bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-omics analysis reveals the influence of genetic and environmental risk factors on developing gut microbiota in infants at risk of celiac disease
Authors: Leonard Maureen M , Karathia Hiren , Pujolassos Meritxell , Troisi Jacopo , Valitutti Francesco , Subramanian Poorani , Camhi Stephanie , Kenyon Victoria , Colucci Angelo , Serena Gloria , Cucchiara Salvatore , Montuori Monica , Malamisura Basilio , Francavilla Ruggiero , Elli Luca , Fanelli Brian , Colwell Rita , Hasan Nur , Zomorrodi Ali R , Fasano Alessio , Team CDGEMM Study
Published: August 2020

Background: Celiac disease (CD) is an autoimmune digestive disorder that occurs in genetically susceptible individuals in response to ingesting gluten, a protein found in wheat, rye, and barley. Research shows that genetic predisposition and exposure to gluten are necessary but not sufficient to trigger the development of CD. This suggests that exposure to other environmental stimuli early in life, e.g., cesarean section delivery, exposure to antibiotics or formula feeding, may also play a key role in CD pathogenesis through yet unknown mechanisms. Here, we use multi-omics analysis to investigate how genetic and early environmental risk factors alter the development of the gut microbiota in infants at risk of CD. Results: Toward this end, we selected 31 infants from a large-scale prospective birth cohort study of infants with a first-degree relative with CD. We then performed rigorous multivariate association, cross-sectional and longitudinal analyses using metagenomic and metabolomic data collected at birth, three months and six months of age to explore the impact of genetic predisposition and environmental risk factors on the gut microbiota composition, function and metabolome prior to the introduction of trigger (gluten). These analyses revealed several microbial species, functional pathways and metabolites that are associated with each genetic and environmental risk factor or that are differentially abundant between environmentally exposed and non-exposed infants or between time points. Among our significant findings, we found that cesarean section delivery is associated with a decreased abundance of Bacteroides vulgatus and Bacteroides dorei and of folate biosynthesis pathway, and with an increased abundance of hydroxyphenylacetic acid, alterations that are implicated in immune system dysfunction and inflammatory conditions. Additionally, longitudinal analysis revealed that, in infants not exposed to any environmental risk factor, the abundances of Bacteroides uniformis and of metabolite 3-3-hydroxyphenylproprionic acid increase over time while those for lipoic acid and methane metabolism pathways decrease, patterns that are linked to beneficial immunomodulatory and anti-inflammatory effects. Conclusions: Overall, our study provides unprecedented insights into major taxonomic and functional shifts in the developing gut microbiota of infants at risk of CD linking genetic and environmental risk factors to detrimental immunomodulatory and inflammatory effects.
Impact of sample size on the stability of risk scores from clinical prediction models: a case study in cardiovascular disease
Authors: Pate Alexander , Emsley Richard , Sperrin Matthew , Martin Glen P. , Staa Tjeerd van
Published: August 2020

Background: Stability of risk estimates from prediction models may be highly dependent on the sample size of the dataset available for model derivation. In this paper, we evaluate the stability of cardiovascular disease risk scores for individual patients when using different sample sizes for model derivation; such sample sizes include those similar to models recommended in national guidelines, and those based on recently published sample size formula for prediction models.Methods: We mimicked the process of sampling N patients from a population to develop a risk prediction model by sampling patients from the Clinical Practice Research Datalink. A cardiovascular disease risk prediction model was developed on this sample and used to generate risk scores for an independent cohort of patients. This process was repeated 1000 times, giving a distribution of risks for each patient. N = 100 000, 50 000, 10 000, Nmin (derived from sample size formula) and Nepv10 (meets 10 events per predictor rule) were considered. The 5 – 95 percentile range of risks across these models was used to evaluate instability. Patients were grouped by a risk derived from a model developed on the entire population (population derived risk) to summarise results.Results: For a sample size of 100 000, the median 5 – 95 percentile range of risks for patients across the 1000 models was 0.77%, 1.60%, 2.42% and 3.22% for patients with population derived risks of 4-5%, 9-10%, 14-15% and 19-20% respectively, for N = 10 000 it was 2.49%, 5.23%, 7.92% and 10.59%, and for N using the formula derived sample size, it was 6.79%, 14.41%, 21.89% and 29.21%. Restricting this analysis to models with high discrimination, good calibration or small mean absolute prediction error reduced the percentile range, but high levels of instability remained.Conclusions: Widely used cardiovascular disease risk prediction models suffer from high levels of instability induced by sampling variation. Many models will also suffer from overfitting (a closely linked concept), but at acceptable levels of overfitting there may still be high levels of instability in individual risk. Stability of risk estimates should be a criterion when determining the minimum sample size to develop models.
Sagittal Abdominal Diameter and its Socioeconomic Correlates: Perspective of Sex Differences
Authors: Li Chang , Harris Marcelline , Tsilimingras Dennis , Liu Sophia , Sheng Ying , Liu Xuefeng
Published: August 2020

Background Sagittal abdominal diameter (SAD) is an anthropometric index associated with visceral adiposity. It remains unclear whether SAD and its socio-economic correlates differ in women and men, which limits the epidemiological and clinical applications of the SAD measurement. The aims of this study are to examine the sex differences in SAD and its socio-economic correlates. Methods A complex stratified multistage clustered sampling design was used to select 6,975 men and 7,079 women aged 18 years or more from the National Health Nutrition and Examination Survey 2011-2016, representative of the US civilian non-institutionalized population. SAD was measured in accordance to the standard protocols using a two-arm abdominal caliper. The sex differences in SAD and its socio-economic correlates were evaluated by performing weighted independent t tests and weighted multiple regression. Results SAD was lower in women than in men in the entire sample, as well as in all subgroups characterized by age, race, body mass index, birth place, and household income except for non-Hispanic blacks and those with household income < $20,000. Adjusted for other characteristics, SAD increased with age and body mass index for both women and men (p<.0001). Compared to white women, Asian women were associated with lower SAD (p=.018), and black women with higher SAD (p<.0001). Compared to white men, Hispanic and Asian men were associated with lower SAD (both p<.0001). Women born in other countries were more likely to have lower SAD than women born in the US (p<.0001), and so were men (p=.0118). Both women and men with a household income of <$75,000 had higher SAD than those with an income of over $75,000. Conclusion SAD is lower in women than in men, in the general population as well as in the most socio-economic subgroups. Socio-economic correlates of SAD were similar in women and men.
Identification of an Autophagy-Related Gene Signature that Can Improve Prognosis of Hepatocellular Carcinoma Patients
Authors: Huo Xingxing , Qi Jian , Huang Kaiquan , Bu Su , Yao Wei , Chen Ying , Nie Jinfu
Published: August 2020

Background: Autophagy is a programmed cell degradation mechanism that has been associated with several physiological and pathophysiological processes, including malignancy. Improper induction of autophagy has been proposed to play a pivotal role in the progression of hepatocellular carcinoma (HCC).Methods: Univariate Cox regression analysis of overall survival (OS) was performed to identify risk-associated autophagy-related genes (ARGs) in HCC data set from The Cancer Genome Atlas (TCGA). Multivariate cox regression was then performed to develop a risk prediction model for the prognosis of 370 HCC patients. The multi-target receiver operating characteristic (ROC) curve was used to determine the model’s accuracy. Besides, the relationship between drug sensitivity and ARGs expression was also examined.Results: A total of 62 differentially expressed ARGs were identified in HCC patients. Univariate and multivariate regression identified five risk-associated ARGs (HDAC1, RHEB, ATIC, SPNS1 and SQSTM1) that were correlated with OS in HCC patients. Of importance, the risk-associated ARGs were independent risk factors in the multivariate risk model including clinical parameters such as malignant stage (HR=1.433, 95% CI=1.293-1.589, P<0.001). In addition, the area under curve for the prognostic risk model was 0.747, which indicates the high accuracy of the model in prediction of HCC outcomes. Interestingly, the risk-associated ARGs were also correlated with drug sensitivity in HCC cell lines.Conclusion: We developed a novel prognostic risk model by integrating the molecular signature and clinical parameters of HCC, which can effectively predict the outcomes of HCC patients.
Effects of Biofilm Transfer and Electron Mediators Transfer on Klebsiella quasipneumoniae sp.203 Electricity Generation Performance in MFCs
Authors: Guo Yating , Wang Guozhen , Zhang Hao , Wen Hongyu , Li Wen
Published: August 2020

Background: Extracellular electron transfer ( EET ) is essential in improving the power generation performance of electrochemically active bacteria ( EAB ) in microbial fuel cells ( MFCs ) . Currently, the EET mechanisms of dissimilatory metal-reducing ( DMR ) model bacteria Shewanella oneidensis and Geobacter sulfurreducens have been thoroughly studied. Klebsiella has also been proved to be an EAB capable of EET, but the EET mechanism has not been perfected. This study investigated the effects of biofilm transfer and electron mediators transfer on Klebsiella quasipneumoniae sp. 203 electricity generation performance in MFCs.Results: Herein, we covered the anode of MFC with a layer of microfiltration membrane to block the effect of the biofilm mechanism, and then explore the EET of the electron mediator mechanism of K.quasipneumoniae sp. 203 and electricity generation performance. In the absence of short-range electron transfer, we found that K.quasipneumoniae sp. 203 can still produce a certain power generation performance, and coated-MFC reached 40.26 mW / m 2 at a current density of 770.9 mA / m 2 whereas the uncoated-MFC reached 90.69 mW / m 2 at a current density of 1224.49 mA / m 2 . The difference in the electricity generation performance between coated-MFC and uncoated-MFC was probably due to the microfiltration membrane covered in anode, which inhibited the growth of EAB on the anode. Therefore, we speculated that K.quasipneumoniae sp. 203 can also perform EET through the biofilm mechanism. The protein content, the integrity of biofilm and the biofilm activity all proved that the difference in the electricity generation performance between coated-MFC and uncoated-MFC was due to the extremely little biomass of the anode biofilm. To further verify the effect of electron mediators on electricity generation performance of MFCs, 10µM 2,6-DTBBQ, 2,6-DTBHQ and DHNA were added to coated-MFC and uncoated-MFC. Combining the time-voltage curve and CV curve, we found that 2,6-DTBBQ and 2,6-DTBHQ had high electrocatalytic activity toward the redox reaction of K.quasipneumoniae sp.203-inoculated MFCs. It was also speculated that K. quasipneumoniae sp. 203 produced 2,6-DTBHQ and 2,6-DTBBQ.Conclusions: To the best of our knowledge, the three modes of EET did not exist separately. K.quasipneumoniae sp.203 will adopt the corresponding electron transfer mode or multiple ways to realize EET according to the living environment to improve electricity generation performance.
Cost-effectiveness analysis of ceritinib vs. crizotinib in previously untreated anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) in Hong Kong
Authors: Loong Herbert , Wong Carlos K H , Leung Linda K S , Chan Catherine P K , Chang Andrea , Zhou Zheng-yi , Xie Jipan , Gibbs Meaghan
Published: August 2020

Introduction: Lower-dose ceritinib (450mg) once-daily with food was approved in 2018 in Hong Kong (HK) for first-line treatment of patients with anaplastic lymphoma kinase-positive (ALK+) advanced non-small cell lung cancer (NSCLC). This study examined the cost-effectiveness of ceritinib vs. crizotinib in the first-line treatment of ALK+ NSCLC from a HK healthcare service provider's or government's perspective. Methods: Costs and effectiveness of first-line ceritinib vs. crizotinib over a 20-year time horizon was evaluated using a partitioned survival model with three health states (stable disease, progressed disease, and death). The efficacy data for ceritinib were obtained from a phase 3 trial comparing ceritinib with chemotherapy for advanced non-small cell lung cancer (ASCEND-4) and extrapolated using parametric survival models. Long-term survival associated with crizotinib were estimated using hazard ratio of crizotinib vs. ceritinib obtained from matching-adjusted indirect comparison based on ASCEND-4 and PROFILE 1014 trials. Drug acquisition, administration, adverse events costs, and medical costs associated with each health state were obtained from public sources and converted to 2018 US Dollars. Incremental costs per quality-adjusted-life-year (QALY) and life-year (LY) gained were estimated for ceritinib vs. crizotinib. Results: The base case results showed that ceritinib was associated with 3.22 QALYs, 4.51 LYs, and total costs of $157,581 over 20 years. Patients receiving crizotinib had 2.68 QALYs, 3.85 LYs, and $150,424 total costs over the same time horizon. The incremental cost per QALY gained for ceritinib vs crizotinib was $13,343. Results were robust to deterministic sensitivity analyses in most scenarios. Conclusion: Ceritinib offers a cost-effective option compared to crizotinib for previously untreated ALK+ advanced NCSLC in HK.
Arabidopsis paralogous genes RPL23aA and RPL23aB encode functionally equivalent proteins
Authors: Xiong Wei , Chen Xiangze , Zhu Chengxin , Zhang Jiancong , Lan Ting , Liu Lin , Mo Beixin , Chen Xuemei
Published: August 2020

Background: In plants, each ribosomal protein (RP) is encoded by a small gene family but it is largely unknown whether the family members are functionally diversified. There are two RPL23a paralogues genes ( RPL23aA and RPL23aB ) found in Arabidopsis thaliana. Knock-down of RPL23aA using RNAi impeded growth and led to morphological abnormalities, whereas knock-out of RPL23aB had no observable phenotype, thus these two RPL23a paralogous proteins have been used as examples of ribosomal protein paralogues with functional divergence in many published papers. Results: In this study, we characterized T-DNA insertion mutants of RPL23aA and RPL23aB . A rare non-allelic non-complementation phenomenon was found in the F1 progeny of the rpl23aa X rpl23ab cross, which revealed a dosage effect of these two genes. Both of RPL23aA and RPL23aB were found to be expressed almost in all examined tissues as revealed by GUS reporter analysis. Expression of RPL23aB driven by the RPL23aA promoter can rescue the phenotype of rpl23aa , indicating these two proteins are actually equivalent in function. Interestingly, based on the publicly available RNA-seq data, we found that these two RPL23a paralogues were expressed in a concerted manner and the expression level of RPL23aA was much higher than that of RPL23aB at different developmental stages and in different tissues. Conclusions: Our findings suggest that RPL23aA and RPL23aB proteins actually have equal function and presence of paralogous genes for the RPL23a protein in plants might be necessary to maintain its adequate dosage.
Current status of periodontitis and its association with tobacco use among adult population of Sunsari district, Nepal
Authors: Goel Khushboo , Sharma Shivalal , Baral Dharnidhar , Agrawal Santosh
Published: August 2020

Background: Tobacco products are considered significant but preventable factors related to initiation and progression of periodontal diseases. We assessed the prevalence of periodontitis and evaluated its association with tobacco use and other factors among the adult population of eastern Nepal.Methods: A community-based cross-sectional study was conducted in the rural municipalities in the province one of eastern Nepal. A total of 440 individuals were interviewed with a set of a standardized pre-tested semi-structured questionnaire. Data on social demographics, adverse oral habits followed by periodontal clinical examination were recorded. Prevalence of periodontitis was assessed by a case definition given by CDC-AAP. Univariate and multivariate logistic regression analysis was used to measure the association between tobacco use and other factors with periodontitis.Results: The overall prevalence of periodontitis was found to be 71.6%. Majority (85.4%) of tobacco users had periodontitis and they were significantly associated with the disease and its severity. The study identified age groups, 45 – 65 years (AOR=7.58, 95% CI, 3.93-14.61), plaque index (AOR=1.01, 95% CI, 1.00-1.02), smoking (AOR=3.14, 95% CI, 1.36-7.27), khaini users (smokeless tobacco, AOR=2.27, 95% CI, 1.12-4.61) and teeth loss (AOR=2.02, 95% CI, 1.21-3.38) as the significant factors associated with periodontitis.Conclusion: The prevalence of periodontitis is high in the surveyed rural adult population. Along with age, plaque, teeth loss and smoking, smokeless tobacco in the form of khaini are identified as significant factors contributing to periodontitis.
New Findings on Submerged Patch Reefs and Reefal Carbonate Rocks at Water Depths of 70-100 meters on the Insular Shelf off Miyako-jima, Southern Ryukyus, Japan
Authors: Inoue Takahiko , Arai Kohsaku
Published: August 2020

Sub-bottom profiling (SBP) surveys and bathymetric mapping conducted off the shore of Miyako-jima, which belongs to the southern Ryukyus in the Ryukyu Island Arc, have revealed the presence of mound-shaped structures 3-8 m high and 50-120 m wide at depths of 70-100 m. The SBP surveys showed that the mounds possess strong distinct, convex upward reflector shapes at the top, which we interpret as submerged reefs and reefal sediments. Additionally, modern stratified sediment layers that cover these mound-shaped structures indicate that those reefs began forming and advancing shoreward in a back-stepping fashion as a result of sea-level rise. An analysis of the mound distribution shown by SBP and multibeam echo sounding (MBES) surveys suggest that they might have been formed during the lowstand stage of sea-level change, which includes the Last Glacial Period, because the distribution of these mounds is limited to water depths of 70 m to 100 m, deeper than where present-day reefs grow. The SBP images hint that such high-resolution seismic profiles, accompanied by detailed bathymetric mapping off the reefal area, have the potential to provide effective indicators of not only coral reef paleoenvironment development, but also the tectonic setting of this offshore area.
A nationwide survey of intraoperative management for one-lung ventilation in Taiwan: time to accountable for diversity in protective lung ventilation
Authors: Kuo Chuan-Yi , Liu Ying-Tung , Chen Tzu-Shan , Lam Chen-Fuh , Wu Ming-Cheng
Published: August 2020

Background: There is a major paradigm shift for intraoperative mechanical ventilator support by the introduction of lung protective ventilation strategies to reduce postoperative pulmonary complications and improve overall clinical outcomes in non-thoracic surgeries. However, there is currently a lack of standardized practice guideline for lung protection during thoracic surgeries that require one-lung ventilation (OLV). This study aimed to collect the expert opinions of the thoracic anesthesiologists in perioperative care for OLV surgery in Taiwan.

Methods: This prospective cross-sectional study was undertaken in 16 tertiary hospitals in Taiwan from January to February 2019. A structured survey form was distributed across the participating hospitals and the thoracic anesthesiologists were invited to complete the form voluntarily. The survey form consisted of three parts, including the basic information of the institutional anesthesia care standards, ventilatory settings for a proposed patient receiving OLV surgery and expert opinions on OLV.

Results: A total of 71 thoracic anesthesiologists responded to the survey. Double-lumen tubes are the most commonly used (93.8%) airway devices for OLV. The most commonly recommended ventilator setting during OLV is a tidal volume of 6-7 ml/kg PBW (67.6%) and a PEEP level of 4-6 cmH2O (73.5%). Dual controlled ventilator modes are used by 44.1% of the anesthesiologists. During OLV, high oxygen fraction (FiO2 >0.8) is more commonly supplemented to achieve an oxygen saturation higher than 94%. The consensus of anesthesiologists on the indices for lung protection in thoracic surgery is considerably low. Large majority of the anesthesiologists (91.5%) highly recommend that an international clinical practice guideline on the protective lung ventilation strategy for thoracic anesthesia should be established.

Conclusions: This study found that the thoracic anesthesiologists in Taiwan share certain common practices in ventilator support during OLV. However, they are concerned about the lack of fundamental clinical evidences to support the beneficial outcomes of the current lung protective strategies applicable to OLV. Large-scale trials are needed to form an evidence-based clinical practice guideline for thoracic anesthesia.
Survival prediction models since liver transplantation - comparisons between Cox models and machine learning techniques
Authors: Kantidakis Georgios , Putter Hein , Lancia Carlo , de Boer Jacob , Braat Andries E , Fiocco Marta
Published: August 2020

Background: Predicting survival of recipients after liver transplantation is regarded as one of the most important challenges in contemporary medicine. Hence, improving on current prediction models is of great interest. Nowadays, there is a strong discussion in the medical field about machine learning (ML) and whether it has greater potential than traditional regression models when dealing with complex data. Criticism to ML is related to unsuitable performance measures and lack of interpretability which is important for clinicians. Methods: In this paper, ML techniques such as random forests and neural networks are applied to large data of 62294 patients from the United States with 97 predictors selected on clinical/statistical grounds, over more than 600, to predict survival from transplantation. Of particular interest is also the identification of potential risk factors. A comparison is performed between 3 different Cox models (with all variables, backward selection and LASSO) and 3 machine learning techniques: a random survival forest and 2 partial logistic artificial neural networks (PLANNs). For PLANNs, novel extensions to their original specification are tested. Emphasis is given on the advantages and pitfalls of each method and on the interpretability of the ML techniques. Results: Well-established predictive measures are employed from the survival field (C-index, Brier score and Integrated Brier Score) and the strongest prognostic factors are identified for each model. Clinical endpoint is overall graft-survival defined as the time between transplantation and the date of graft-failure or death. The random survival forest shows slightly better predictive performance than Cox models based on the C-index. Neural networks show better performance than both Cox models and random survival forest based on the Integrated Brier Score at 10 years. Conclusion: In this work, it is shown that machine learning techniques can be a useful tool for both prediction and interpretation in the survival context. From the ML techniques examined here, PLANN with 1 hidden layer predicts survival probabilities the most accurately, being as calibrated as the Cox model with all variables.
Rubidium chloride modulated the fecal microbiota community in mice
Authors: Chen Qian , He Zhiguo , Zhuo Yuting , Li Shuzhen , Yang Wenjing , Hu Liang , Zhong Hui
Published: August 2020

Background: The microbiota plays an important role in host health. Although rubidium (Rb) has been used to study for depression and cancers, the interaction between microbial commensals and Rb is still unexplored. To gain the knowledge of the relationship between Rb and microbes, 51 mice receiving RbCl-based treatment and 13 untreated mice were evaluated of their characteristics and bacterial microbiome changes.Results: The 16S ribosomal RNA gene sequencing of feces showed RbCl generally maintained fecal microbial community diversity, while the shifts in fecal microbial composition were apparent after RbCl exposure for the first time. RbCl significantly enhanced the abundances of Rikenellaceae, Alistipes, Clostridium XlVa and sulfate-reducing bacteria including Deltaproteobacteria, Desulfovibrionales, Desulfovibrionaceae and Desulfovibrio. While, RbCl significantly inhibited the abundances of Tenericutes, Mollicutes, Anaeroplasmatales, Anaeroplasmataceae and Anaeroplasma lineages. Besides, with regarding to the composition of archaea, RbCl significantly enhanced the abundances of Crenarchaeota, Thermoprotei, Sulfolobales, Sulfolobaceae and Sulfolobus lineages. Conclusions: These results revealed that enrichments of Clostridium XlVa and Alistipes could affect the levels of serotonin, a critical signaling molecule of brain-gut-microbiota axis. Therefore, anticancer and anti-depressant effects of RbCl might be partly mediated by modifying brain-gut-microbiota axis.
Characterizing glycosyltransferases by a combination of sequencing platforms applied to the leaf tissues of Stevia rebaudiana
Authors: Zhang Shaoshan , Liu Qiong , Lyu Chengcheng , Chen Jinsong , Xiao Renfeng , Chen Jingtian , Yang Yunshu , Zhang Huihui , Hou Kai , Wu Wei
Published: August 2020

Background: Stevia rebaudiana (Bertoni) is considered one of the most valuable plants because of the steviol glycosides (SGs) that can be extracted from its leaves. Glycosyltransferases (GTs), which can transfer sugar moieties from activated sugar donors onto saccharide and nonsaccharide acceptors, are widely distributed in the genome of S. rebaudiana and play important roles in the synthesis of steviol glycosides.Results: Six stevia genotypes with significantly different concentrations of SGs were obtained by induction through various mutagenic methods, and the contents of seven glycosides (stevioboside, Reb B, ST, Reb A, Reb F, Reb D and Reb M) in their leaves were considerably different. Then, NGS and single-molecule real-time (SMRT) sequencing were combined to analyse leaf tissue from these six different genotypes to generate a more complete and correct full-length transcriptome of S. rebaudiana . Two phylogenetic trees of glycosyltransferases (SrUGTs) were constructed by the neighbour-joining method and successfully predicted the functions of SrUGTs involved in SG biosynthesis. With further insight into glycosyltransferases (SrUGTs) involved in SG biosynthesis, the weighted gene co-expression network analysis (WGCNA) method was used to characterize the relationships between SrUGTs and SGs, and forty-four potential SrUGTs were finally obtained, including SrUGT85C2 , SrUGT74G1 , SrUGT76G1 and one SrUGT91D2, which have already been reported to be involved in the glucosylation of steviol glycosides, illustrating the reliability of our results.Conclusion: Combined with the results obtained by previous studies and those of this work, we systematically characterized glycosyltransferases in S. rebaudiana and forty-four candidate SrUGTs involved in the glycosylation of steviol glucosides were obtained. Moreover, the complete and correct full-length transcriptome obtained in this study will provide valuable support for further research investigating S. rebaudiana .
Leaf Open Time Sinogram (LOTS): A novel approach for Patient specific quality assurance of Total marrow irradiation
Authors: Thiyagarajan Rajesh , Sharma Dayananda Shamurailatpam , Kaushik Suryakant , Sawant Mayur , Krishnan Ganapathy , Nambiraj Arunai , CHILUKURI SRINIVAS , Sundar Sham , Patro Kartikeswar , Arjunan Manikandan , MP Noufal , Sivaraman Rangasamy , Easoee Jose , Jalali Rakesh
Published: August 2020

There is no ideal detector-phantom combination to perform patient specific quality assurance (PSQA) for total marrow (TMI) and Lymphoid (TMLI) irradiation plan. In this study, 3D dose reconstruction using mega voltage computed tomography detectors measured leaf open time sinogram (LOTS) was investigated for PSQA of TMI/TMLI patients in helical tomotherapy. The feasibility of this method was first validated for ten non-TMI/TMLI patients, by comparing reconstructed dose with a) ion-chamber (IC) and helical detector array (ArcCheck) measurement and b) planned dose distribution using 3Dγ analysis for 3%@3mm and dose to 98%(D98%) and 2%(D2%) of PTVs. Same comparison was extended for ten treatment plans from five TMI/TMLI patients. In all non-TMI/TMLI patients, reconstructed absolute dose was within ±1.8% of planned and IC measurement. The planned dose distribution agrees with reconstructed and ArcCheck measured dose with mean(SD) 3Dγ of 98.7%(1.57%) and 2Dγ of 99.48%(0.81%). The deviation in D98% and D2% were within 1.71% and 4.1% respectively. In all 25 measurement locations from TMI/TMLI patients, planned and IC measured absolute dose agrees within ±1.2%. Although sectorial fluence verification using ArcCHECK measurement for PTVs chest from five upper body TMI/TMLI plans showed mean±SD 2Dγ of 97.82%±1.27%, the reconstruction method resulted poor mean(SD) 3Dγ of 92.00%(±5.83%), 64.80%(±28.28%), 69.20%(±30.46%), 60.80%(±19.37%) and 73.2% (±20.36%) for PTVs brain, chest, torso, limb and upper body respectively. The corresponding deviation in median D98% and D2% of all PTVs were <3.8% and 9.5%. Re-optimization of all upper body TMI/TMLI plans with new pitch and modulation factor of 0.3 and 3 leads significant improvement with 3Dγ of 100% for all PTVs and median D98% and D2% <1.6%. LOTS based PSQA for TMI/TMLI is accurate, robust and efficient. A field width, pitch and modulation factor of 5cm, 0.3 and 3 for upper body TMI/TMLI plan is suggested for better dosimetric outcome and PSQA results.
Prevalence of middle mesial canal and radix entomolaris of mandibular first permanent molars in a western Chinese population: an in vivo cone-beam computed tomographic study
Authors: Qiao Xin , Zhu Hualing , Yan Yujia , Li Jinglin , Ren Jiayin , Gao Yuan , Zou Ling
Published: August 2020

Background: The aim of this study was to investigate the prevalence of the middle mesial canal (MMC) and radix entomolaris (RE) in mandibular first permanent molars in a western Chinese population using cone-beam computed tomography (CBCT).Methods: A total of 1174 CBCT images of the mandibular first molars were collected from West China Hospital of Stomatology, Sichuan University. The following information was recorded and evaluated: the detection rate and location of the MMC and RE, the curvature of the RE, the canal configuration and bilateral symmetry.Results: The detection rates of the MMC and RE were 3.41% and 25.04%, respectively, as calculated by individuals, and 1.79% and 22.15%, respectively, as calculated by total teeth. The average curvature in the buccolingual (BL) orientation ( 40.63±14.3 9°) was significantly larger than that in the mesiodistal (MD)orientation ( 17.64±7.8 2°) (p<0.05). Of 587 patients, 71.72% (421/587) had bilateral symmetry according to the root canal morphology. The incidence of three-rooted mandibular first molars was higher in males than in females, while the incidence of two-rooted mandibular first molars was higher in females than in males.Conclusions: Our results showed that the RE could be detected in almost 1/4 of the western Chinese population; thus, RE detection requires special attention and careful assessment in endodontic treatment.
Changes In Self-Reported Sleep Duration With Age - A 36-Year Longitudinal Study Of Finnish Adults
Authors: Hublin Christer , Haasio Lassi , Kaprio Jaakko
Published: August 2020

Background: Sleep deprivation is often claimed to be increasingly common, but most studies show small changes in sleep duration over the last decades. Our aim was to analyze long-term patterns in self-reported sleep duration in a population-based cohort. Methods: Members of the Older Finnish Twin Cohort have responded to questionnaires in 1975 (N = 30,915 individuals, response rate 89%, mean age 36 years), 1981 (24,506, 84%, 41 years), 1990 (12,502, 77%, 44 years), and 2011 (8510, 72%, 60 years). Weibull regression models were used to model the effects of follow-up time and age simultaneously. Results: Sleep duration has decreased in all adult age groups and in both genders. The mean duration was in men 7.57 hours in 1975 and 7.39 in 2011, and in women 7.69 and 7.37, respectively. The decrease was about 0.5 minutes in men and 0.9 in women per year of follow-up. In the age-group 18-34 years, mean sleep length was 7.69 hours in 1975 and 7.53 in 1990. Among 35-54-year-old it was 7.57 hours in 1975 and 7.34 in 2011, and in the age group of 55+ year olds 7.52 and 7.38, correspondingly. The change was largest in middle-aged group: about 23 minutes or about 0.6 minutes per year of follow-up. Conclusions: There has been a slight decrease in mean sleep duration during the 36-year follow-up. Although the sleep duration was longer in 1970s and 1980s, the probable main cause for the change in this study population is the effect of aging.
Sedimentation and sediment geochemistry in a tropical mangrove channel meander, Sungai Kerteh, Peninsular Malaysia
Authors: Shaari Hasrizal Bin , Nasir Qatrunnada Mohd , Pan Hui-Juan , Mohamed Che Abd Rahim , Yusoff Abdul Hafidz , Khalik Wan Mohd Afiq Wan Mohd , Naim Erick , Setiawan Riza Yuliratno , Anthony Edward J.
Published: August 2020

Tropical mangrove swamps are commonly characterized by dense networks of tidal channels that may show pronounced meandering and dendritic patterns. Channel meanders are sometimes accompanied by cut offs, and, like classical fluvial meanders, record changes in hydrology and sedimentation over time. Channel meandering can, thus, be an important process that contributes to spatial and temporal variability in the preserved record of the sedimentology and geochemistry of mangrove sediments. The aim of this study is to highlight changes in channel meander sedimentation in response to a meander cut-off in a tropical mangrove swamp. Two short sediment cores were sampled, respectively from a point bar (core KR1, 122 cm) at the junction with the neck cut-off and inside the cut-off (core KR2, 98 cm) in the Sungai Kerteh mangroves of Peninsular Malaysia. The profile comparison was based on sediment characteristics, total organic carbon (TOC) and selected elements (Fe, Na, Mg, Mn, Ba and Sr). A smaller standard deviation of mean grain size (MGS) was found at the point bar (4.37±0.51 ϕ) than in the cut-off (4.43 ±1.76 ϕ), indicating a difference in flow velocity between the two settings. In turn, these changes in grain size influence channel meander evolution via associated changes in TOC and heavy metals. In order to clarify these relationships, we used principal components analysis and factor analysis. An increased accumulation of selected elements and TOC at the cut-off site from a depth of ~ 60 cm to the core-top segment was probably associated with a slowing down of sediment settling. A higher TOC recorded in the cut-off (2.74±1.42%) compared to the point bar (1.14±0.46%) suggests a propensity for prolonged in-situ accumulation of organic matter in the abandoned meander bend. This study provides grain-size and sediment geochemical information that is consistent with patterns of active and inactive sedimentation in the meander bends of mangrove channels.
Changes in health-related quality of life before and after a 12-month enhanced primary care model among chronically ill primary care patients in Australia.
Authors: John James , Tannous W Kathy , Jones Amanda
Published: August 2020

Purpose: Evidence suggests that Patient-centred Medical Home (PCMH) model facilitates person-centred care and improves health-related quality of life for patients with chronic illness. This study aims to evaluate changes in health-related quality of life (HRQoL), before and after enrolment into a 12-month integrated care program called ‘WellNet’. Methods: This study includes 616 eligible consented patients aged 40 years and above with one or more chronic conditions from six general practices across Sydney, Australia. The WellNet program included a team of general practitioners (GPs) and clinical coordinators (CCs) providing patient-tailored care plans configured to individual risk and complexity. HRQoL was recorded using the validated EuroQol five dimensions five levels (EQ-5D-5L) instrument at baseline and 12 months. Additionally, patients diagnosed with osteoarthritis also reported HRQoL using short versions of Knee and/or Hip disability and osteoarthritis outcome scores (KOOSjr and HOOSjr). A case-series study design with repeated measures analysis of covariance (ANCOVA) was used to assess changes in mean differences of EQ-5D index scores after controlling for baseline covariates. Additionally, backward stepwise multivariable linear regression models were conducted to determine significant predictors of EQ-5D index scores at follow-up. Results: Out of 616 patients, 417 (68%) reported EQ-5D scores at follow-up. Almost half (48%) of the WellNet patients reported improved EQ-5D index scores at follow-up. After controlling for baseline covariates, the adjusted mean difference was statistically significant whilst also meeting the bare minimal clinically important difference (MCID) with a change of 0.03 (95% CI 0.01, 0.05). The multivariable regression models determined that baseline EQ-5D scores and positive diagnosis of a respiratory illness were significant predictors of HRQoL at follow-up. There were significant improvements across both KOOS and HOOS assessments, specifically, the pain and symptom scores in both scales met statistical significance in addition to meeting the MCID.Conclusion: Patient-tailored chronic disease management (CDM) plans designed by team of GPs and CDM clinical coordinators could lead to better HRQoL among primary care patients.
WNK1 Antagonist Decreased Sevoflurane-induced Neurotoxicity in HT22 Hippocampal Neurons via the WNK1/NKCC1 Signalling Pathway
Authors: Bai Ya-Fan , Li Wen-Jing , Zhang Li , Li Jun-Fa , An Li-Xin
Published: August 2020

Background : . The GABA A R plays an important role in the neurotoxicity caused by sevoflurane, but the mechanism of its regulation in this context is unknown. The present study aimed to reveal the WNK1/NKCC1 pathway as a regulator of the neurotoxicity caused by sevoflurane on the HT22 hippocampal neuron cell line. Methods : HT22 cultured hippocampal neurons were divided into three groups: control group, 4.1% sevoflurane treatment group for 6h, WNK-463 (specific antagonist of WNK1, 1µmol) + sevoflurane treatment group. Cell viability and the optimum concentration of WNK-463 were measured by MTS method. Cell apoptosis was detected by Tunel method, and the content of cleaved caspase-3 protein apoptosis factor was detected by Western blot. Pathway protein detection including the expression of WNK1, NKCC1 were detected. Calcium imaging measures intracellular calcium ion concentration and verifies downstream targets. Results : The neurotoxic effects of sevoflurane on hippocampal neurons were observed. As setting the results of control group is “1”, compared with sevoflurane group, WNK-463 downregulated the protein expression of cleaved caspase-3 (1.96±0.49 vs 1.29±0.38), increased cell viability (0.68 vs 0.96) and decreased apoptosis (13.31±4.67/vision vs 7.05±3.82/vision, *** P < 0.001). Compared with the control group, sevoflurane treatment increased the expression of WNK1 kinase and NKCC1 protein, whereas WNK-463 reversed this increase without affecting the control HT22 cells (* P < 0.05). Compared with the control group, sevoflurane exposure in HT22 cells increased intracellular Ca 2+ concentrations, while WNK-463 reversed this change (1.0 vs 2.08±1.36 vs 1.26±0.77, ** P < 0.01). Conclusion : This study demonstrated a neuroprotective role of the WNK1 antagonist WNK-463 in sevoflurane-induced neurotoxicity. WNK-463 promoted hippocampal neuron viability and reduced the apoptosis and intracellular calcium overload caused by sevoflurane on HT22 hippocampal neurons, possibly via the modulation of the WNK1/NKCC1 pathway.
Effectiveness of extracorporeal blood purification (hemoadsorption) in patients with severe coronavirus disease 2019 (COVID-19)
Authors: Asgharpour Masoumeh , Mehdinezhad Hamed , Bayani Masoumeh , Zavareh Mahmoud Sadeghi Haddad , Hamidi Seyed Hossein , Akbari Roghayyeh , Ghadimi Reza , Bijani Ali , Mouodi Simin
Published: August 2020

Background

Extracorporeal blood purification has been proposed as one of the therapeutic approaches in patients with coronavirus infection, because of its beneficial impact on elimination of inflammatory cytokines.

Methods

This controlled trial has been conducted on critically ill COVID-19 patients admitted in the state hospital affiliated to Babol University of Medical Sciences, Iran who received different antiviral and antibacterial drugs, and different modalities of respiratory treatments and did not have positive clinical improvement. No randomization and blindness was considered. All of the participants underwent three sessions of resin-directed hemoperfusion using continuous renal replacement therapy with a mode of continuous venovenous hemofiltration (CVVH).

Results

Five men and five women with a mean age of 57.30±18.07 years have been enrolled in the study; and six of them have improved after the intervention. Peripheral capillary oxygen saturation (SpO2) changed after each session. Mean SpO2 before the three sessions of hemoperfusion was 89.60%±3.94% and increased to 92.13%±3.28% after them (p<0.001). Serum IL-6 showed a reduction from 139.70±105.62 to 72.06±65.87 pg/mL (p=0.073); and c-reactive protein increased from 136.25±84.39 to 78.25±38.67 mg/L (P=0.016).

Conclusions

Extracorporeal hemoadsorption could improve the general condition in most of recruited patients with severe coronavirus disease; however, large prospective multicenter trials in carefully selected patients are needed to definitely evaluate the efficacy of hemoperfusion in COVID-19 patients.
Perceived barriers to the adoption of active surveillance in low-risk prostate cancer: A Qualitative Analysis of Community and Academic Urologists
Authors: Ellis Shellie D , Hwang Soohyun , Morrow Emily , Kimminau Kim S. , Goonan Kelly , Petty Laurie , Ellerbeck Edward , Thrasher J Brantley
Published: August 2020

Background: Clinical practice guidelines recommend active surveillance as the preferred treatment option for low-risk prostate cancer, but only a minority of eligible men receive active surveillance, and practice variation is substantial. The aim of this study is to describe barriers to urologists’ recommendation of active surveillance in low-risk prostate cancer and explore variation of barriers by setting. Methods: We conducted semi-structured interviews among 22 practicing urologists, evenly distributed between academic and community practice. We coded barriers to active surveillance according to a conceptual model of determinants of treatment quality to identify potential opportunities for inResults: Community and academic urologists were generally in agreement on factors influencing active surveillance. Urologists perceived patient-level factors to have the greatest influence on recommendations, particularly tumor pathology, patient age, and judgements about the patient’s ability to adhere to follow-up protocols. They also noted cross-cutting clinical barriers, including concerns about the adequacy of biopsy samples, inconsistent protocols to guide active surveillance, and side effects of biopsy procedures. Urologists had differing opinions on the impact of environmental factors, such as financial disincentives and fear of litigation. Conclusions: Despite national and international recommendations, both academic and community urologists note a variety of barriers to implementing active surveillance in low risk prostate cancer. These barriers will need to be specifically addressed in efforts to help urologists offer active surveillance more consistently.
Cerebrospinal fluid α-synuclein predicts neurodegeneration and clinical progression in non-demented elders
Authors: Li Jie-Qiong , Bi Yan-Lin , Shen Xue-Ning , Wang Hui-Fu , Xu Wei , Tan Chen-Chen , Dong Qiang , Wang Yan-Jiang , Tan Lan , Yu Jin-Tai
Published: August 2020

BackgroundAccumulating reports suggest that α-synuclein is involved in Alzheimer disease (AD) pathogenesis. Cerebrospinal fluid (CSF) α-synuclein could be a potential biomarker of AD. We sought to test whether CSF α-synuclein is associated with other AD biomarkers and could predict neurodegeneration and clinical progression in non-demented elders. MethodsAssociations were investigated between CSF α-synuclein and other AD biomarkers at baseline in non-demented Chinese elders. The predictive values of CSF α-synuclein in longitudinal neuroimaging change and conversion risk of non-demented elders were assessed using linear mixed effects models and multivariate Cox proportional hazard models, respectively, in Alzheimer's disease Neuroimaging Initiative (ADNI) database.ResultsWe detected that CSF α-synuclein levels correlated with AD-specific biomarkers CSF total tau and phosphorylated tau levels in 651 Chinese Han participants (training set). These positive correlations were replicated in ADNI database (validation set). Using a longitudinal cohort from ADNI, CSF α-synuclein concentrations increased with disease severity. CSF α-synuclein had high diagnostic accuracy for AD based on the “ATN” system (A+T+) vs controls (A-T-) (area under the receiver operating characteristic curve, 0.84). Moreover, CSF α-synuclein predicted longitudinal hippocampus atrophy and conversion from MCI to AD dementia.ConclusionsCSF α-synuclein is associated with CSF tau levels and could predict neurodegeneration and clinical progression in non-demented elders. This finding indicates CSF α-synuclein is a potentially useful, early biomarker for AD.