bluuebunny/crossref_metadata_2025 huggingface dataset:
Multicenter investigation of pediatric gastrointestinal tract magnets ingestion in China
Authors: Wang Kai , Zhang Dan , Li Xianling , Wang Zengmeng , Hou Guangjun , Jia Xinjian , Niu Huizhong , Qi Shiqin , Deng Qingqiang , Jiang Bin , Bian Hongqiang , Yang Heying , Chen Yajun
Published: February 2020

Purpose: To describe the incidence and management of gastrointestinal tract Buckyball magnets ingestions in a multicenter Chinese pediatric patient population, and discuss the preventive measures.
Methods: Medical records of 74 pediatric patients from 9 large Chinese hospitals during the past 10 years, who were diagnosed as buckyball magnets ingestion and got invasive treatment, were retrospectively studied. The follow-up was through telephone and outpatient service to estimate the post-surgery condition. Information collection was through online questionnaire.
Results: Among the 74 cases, there were 50 boys (68%) and 24 girls (32%). The median age was 36 (interquartile range (IQR) 22-77) months, with a range of 7 months to 11 years, and it showed two peaks, the first between 1 and 3 years, and the second between 6 to 11 years. The annual case number showed a sharp increase over time, and the majority of ingestions were unintentional. The median time of ingestion until the onset of emergent symptoms was 2 (IQR 1-5) days, and ranged from 4 hours to 40 days. Twenty-one patients had no symptoms, and the remaining cases presented with abdominal pain, vomiting, fever, abdominal distension, excessive crying, melena, and the ceasing of flatus and defecation. Gastroscopy, colonoscopy, laparoscopic surgery and laparotomy surgery were performed in accordance with the algorithm from the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN). The median number of Buckyball magnets ingested was 4 (IQR 2-8), with a range from 1 to 39. During the median follow-up period of 6 (IQR 1-15) months, 3 patients had intestinal obstruction, and one underwent a second operation. The remaining 71 patients courses were uneventful during the follow-up period. None of the 74 patients reported a second swallowing of foreign bodies.
Conclusions: The incidence of pediatric gastrointestinal tract magnets ingestion in China is increasing. Management of such patients should follow the NASPGHAN algorithm. Preventive measures to limit children’s access to Buckyball magnets should be taken from three levels, namely the national administration, producer, and consumer.
Keywords: Pediatric, Gastrointestinal tract, Magnetic foreign body, Buckyball
PS4DR: A multimodal workflow for identification and prioritization of drugs based on pathway signatures
Authors: Emon Mhammad Asif , Domingo-Fernández Daniel , Hoyt Charles Tapley , Hofmann-Apitius Martin
Published: February 2020

Background:
During the last decade, there has been a surge towards computational drug repositioning owing to constantly increasing -omics data in the biomedical research field. While numerous existing methods focus on the integration of heterogeneous data to propose candidate drugs, it is still challenging to substantiate their results with mechanistic insights of these candidate drugs. Therefore, there is a need for more innovative and efficient methods which can enable better integration of data and knowledge for drug repositioning.
Results:
Here, we present a customizable workflow ( PS4DR) which not only integrates high-throughput data such as genome-wide association study (GWAS) data and gene expression signatures from disease and drug perturbations but also takes pathway knowledge into consideration to predict drug candidates for repositioning. We have collected and integrated publicly available GWAS data and gene expression signatures for several diseases and hundreds of FDA-approved drugs or those under clinical trial in this study. Additionally, different pathway databases were used for mechanistic knowledge integration in the workflow. Using this systematic consolidation of data and knowledge, the workflow computes pathway signatures that assist in the prediction of new indications for approved and investigational drugs.
Conclusion:
We showcase PS4DR with applications demonstrating how this tool can be used for repositioning and identifying new drugs as well as proposing drugs that can simulate disease dysregulations. We were able to validate our workflow by demonstrating its capability to predict FDA-approved drugs for their known indications for several diseases. Further, PS4DR returned many potential drug candidates for repositioning that were backed up by epidemiological evidence extracted from scientific literature. Source code is freely available at https://github.com/ps4dr/ps4dr .
Effects of resveratrol on cariogenic virulence properties of Streptococcus mutans
Authors: Li Jinheng , Zhu Yaqin , Wu Tiantian , Peng Weiwei
Published: February 2020

Background: Streptococcus mutans is the principal etiological agent of human dental caries. The major virulence factors of S. mutans are acid production, acid tolerance, extracellular polysaccharide (EPS) synthesis and biofilm formation. The aim of this study is to evaluate the effect of resveratrol, a natural compound, on virulence properties of S. mutans . Methods: The effect of resveratrol on acidogenicity was investigated by pH drop and lactate dehydrogenase (LDH) assay, on aciduricity through survival rate at pH 5.0 and F-ATPase assay, on EPS synthesis (including water-soluble polysaccharide and water-insoluble polysaccharide) by quantitative measurement, on biofilm formation by crystal violet assay and structure observation. The expression of related virulence genes was also detected . Results: Resveratrol at sub-MIC levels can significantly decrease acid production, acid tolerance, EPS synthesis and biofilm formation. Related virulence gene expression ( ldh , relA , gtfC , comDE ) was down-regulated with increasing concentrations of resveratrol. Conclusion: Resveratrol has an inhibitory effect on S. mutans cariogenic virulence properties and it represents a promising anticariogenic agent .
Nitric oxide is involved in the brassinolide-induced adventitious root development in cucumber
Authors: Yutong Li , Wu Yue , Liao Weibiao , Hu Linli , Dawuda Mohammed Mujitaba , Jin Xin , Tang Zhongqi , Yang Jianjun , Yu Jihua
Published: February 2020

Background: Brassinolide (BR), as a new type of plant hormones, is involved in the processes of plant growth and stress response. Previous studies have reported the roles of BR in regulating plant developmental processes and also response tolerance to abiotic stresses in plants. The main purpose of our study was to explore whether nitric oxide (NO) plays a role in the process of BR-induced adventitious root formation in cucumber ( Cucumis sativus L.).
Results: Exogenous application of 1 μM BR significantly promoted adventitious rooting, while high concentrations of BR (2-8 μM) effectively inhibited adventitious rooting. NO donor (S-nitroso-N-acerylpenicillamine, SNAP) promoted the occurrence of adventitious roots. Simultaneously, BR and SNAP applied together significantly promoted adventitious rooting and the combined effect was superior to the application of BR or SNAP alone. Moreover, NO scavenger (c-PTIO) and inhibitors (L-NAME and Tungstate) inhibited the positive effects of BR on adventitious rooting. BR at 1 μM also increased endogenous NO content, NO synthase (NOS-like) and Nitrate reductase (NR) activities, while BRz (a specific BR biosynthesis inhibitor) decreased these effects. In addition, the relative expression level of NR was up-regulated by BR and SNAP, whereas BRz down-regulated it. The application of NO inhibitor (Tungstate) in BR also inhibited the up-regulation of NR .
Conclusion: BR promoted the formation of adventitious roots by inducing the production of endogenous NO in cucumber.
Knowledge, attitudes and practices towards viral haemorrhagic fevers amongst healthcare workers in urban and rural public healthcare facilities in the N’zérékoré Prefecture, Guinea: a cross-sectional study
Authors: Raab Manuel , Pfadenhauer Lisa M. , Millimouno Tamba Jacques , Hoelscher Michael , Froeschl Guenter
Published: February 2020

Introduction: The 2013-2016 Ebola epidemic in West Africa began in Guinea’s Forest region, a region now considered to be at high risk for future epidemics of viral haemorrhagic fevers (VHF). Good knowledge, attitudes and practices towards VHF amongst healthcare workers in such regions are a central pillar of infection prevention and control (IPC). To inform future training in IPC, this study assesses the knowledge, attitudes and practices (KAP) towards VHF amongst healthcare workers in public healthcare facilities in the most populated prefecture in Forest Guinea, and compares results from urban and rural areas.
Methods: In June and July 2019, we interviewed 102 healthcare workers in the main urban and rural public healthcare facilities in the N’zérékoré prefecture in Forest Guinea. We used an interviewer-administered questionnaire adapted from validated KAP surveys.
Results: The great majority of respondents demonstrated good knowledge and favourable attitudes towards VHF. However, respondents reported some gaps in preventive practices such as VHF suspect case detection. They also reported a shortage of protective medical equipment used in everyday clinical work in both urban and rural healthcare facilities and a lack of training in IPC, especially in rural healthcare facilities. However, whether or not healthcare workers had been trained in IPC did not seem to influence their level of KAP towards VHF.
Conclusions: Three years after the end of the Ebola epidemic, our findings suggest that public healthcare facilities in the N’zérékoré prefecture in Forest Guinea still lack essential protective equipment and some practical training in VHF suspect case detection. To minimize the risk of future VHF epidemics and improve management of outbreaks of infectious diseases in the region, current efforts to strengthen the public healthcare system in Guinea should encompass questions of supply and IPC training.
In Silico Design of a Peptide Receptor for Dopamine Recognition
Authors: Rodriguez-Salazar Luna , Pulido James Guevara
Published: February 2020

Background: Dopamine (DA) is an important neurotransmitter with a fundamental role in regulatory functions related to the central, peripheral, renal, and hormonal nervous systems. Dopaminergic neurotransmission dysfunctions are commonly associated with several diseases; thus, in situ quantification of DA is a major challenge.
To achieve this goal, enzyme-based biosensors have been employed for substrate recognition in the past. However, owing to their sensitivity to changes in temperature and pH levels. Results: New peptide bioreceptors have been developed. Based on this, 45 in silico bioreceptors were designed to exhibit a higher affinity than that of the DA transporters (DATs).
The design was based on the active sites of crystallized enzyme structures that are physiologically related to DA. These affinities were calculated using AutoDock Vina and by assessing the interaction energy between DA and the active DAT site. The controlled variables in the design were amino acids, bond type, steric volume, stereochemistry, affinity, and interaction distances. Conclusions: Three bioreceptor candidates presenting promising values ​​in terms of DA affinity and distance were obtained.
Adiposity reduces the risk of osteoporosis in Chinese rural population: the Henan Rural Cohort Study
Authors: Tian Huiling , Pan Jun , Qiao Dou , Dong Xiaokang , Li Ruiying , Wang Yikang , Tu Runqi , Abdulai Tanko , Liu Xiaotian , Hou Jian , Zhang Gongyuan , Wang Chongjian
Published: February 2020

Background: Adiposity plays a crucial role in the risk of osteoporosis. However, the impact of body fat distribution on the skeleton is contentious. The study was designed to explore the association of various adiposity indices on estimated bone mineral density (BMD) and the risk of osteoporosis based on body mass index (BMI), body fat percentage (BFP), waist circumference (WC), waist to hip ratio (WHR), waist to height ratio (WHtR), and visceral fat index (VFI). Methods: A total of 8475 subjects derived from the Henan Rural Cohort Study were analyzed. The estimated BMD of study participants were measured by calcaneal quantitative ultrasound (QUS). Linear and binary logistic regression was performed to estimate the association of adiposity and the outcomes. Results: The mean age of the study participants was 55.23 ± 11.09 years and 59.61% were women. The crude and age-standardized prevalence of high risk for osteoporosis was 16.24% and 11.82%. Per unit increment in adiposity indices was associated with 0.005-0.021 g/cm 2 increase in estimated BMD. The adjusted odds ratios (95% confidence interval) for high osteoporosis risk in per 1 SD increase of WC, WHR, WHtR, BMI, BFP, and VFI were 0.820 (0.748, 0.898), 0.872 (0.811, 0.938), 0.825 (0.765, 0.891), 0.798 (0.726, 0.878), 0.882 (0.800, 0.972), and 0.807 (0.732, 0.889), respectively. Stratified analyses indicated greater effects on individuals aged 55 years or more. Conclusions: The adiposity indices have an inverse association with the risk of osteoporosis among Chinese rural population, especially in the elderly.
Enhancement of tendon-bone interface healing and graft maturation with cylindrical Titanium-Web (TW) in a miniature swine anterior cruciate ligament reconstruction model: Histological and collagen-based analysis
Authors: Ryu Keisho , Saito Mitsuru , Kurosaka Daisaburo , Kitasato Seiichiro , Omori Toshiyuki , Hayashi Hiroteru , Kayama Tomohiro , Marumo Keishi
Published: February 2020

Background: Tendon-bone interface healing and ligamentization of the graft in anterior cruciate ligament (ACL) reconstruction with autografts are important factors affecting treatment outcome. This study aimed to investigate the effectiveness of a cylindrical titanium-web (TW) in tendon-bone interface healing and graft maturation in ACL reconstruction. Methods: Fourteen mature female CLAWN miniature swine underwent bilateral ACL reconstructions with patellar tendon (PT) autografts. In one limb, the TW/tendon complex was placed into the proximal side of the tibial tunnel. Only the graft was transplanted into the tunnel in the control limb. The proximal side of the graft was sutured into the stump of the native ACL and the distal end was stapled to the tibia. The animals were euthanized at 4 and 15 weeks postoperatively, for histological and biochemical analyses. Results: Microscopic images in TW limbs showed that ingrowth of tendon-like tissue and mineralized bone tissue into the TW connected the bone and the tendon directly. In contrast, fibrous tissue intervened between the bone and tendon in the control limbs. The total amount of collagen cross-links (which defines the strength of collagen fibers) and the maturation of collagen cross-links in TW tendons were significantly higher (p<0.05) than those of control limbs. There was no significant difference in the ratio of dihydroxy-lysinonorleucine to hydroxy-lysinonorleucine (an indicator of tissue specific collagen maturation) between TW tendons and that of the native PT. Conclusions: TW promoted the maturation and formation of collagen cross-links in the grafted tendon while maintaining the cross-link pattern of native tendon collagen, and enabled direct binding of tendon to bone.
Systematic review of statistical methods for safety data in malaria chemoprevention in pregnancy trials
Authors: Patson Noel , Mukaka Mavuto , Otwombe Kennedy N , Kazembe Lawrence , Mathanga Don P , Mwapasa Victor , Kabaghe Alinune N , Eijkemans Marinus JC , Laufer Miriam K , Chirwa Tobias
Published: February 2020

Background

Drug safety assessments in clinical trials present unique analytical challenges. Some of these include adjusting for individual follow-up time, repeated measurements of multiple outcomes and missing data among others. Furthermore, pre-specifying appropriate analysis becomes difficult as some safety endpoints are unexpected. Although existing guidelines such as CONSORT encourage thorough reporting of adverse events (AEs) in clinical trials, they provide limited details for safety data analysis. The limited guidelines may influence suboptimal analysis by failing to account for some analysis challenges above. A typical example where such challenges exist are trials of antimalarial drugs for malaria prevention during pregnancy. Lack of proper standardized evaluation of the safety of antimalarial drugs has limited the ability to draw conclusions about safety. We have therefore conducted a systematic review to establish the current practice in statistical analysis for antimalarial drug safety in pregnancy.

Methods

We searched PubMed, Embase, Scopus, Malaria in Pregnancy Library and Cochrane Central Register of Controlled Trials for original English articles reporting Phase III (randomized controlled trials) RCTs on antimalarial drugs for malaria prevention in pregnancy published from January 2010 to July 2019.

Results

Eighteen trials were included in this review that collected multiple longitudinal safety outcomes including AEs. Statistical analysis and reporting of the safety outcomes in all the trials used descriptive statistics; proportions/counts (n=18, 100%) and mean/median (n=2, 11.1%). Results presentation included tabular (n=16, 88.9%) and text description (n=2, 11.1%). Univariate inferential methods were reported in most trials (n=16, 88.9%); including Chi-square/Fisher`s exact test (n=12, 66.7%), t-test (n=2, 11.1%) and Mann-Whitney/Wilcoxon test (n=1, 5.6%). Multivariable methods, including Poisson and negative binomial were reported in few trials (n=4, 22.2%). Assessment of a potential link between missing efficacy data and safety outcomes was not reported in any of the trials that reported efficacy missing data (n=7, 38.9%).

Conclusion

The review demonstrated that statistical analysis of safety data in antimalarial drugs for malarial chemoprevention in pregnancy RCTs are inadequate. The analysis insufficiently account for multiple safety outcomes potential dependence, follow-up time and informative missing data which can compromise antimalarial drug safety evidence development, based on the available data.
Long Acting Reversible Contraception utilization and associated factors among women in extended postpartum period Hossana Town, Southern Ethiopia: cross sectional study
Authors: Woldu Biruktawit Fekade , Ermolo Tadesse Lelago , Lemu Lidiya Gutema , Gejo Negeso Gebeyehu
Published: February 2020

Background: In low and middle-income countries, 95% of postpartum women want to avoid a pregnancy for 2 years, but 70% are not using contraception. Delay in use of contraception by couples during postpartum period can result in many unwanted pregnancies. Long-acting reversible contraception (LARC) is ideal for postpartum women. Therefore this study aimed at assessing the prevalence and factors associated with LARC use among postpartum women. Methods: Facility based cross sectional study was conducted from July 23-Aug 25, 2018. Systematic random sampling technique was employed to recruit a total of 381 women in extended postpartum period visiting Child Immunization service in hosanna health institutions. Pretested structured questionnaire was used for data collection. Data was analyzed by SPSS version 20. Binary and multivariate logistic regression analysis was done. The presence and strength of association was determined using AOR with its 95% CI. Variables with P value less than 0.05 were considered as statistical significant. Results: The prevalence of LARC use was 36.5% (95%CI (33.05-39.95)). The main reason for not using LARC was fear of side effect and false information. Previous use of LARC (AOR=3.3, 95%CI (1.7-6.5)) and have ever discussed with health providers on LARC (AOR=2.5, 95%CI (1.1-5.74)) were found to be significantly associated with LARC use. Conclusions: the utilization of LARC among postpartum women was found to be high in this study. Increase women’s access to realistic information on LARC, mainly on IUCD, both at community and health institution level need to be emphasized to enhance its uptake.
A multiplex guide RNA expression system and its efficacy for plant genome engineering
Authors: Oh Youngbin , Lee Bora , Kim Hyeonjin , Kim Sang-Gyu
Published: February 2020

Background
The Streptococcus pyogenes CRISPR system is composed of a Cas9 endonuclease (SpCas9) and a single-stranded guide RNA (gRNA) harboring a target-specific sequence. Theoretically, SpCas9 proteins could cleave as many targeted loci as gRNAs bind in a genome.
Results
We introduce a PCR-free multiple gRNA cloning system for editing plant genomes. This method consists of two steps: (1) cloning the annealed products of two single-stranded oligonucleotide fragments harboring a complimentary target-binding sequence on each strand between tRNA and gRNA scaffold sequences in a pGRNA vector; and (2) assembling tRNA-gRNA units from several pGRNA vectors with a plant binary vector containing a SpCas9 expression cassette using the Golden Gate assembly method. We validated the editing efficiency and patterns of the multiplex gRNA expression system in wild tobacco (Nicotiana attenuata) protoplasts and in transformed plants by performing targeted deep sequencing. Two proximal cleavages by SpCas9-gRNA largely increased the editing efficiency and induced large deletions between two cleavage sites.
Conclusions
This multiplex gRNA expression system enables high-throughput production of a single binary vector and increases the efficiency of plant genome editing.
Optical coherence tomography angiography evaluation of the effects of phacoemulsification cataract surgery on macular hemodynamics in Chinese normal eyes
Authors: Jia Xinyu , Wei Yinjuan , Song Hui
Published: February 2020

Background: To quantitatively evaluate the possible effects of phacoemulsification cataract surgery on macular hemodynamics using optical coherence tomography angiography (OCTA). Methods ： Prospective observational study. Superficial and deep macular vascular densities as well as parameters of foveal avascular zone (FAZ) were measured preoperatively (baseline) and at 1 day, 1 week and 4 weeks postoperation in normal eyes (≥22 mm and≤24 mm) of patients scheduled for phacoemulsification cataract surgery with intraocular lens implantation. Correlations between the rate of change of pre- and post-operative vascular densities and surgical parameters were analyzed. Results : 123 eyes of 107 patients were recruited. Compared with baseline measurements, no statistically significant variation was found in macular vascular densities of day one after surgery (P>0.05). While both superficial and deep macular vascular densities were significantly increased postoperatively on week 1 and week 4 (P<0.05; P<0.05). There were no statistically significant differences in any of the FAZ parameters between the baseline measurements and the entire follow-up period (P>0.05 for all). There were no statistically significant correlations between main surgical parameters and the macular vascular densities. Conclusions : In normal eyes, macular blood perfusion gradually increased after phacoemulsification cataract surgery and was stabilized in one week. Foveal avascular zone was basically stable before and after surgery. Main parameters and intraoperative perfusion of phacoemulsification surgery may not be the key factors affecting macular hemodynamics.
Management of Retinitis Pigmentosa via Platelet Rich Plasma or Combination with Electromagnetic Stimulation: Retrospective Analysis of One-year Results
Authors: Arslan Umut , Özmert Emin
Published: February 2020

Purpose To investigate whether the natural progression rate of retinitis pigmentosa can be decreased with subtenon autologous platelet rich plasma application alone or combination with retinal electromagnetic stimulation.Material and methods The study includes retrospective analysis of 60 retinitis pigmentosa patients. Patients constitute 3 groups with similar demographic characteristics. The combined management group consists of 20 retinitis pigmentosa patients (40 eyes) who received combined retinal electromagnetic stimulation and subtenon platelet rich plasma as Group1; The subtenon platelet rich plasma-only group consisted of 20 retinitis pigmentosa patients (40 eyes) as Group2; The natural course (control) group consists of 20 retinitis pigmentosa patients (40 eyes) who did not receive any treatment were classified as Group3. Horizontal and vertical ellipsoid zone width, fundus perimetry deviation index and best corrected visual acuity changes were compared within and between groups after one year follow up period.Results Horizontal ellipsoid zone percentage changes were detected +1 % in Group1, -2.85% in Group2, -9.36% in Group3 (Δp 1>2>3). Vertical ellipsoid zone percentage changes were detected +0.34 % in Group1, -3.05% in Group2, -9.09% in Group3 (Δp 1>2>3). Fundus perimetry deviation index percentage changes were detected +0.05% in Group1, -2.68% in Group2 and -8.78% in Group3 (Δp 1>2>3). Conclusion Platelet-rich plasma is a good source of growth factors, but its half-life is 4-6 months. Subtenon autologous platelet rich plasma might more effectively slow down photoreceptor loss when repeated as booster injections and combined with retinal electromagnetic stimulation.
Combined and interaction effect of Chlamydia pneumoniae infection and smoking on lung cancer: a case-control study in southeast China
Authors: Xu Xin , Liu Zhiqiang , Xiong Weimin , Qiu Minglian , Kang Shuling , Xu Qiuping , Cai Lin , He Fei
Published: February 2020

Background: This case-control study investigated the role of Chlamydia pneumoniae (Cpn) infection in the pathogenesis of lung cancer and the combined and interaction effect of Chlamydia pneumoniae infection and smoking or other environmental factors. Methods: The study was comprised of 449 lung cancer patients and 512 age- and gender-matched healthy controls. All participants provided a 5-ml fasting peripheral venous blood sample for testing Cpn-specific IgG and IgA by using micro-immunofluorescence. Besides analyzing the associations between Cpn and lung cancer, combined effect analysis, logistic regression, and the excel table made by Andersson were used to analyze the combined and interaction effects of Cpn and environmental factors on lung cancer. Results: Compared to those with no evidence of serum Cpn IgA or Cpn IgG, those with both Cpn IgG+ and IgA+ had 2.00 times the risk (95% CI: 1.34 - 3.00) of developing lung cancer. Smokers with Cpn IgG+ or IgA+ were associated with a significantly increased risk of lung cancer, the adjusted OR was 1.79 (95% CI: 1.10-2.91) or 2.27(95% CI:1.38-3.72), respectively. Those exposed to passive smoking with Cpn IgG+ or IgA+ also increased the risk of lung cancer, the adjusted OR was 1.82 (95% CI: 1.20-2.77) or 1.87(95% CI:1.22-2.87), respectively. The similar results were also observed among alcohol drinking people. Multiplicative and additive interactions were not observed between Cpn infection and environmental factors. The combined effects of Cpn IgG+ or IgA+ and smoking, passive smoking, family history of cancer were found on lung cancer. Conclusion: The Cpn infection was potentially associated with primary lung cancer in the Chinese Han population and had combined effects with smoking, passive smoking, and the family history of cancer. Keywords: Chlamydia pneumoniae infection, case-control study, environmental factors, lung cancer
The exploration of use of an online knowledge base on patient experiences and health care quality: An observational cohort study in primary health care
Authors: Gerdeskold Christian , Toth-Pal Eva , Wårdh Inger , Nilsson Gunnar H. , Nager Anna
Published: February 2020

Background Evidence-based information available at the point of care improves patient care outcomes. Online knowledge bases can increase the application of evidence-based medicine and influence patient outcome data which may be captured in quality registries. The aim of this study was to explore the effect of use of an online knowledge base on patient experiences and health care quality. Methods The study was conducted as a retrospective, observational study of 24 primary health care centers in Sweden exploring their use of an online knowledge base. Frequency of use was compared to patient outcomes in two national quality registries. A socio-economic care need index was applied to assess whether the burden of care influenced the results from those quality registries. Non-parametric statistical methods and linear regression were used. Results Frequency of knowledge base use showed two groups: frequent and non-frequent users, with a significant use difference between the groups (p<0.001). Outcome data showed significant higher values for all seven National Primary Care Patient Survey dimensions in the frequent compared to the non-frequent knowledge base users (p<0.001), whereas 10 out of 11 parameters in the National Diabetes Register showed no differences between the groups (p>0.05). Adjusting for care need index had almost no effect on the outcomes for the groups. Conclusions Frequent users of a national online knowledge base received higher ratings on patient experiences, but figures on health care quality in diabetes showed near to no correlation. The findings indicate that some effects may be attributed to the use of knowledge bases and requires a controlled evaluation.
Inhibition of HIF1A-AS1 promoted starvation-induced hepatocellular carcinoma cells apoptosis by reducing HIF-1α/mTOR mediated autophagy
Authors: Hong Fenfen , Li Yang , Gao Yu , Zheng Linfeng , Li Xianpeng , Xu Feng
Published: February 2020

Background: Hepatocellular carcinoma (HCC) is still a major health burden in China considering its high incidence and mortality. Long non-coding RNAs (lncRNAs) were found playing vital roles in tumor progression, suggesting a new way of diagnosis and prognosis prediction, or treatment of HCC. This study was designed to investigate the role of HIF1A-AS1 during the progression of HCC, and to explore its related mechanisms. Methods: The expression of HIF1A-AS1 was detected in 50 paired carcinoma tissues and adjacent normal tissues by quantitative real-time PCR assay. HCC cells apoptosis was induced by nutrient-deficient culture medium, and detected by Cell Counting Kit‐8 and flow cytometer assays. HIF1A-AS1 inhibition in HCC cells was accomplished by small interfering RNA transfection. Results: HIF1A-AS1 was overexpressed in HCC tissues and was associated with tumor size, TNM stage and lymph node metastasis. Compared with low HIF1A-AS1 group, high HIF1A-AS1 group had a shorter overall survival and a worse disease-free survival. HIF1A-AS1 expression was significantly higher in HCC cell lines (7721 and Huh7) than that in normal hepatocyte cell line L02 under normal culture condition. However, under nutrient-deficient condition, HIF1A-AS1 expression was significantly increased in both HCC and normal hepatocyte cell lines, and was increased with the prolongation of nutrient-free culture. inhibition of HIF1A-AS1 promoted starvation-induced HCC cells apoptosis. Furthermore, inhibition of HIF1A-AS1 could also reduce starvation-induced HCC cells autophagy. The expression of HIF-1α and phosphorylated mTOR was significantly decreased in HCC cells after HIF1A-AS1 inhibition. Conclusions: HIF1A-AS1, overexpressed in HCC and associated with HCC prognosis, could regulate starvation-induced HCC cells apoptosis by reducing HIF-1α/mTOR mediated autophagy, promoting HCC cell progression. Trial registration: This research is retrospectively registered.
Clinical Application of the Reverse Puncture Technique for Total Laparoscopic Colorectal Resection with Natural Orifice Specimen Extraction
Authors: Kong Qi , Xia Yabin , Hao Hu , Jina Yan , Wu Longchao , Xu Li , Huang Xiaoxu
Published: February 2020

Objective To explore the feasibility, safety and short-term effects of the reverse puncture technique for total laparoscopic colorectal resection with natural orifice specimen extraction surgery (NOSES). Materials and Methods The clinical data of 28 patients undergoing total laparoscopic anterior resection with NOSE from July 2016 to July 2019 were retrospectively analysed. The operation was performed following the principle of total mesorectal excision. The reverse puncture technique was used to put the anvil into the proximal sigmoid colon. Then, intra-abdominal anastomosis of the proximal colon and distal rectum was carried out, and the short-term efficacy was evaluated. Results All 28 patients successfully underwent surgery, and the average operative time was 186 (160~220) min. The average time of anvil placement was 15 (12~18) min, the blood loss volume ranged from 60 to 150 ml, and the average length of hospital stay was 9.2 (7-11) d. All of the distal resection margins were confirmed to be negative by the pathological results. No surgery-associated complications, such as anastomosis stricture, leakage, or bleeding, were observed, and no local recurrence or metastasis occurred after 6 months of follow-up. Conclusion Reverse puncture for total laparoscopic colorectal resection with NOSE can avoid purse-string sutures under laparoscopy and avoid the auxiliary incision at the abdominal wall, which minimizes pain after operation. This approach is safe and feasible with a shortened hospital stay and rapid recovery, which results in good short-term clinical outcomes.
Efficacy of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in the Management of Malignant Ascites
Authors: Jiao Jie , Li Chengzhen , Yu Guanying , Zhang Lei , Shi Xiaoyan , Yan Jingdu , Zhang Houjun , Guo Peiming
Published: February 2020

Objective: The purpose of this study is to compare the difference of clinical efficacy between conventional intraperitoneal chemotherapy and HIPEC, so as to explore the clinical application value and advantages of HIPEC. Design: A retrospective analysis was conducted on 80 patients with malignant ascites admitted to our hospital from June 2017 to June 2019. The general clinical data and qualitative data of the treatment results of 80 patients with malignant ascites were processed by SPSS19.0 using χ2 test and quantitative data were processed by t test. P <0.05, statistical data can be considered statistically significant. Results: 1. There was no significant change in vital signs and temperature in the observation group during the treatment, and the difference was not statistically significant 2. The short-term total effective rate of patients in the observation group was 91.11%, and the short-term total effective rate of the patients in the control group was 40%. 3. There was no significant difference in the incidence of adverse reactions between the two groups of patients. Conclusion: Intraperitoneal hyperthermic chemotherapy combined with intravenous chemotherapy can significantly control malignant ascites, and has small adverse reactions, which is worthy of clinical promotion and application. Key words: efficacy; malignant ascites; intraperitoneal hyperthermic chemotherapy.
Functional production of human antibody by the filamentous fungus Aspergillus oryzae
Authors: Huynh Hung Hiep , Morita Naoki , Sakamoto Toshihiro , Katayama Takuya , Miyakawa Takuya , Tanokura Masaru , Chiba Yasunori , Shinkura Reiko , MARUYAMA Jun-ichi
Published: February 2020

Background: Monoclonal antibodies (mAbs) as one of the biopharmaceuticals take a pivotal role in the current therapeutic application. Generally, mammalian cell lines such as Chinese hamster ovary (CHO) cell lines are used to produce the recombinant antibody. However, there are still concerns about the high cost and the risk of pathogenic contamination when using mammalian cells. Aspergillus oryzae, the filamentous fungus recognized as a GRAS (Generally Regarded As Safe) organism, has an ability to secrete a large amount of proteins into the culture supernatant, and thus the fungus has been used as one of the cost-effective microbial hosts for heterologous protein production. Pursuing this strategy, human anti-TNFα antibody adalimumab, one of the world’s best-selling antibodies for the treatment of immune-mediated inflammatory diseases including rheumatoid arthritis, was chosen to attempt for producing the full length of mAbs by A. oryzae. Generally, N-glycosylation in antibody affects the immune effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) via binding to the Fc receptor (FcγR) on immune cells. The CRISPR/Cas9 system was used to firstly delete the Aooch1 encoding a key enzyme for the hyper-mannosylation process in fungi to investigate the binding ability of antibody with FcγRIIIa.Results: The adalimumab was expressed in A. oryzae by the fusion protein system with α-amylase AmyB. The full-length adalimumab consisting of two heavy and two light chains was successfully produced in the culture supernatants. Among the producing strains, the highest amount of antibody was obtained from the ten-protease deletion strain (39.7 mg/L). Two-step purifications by Protein A and size-exclusion chromatography were applied to obtain the high purity sample for further analysis. The antigen-binding and TNFα neutralizing activities of the adalimumab produced by A. oryzae were comparable with those of the commercial product – Humira. No apparent binding with the FcγRIIIa was detected with the recombinant adalimumab even by altering the N-glycan structure under the Aooch1 deletion, which suggests only a little additional activity of immune effector functions.Conclusion: These results demonstrated an alternative low-cost platform for human antibody production by using A. oryzae, possibly offering a reasonable expenditure for patient’s welfare.
Determinants of Obesity and Metabolic Health in the Afghan Population: Protocol, Methodology and Preliminary Results
Authors: Sahrai Mohammad Sediq , Huybrechts Inge , Biessy Carine , Rinaldi Sabina , Ferrari Pietro , Wasiq Abdul Wahed , Gunter Marc J. , Dossus Laure
Published: February 2020

Background: Non-communicable diseases (NCDs) cause more than 70% of deaths worldwide and share modifiable risk factors including obesity and metabolic abnormalities. Over the past 15 years many changes in lifestyle, dietary patterns, physical activity and socioeconomic status have been observed in the Afghan population. This study aims to investigate which specific lifestyle factors, dietary patterns and characteristics of Westernization are associated with an increased risk of being overweight or obese and with poor metabolic health in the Afghan population.Methods: A population-based cross-sectional study was conducted where a total of 729 male and female participants were recruited. Face to face interviews and anthropometric measurements were conducted by trained health staff using standardized questionnaires which included information on socio-demographic and housing characteristics, income, occupation, ethnicity, personal and family medical history, stress, anthropometry, diet and physical activity. Bioelectric impedance analysis (BIA) was used to estimate body composition, including overall body fatness. Physical activity was measured by using the short version of the International Physical Activity Questionnaire (IPAQ). For a comprehensive assessment of dietary intake, a food frequency questionnaire (FFQ) specific to the Afghan population was developed which included all local food items relevant to the population. Lipid profile and fasting glucose were measured in a local laboratory. Biospecimens were collected using dried blood spots (DBS) and faecal occult blood test (FOBT) cards to perform microbiome and biomarker-based research.Discussion: This is the first study which will assess dietary patterns, lifestyle factors and their association with obesity and metabolic health in Afghanistan. Such a study will aid the development of dietary and lifestyle guidelines in Afghanistan which will promote better health and educate people to make healthy food choices. The findings will also help in designing and implementing effective public health strategies to promote a healthy lifestyle and prevent the epidemic of overweight and obesity, and hence, reduce the burden of non-communicable diseases in the region.
Juvenile Spondyloarthritis: focus on uveitis.
Authors: Marino Achille , Weiss Pamela F. , Brandon Timothy G. , Lerman Melissa Ann
Published: February 2020

Background Juvenile spondyloarthritis (JSpA) represents a group of inflammatory arthritides with several distinctive features (enthesitis, involvement of spine and sacroiliac joint, HLA-B27 association and development of uveitis). There are limited data on the course of uveitis in children with JSpA. This study aims to estimate the prevalence of uveitis and to look at the presence of HLA-B27 in relation to uveitis occurrence and ocular symptoms in a cohort of JSpA patients. Findings This is a cross sectional/retrospective study involving patients with JSpA followed in a tertiary referral hospital. Two hundred twenty-three patients were enrolled in the study. The prevalent diagnosis was enthesitis-related arthritis (ERA) (62%) followed by juvenile psoriatic arthritis (PsA), undifferentiated arthritis (UA), and the arthropathies associated with inflammatory bowel disease (IBD-A) (18%, 13%, 12%, respectively). Uveitis was reported in twenty-four patients (11%) of the JSpA cohort (JSpA-U). ERA patients had the highest uveitis prevalence (ERA-U) (13%) with similar prevalences in UA, PsA (7%) and in IBD-A (7% each). The prevalence of HLA-B27 positivity was 45% amongst JSpA-U (N=22), with fewer than half of patients with ERA-U HLA-B27 positive (44%). The overall prevalence of symptomatic uveitis was 79%. Neither the likelihood of uveitis, nor of symptomatic uveitis, varied by HLA-B27 status either in the entire cohort nor in those with ERA. Conclusions About one-tenth of patients developed uveitis, the majority of which was symptomatic. Fewer than half of the patients with uveitis were HLA-B27 positive. HLA-B27 status was not statistically associated with either the development of uveitis or symptomaticity of uveitis.
Association between long-term exposure to ambient air pollutants and mortality rates because of circulatory and respiratory diseases in South Korea
Authors: Kwon Jinhee , Hwang Jeongeun , Yi Hahn , Bae Hyun-Jin , Jang Miso , Kim Namkug
Published: February 2020

Background : Associations between long-term exposure to common air pollutants including nitrogen dioxide, carbon monoxide, sulfur dioxide (SO 2 ), ozone, and particulate matter (PM 10 ) and health consequences have been studied. We investigated spatial effects of exposure to air pollution on mortality by circulatory and respiratory diseases nation-wide and in metropolitan. Methods: Means of daily concentration of the common air pollutants from 2005 to 2016 were calculated by district unit using linear interpolation. Age-standardized mortality rates of people suffering from heart disease (HD); cerebrovascular disease (CVD); ischemic heart disease (IHD); pneumonia (PN) and chronic lower respiratory disease (CLRD) were acquired from population census data. Sub-divided comparisons were performed to adjust spatial heterogeneity. Pearson’s correlation coefficients between mortality rates and air pollutant concentrations were investigated. Multivariable linear regressions were performed to investigate associations considering confounding factors. Results: Air pollutant concentration in metropolitan was the highest, except SO 2 ; in particular, PM 10 concentration was higher than air quality standard (PM 10 : 55.27 µg/m 3 , air quality standard: 50.00 µg/m 3 , P<0.05). Pearson’s correlation coefficient between PM 10 and mortality rates was significant ( r =0.313, 0.596, 0.420, -0.277 and 0.523 for HD, CVD, IHD, PN, and CLRD, all P<0.05) in metropolitan. The powers of regression model for PM 10 , smoking rate, education level, and population density were 0.532 and 0.482 (adjusted R 2 ) for mortality rates of CVD and CLRD, respectively. Conclusion : Long-term exposure study with sub-divided analysis showed overall associations between air pollution exposure and circulatory and respiratory disease mortalities. PM 10 exposure was significantly associated with mortality of CVD and CLRD in metropolitan.
Serum Fetuin-A levels were increased and associated with insulin resistance in women with polycystic ovary syndrome
Authors: Liu Sha , Hu Wenjing , He Yirui , Li Ling , Liu Hua , Gao Lin , Yang Gangyi , Liao Xin
Published: February 2020

Background Insulin resistance (IR) is a common characteristic in women with polycystic ovary syndrome (PCOS). It has been reported that circulating Fetuin-A levels were associated with IR and type 2 diabetes mellitus (T2DM). However, previous reports on changes in circulating Fetuin-A concentrations in women with PCOS have been inconsistent. Methods 207 subjects were screened for PCOS according to the diagnostic guideline of the Rotterdam consensus criterion. Serum Fetuin-A levels were measured using an ELISA kit. An independent t- test or Nonparametric tests was used to detect differences between PCOS and control groups. The association of the serum Fetuin-A with other parameters was examined by spearman’s correlation analysis. Results Our findings show that circulating Fetuin-A concentration ranged from 196.6 to 418.2 µg/L for most women without PCOS (95%). Women with PCOS have higher circulating Fetuin-A levels than healthy women (437.9 ± 119.3 vs. 313.8 ± 60.5 μg/L; p < 0.01). Serum Fetuin-A was positively correlated with BMI, WHR, TG, TC, LDL-C, HOMA-IR, LH, T and DHEA-S. Multivariate regression analysis showed that WHR, TG, HOMA-IR and DHEA-S were independent predictors of the levels of circulating Fetuin-A. Binary logistic regression revealed that serum Fetuin-A was associated with the .occurrence of PCOS. In addition, our ROC curve analysis found that the cutoff values for Fetuin-A to predict PCOS and IR were 366.3 and 412.6 µg/L. ConclusionBlood Fetuin-A may be a useful biomarker for screening women for PCOS and IR.
The Alpha-fetoprotein Serum is still Reliable as a Biomarker for the Surveillance of Hepatocellular Carcinoma in Indonesia
Authors: Jasirwan Chyntia Olivia Maurine , Fahira Alessa - , Siregar Lianda - , Loho Imelda -
Published: February 2020

Background and Aims: Hepatocellular carcinoma (HCC), the most common type of liver cancer, is one of the leading causes of cancer-related death worldwide with an inferior prognosis. In Indonesia, the average life expectancy is less than 3 months, with most patients being in an advanced stage where in the survival rate is very low. Early detection through surveillance program is very crucial. HCC guidelines worldwide have provided surveillance recommendation through the examination of α-fetoprotein (AFP) and ultrasound for patients at risk in developing HCC. However, there have been some controversies regarding the usage of AFP concerning its low sensitivity and specificity in detecting HCC. Therefore, the effectiveness of AFP in the surveillance of HCC patients and identifying the parameters most associated with the increase of AFP≥10 ng/ml in Indonesia should be evaluated.Methods: We analysed medical records of HCC patients and those at high-risk of developing HCC through cross-sectional study, including patients with cirrhosis and hepatitis B and C, from 2015 to 2017 who underwent treatment at the Cipto Mangunkusumo National Hospital and Dharmais National Cancer Hospital, Indonesia.Results: The sensitivity and specificity of AFP in the surveillance of HCC in Indonesia with a cut-off of 10 ng/ml were 82.6% and 68.9%, respectively. The parameters most associated with the increase of AFP ≥10 ng/ml according to multivariate analysis were the etiology of hepatitis B, the stage of Barcelona Clinic Liver Cancer B and C, and the presence of cirrhosis, respectively.Conclusion: AFP can still be used in the surveillance of HCC in Indonesia for its high sensitivity value.