bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a gene signature closely related to immunosuppressive tumor microenvironment predicting prognosis of patients in EGFR mutant lung adenocarcinoma
Authors: Li Jia , Li Huahua , Zhang Chenyue , Zhang Chenxing , Wang Haiyong 
Published: August 2020

Abstract
Background: Lung adenocarcinomas (LUAD) harboring epidermal growth factor receptor (EGFR) mutations generally are unable to benefit from immune checkpoint inhibitors (ICIs), due to an immunosuppressive tumor microenvironment (TME) and a lower tumor mutation burden (TMB). Currently, there has been no gene signature that can comprehensively evaluate the TME and predict the prognosis of EGFR mutant LUAD patients. Methods: Using the cancer genome atlas (TCGA) database of EGFR mutant LUAD based on the immune score derived from the ESTIMATE algorithm, we screened the differential immune-related genes with prognostic value and compared the TMB profiles. Gene ontology (GO) and Kyoto encyclopedia of gene and genomic (KEGG) enrichment analysis were used to analyze the potential functions. The least absolute shrinkage and selectionator operator (LASSO) cox regression model was applied to identify a gene signature and constructed risk model. Kaplan-Meier survival and receiver operating characteristic (ROC) analysis were used to evaluate the prognostic value of the gene signature. CIBERSORT was used to evaluate the abundance of immune cells infiltration.Results: We screened 396 the differential immune-related genes based on immune score, whose potential functions were significantly related to T cell differentiation, immune response, cell cycle and cell proliferation. The disparities of TMB profile could be found between the high and low immune score group. Then, we identified a three-gene signature, including B and T lymphocyte attenuator (BTLA), BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) and centromere protein E (CENPE). The three-gene signature could well identify at-risk patients of EGFR-mutant LUAD patients in the training and validating set, and the high-risk patients were related to shorter overall survival (OS) (p=0.0053 and p=0.035). The immune activity of B cells and macrophages were higher in the low-risk group, in contrast the immune activity of Natural Killer (NK) cells and T cells were higher in the high-risk group. Conclusions: The three-gene signature closely related to immunosuppressive TME could predict risk prognosis of patients in EGFR mutant LUAD.
Fine and dynamic tuning the glycolytic flux ratio of an artificial carbon saving pathway for high yield of mevalonate in Escherichia coli
Authors: Li Ying , Xian He , Xu Ya , Zhu Yuan , Sun Zhijie , Wang Qian , Qi Qingsheng 
Published: August 2020

Abstract
Background In natural Escherichia coli, glucose is mainly metabolized via the Embden-Meyerhoff-Parnas (EMP) pathway. However, in the metabolic process of conversion of pyruvate to acetyl-CoA, one-third of the carbon is lost at CO2. To decrease the loss of glucose in the metabolic process and enhance the carbon conversion efficiency production of desired products by E. coli, we constructed a carbon saving pathway, EP-bifido pathway. As the balance of energy and reducing power was not optimal, we use synthetic biology methods to precisely and dynamically adjust the EMP pathway and pentose phosphate pathway (PPP) flux to improve the production of mevalonate (MVA) via the EP-bifido pathway. ResultHere, we enhanced the MVA titer and yield in E. coli in two ways. First, the promoter of the first gene of the PPP, zwf, was replaced with a set of promoters of different strength to enhance PPP flux for NADPH supply. Compared with the previous EP-bifido strains, the zwf-modified strains showed obvious differences in NADPH, NADH, and ATP synthesis levels and production routes. Among them, strain BP10BF accumulated 11.2 g/L of MVA after 72 h of fermentation and the molar conversion rate from glucose reached 62.2%. Second, the expression of pfkA was suppressed at a certain time by the clustered regularly interspaced short palindromic repeats interference (CRISPRi) system to avoid the growth defect caused by pfkA direct knock-out. The resulting MVA yield of strain BiB1F was 8.53 g/L, and the conversion rate from glucose reached 68.7%. ConclusionThis is the highest MVA conversion rate reported in shaken flask fermentation. The CRISPRi and promoter fine-tuning provided an effective strategy for metabolic flux redistribution in many metabolic pathways and promotes the chemicals production.
How a cardiovascular patient education system can be improved: Introducing a novel model for identifying hospital educational challenges and solutions
Authors: Saboktakin Atiyeh , Sepehri Mohammad Mehdi , Khasha Roghaye 
Published: August 2020

Abstract
Background: Cardiovascular diseases (CVDs) have always been considered by healthcare specialists for different reasons, including extensive prevalence, high cost, chronicity, and high risk of death. the recovery from CVDs is highly influenced by the behavior and lifestyle. As a result, it seems necessary to train and develop special abilities for patients and their companions, the development of efficient and effective training systems should be considered by healthcare specialists. Methods: Hence, in this study, an existing training system for cardiovascular patients is reviewed, and using field observation and targeted interviews with hospital experts, all aspects of its training process, including involved components, inputs, outputs, processes and interactions are extracted. Then the process maps of the training system are drawn up through the BPMN (Business Process Model and Notation) methodology. Next, its challenges and difficulties are identified with the aid of semi-structured interviews with experts, and due to the importance and different influence of the identified problems, these challenges are prioritized using the Multi Criteria Decision Making method (MCDM). Results: The most important identified challenges included high nursing workload and shortage of time, lack of understanding of training concepts by patients, lack of attention to training, disruption of training process by the patients’ companions, and patient's weakness in understanding the standard language. In identifying the root causes, learner, educator, and educational tools are the most effective in the training process; therefore, the improvement scenarios were designed accordingly. Conclusions: In the present study, a novel framework for cardiovascular patients' education has been designed and presented based on the analysis of the results of ranking the challenges and their root causes.
Enhancement of L-amino Acid Oxidase Production by Bacillus Subtilis H-8 With Oxygen-vector and Asymmetric Degradation of DL Arginine to D-arginine
Authors: xu peng , Pan Changpei , Cui Gongcheng , Wei ChunYan , Wang Lijuan , Li Yanting , Li Xiangping , Huang Shihai 
Published: August 2020

Abstract
The Bacillus subtilis H-8 independently screened by our laboratory can produce L-amino acid oxidase (L-AAO), and DL-arginine can be degraded asymmetrically by suspending the wet bacteria in the degradation liquid. By adding oxygen-vectors to the fermentation medium, the collected amount of wet bacteria can be increased. Taking n-dodecane, n-hexadecane, oleic acid, paraffin, and n-hexane as oxygen-vectors, the optimal oxygen-vector oleic acid was 1.2% (v/v). The weight of wet cells increased by 66.83% compared with before, and the activity of L-AAO in fermentation broth increased by 38.88% compared with before. The standard sample DL-arginine was derivatized by phenyl isothiocyanate, and then subjected to high performance liquid chromatography(HPLC), and the obtained peak area and arginine content were used as standard curves to measure the DL-arginine. The content of D-arginine and L-arginine in the initial degradation solution was 50% each, and the bacterial cells are added to the initial degradation solution of DL-arginine. After 21 hours of reaction, L-arginine was completely Degraded, remaining 47% of D-arginine.D-alanine was easily extracted from the reaction solution using cation-exchange resin,after centrifugation, decolorization, concentration and vacuum drying, and the chemical and optical purity of the extracted d-alanine was 92.68 and 97.46%, respectively.
Impact of Spinal Muscular Atrophy on Caregivers’ Daily Activities and Health-Related Quality of Life
Authors: Chen Er , Bawa Komal , Noone Josh , Whitmire Sarah , Buchenberger Daniel , Arnold William David , Mills Rosalina , Dixon Stacy 
Published: August 2020

Abstract
Background:Spinal muscular atrophy (SMA) is a genetic debilitating disease affecting approximately 10,000 individuals in the United States. Individuals with SMA frequently require caregiver support and care. Through a partnership with Cure SMA, we surveyed caregivers of individuals with SMA <18 years of age to understand the impact of SMA on caregivers with respect to their daily activities and health-related quality of life (HRQoL). In addition to structured questions, a standardized HRQoL instrument, the EQ-5D-5L and visual analogue scale, were administered.Results:The sample consisted of 45 unpaid caregivers of children with SMA. Of them, 22% reported that they were sole caregivers that received no additional caregiving support and 98% were parents of an affected individual. The majority of caregivers cared for individuals with type 2 (58%), followed by type 1 (38%) and type 3 (4%) SMA. Sixty-four percent of the individuals with SMA were able to sit without support or better, while 31% had some motor function and 5% reported no motor function. Across SMA types, caregivers reported spending a median 80 hours per month managing the overall care and treatment of the affected individual.. Most of the individuals (91%) were reported to have received nusinersen. Caregiver time investment correlated directly with disease severity measured by both SMA type and patient motor function level. The mean EQ-5D utility score for caregivers was 0.71 and their mean score on the EQ-5D visual analogue scale was 76. Specifically, 42% of caregivers reported any inability to do their usual activities and 73% reported any anxiety or depression.Conclusions:SMA negatively affects caregiver’s daily activities and HRQoL, representing a substantial burden. Disease severity is associated with an increasing amount of time required for care and support for patients with SMA and a decrease in a caregiver’s HRQoL. As treatments become available, evaluation of these treatments should include effects on the family as well.
Seasonal Variation of Nutritional Status and Oxidative Stress in Haemodialysis Patients - Are They Related?
Authors: Begovic Tanja Ilic , Radic Josipa , Radic Mislav , Modun Darko , Seselja-Perisin Ana , Tandara Leida 
Published: August 2020

Abstract
BackgroundSeasonal variations in body composition and parameters that reflect nutritional status are well established in haemodialysis (HD) patients. However, no study has assessed changes in oxidative stress (OS). The objectives of our study were to assess seasonal variations in OS, body composition and other nutritional parameters, as well as their interactions. MethodsSeasonal variations in fat tissue mass (FTM), fat tissue index (FTI), adipose tissue mass (ATM), lean tissue mass (LTM), lean tissue index, body cell mass (BCM and overhydration (OH), OS (the blood levels of derivatives of reactive oxygen metabolites (d-ROMs), thiobarbituric reactive substances (TBARS), plasma protein reduced thiol content (THIOLS) and ferric reducing ability of plasma (FRAP) were measured) and other nutritional parameters were assessed in 45 HD patients aged 70 (60.5-76.5) years. ResultsSignificantly increase in FTM (P=<0.001), FTI (P=<0.001) and ATM (P=<0.001) and significantly decrease in LTI (P=<0.001), LTM (P=<0.001), BCM (P=<0.001) and OH (P=0.004) over season was found. Also, significantly seasonal variations in d-ROMs (P=0.02) and THIOLS (P=0.02) were found. Statistically significant predictor of LTM and BCM was d-ROM (β =-0.57 (95% CI -1.08 to -0.06); P=0.03; β =-0.04 (95% CI -0.075 to -0.006); P=0.02). Furthermore, statistically most significant predictor of d-ROM was hip circumference (β =2.66 (95% CI 0.28 to 5.04); P=0.03), while for THIOLS it was WHtR (β=251(95% CI 16.6 to 477.2); P=0.03) and serum prealbumin level (β=263 (95% CI 6.8 to 521.1); P=0.04). ConclusionsThese results suggest seasonal variations of OS in HD patients and possible interaction between OS and nutritional status in HD patients.
Identification of a novel small nucleolar RNAs prognostic signature for patients with acute myelocytic leukemia
Authors: Huang Rui , Liao Xiwen , Li Qiaochuan 
Published: August 2020

Abstract
Background: This study mainly used The Cancer Genome Atlas (TCGA) RNA sequencing dataset to screen prognostic snoRNAs of acute myeloid leukemia (AML), and used for the construction of prognostic snoRNAs signature for AML. Methods: A total of 130 AML patients with RNA sequencing dataset were used for prognostic snoRNAs screenning. SnoRNAs co-expressed genes and differentially expressed genes (DEGs) were used for functional annotation, as well as gene set enrichment analysis (GSEA). Connectivity Map (CMap) also used for potential targeted drugs screening. Results:Through genome-wide screening, we identified 30 snoRNAs that were significantly associated with the prognosis of AML. Then we used the step function to screen a prognostic signature composed of 14 snoRNAs (SNORD72, SNORD38, U3, SNORA73B, SNORD79, SNORA73, SNORD12B, SNORA74, SNORD116-12, SNORA65, SNORA14, snoU13, SNORA75, SNORA31), which can significantly divide AML patients into high- and low-risk groups. Through GSEA, snoRNAs co-expressed genes and DEGs functional enrichment analysis, we screened a large number of potential functional mechanisms of this prognostic signature in AML, such as phosphatidylinositol 3-kinase-Akt ,Wnt, epithelial to mesenchymal transition, T cell receptors, NF-kappa B, mTOR and other classic cancer-related signaling pathways. In the subsequent targeted drug screening using CMap, we also identified six drugs that can be used for AML targeted therapy, they were alimemazine, MG-262, fluoxetine, quipazine, naltrexone and oxybenzone. Conclusion: Our current study was constructed an AML prognostic signature based on the 14 prognostic snoRNAs, which may serve as a novel prognostic biomarker for AML.
Non-invasive intra-uterine administration of Botulinum Toxin A enhances endometrial angiogenesis and improves the rates of embryo implantation
Authors: Koo Hwa Seon , Yoon Min-Ji , Hong Seon-Hwa , Ahn Jungho , Cha Hwijae , Lee Danbi , Park Chan Woo , Kang Youn-Jung 
Published: August 2020

Abstract
Background. Endometrial angiogenesis plays crucial roles in determining the endometrial receptivity. Defects in endometrial receptivity often cause repeated implantation failure, which is one of the major unmet needs for infertility and contributes a major barrier to the assisted reproductive technology. Despite the numerous extensive research work, there are currently no effective evidence-based treatments to prevent or cure this condition.Method. As a non-invasive treatment strategy, Botulinum toxin A (BoTA) was administered into one side of mouse uterine horns and saline was infused into the other side of horns for the control. Impact of BoTA was assessed in the endometrium at 3 or 8 days after infusion.Results. We demonstrated that BoTA administration enhances the capacity of endothelial cell tube formation and sprouting. The intrauterine BoTA administration significantly induced endometrial angiogenesis displaying increased numbers of vessel formation and expression levels of related-marker genes. Moreover, BoTA intrauterine application promoted the endometrial receptivity and the rates of embryo implantation were improved with BoTA treatment with no morphologically retarded embryos. Conclusion. Intrauterine BoTA treatment has a beneficial effect on vascular reconstruction of functional endometrium prior to embryo implantation by increasing endometrial blood flow near the uterine cavity suggesting BoTA treatment as a potential therapeutic strategy for patients who are suffering from repeated implantation failure with the problems with endometrial receptivity.
Under Fire –simultaneous Volatilome and Transcriptome Analysis Unravels Fine-scale Responses of Tansy Chemotypes to Dual Herbivore Attack
Authors: Clancy Mary V. , Haberer Georg , Jud Werner , Niederbacher Bishu , Niederbacher Simon , Senft Matthias , Zytynska Sharon , Weisser Wolfgang W. , Schnitzler Jörg-Peter 
Published: August 2020

Abstract
Background Tansy plants (Tanacetum vulgare L.) are known for their high intraspecific chemical variation, especially of volatile organic compounds (VOC) from the terpenoid group of substances. These VOCs are closely involved in plant-insect interactions and, when profiled, can be used to classify plants into groups known as chemotypes. Tansy chemotypes have been shown to influence plant-aphid interactions, however, to date no information is available on the response of different tansy chemotypes to simultaneous herbivory by more than one insect species. Results Using a multi-cuvette system, we investigated the responses of five tansy chemotypes to feeding by sucking and/or chewing herbivores (aphids and caterpillars; Metopeurum fuscoviride Stroyan and Spodoptera littoralis Boisduval). We did not observe any strong changes in plant VOC emissions when exposed to sucking aphids, while polyphagous caterpillars strongly increased VOC emissions for each plant chemotype. Herbivory by caterpillars following aphid infestation led to a plant chemotype-specific change in the patterns of terpenoids stored in trichome hairs and in VOC emissions. The transcriptomic analysis of a plant chemotype represents the first de novo assembly of a transcriptome in tansy and demonstrates priming effects of aphids on a subsequent herbivory. Overall, we show that the five chemotypes do not react in the same way to the two herbivores. As expected, we found that caterpillar feeding increased VOC emissions. However, the previous aphid infestation only led to a further increase in VOC emissions for some chemotypes. Conclusions We were able to show that different chemotypes respond to the double herbivore attack in different ways, and that pre-treatment with aphids had a priming effect on plants when they were subsequently exposed to a chewing herbivore. Our results will be important for the study of chemical communication of plants in nature. If neighbouring chemotypes in a field population react differently to herbivory/dual herbivory, this could possibly have effects from the individual level to the group level. Individuals of some chemotypes may respond more efficiently to herbivory stress than others, and in a group environment these "louder" chemotypes may affect the local insect community, including the natural enemies of herbivores, and other neighbouring plants.
Short-Term Physical Exercise Impacts On The Human Holobiont Obtained By A Randomised Intervention Study
Authors: Moitinho-Silva Lucas , Wegener Michelle , May Sandra , Schrinner Florian , Akhtar Awais , Boysen Teide Jens , Schaeffer Eva , Hansen Clint , Schmidt Timo , Ruehlemann Malte Christoph , Huebenthal Matthias , Rausch Philipp , Kondakci Mustafa T , Maetzler Walter , Weidinger Stephan , Laudes Matthias , Suess Philip , Schulte Dominik , Junker Ralf , Sommer Felix , Weisser Burkhard , Bang Corinna , Franke Andre 
Published: August 2020

Abstract
Background: Human well-being has been linked to the composition and functional capacity of the intestinal microbiota. As regular exercise is known to improve human health, it is not surprising that exercise was previously described to positively modulate the gut microbiota, too. However, most previous studies mainly focused on either elite athletes or animal models. Thus, we conducted a randomised intervention study that focused on the effects of different types of training (endurance and strength) in previously physically inactive, healthy adults in comparison to controls that did not perform regular exercise. Overall study duration was ten weeks including six weeks of intervention period. In addition to 16S rRNA gene amplicon sequencing of longitudinally sampled faecal material of participants (six time points), detailed body composition measurements and analysis of blood samples (at baseline and after the intervention) were performed to obtain overall physiological changes within the intervention period. Activity tracker devices (wrist-band wearables) provided activity status and sleeping patterns of participants as well as exercise intensity and heart measurements.Results: Different biometric responses between endurance and strength activities were identified, such as a significant increase of lymphocytes and decrease of mean corpuscular haemoglobin concentration (MCHC) only within the strength intervention group. In the endurance group, we observed a significant reduction in hip circumference and an increase in physical working capacity (PWC). Though a large variation of microbiota changes were observed between individuals of the same group, we did not find specific collective alterations in the endurance nor the strength groups, arguing for microbiome variations specific to individuals, and therefore, were not captured in our analysis. Conclusion: We could show that different types of exercise have distinct but moderate effects on the overall physiology of humans and very distinct microbial changes in the gut. The observed overall changes during the intervention highlight the importance of physical activity on well-being. Future studies should investigate the effect of exercise on a longer timescale, investigate different training intensities and consider high-resolution shotgun metagenomics technology.Trial registration: DRKS, DRKS00015873. Registered 12 December 2018; Retrospectively registered. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00015873
Evaluating The Performance Of Malaysian Health Care Providers With Partial Least Squares Path Modeling
Authors: Salleh Mohd Idzwan Mohd , Abdullah Rosni , Zakaria Nasriah 
Published: August 2020

Abstract
Background: The Ministry of Health Malaysia invested significant resources to implement an electronic health record (EHR) system to ensure the full automation of hospitals for coordinated care delivery. Thus, evaluating whether the system has been utilized effectively is necessary, particularly on how it predicts the work performance of the health care providers. Methods: Convenience sampling was employed for data collection in three government hospitals for seven months. A standardized effectiveness survey for EHR systems was administered to health care providers (specialists, medical officers, and nurses) as they participated in medical education programs. Power analysis was conducted before and after the study to ensure adequate sample sizes and sufficient power. The empirical data was assessed by employing partial least squares-structural equation modeling for hypotheses testing. Results: As a results, knowledge quality had the highest score in predicting performance and had a large effect size, whereas system compatibility became the strongest component of system quality. The findings indicated that EHR systems supported the clinical tasks and workflows of care providers, which increased system quality, whereas increased quality of knowledge improved user performance. Conclusion: Therefore, knowledge quality and effective use should be incorporated into the evaluation study of EHR system effectiveness in health institutions. Data mining feature can be integrated into current systems for generating health populations and disease trend analysis easily and systematically, therefore improving clinical knowledge of care providers and effective use to maintain their productivity. The validated survey instrument can be further tested with empirical surveys in other public and private hospitals with different interoperable EHR systems.