kulon Progo District, Yogyakarta Province, Indonesia. Parents of female primary school students grades 5th and 6th were selected using a school-based proportional random sampling. A pediatric resident provided a structured-educational intervention, which consists of the burden and risk of HPV disease, as well as the benefit and safety of the vaccine. Parents were required to complete validated self-administered questionnaires before and after the structured-educational intervention. Results: A total of 506 parents participated. Before receiving the structured-educational intervention, parents' awareness of HPV infection and the vaccines were low. Only 49.2% of parents had heard HPV infection, and 48.8% had heard about the vaccine. After the structured-educational intervention, there were significant improvements in parent’s awareness, knowledge, and perceptions of HPV infection, cervical cancer, and HPV vaccination (all p<0.001). HPV vaccine's acceptability increased from 74.3% to 87.4% (p<0.001). There was a significant correlation between increasing HPV vaccine acceptability with the improvement of awareness, knowledge, and perception toward HPV infection, cervical cancer and HPV vaccination (r=0.32 to 0.53, p<0.001). After the structured-educational intervention, better knowledge and positive perceptions of HPV vaccination were predictive of HPV vaccine's acceptability with OR 1.90 (95%CI:1.40-2.57) and OR 1.31(95%CI:1.05-1.63), respectively. Conclusions: A structured-educational intervention may improve parental awareness, knowledge, and perceptions toward HPV and the acceptability of the vaccine. Further study, a randomized control trial with longer follow-up are needed to evaluate the long-term and actual effectiveness of improving parents’ knowledge, perceptions and HPV vaccine acceptability.
A comparative case study of prescribing and non-prescribing physiotherapists and podiatrists
Authors: Carey Nicola , Edwards Judith , Otter Simon , Gage Heather , Williams Peter , Courtenay Molly , Moore Ann , Stenner Karen
Published: November 2020

BackgroundIncreasing numbers of nurses, pharmacists and allied health professionals across the world have prescribing rights for medicines: over 90,000 of the eligible United Kingdom workforce are qualified as non-doctor prescribers. In order to inform future developments, it is important to understand the benefits and impact of prescribing by allied health professionals including physiotherapists and podiatrists.Aim: to compare outcomes of physiotherapist and podiatrist Independent Prescriber (PP- IP) patients with those of physiotherapist and podiatrist non-prescribers (PP-NPs). Outcome measures included patient satisfaction, ease of access to services, quality of life and cost implications.Design: a mixed method comparative case study Methods: Using mixed methods of data collection, outcomes were compared between 7 sites where care was provided from a PP-IP (3 podiatrist and 4 physiotherapist IPs) and 7 sites from a PP-NP (3 podiatrist and 4 physiotherapist NPs). Patients were followed up for 2 months (2015-2016). Results: 489 patients were recruited: n=243 IP sites, and n=246 NP sites. Independent prescribing was found to be highly acceptable, and equivalent in terms of quality of life (p>0.05) and patient satisfaction (p≤0.05) compared to care provided by NPs. PP-IP care delivery was found to be more resource intensive than PP-NP, with longer consultation duration for IPs (around 6.5 mins), and a higher proportion of physiotherapy patients discussed with medical colleagues (around 9.5 minutes). ConclusionThis study provides new knowledge that PP-IPs provide high levels of care. PP-IP care delivery was found to be more resource intensive. Further research is required to explore cost effectiveness. A more focussed exploration within each profession using targeted outcome measures would enable a more robust comparison, inform future developments around the world and help ensure non-doctor prescribing is recognised as an effective way to alleviate shortfalls in the global workforce.
Preoperative risk grade predicts the long-term prognosis of intrahepatic cholangiocarcinoma: a retrospective cohort analysis
Authors: Zhao Jianping , Chen Yao , Wang Jingjing , Wang Jian , Wang Ying , Chai Songshan , Zhang Yuxin , Chen Xiaoping , zhang wanguang
Published: November 2020

Background: Cumulating evidence indicates that the systemic inflammatory response (SIR) plays a crucial role in the prognosis of various cancers. We aimed to generate a preoperative risk grade (PRG) by integrating SIR markers to preoperatively predict the long-term prognosis of intrahepatic cholangiocarcinoma (ICC).Methods: 468 consecutive ICC patients who underwent hepatectomy between 2010 to 2017 were enrolled. The PRG and a nomogram were generated and their predictive accuracy was evaluated. Results: The PRG consisted of two non-tumor-specific SIR markers platelet-to-lymphocyte ratio (PLR) and albumin (ALB), which were both the independent predictors of overall survival (OS). Multivariate analysis showed that the PRG was significantly associated with OS (PRG =1: Hazard ratio (HR) = 3.800, p < 0.001; PRG = 2: HR = 7.585, p < 0.001). The C-index of the PRG for predicting survival was 0.685 (95% CI: 0.655 to 0.716), which was statistically higher than that of the following systems: American Joint Committee on Cancer (AJCC) 8th edition (C-index 0.645), Liver Cancer Study Group of Japan (LCSGJ) (C-index 0.644) and Okabayashi (C-index 0.633) (p < 0.05). Besides, the C-index of the nomogram only consisting of the tumor-specific factors (serum carcinoembryonic antigen, carbohydrate antigen 19-9, tumor number) could be improved to 0.737 (95% CI: 0.062-0.768) from 0.625 (95% CI: 0.585-0.665) when the PRG was incorporated (p < 0.001).Conclusions: The PRG integrating two non-tumor-specific SIR markers PLR and ALB was a novel method to preoperative predicting the prognosis of ICC.
Identification of Potential Biomarkers for Abdominal Pain in IBS Patients by Bioinformatics Approach
Authors: Lin Zhongyuan , Wang Yimin , Lin Shiqing , Liu Decheng , Mo Guohui , Zhang Hui , dou Yunling
Published: November 2020

Background: Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disease characterized by chronic abdominal discomfort and pain. The mechanisms of abdominal pain, as a relevant symptom, in IBS are still unclear. We aimed to explore the key genes and neurobiological changes specially involved in abdominal pain in IBS.Methods: Gene expression data (GSE36701) was downloaded from Gene Expression Omnibus (GEO) database. Fifty-three rectal mucosa samples from Irritable Bowel Syndrome with diarrhea (IBS-D) patients and 40 samples from healthy volunteers (HV) as controls were included. Differentially expressed genes (DEGs) between two groups were identified using the GEO2R online tool. Functional enrichment analysis of DEGs was performed on the DAVID database. Then a protein-protein interaction (PPI) network was constructed and visualized using STRING database and Cytoscape. Results: The microarray analysis demonstrated a subset of genes (CCKBR, CCL13ACPP, BDKRB2, GRPR, SLC1A2, NPFF, P2RX4, TRPA1, CCKBR, TLX2, MRGPRX3, PAX2, CXCR1) specially involved in pain transmission. Among these genes, we identified GRPR, NPFF and TRPA1 genes as potential biomarkers for irritating abdominal pain of IBS patients.Conclusions: Overexpression of certain pain-related genes (GRPR, NPFF and TRPA1) may contribute to chronic visceral hypersensitivity, therefore be partly responsible for recurrent abdominal pain or discomfort in IBS patients. Several synapses modification and biological process of psychological distress may be risk factors of IBS.
Exosomal miR-29b found in aqueous humour mediates calcium signaling in diabetic patients with cataract
Authors: Gao Chao , Liu Xin , Fan Fan , Yang Jianing , Zhou Xiyue , Mei Hengjun , Lin Xiaolei , Luo Yi
Published: November 2020

Background: Ca2+ was supposed to play an important role in the cataract formation. Exosomal miR-29b from aqueous humour may play an important role in the mechanism of diabetes and cataracts. The purpose of this study was to investigate the role of exosomal miR-29b and Ca2+ in regulating the function of human lens epithelial cells. Methods: Exosomes were isolated from human aqueous humour by ultracentrifugation, and visualized by nanoparticle tracking and transmission electron microscopy. Exosomal miRNA sequencing was performed to identify differentially expressed miRNAs between diabetes and cataracts group (DMC) and age-related cataracts group (ARC). TargetScan was used to predict potential target of certain miRNA. The expression of CACNA1C mRNA was determined by quantitative real-time PCR and CACNA1C protein was determined by Western blotting. Concentration of Ca2+ in human aqueous humour and the culture supernatant of cells was detected by the Calcium Assay Kit. Cell Counting Kit-8 was used to determine cell viability. Results: Exosomes were isolated from human aqueous humour, which had a typical cup-shaped phenotype and a particle size distribution in accordance with micro extracellular vesicles. Exosomal miRNA sequencing revealed that miR-29b was significantly downregulated in diabetes and cataracts group (DMC) compared with age-related cataracts group (ARC). Ca2+ concentration of human aqueous humour in DMC was higher than that in ARC. The culture supernatant of cells transfected with miR-29b inhibitors had a higher concentration of Ca2+ than that transfected with miR-29b mimics. miR-29b reduced the viability of human lens epithelium cells (HLECs) by upregulating CACNA1C expression.Conclusions: Exosomes isolated from human aqueous humour contained abundant miRNAs. A significantly expressed miRNA, miR-29b, could affect the concentration of Ca2+ and regulate HLEC processes by upregulating CACNA1C.
Lameness in fattening pigs – Mycoplasma hyosynoviae, osteochondropathy and reduced dietary phosphorus level as three influencing factors: A case report
Authors: Wegner Birte , Tenhündfeld Jörg , Vogels Johanna , Beumer Marius , Kamphues Josef , Hansmann Florian , Rieger Hanna , Beilage Elisabeth grosse , Hennig-Pauka Isabel
Published: November 2020

BackgroundMultiple diagnostic procedures, their results and interpretation in a case with severe lameness in fattening pigs are described. It is shown that selected diagnostic steps lead to identification of various risk factors for disease development in the affected herd. One focus of this case report is the prioritization of diagnostic steps to verify the impact of the different conditions, which finally led to the clinical disorder. Assessing a sufficient dietary phosphorus (P) supply and its impact on disease development proved most difficult. The diagnostic approach based on estimated calculation of phosphorus intake is presented in detail.Case presentationOn a farrow-to-finishing farm, lameness occurred in pigs with 30-70 kg body weight. Necropsy of three diseased pigs revealed claw lesions and alterations at the knee and elbow joints. Histologic findings were characteristic of osteochondrosis. All pigs were positively tested for Mycoplasma hyosynoviae in affected joints. P values in blood did not indicate a P deficiency, while bone ashing in one of three animals resulted in a level indicating an insufficient mineral supply. Analysis of diet composition revealed a low phosphorus content in two diets, which might have led to a marginal P supply in individuals with high average daily gains with respect to development of bone mass and connective tissue prior to presentation of affected animals. Finally, the impact of dietary factors for disease development could not be evidenced in all submitted animals in this case.ConclusionsMycoplasma (M.) hyosynoviae was identified to be an important etiologic factor for disease. Other, non-infectious factors, such as osteochondrosis and claw lesions might have favored development of lameness. In addition, a relevant marginal P supply for pigs was found in a limited time period in a phase of intense growing, but the potential interaction with infection by M. hyosynoviae is unknown. The presented case of severe lameness in fattening pigs revealed that three different influences presumably act in pathogenesis. Focusing only on one factor and ignoring others might be misleading regarding subsequent decision-making for prevention and therapy. Finally, clinical symptoms disappeared after some changes in diet composition and anti-inflammatory treatment of individual animals.
Epidemiological characteristics of four common respiratory viral infections in children
Authors: Zhu Guohong , Xu Dan , Zhang Yuanyuan , Wang Tianlin , Zhang Lingyan , Gu Weizhong , Shen Meiping
Published: November 2020

Background: Viruses are the main infectious agents of acute respiratory infections (ARIs) in children. We aim to describe the epidemiological characteristics of viral pathogens of acute respiratory tract infections in outpatient children.Methods: From April 2018 to March 2019, the results of viral detection using oral pharyngeal swabs from 103,210 children with acute respiratory tract infection in the outpatient department of the Children’s Hospital, Zhejiang University School of Medicine, were retrospectively analyzed. Viral antigens, including adenovirus (ADV), influenza A (FLUA), influenza B (FLUB) and respiratory syncytial virus (RSV), were detected by the colloidal gold method.Results: At least one virus was detected in 38,355 cases; the positivity rate was 37.2%. A total of 1910 cases of mixed infection with two or more viruses were detected, and the positivity rate of multiple infection was 1.9%. The ADV positivity rate was highest in the 3-6-year-old group (18.7%), the FLUA positivity rate was highest in the >6-year-old group (21.6%), the FLUB positivity rate was highest in the >6-year-old group (6.6%), and the RSV positivity rate was highest in the <1-year-old group (10.6%). There was a significant difference in the positivity rate of viral infection among different age groups (χ2 = 1280.7, P < 0.001). The rate of positive viral infection was highest in winter (47.1%). The ADV infection rate was highest in spring (18.2%). The rates of FLUA and FLUB positivity were highest in winter (28.8% and 3.6%, respectively). The rate of RSV positivity was highest in autumn (17.4%). The rate of positive viral infection in different seasons was significantly different (χ2 = 6459.1, P < 0.001).Conclusions: Viral infection rates in children differ for different ages and seasons. The positivity rate of ADV is highest in the preschool period and that of RSV is highest in infants; that of FLU increases with age. The total positive rate of viral infection in different seasons is highest in winter, as is the rate of FLU positivity.
The therapeutic efficacy of mesenchymal stromal cells on experimental colitis was improved by the IFN-γ and poly(I:C)-priming through promoting the expression of indoleamine 2,3-dioxygenase.
Authors: Lim Ji-Young , Kim Byung-Su , Ryu Da-Bin , Kim Tae Woo , Park Gyeongsin , Min Chang-Ki
Published: November 2020

Background: Inflammatory bowel disease is a chronic and excessive inflammation of the colon and small intestine. We previously reported that priming of mesenchymal stromal cells (MSC) with poly(I:C) induced them to express indoleamine 2,3-dioxygenase (IDO). We tried to find out whether the IFN-γ and poly(I:C)-primed MSCs have better therapeutic efficacy on the experimental colitis in the IDO1-dependent manner. Methods: To compare the therapeutic effects between the unstimulated MSCs and primed MSCs on murine colitis, mice (C57BL6) were administered with 2.5% dextran sodium sulfate (DSS) in drinking water for 5 days and injected with MSCs intraperitoneally on days 1 and 3 following DSS ingestion. The disease activity index score and body weight loss were assessed daily until day 9. Results: Mice receiving the IFN-γ and poly(I:C)-primed MSCs showed a reduced disease activity index and less weight loss. Colon tissue from the same mice presented attenuated pathological damage, increased Paneth cells, increased IDO1-expressing cells, and better proliferation of enterocytes. The primed MSC treatment upregulated the mRNA expression of intestinal stem cell markers (Lgr5, Olfm4, and Bmi1), enterocyte differentiation markers (Muc2, Alpi, Chga, and occludin), and regulatory T (Treg) cells (Foxp3). The same treatment decreased inflammatory cell infiltration to lymphoid organs and the level of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, and MCP-1) in colon tissue. Notably, in vivo pharmacologic inhibition of the IDO1 activity blocked the Foxp3 up-regulation in colon tissue and diminished the protective effects of the primed MSC. Conclusions: The priming of MSCs with the IFN-γ and poly(I:C) is a promising new strategy to improve the therapeutic efficacy of MSC and is worth further research.