bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Sugar Industry Waste (Filter Cake) and Agro-waste Crop Residue as Potential Source of Livestock Feed Raw Materials
Authors: Abera Adugna Ayu , Duraisamy Ramesh D , Seda Tolera Badessa
Published: August 2020

The potential searching on sources of livestock feed material is the major constrain in the sustainability of livestock sector for the future. The utilization of cereal crop residues (CCRs) is limited because they contain a large proportion of lignocellulosic compounds and little nitrogen. The filter cake is a poorly studied potential as forage for ruminants. In addition, they show higher fiber content. The analysis on characterization of filter cake, Teff straw, barley straw and corn cob were carried out through proximate analysis such as moisture content (MC), dry mater (DM), organic dry matter (ODM), ash content (AC), crude protein (CP), crude fiber (CF), Elemental analyzer, UV-Visible spectroscopy and Fourier transform infrared spectroscopy were used for analyzing the elemental profiles and functional feed constitutions. The proximate analysis of raw material feed stocks (in %) contains in the range of DM (96. 54 ± 0.7-89.5±0.5), ODM (98.33±0.3-79.4±0.4), MC (3.45±0.7-10.5±0.5), CP (2.32±0.58-12.92±0.36), CF (15.5±0.50-85±0.5), AC (1.69±0.03-20.6±0), FT (1.44±0.1-10.5±0.82), Carbohydrates (45.27- 90.42), energy value (327.26- 386.56 kcal.) and Sucrose of (3.85±0.83). And its elemental compositions can be addressed by their mineral matter contain up 1.69±0.03-20.6±0 %.The moisture content and dry matter contents may vary depends on factors such as cultivator of crops and cane, location, climate, dry length, soil pest diseases, cultivation practices, the harvesting practice and the processing of cans and crops. Large quantities of fibrous crop residues are already used as animal feed in many areas across these countries. There are too many areas in developing countries where ruminant livestock starves due to lack of feed. So this study shows that the direction of searching and compensating the availability of such important croup residues and the sugar industry by product (filter cake) as the raw sources of livestock feeds.
Scientific Collaboration on COVID-19 Amidst Geopolitical Tensions between the US and China
Authors: Lee Jenny J. , Haupt John P.
Published: August 2020

As the threat of COVID-19 and US-China tensions are increasing, this study focused on this intensifying intersection between geopolitics and global science in the midst of a pandemic. This scientometric study examined the US’ and China’s international collaboration patterns on science and engineering (S&E) COVID-19 articles through the lenses of scientific nationalism and scientific globalism. While scientific nationalism would assume that the current political rhetoric and protectionist policies would lead to a decrease in international collaboration, our findings showed the reverse. The world’s proportion of international collaborations generally increased. Findings also revealed that despite geopolitical tensions, the highest number of internationally coauthored S&E COVID-19 articles between two countries involve the US and China. Their collaboration rate on COVID-19 is higher than during the past five-years as well as on non-COVID-19 articles published during 2020.
Analysis of clinicopathological and molecular features of crawling-type gastric adenocarcinoma
Authors: Fujita Yasuko , Uesugi Noriyuki , Sugimoto Ryo , Eizuka Makoto , Toya Yosuke , Akasaka Risaburou , Matsumoto Takayuki , Sugai Tamotsu
Published: August 2020

Background: Crawling-type adenocarcinoma (CRA) is an important gastric cancer (GC) subtype that exhibits a specific histological pattern and has characteristic clinicopathological findings. Despite its characteristic histology, little is known about the molecular characteristics of CRA. Methods: We examined 254 GC cases, including 51 cases of CRA and 126 cases having conventional differentiated adenocarcinomas (CDAs). Results for immunohistochemistry (mucin phenotype; Muc5AC, Muc6, Muc2 and CD10, CDX-2, MLH-1 and β-catenin), mutation analysis ( TP53 , KRAS and BRAF ), microsatellite instability (BAT25, BAT26, D2S123, D5S346 and D17S250), DNA methylation status by a two-panel method ( RUNX3 , MINT31 , LOX, NEUROG1 , ELMO1 and THBD ), MLH-1 promoter methylation, and allelic imbalance (AI; 1p, 3p, 4p, 5q, 8p, 9p, 13q, TP53, 18q and 22q) were examined. Results: CRAs were more likely to occur in the middle third of the stomach, in younger patients and to be macroscopically depressed. Nuclear accumulation of β-catenin and loss of MLH-1 expression were less frequent among CRA cases compared to CDA cases. At a molecular level, CRA is often characterized by the deletion mutation c.529_546 (18-base pair deletion at codon 177-182 in exon 5), in the TP53 gene (10 cases). Although the low methylation epigenotype was significantly more frequent for CRAs compared to CDAs, multiple AIs were more often seen in CRAs relative to CDAs. Conclusions: The results demonstrated that TP53 mutations, particularly c.529_546del, and multiple AIs are closely associated with CRA carcinogenesis. Our results suggest that CRA is an independent entity of GC in terms of clinicopathologic and molecular findings.
The properties of MOF-Zn2(EBNB)2(BPY)2·2H2O and its basic study of loading Methadone
Authors: Linxin Deng , Song Li , Sun Xuehua
Published: August 2020

The ligands of (E)-bis(p-3-nitrobenzoic acid) vinyl (C16H10N2O8) were synthesized in three steps, and then the MOF-Zn2(EBNB)2(BPY)2·2H2O was synthesized by solvothermal method. This structure was characterized by X-ray single crystal diffraction, SEM and TG. The drug loading and in vitro release of Zn2(EBNB)2(BPY)2·2H2O were also studied with Methadone as model drug. The result shows that the highest loading amount of Zn2(EBNB)2(BPY)2·2H2O to Methadone was 0.256g/g, and the drug delivery system was a two-phase mode. The results of in vitro cytotoxicity test shows that Zn2(EBNB)2(BPY)2·2H2O has good biocompatibility.
Group Testing Can Improve the Cost-Efficiency of Prospective-Retrospective Biomarker Studies
Authors: Zhang Wei , Zhang Zhiwei , Krushkal Julia , Liu Aiyi
Published: August 2020

Background: Cancer treatment is increasingly dependent on biomarkers for prognostication and treatment selection. Potential biomarkers are frequently evaluated in prospective-retrospective studies in which biomarkers are measured retrospectively on archived specimens after completion of prospective clinical trials. In light of the high costs of some assays, random sampling designs have been proposed that measure biomarkers for a random sub-sample of subjects selected on the basis of observed outcome and possibly other variables. Compared with a standard design that measures biomarkers on all subjects, a random sampling design can be cost-efficient in the sense of reducing the cost of the study substantially while achieving a reasonable level of precision.Methods: For a biomarker that indicates the presence of some molecular alteration (e.g., mutation in a gene), we explore the use of a group testing strategy, which involves physically pooling specimens across subjects and assaying pooled samples for the presence of the molecular alteration of interest, for further improvement in cost-efficiency beyond random sampling. We propose simple and general approaches to estimating the prognostic and predictive values of biomarkers with group testing, and conduct simulation studies to validate the proposed estimation procedures and to assess the cost-efficiency of the group testing design in comparison to the standard and random sampling designs.Results: Simulation results show that the proposed estimation procedures perform well in realistic settings and that a group testing design can have considerably higher cost-efficiency than a random sampling design. Conclusions: Group testing can be used to improve the cost-efficiency of biomarker studies.
Physiological and Biochemical Properties of Cotton in Response to Copper Stress
Authors: Zhou Hao , Zhou Ke-Hai , Zhao Gang , Wang Pei-Pei , Yang Dai-Gang , Ma Xiong-Feng , Gao Jun-Shan
Published: August 2020

Backgroundcopper (Cu) is an essential micronutrient, required for plant growth and development. However, high concentrations of Cu can be extremely toxic to plant. This study investigate the tolerance mechanism of cotton under copper stress and its potential for soil pollution improvement.ResultsThe hybrid cotton variety (Zhongmian 63) and its two parent lines were selected as materials. Cotton seedling were treated with different Cu concentrations (0, 0.2, 50, 100, 200 μM) for 10 days in hydroponic condition. The results showed that the stem height, root length, and leaf area of cotton seedlings appear to have a down trend with the increase of Cu concentration. Increasing Cu concentration promoted Cu accumulation in roots, stems, and leaves of all the three cotton genotypes, however, the roots region was the main Cu storage organ, followed by leaves and stems regions. Compared with the parent lines, the roots of Zhongmian 63 are more capable of enriching Cu and have the least amount of Cu transported to the shoots. Therefore, the toxicity of Cu to cotton seedling is effectively alleviated. Cu-caused oxidative stress to cotton leaves was evident by over accumulation of H2O2 and MDA. POD activity and soluble sugar content increased firstly and then decreased compared with the control group. GSH content increased and photosynthetic pigment content decreased with increasing copper concentration in nutrient solution. ConclusionOur results suggest that the hybrid cotton variety Zhongmian 63 performed well under Cu stress. This lays the theoretical foundation for further analysis on molecular mechanism of cotton resistance to copper and promoting the large-scale planting Zhongmian 63 in the copper-contaminated area.
A comparison of the relationship between parental efficacy and social support systems of single teen mothers across different family forms
Authors: Coert Samantha Linn , Adebiyi Babatope O. , Rich Edna , Roman Nicolette V.
Published: August 2020

BackgroundTeenage parenting is recognised as one of the greatest health and social problems in South Africa. Research in South Africa has shown that by the age of 18 years, more than 30% of teens have given birth at least once. Teen mothers may feel disempowered because they are ‘othered’ and consequently, may develop forms of resistance which in most cases may inhibit their ability to parent. Social support is therefore, an imperative intervention for successful teen parenting but this is not clearly understood in South Africa. This study aimed to compare the relationship between parental efficacy and social support systems of single teen mothers across different family forms. MethodsA quantitative methodology with a cross-sectional comparative correlation design was conducted with 160 single teen mothers who resided with a family in a low socio-economic community. The participants completed a self-report questionnaire that comprised of the Social Provisions Scale (SPS), and the Parenting Sense of Competence (PSOC) scale. Descriptive statistics and Pearson correlation were used to investigate the data. ResultsA significant positive relationship between social support and parental efficacy was found. These findings are important for planning and applying parenting programmes amongst single teen mothers and facilitating awareness regarding the importance of social support and family forms when considering parenting practices.ConclusionThe current study revealed, that a relationship between parental efficacy and social support of single teen mothers do exist and for most, it was statistically significant, meaning any changes from the two variables may affect each other and the performance of single teen mothers.
Insights into the Diversification of Subclade IVa bHLH Transcription Factors in Fabaceae
Authors: Suzuki Hayato , Seki Hikaru , Muranaka Toshiya
Published: August 2020

Background: Fabaceae plants appear to contain larger numbers of subclade IVa basic-helix-loop-helix (bHLH) transcription factors than other plant families, and some members of this subclade have been identified as saponin biosynthesis regulators. We aimed to systematically elucidate the diversification of this subclade and obtain insights into the evolutionary history of saponin biosynthesis regulation in Fabaceae.Results: In this study, we collected sequences of subclade IVa bHLH proteins from 40 species, including fabids and other plants, and found greater numbers of subclade IVa bHLHs in Fabaceae. We confirmed conservation of the bHLH domain, C-terminal ACT-like domain, and exon-intron organisation among almost all subclade IVa members in model legumes, supporting the results of our classification. Phylogenetic tree-based classification of subclade IVa revealed the presence of three different groups. Interestingly, most Fabaceae subclade IVa bHLHs fell into group 1, which contained all legume saponin biosynthesis regulators identified to date. These observations support the co-occurrence and Fabaceae-specific diversification of saponin biosynthesis regulators. Comparing the expression of orthologous genes in Glycine max, Medicago truncatula, and Lotus japonicus, orthologues of MtTSAR1 (the first identified soyasaponin biosynthesis regulatory transcription factor) were not expressed in the same tissues, suggesting that group 1 members have gained different expression patterns and contributions to saponin biosynthesis during their duplication and divergence. On the other hand, groups 2 and 3 possessed fewer members, and their phylogenetic relationships and expression patterns were highly conserved, indicating that their activities may be conserved across Fabaceae.Conclusions: This study suggests subdivision and diversification of subclade IVa bHLHs in Fabaceae plants. The results will be useful for candidate selection of unidentified saponin biosynthesis regulators. Furthermore, the functions of groups 2 and 3 members are interesting targets for clarifying the evolution of subclade IVa bHLH transcription factors in Fabaceae.
Role of BMI in PCOS Towards Cardiovascular Risk Factors
Authors: Arshad Farhatul-Ain , Mehmood Rubaida , Kausar Nahid , Bibi Asia , Khan Muhammad Annus
Published: August 2020

Background: Polycystic ovary syndrome (PCOS) is a prevalent disorder in which blood markers of cardiac disorders have been frequently established. However, the impact of obesity on PCOS is still to be discovered. This study was designed to determine if cardiac disorder in PCOS women may explain by altered BMI and biochemical parameters.Methods: A prospective study was carried out by having 100 samples of obese (50) and non-obese (50) PCOS patients. Blood samples (<5ml) were collected, statistical analysis and correlation of BMI were done with hormonal and lipid profile.Results: On Pearson correlation analysis of BMI with lipid and hormonal profile, cholesterol showed a positive correlation in obese PCOS. Spearman correlation analysis of BMI showed positive significant correlation with testosterone in non-obese PCOS. Obese and non-obese groups were further subdivided into married (obese, non-obese), unmarried (obese and non-obese) groups. Negative correlation with LH in married obese, while none of the significant results had been found in married non-obese. In the case of unmarried obese, testosterone showed negative and estradiol showed a positive correlation in unmarried non-obese.Conclusions: The data from this study concluded that young PCOS women have evidence for altered endocrine functions along with elevated BMI. Furthermore correlation of BMI and testosterone might be one of the major factors of developing adiposity and infertility that further causes cardiac diseases. Lifestyle modifications are also beneficial for lessen the ovarian cysts and promote fertility in pubertal females. However, the evidence is limited and more investigations are still needed.
A Comparative Analysis of Transcription Networks Active in Juvenile and Mature Wood in Populus
Authors: Luo Laifu , Zhu Yingying , Gui Jinshan , Yin Tongmin , Luo Wenchun , Liu Jianquan , Li Laigeng
Published: August 2020

Background: Juvenile wood (JW) and mature wood (MW) have distinct physical and chemical characters, reflecting the different wood formation over the tree life-span. However, the regulatory mechanisms that distinguish or modulate the characteristics of JW and MW in relation to each other have not been mapped. Using RNA sequencing (RNA-seq) and whole genome bisulfite sequencing (WGBS), we analyzed wood properties associated with JW and MW forming tissue from Populus trees with an identical genetic background.Results: JW and MW of Populus displayed different wood properties as the result of significant differences in transcriptional programs and patterns of DNA methylation. Differences were concentrated in gene networks involved in regulating hormonal signaling pathways responsible for auxin distribution and brassinosteroids biosynthesis as well as genes active in regulating cell expansion and secondary cell wall biosynthesis. An observed correlation between gene expression profiling and DNA methylation indicated that DNA methylation affected expression of the genes related to auxin distribution and brassinosteroids signal transduction, cell expansion in JW and MW formation. Conclusions: Auxin distribution, brassinosteroids biosynthesis and signaling play critical roles in formation of JW and MW. DNA methylation is involved in formatting the transcriptional programs in different development phases which contribute to JW and MW formation. The study sheds light to better understand the molecular networks underlying regulation of wood properties which could inform improvement of wood formation.
Weighted Gene Coexpression Network Analysis-Based Identification of Key Modules and Hub Genes that Regulate the Drought Stress Response in the Rice Drought-Sensitive Line PY6
Authors: Yu Baiyang , Liu Jianbin , Wu Di , Liu Ying , Cen Weijian , Wang Shaokui , Li Rongbai , Luo Jijing
Published: August 2020

Drought stress is an adverse factor with deleterious effects on several aspects of rice growth. However, the mechanism underlying drought resistance in rice remains unclear. To understand the molecular mechanism of the drought response in rice, drought-sensitive CSSL (Chromosome Single-substitution Segment Line) PY6 was used to map QTLs of sensitive phenotypes and to reveal the impact of the QTLs on transcriptional profiling. The dss-1 locus was mapped onto the short arm of chromosome 1 of rice. According to transcriptomic analysis, the identified differentially expressed genes (DEGs) exhibited a downregulated pattern and were mainly enriched in photosynthesis-related GO terms, indicating that photosynthesis was greatly inhibited under drought. Further, according to weighted gene coexpression network analysis (WGCNA), 4 and 3 modules were strongly correlated with H2O2 and MDA, respectively. Likewise, GO analysis revealed that the photosynthesis-related GO terms were consistently overrepresented in H2O2-correlated modules. Functional annotation of the DEGs in the H2O2 and MDA-correlated modules revealed cross-talk between abiotic and biotic stress responses for these genes, which were annotated as encoding WRKYs and PR family proteins, were notably differentially expressed between PY6 and PR403.We speculated that drought-induced photosynthetic inhibition leads to H2O2 and MDA accumulation, which can then trigger the reprogramming of the rice transcriptome, including the hub genes involved in ROS scavenging, to prevent oxidative stress damage. Our results shed light on and provide deep insight into the drought resistance mechanism in rice.
Genetic predisposition to television watching increases the risk of type 2 diabetes: a bidirectional and multivariable Mendelian randomization study
Authors: Chen Songzan , Yang Fangkun , Xu Tian , Wang Yao , Zhang Kaijie , Fu Guosheng , Zhang Wenbin
Published: August 2020

Background: Excessive sedentary behaviors have been reported to be associated with increased risk of type 2 diabetes, but whether this association is causal remains unclear. In current study, we aimed to investigate the causal association between domain-specific sedentary behaviors and the risk of type 2 diabetes using a two-sample Mendelian randomization (MR) study. Methods: We identified 165 single nucleotide polymorphisms as instrumental variables for television watching, 43 for computer use and 5 for driving behavior from a recently published genome-wide association study (n = 408,815). Genetic association estimates for type 2 diabetes were obtained from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium (74,124 cases and 824,006 controls). The inverse variance-weighted method was used to estimate the effect of genetically predicted sedentary behaviors on the risk of type 2 diabetes. Reverse MR analysis was performed to investigate the reverse causation. The weighted median method, MR-Egger method, and MR Pleiotropy Residual Sum and Outlier method were employed in the sensitivity analyses. In addition, multivariable MR analysis and mediation analysis were conducted to explore the potential mechanistic elements.Results: Genetic predisposition to excessive television watching was associated with increased risk of type 2 diabetes. The OR (95% CI) per 1.5h (1 standard deviation) increment in television watching time was 1.82 (1.61, 2.07) for type 2 diabetes. This association was substantially attenuated after adjustment for anthropometric traits (adjusting BMI: OR = 1.35, 95% CI = 1.17 – 1.57, P = 4.1 × 10-5; adjusting WHR: OR = 1.26, 95% CI = 1.09 – 1.45, P = 1.4 × 10-3) and educational attainment (OR = 1.49, 95% CI = 1.16 – 1.91, P = 1.7 × 10-3). There was limited evidence of associations of computer use and driving behavior with the risk of type 2 diabetes. Conclusions: Our study clarifies the causal effect of excessive television watching on the increased risk of type 2 diabetes from a genetic perspective, which may be partly mediated via anthropometric and educational traits. Television watching may serve as a behavioral target to prevent incident diabetes.
Comparative cellular, physiological and transcriptome analyses reveal the potential easy dehulling mechanism of rice tartary buckwheat (Fagopyrum Tararicum)
Authors: Li Hongyou , Wu Chaoxin , Lv Qiuyu , Shi Taoxiong , Chen Qijiao , Chen Qingfu
Published: August 2020

Background
Tartary buckwheat has gained popularity in the food marketplace due to its abundant nutrients and high bioactive flavonoid content. However, its difficult dehulling process has severely restricted its food processing industry development. Rice tartary buckwheat, a rare local variety, is very easily dehulled, but the cellular, physiological and molecular mechanisms responsible for this easy dehulling remains largely unclear.
Results
In this study, we integrated analyses of the comparative cellular, physiological, transcriptome, and gene coexpression network to insight into the reason that rice tartary buckwheat is easy to dehull. Compared to normal tartary buckwheat, rice tartary buckwheat had significantly brittler and thinner hull, and thinner cell wall in hull sclerenchyma cells. Furthermore, the cellulose, hemicellulose, and lignin contents of rice tartary buckwheat hull were significantly lower than those in all or part of the tested normal tartary buckwheat cultivars, respectively, and the significant difference in cellulose and hemicellulose contents between rice tartary buckwheat and normal tartary buckwheat began at 10 days after pollination (DAP). Comparative transcriptome analysis identified a total of 9,250 differentially expressed genes (DEGs) between the rice- and normal-tartary buckwheat hulls at four different development stages. Weighted gene coexpression network analysis (WGCNA) of all DEGs identified a key module associated with the formation of the hull difference between rice- and normal-tartary buckwheat. In this specific module, many secondary cell wall (SCW) biosynthesis regulatory and structural genes, which involved in cellulose and hemicellulose biosynthesis, were identified hub genes and displayed coexpression. These identified hub genes of SCW biosynthesis were significantly lower expression in rice tartary buckwheat hull than in normal tartary buckwheat at the early hull development stages. Among them, the expression of 17 SCW biosynthesis relative-hub genes were further verified by quantitative real-time polymerase chain reaction (qRT-PCR).
Conclusions
Our results show that the lower expression of SCW biosynthesis regulatory and structural genes in rice tartary buckwheat hull in the early development stages contribute to its easy dehulling by reducing the content of cell wall chemical components, which further effect the cell wall thickness of hull sclerenchyma cells, and hull thickness and mechanical strength.
Outcomes and risk factors for the survival of COVID-19 related ARDS patients treated with extracorporeal membrane oxygenation
Authors: Wang Luyun , Chen Kengquan , Chen Peng , Ni Li , Jiang Jiangang , Wang Daowen
Published: August 2020

Background: In current pandemic of COVID-19, approximately 15% to 30% of critically ill COVID-19 patients developed acute respiratory distress syndrome (ARDS) with a high mortality. Extracorporeal membrane of oxygenation (ECMO) provides direct support for both lung and heart in ARDS. However, the role of ECMO in COVID-19 related ARDS was still controversial. The aim of this study was to provide insights into the mortality, intensive care unit (ICU) management, risk factors for mortality, 180-day short term prognosis of the COVID-19 related severe ARDS patients receiving ECMO treatment. Methods: From Feb 2nd, 2020 to April 27th, 2020, we included adult COVID-19 related ARDS patients admitted to intensive care unit in Tongji Hospital. Totally, 53 patients were retrospectively analyzed. They were divided into ECMO (mechanical ventilation with ECMO, n=16) and non-ECMO group (mechanical ventilation, n=37). The primary outcome was all-cause 60-day mortality. The secondary outcomes were complications on ECMO, successful weaning from ECMO, and all-cause 180-day mortality. Results: The all-cause 60-day mortality was 37.5% (6/16) in ECMO group and 86.5% (32/37) in non-ECMO group (HR, 0.196; 95% CI, 0.053-0.721; p=0.014). 10 (62.5%) patients were successfully weaned from ECMO. The all-cause 180-day mortality was 56.3% (9/16) in ECMO group and 33 (89.2%, 33/37) in non-ECMO group (HR, 0.298; 95% CI, 0.130-0.680; p=0.004). All the patients in ECMO group suffered from at least one device-related complication with coagulopathy (81.3%) being most frequently seen. Up to 180-day follow up after disease onset, the ECMO-treated survivors maintained good quality of life without severe complications or disabilities. Hypercapnia, thrombopenia, myocardial injury and elevation of IL-8 and IL-10 during ECMO treatment were strongly associated with death.Conclusion: This study showed the COVID-19 patients significantly benefited from ECMO treatment during severe ARDS, which supported the application of ECMO as an indicated strategy in the management of COVID-19 related ARDS.
Joint modeling versus discriminant analysis for dynamic prediction of a binary outcome based on longitudinal data: A simulation study
Authors: Dandis Rana , IntHout Joanna , Roes Kit , Teerenstra Steven
Published: August 2020

Background:In literature, much emphasis has been placed on new statistical methods for dynamic risk prediction using longitudinal biomarker information. However, few studies have compared their performance for predicting a long-term binary outcome. In this paper we perform a simulation study to compare the dynamic predictive performance of two commonly used methods namely: longitudinal discriminant analysis (LoDA) and joint modeling (JM-Bin) for longitudinal and binary data.Methods: Motivated by a real-world dataset, we simulate different scenarios in which we changed the event rate (i.e. the percentage of patients) and the subject-specific variability of the biomarker to assess their influence on the predictive performance of the two approaches. More specifically, we allow the variability to be different between the subjects based on their outcome, i.e., the between- and/or within- subjects variability is larger in patients compared to healthy subjects. Time-dependent predictive measures (mean squared error of prediction, area under ROC curve) are used to evaluate the dynamic predictive performance.Results: Results show that LoDA produces more accurate predictions than JM-Bin in most of the simulation scenarios. In general, increasing the biomarker’s between-subjects variability reduces the predictive accuracy of both approaches to the same extent. The increase in the number of events does not influence the prediction accuracy of both methods. Conclusions: The predictive performance of LoDA is especially better than JM-Bin when the biomarker’s (within- and/or between-subjects) variability is different between the outcome groups.
Safety and Efficacy of adding Dapagliflozin to Furosemide in Type 2 Diabetic Patients with Decompensated Heart Failure and Reduced Ejection Fraction
Authors: Ibrahim Ayman , Ghaleb Ramadan , Mansour Hossam , Hanafy Amr , Mahmoud Naggeh M. , Elsharef M Abdelfatah , Salama Mohamed Kamal , Elsaughier Saud M. , Abdel-Wahid Lobna , Mohamed Mona Embarek , Ibrahim Ahmed Khair , Abdel-Galeel Ahmed
Published: August 2020

Background: Heart failure is the most common cause of hospitalization in elderly patients. It is likely that many of the mechanisms that contribute to reductions in systolic and diastolic function seen in diabetic patients also place them at an increased risk of heart failure. Diuretic therapy, especially loop diuretics, is the usual way of managing congestion, particularly in volume-overloaded patients. Little is known about the beneficial effect of dapagliflozin when added to loop diuretics in managing patients with decompensated heart failure. Aim: To assess the effect of addition of dapagliflozin to furosemide in managing decompensated patient with heart failure and reduced left ventricular ejection fraction. Patients and methods: The study included 100 type 2 diabetic patients who were admitted with decompensated heart failure. The study population was randomly divided into two arms. Serum electrolytes and kidney functions were followed up during hospital stay. Results: With dapagliflozin, there was statistically significant difference between the two groups regarding the change in body weight and body mass index. Also, the diuresis parameters including urine output, total fluid loss, and fluid balance showed statistically significant difference in favor the use of dapagliflozin with no significant change in serum potassium or kidney functions. There was significant improvement in patient-reported dyspnea score with the use of dapagliflozin. Conclusions: Dapagliflozin may provide a new drug option in the treatment of heart failure especially among vulnerable group as diabetics. It has no remarkable effects on serum potassium level and kidney functions.
Correlation Analysis of Oxygen Consumptions Between Stepper and Treadmill Movements and Implication for Rehabilitation
Authors: Mukrikakkada Anwar Hussain , Arnold Graham , Abboud Rami , Wang Weijie
Published: August 2020

Background: Stepper movement is popular as a home-based exercise. However, it has not been fully investigated how much energy is consumed during movement. This study aimed to investigate oxygen consumption for stepper movements at different cadence levels and to look into whether there are correlations between stepper movement and treadmill walking. Methods: Twenty two healthy volunteers (10 males, 12 females, aged between 18 and 40) participated in the study. The participants performed stepper movements and treadmill walking at three different cadences, a self-determined comfortable cadence, a 20% higher and a 20% lower ones than the comfortable one. Their oxygen consumption was measured using Oxycon mobile® system. A set of parameters, e.g. VO2, Metabolic unit, Energy expenditure, etc were obtained. Statistical analysis was carried out to investigate correlations between stepper and treadmill movements in terms of oxygen consumptions. Results: Strong correlations were found between two types of movements, most of metabolic parameters had correlation coefficients ranged proximately between 0.5 to 0.8, p<0.001. In the conformable cadence level, VO2 for stepper movements was 826.49±56.02 (ml/min) while VO2 for treadmill walking was 787.16±56.02. Usually, stepper movements have oxygen consumption similar to or slightly higher than that in treadmill walking.Conclusions: This study indicates that stepper movement has similar oxygen consumption level to treadmill at a comfortable cadence level and at a 20% higher than the comfortable one, but stepper movement consumes more energy than treadmill walking by approximately 10% at lower cadence (i.e. 20% lower than the comfortable one). The study shows that the stepper movements is highly correlated with treadmill walking in terms of oxygen consumption, and thus stepper movement data provided can be used to predict the treadmill data in rehabilitation.
Association Between Platelet Count and Mucosal Healing in Japanese Patients With Ulcerative Colitis: Cross-Sectional Study
Authors: Furukawa Shinya , Yagi Sen , Shiraishi Kana , Mori Kenichirou , Ninomiya Tomoyuki , Kawasaki Keitarou , Mizukami Yuji , Suzuki Seiyuu , Uraoka Masayoshi , Shibata Naozumi , Nakamura Sanae , Imamine Satoshi , Murakami Hidehiro , Ohashi Katsuhisa , Torisu Masamoto , Hasebe Aki , Yano Harumi , Murakami Masato , Takeshita Eiji , Ikeda Yoshio , Hiasa Yoichi
Published: August 2020

Background: Mucosal healing (MH) has been indicated as the therapeutic goal for ulcerative colitis (UC). Platelet count is known as an inflammation evaluation. However, the association between platelet count and MH among patients with UC is still scarce. We therefore assessed this issue among Japanese patients with UC.Methods: The study subjects consisted of 345 Japanese patients with UC. Platelet count was divided into quartiles on the basis of the distribution of all study subjects (low, moderate, high, and very high). Several endoscope specialists were responsible for evaluating MH and partial MH, which was defined as a Mayo endoscopic subscore of 0 and 0-1, respectively. Estimations of crude odds ratios (ORs) and their 95% confidence intervals (CIs) for partial MH and MH in relation to platelet count were performed using logistic regression analysis. Age, sex, CRP, steroid use, and anti-Tumor necrosis factor α (TNFα) preparation were selected a priori as potential confounding factors.Results: The percentage of partial MH and MH were 63.2 and 26.1%, respectively. Moderate and very high was independently inversely associated with partial MH (moderate: OR 0.40 [95%CI: 0.19-0.810], very high: OR 0.37 [95%CI: 0.17-0.77], p for trend= 0.034). Similarly, moderate, high, and very high were independently inversely associated with MH (moderate: OR 0.37 [95% CI: 0.18-0.73], high: OR 0.41 [95% CI: 0.19-0.83], and very high: OR 0.45 [95% CI: 0.21-0.94], p for trend = 0.033) after adjustment for confounding factors.Conclusions: Among patients with UC, platelet count was independently inversely associated with MH.
MiR-496 Inhibits the Proliferation Through Targeting LYN and AKT/mTOR Signaling Pathway in Gastric Cancer
Authors: Su Rui , Zhao Enhong , Zhang Jun
Published: August 2020

MiRNA operates as a tumor suppressor or carcinogen to regulate cell proliferation, metastasis, invasion, differentiation, apoptosis and metabolic process. In the present research, we investigated the effect and mechanism of miR496 in human gastric cancer cells. Cell proliferation was measured by CCK8 and clonogenic assay. Transwell test was performed to detect cell migration and invasion. Flow cytometry analysis was used to evaluate cell apoptosis. Bioinformatics software targetscan was used for the screening of miR-496’s target gene. MiR-496 was down regulated in three gastric cancer cell lines, SGC-790, AGS and MKN45 compared with normal gastric epithelial cell line GES-1. MiR-496 mimics inhibited the proliferation of AGS cells after the transfection for 48 h and 72 h. The migration and invasion of AGS cells were also inhibited by the transfection of miR-496 mimics. In addition, miR-496 mimics induced the apoptosis through up regulating the levels of Bax and Active Caspase3 and down regulating the levels of Bcl-2 and Total Caspase3. Bioinformatics analysis showed that there was a binding site between miR-496 and LYN kinase (LYN). MiR-496 mimics could inhibit the expression of LYN in AGS cells. The overexpression of LYN blocked the inhibition of tumor cell growth, as well as the inhibition of AKT/mTOR signaling pathway induced by miR-496 in gastric cancer cells. In conclusion, miR-496 inhibited the proliferation through the AKT/mTOR signaling pathway via targeting LYN in gastric cancer cells. Our research provides a new potential target for clinical diagnosis and targeted treatment of gastric cancer.
Vaccine Adverse Event Enrichment Tests
Authors: Zhao Lili , Li Shuoran
Published: August 2020

Background: Vaccination safety is critical for individual and public health. Many existing methods have been used to conduct safety studies with the VAERS (Vaccine Adverse Event Reporting System) database. However, these methods frequently identify many adverse event (AE) signals and they are often hard to interpret in a biological context. The AE ontology introduces biologically meaningful structures to the VAERS database by connecting similar AEs, which provides meaningful interpretation for the underlying safety issues. In this paper, we develop rigorous statistical methods to identify interesting AE groups by performing AE enrichment analysis. Results: We extend existing gene enrichment tests to perform AE enrichment analysis. Unlike the continuous gene expression data, AE data are counts. Therefore, AE data has many zeros and ties. We propose two enrichment tests, AEFisher and AEKS. AEFisher is a modified Fisher's exact test based on pre-selected significant AEs, while AEKS is based on a modified Kolmogorov-Smirnov statistic. Both tests incorporate the special features of the AE data. The proposed methods were evaluated using simulation studies and were further illustrated on two studies using VAERS data. Conclusion: By appropriately addressing the issues of ties and excessive zeros in AE count data, our enrichment tests performed well as demonstrated by simulation studies and analyses of VAERS data. The proposed methods were implemented in R package AEenrich and can be installed from the Comprehensive R Archive Network, CRAN, and source code are available at https://github.com/umich-biostatistics/AEenrich.
Decomposition and stabilization of the organic matter in an old-growth tropical riparian forest: effects of soil properties and vegetation structure
Authors: Fernandes Pedro , Souza Andrea Teixeira , Tanaka Marcel , Sebastiani Renata
Published: August 2020

Background: Nutrient cycling in tropical forests has large importance for primary productivity, and decomposition of litterfall is a major process influencing nutrient balance in forest soils. Although large-scale factors strongly influence decomposition patterns, small-scale factors can have major influences, especially in old-growth forests that have high structural complexity and strong plant-soil correlations. Methods: We evaluated decomposition rates and stabilization of soil organic matter using the Tea Bag Index in an old-growth riparian forest in southeastern Brazil. We buried 50 pairs of green and red tea at two distances from the watercourse to evaluate the effects of forest structure and soil properties on decomposition processes. Forest structure and soil properties were described using Principal Components Analysis (PCA). The main axes for each analysis were considered predictors of decomposition processes using a structural equations model.Results: Decomposition rates presented a large variation among tea bags and were positively correlated with forest structure, as characterized by higher basal area, larger trees, and tree density. Higher decomposition rates were probably correlated with higher litter production and microbial activity. On the other hand, stabilization factor was related mainly to soil chemical properties, with higher values with increased soil fertility as indicated by the PCA axes. Further analyses evaluated the effects of clay content, soil moisture, soil organic matter, soil base saturation, and soil fertility as predictors of the stabilization factor. These predictors were highly correlated, but clay content was the best predictor, explaining 79% of the variation among plots. Conclusions: These results showed that this old-growth forest presented high heterogeneity in both forest structure and soil properties at small spatial scales, that influenced decomposition processes and contributed to small-scale variation in nutrient cycling. Heterogeneity in ecological processes can contribute to the resilience of old-growth forests, strengthening ecosystem functions such as nutrient cycling and carbon fixation, and highlighting the importance of restoration strategies focused in the recovery of ecosystem processes
Clinical Outcomes and Adverse Events of the Stomach Endoscopic Submucosal Dissection of the Mid to Upper Stomach Under General Anesthesia and Monitored Anesthetic Care
Authors: Chang Jong-In , Kim Tae Jun , Hwang Na Young , Sohn Insuk , Min Yang Won , Lee Hyuk , Min Byung-Hoon , Lee Jun Haeng , Rhee Poong-Lyul , KIM JAE
Published: August 2020

Background: Endoscopic submucosal dissection (ESD) of gastric tumors in the mid to upper stomach is a technically challenging procedure. This study compared the therapeutic outcomes and adverse events following ESD of tumors in this area, performed in conjunction with either general anesthesia (GA) or monitored anesthetic care (MAC).Methods: Between 2012 and 2018, 674 patients underwent ESD of gastric tumors in the midbody, high body, fundus, or cardia (100 patients received GA; 574 received MAC). The results were analyzed using propensity score (PS)-matched (1:1) patients receiving either GA or MAC.Results: PS matching identified 95 patients who received GA and 95 matched patients who received MAC. Both groups showed high rates of en-bloc resection (GA, 98.5%; MAC, 98.9%; p = 0.18) and complete resection, defined as tumors excised with histologically confirmed negative margins (GA, 82.1%; MAC, 90.5%; p = 0.14). There were no significant differences in the frequencies of adverse events (GA, 16.8%; MAC, 9.5%; p = 0.13) between the anesthetic groups. A logistic regression analysis indicated that the anesthetic method was not a factor impacting the frequencies of complete resection or adverse events. Conclusion: At our high-volume center, good therapeutic outcomes were achieved following ESD of tumors in the mid to upper stomach, regardless of the anesthetic method used. Our results demonstrate the efficacy and safety non-inferiority of the ESD procedure performed in conjunction with MAC, compared with GA.
Statistical methods for the analysis of adverse event data in randomised controlled trials: a comprehensive review and taxonomy
Authors: Phillips Rachel , Sauzet Odile , Cornelius Victoria
Published: August 2020

Background Statistical methods for the analysis of harm outcomes in randomised controlled trials (RCTs) are rarely used, and there is a reliance on simple approaches to display information such as in frequency tables. We aimed to identify whether any statistical methods had been specifically developed to analyse prespecified secondary harm outcomes and non-specific emerging adverse events (AEs). Methods A scoping review was undertaken to identify articles that proposed original methods or the original application of existing methods for the analysis of AEs that aimed to detect potential adverse drug reactions (ADRs) in phase II-IV parallel controlled group trials. Methods where harm outcomes were the (co)-primary outcome were excluded. Information was extracted on methodological characteristics such as: whether the method required the event to be prespecified or could be used to screen emerging events; and whether it was applied to individual events or aggregate events. Each statistical method was appraised and a taxonomy was developed for classification.Results Forty-four eligible articles proposing 73 individual methods were included. A taxonomy was developed and articles were categorised as: visual summary methods (8 articles proposing 20 methods); hypothesis testing methods (11 articles proposing 16 methods); estimation methods (15 articles proposing 24 methods); or methods that provide decision-making probabilities (10 articles proposing 13 methods). Methods were further classified according to whether they required a prespecified event (9 articles proposing 12 methods), or could be applied to emerging events (35 articles proposing 61 methods); and if they were (group) sequential methods (10 articles proposing 12 methods) or methods to perform final/one analyses (34 articles proposing 61 methods). Conclusions This review highlighted that a broad range of methods exist for AE analysis. Immediate implementation of some of these could lead to improved inference for AE data in RCTs. For example, a well-designed graphic can be an effective means to communicate complex AE data and methods appropriate for counts, time-to-event data and that avoid dichotomising continuous outcomes can improve efficiencies in analysis. Previous research has shown that adoption of such methods in the scientific press is limited and that strategies to support change are needed.
Daily, Oral FMT for Long-Term Maintenance Therapy in Ulcerative Colitis: Results of a Single-Center, Prospective, Randomized Pilot Study.
Authors: Crothers Jessica Wood , Chu Nathaniel D. , Nguyen Le Thanh Tu , Phillips Magen , Collins Cheryl , Fortner Karen , Rio-Geurra Roxana del , Lavoie Brigitte , Callas Peter , Velez Mario , Cohn Aaron , Elliott Ryan J. , Wong Wing Fei , Vo Elaine , Wilcox Rebecca , Smith Mark , Kassam Zain , Budd Ralph , Alm Eric J. , Mawe Gary M. , Moses Peter L
Published: August 2020

This randomized study was designed to assess the safety and feasibility of long-term fecal microbiota transplantation (FMT) in subjects with mild to moderate UC using frozen, encapsulated oral FMT (cFMT). FMT induction was implemented by colonoscopy, followed by 12 weeks of daily oral administration of frozen encapsulated cFMT. Ribosomal 16S bacterial sequencing was used to assess donor-induced changes in the gut microbiota. Changes in T regulatory (Treg) and mucosal associated invariant T (MAIT) cell populations were evaluated as an exploratory endpoint. Twelve subjects with active UC were randomized: 6 subjects completed the full 12-week course of FMT plus cFMT, and 6 subjects received sham treatment by colonic installation and longitudinal oral treatment. Chronic administration of cFMT was found to be safe and well-tolerated. Protocol adherence was high, and none of the study subjects experienced FMT-associated treatment emergent adverse events. While n-values were too small to draw firm conclusions, 3/6 subjects that received cFMT exhibited multiple signs of clinical improvement. These pilot data suggest that daily encapsulated cFMT may extend the durability of index FMT-induced changes in gut bacterial community structure and that an association between MAIT cell cytokine production and clinical response to FMT may exist in UC populations. Oral frozen encapsulated cFMT is a promising FMT delivery system and may be preferred for longterm treatment strategies in UC and other chronic diseases but further evaluations will have to address home storage concerns. Larger trials should be done to explore the benefits of cFMT and to determine its long-term impacts on the colonic microbiome. Trial registration: ClinicalTrials.gov (NCT02390726). Registered 17 March 2015, https://clinicaltrials.gov/ct2/show/NCT02390726?term=NCT02390726&draw=2&rank=1.