bluuebunny/crossref_metadata_2025_split huggingface dataset:
Progressive Genetic Modifications with Growth Hormone Receptor Knockout Extends Cardiac Xenograft Survival to 9 Months
Authors: Mohiuddin Muhammad , Goerlich Corbin , Singh Avneesh , Zhang Tianshu , Tatarov Ivan , Lewis Billeta , Sentz Faith , Hershfeld Alena , Braileanu Gheorghe , Odonkor Patrick , Strauss Erik , Williams Brittney , Burke Allen , Hittman Jamie , Bhutta Adnan , Tabatabai Ali , Gupta Anuj , Vaught Todd , Sorrells Lorri , Kuravi Kasinath , Dandro Amy , Eyestone Will , Kaczorowski David , Ayares David , Griffith Bartley 
Published: April 2021

Abstract
We report orthotopic (life-supporting) survival of genetically engineered porcine cardiac xenografts (with 3-9 progressive gene modifications) for almost 9 months in baboon recipients. This work builds on our previously reported heterotopic cardiac xenograft (3 gene modifications) survival up to 945 days with an anti-CD40 monoclonal antibody-based immunosuppression. In this current study, life-supporting xenografts containing multiple human complement regulatory, thromboregulatory, and anti-inflammatory proteins, in addition to growth hormone receptor knockout (KO) and carbohydrate antigen KOs, were transplanted. Selective "multi-gene" xenografts demonstrate survival greater than 8 months without the use of adjunctive medications and without evidence of abnormal xenograft thickness or rejection. These data demonstrate that selective “multi-gene" modifications improve cardiac xenograft survival significantly and may be foundational for paving the way to bridge transplantation in humans.
Ethical, Legal and Social Implications of Symptom Checker Applications in Primary Health Care (CHECK.APP): Study Protocol of an Interdisciplinary Mixed-Methods Study
Authors: Koch Roland , Wetzel Anna-Jasmin , Preiser Christine , Müller Regina , Klemmt Malte , Ranisch Robert , Ehni Hans-Jörg , Wiesing Urban , Rieger Monika A. , Henking Tanja , Joos Stefanie 
Published: April 2021

Abstract
Background: Symptom checker applications (SCA) are accessible tools that provide early symptom assessment for users. Ethical, legal, and social implications of SCA, their impact on the patient-physician relationship, the health care providers and the health care system have sparsely been examined. This study protocol describes an approach to investigate possible impacts and implications of SCA on different levels of health care provision. It considers the perspectives of users, non-users, general practitioners and (international) health care experts. We aim to assess a comprehensive overview of the use of SCA and reveal problematic issues.Methods: The primary outcomes of this study are empirically informed, multi-perspective recommendations for different stakeholders on ethical, legal, and social implications of SCA. Quantitative and qualitative methods will be used in several consecutive and interconnected parts: Study part 1 comprises a survey that will be analyzed with a logistic regression. It aims to assess the user degree of SCA in Germany as well as predictors for SCA usage. Study part 2 will comprise self-observational diary and user-interviews, which will be analyzed as integrated cases to assess the user perspectives, usage pattern and arising problems. Study part 3 will comprise GP interviews to assess their experiences, perspectives, self-image, and concepts and will be analyzed with the basic procedure by Kruse. Moreover, interviews with health care experts will be conducted in study part 3 and will be analyzed by using the reflexive thematical analysis by Braun and Clark. Discussion: Possible ethical, social and legal implications of a widespread use of SCA affect stakeholders and stakeholder groups on different levels of health care. The proposed methodological approach provides a multi-faceted and diverse empirical basis for a broad discussion on these implications.Trial registration: The study is registered in the German Clinical Trials Register (DRKS) with the ID: DRKS00022465 since the 7th of August 2020.
Influences of Suvorexant and Mirtazapine on Chronic Pain-related Sleep Disorder in Neuropathic Pain Model Mice&nbsp;
Authors: Ito Hisakatsu , Tusneki Hiroshi , Sasaoka Toshiyasu , Toyooka Naoki , Yamazaki Mitsuaki 
Published: April 2021

Abstract
Chronic pain and sleep disorders are independently associated with a reduction in the quality of life. They can be both a cause and consequence of each other; therefore, they should be treated simultaneously. However, optimal treatments for chronic pain-related sleep disorders are not well established. Here, we aimed to investigate the effects of suvorexant, a novel sleep drug, and mirtazapine, a noradrenergic and specific serotonergic antidepressant, on pain-related sleep disorders in a preclinical neuropathic pain mouse model, which was produced by partial sciatic nerve ligation. We calculated the quantity, duration, and depth of sleep by analyzing the electroencephalogram. Voluntary activity was also evaluated by counting the number of wheel rotations with special cages. Daily administration of suvorexant and mirtazapine normalized the reduced rapid eye movement (REM) and non-REM sleep and improved the fragmented sleep, further regaining the depth of sleep at sleep onset in the chronic pain state. Suvorexant decreased voluntary activity, which was prolonged after the end of administration; however, mirtazapine did not decrease it. Both suvorexant and mirtazapine could be potential therapeutic agents for chronic pain-related sleep disorders.
Maximum Resection and Immunotherapy Improve Glioblastoma Patient Survival: A Single-institution Prognostic Analysis&nbsp;
Authors: Ishikawa Eiichi , Sugii Narushi , Matsuda Masahide , Kohzuki Hidehiro , Tsurubuchi Takao , Akutsu Hiroyoshi , Takano Shingo , Matsumura Akira 
Published: April 2021

Abstract
Purpose. Glioblastoma (GBM) is a refractory disease with a poor prognosis and various methods, including maximum resection and immunotherapy, have been tested to improve outcomes. This retrospective study analyzed the prognostic factors of initially diagnosed glioblastoma patients at our institution to analyze the effect of these methods on prognosis. Methods. Two hundred seventy-seven patients with initially diagnosed glioblastoma who were treated in our institution from 2009 to 2020. Various data, including extent of removal (EOR) and type of adjuvant therapy, were examined and prognostic relationships were analyzed. Results. The median OS of the entire 277-case cohort, 200 non-biopsy cases, and 77 biopsy cases were 16.6 months, 19.7 months, and 9.7 months, respectively. Gross total removal (GTR; 100% of EOR) was achieved in 32.9% of the cases. Univariate analysis revealed younger age, right side, higher Karnofsky performance status, GTR, intraoperative MRI use for removal, proton therapy, combination immunotherapy, and discharge to home as good prognostic factors. Intraoperative MRI use and EOR were closely related. In the multivariate analysis, GTR, proton therapy, and combination of immunotherapies including autologous formalin-fixed tumor vaccine were the significant prognostic factors. A multivariate analysis of 91 GTR cases showed that immunotherapy contributed to prognostic improvements. The median OS and 5-year OS% values were 36.9 months and 43.3% in GTR cases receiving immunotherapy. Conclusion. GTR, proton therapy, and immunotherapy were good prognostic factors in single-center GBM cases. Tumor vaccine therapy for GTR cases achieved a notably high median survival time and long-term survival ratio, indicating its usefulness in GTR cases.
CHAF1A–PCNA interaction promotes cervical cancer progression via the PI3K/AKT/FoxO1 signaling pathway
Authors: Wen Li , Luo Yuli , Duan Zhaoning , Li Xiaoge , Jia Ying 
Published: April 2021

Abstract
Background

An increasing number of studies demonstrate that histone chaperones play critical roles in tumorigenesis and development. In previous research, we confirmed that CHAF1A was highly expressed in cervical cancer (CC) and was correlated with poor prognosis. However, the biological function and specific mechanism of CHAF1A in the development of CC have not been reported.
Methods

CHAF1A knockdown in SiHa and HeLa.cells by lentivirus vector is verified by RT-PCR and Western blot analysis.CCK-8, flow cytometry assays, colony formation, cell migration assay and real-time cell analysis assay were performed to determine the cellular function of CHAF1A in CC.Tumor xenograft assay was conducted on nude mice to assess the effect of CHAF1A in vivo. Cell immunofluorescence and co-immunoprecipitation were applied to examine the interaction between CHAF1A and PCNA.
Results

We found that CHAF1A knockdown in SiHa and HeLa cell lines inhibited proliferation and promotedits apoptosis. Further research indicated that CHAF1A promoted proliferation and inhibited apoptosis in CC by activating the PI3K/Akt/FoxO1 signaling pathway. Moreover, CHAF1A directly interacts with PCNA and co-promotes CC progression.
Conclusions

The discovery of the mechanism of action of CHAF1A in CC may provide a new direction for the treatment of CC.
Risk factors of synchronous peritoneal metastases in colorectal cancer: a meta-analysis
Authors: Zhang Yuanxin , Qin Xiusen , Wang Huaiming , Wu Zhijie , Liu Duo , Du Yang , Wang Hui 
Published: April 2021

Abstract
Background: Early detection of synchronous colorectal peritoneal metastasis (CPM) is difficult due to the absence of typical symptoms and the low accuracy of imaging examinations. Better knowledge of risk factors for synchronous CPM may be essential for early diagnosis and strengthening management. This study aimed to clarify the risk factors. Methods: This meta-analysis was based on PRISMA guidelines. A systematic search of PubMed, Embase and Cochrane Library databases was performed. The pooled data was assessed by a random-effects model. Results: 25 studies containing 171932 patients were included. Synchronous CPM was associated positively with female (OR 1.299; 1.118 to 1.509; P = 0.001), T4 (OR 12.331; 7.734 to 19.660; P < 0.001), N1-2 (OR 5.665; 3.628 to 8.848; P < 0.001), poorly differentiated grade (OR 2.560; 1.537 to 4.265; P < 0.001), right-sided colon cancer (OR 2.468; 2.050 to 2.970; P < 0.001), mucinous adenocarcinoma (OR 3.565; 2.095 to 6.064; P < 0.001), signet-ring cell carcinoma (OR 4.480; 1.836 to 10.933; P = 0.001), elevated serum CA19-9 (OR 12.868; 5.196 to 31.867; P < 0.001), PROK1/PROKR2-positive (OR 2.244; 1.031 to 4.884; P = 0.042) and BRAF mutations (OR 2.586; 1.674 to 3.994; P < 0.001). However, it’s associated negatively with rectal cancer and non-mucinous adenocarcinoma, and not associated with KRAS, NRAS, PIK3CA mutations and MSI-H/dMMR. Conclusions: These risk factors are the alerts that could predict the presence of synchronous CPM and contribute to strengthening management and optimal therapeutic strategy.
Increased expression of HIST1H1D in esophageal carcinoma predicts poor survival: A study base on TCGA database
Authors: Huang Shan , Huang Hanwen , Liao Mingchu , Tian Caiqun , Deng Rong , Du Peng , Zhu Mengyuan , Pan Xiaofen 
Published: April 2021

Abstract
Background: Expression level of HIST1H1D, a linker histone H1 gene, was reported to be associated with poor prognosis in some malignant tumors. Online database showed that HIST1H1D was increased in esophageal carcinoma. The current study aimed to evaluated the role of HIST1H1D in esophageal carcinoma using online data from The Cancer Genome Atlas (TCGA).Methods. Wilcoxon signed-rank test, cox regression analysis and multivariant analysis were used to analyze the relationship between clinical characteristic and HIST1H1D expression level. Kaplan-Meier method was used to analyze the association of HIST1H1D and overall survival. Gene set enrichment analysis (GSEA) was used to identify HIST1H1D-related signaling pathway.Results. Compared to normal sample, HIST1H1D was significantly increased in esophageal carcinoma sample (p=0.000). High HIST1H1D expression was associated with poor survival (p=0.035). Univariate analysis showed that high HIST1H1D expression was associated with a poor overall survival (HR:1.19, 95% confidence interval [CI]: 1.05-1.34, p=0.01). Multivariate analysis indicated that HIST1H1D remained an independent prognostic predictor of overall survival (HR:1.18, 95% confidence interval [CI]: 1.02-1.36, p=0.03). GSEA revealed that alpha linolenic acid metabolism, arachidonic acid metabolism, histidine metabolism, vascular smooth muscle contraction, primary bile acid biosynthesis, phenylalanine metabolism and ether lipid metabolism were enriched in HIST1H1D high expression phenotype.Conclusions: HIST1H1D may sever as a potential prognostic predictor of poor survival in esophageal carcinoma. Lipid metabolism, histidine metabolism, vascular smooth muscle contraction, primary bile acid biosynthesis, phenylalanine metabolism and ether lipid metabolism may be the key signaling pathway regulated by HIST1H1D.
Graded Rough Sets based on Neighborhood Operator Over two Different Universes and its Application
Authors: Khalil Ahmed Mostafa 
Published: April 2021

Abstract
Abstract The major concern of this paper is to present the notion of rough set based on neighborhood operator on universe set, along with its properties, and examples. Then, we generalize several notions of covering rough sets to neighborhood rough sets with respect to the graded n. Further, we present some notions such as probabilistic neighborhood rough approximations of X, (Type-I / Type-II) probabilistic neighborhood rough approximations of X with error α and β, and (Type-I / Type-II) probabilistic neighborhood rough approximations of X with respect to N . The interesting properties of above notions are investigated in detail. On the other hand, we define the notion of rough set based on neighborhood operator over two different universes. Subsequently, we present some notions (Type-I / Type-II / Type-III) graded n-neighborhood rough sets and give a two approaches to decision-making problems based on the (Type-II / Type-III) grade n-neighborhood rough sets. Then, we construct the decision steps and give two algorithms of the decision methods. Also, we will give two illustrative examples to show the applicability of the rough set based on neighborhood operator over two different universes to solve the rough decision-making problems. Finally, we give a comparison between the Liu et al.’s approach and our approach.
Seasonal Variations and Health Risk Assessment of Trace Elements in Seti River Basin, Gandaki Province, Nepal
Authors: Pant Ramesh Raj , Bishwakarma Kiran , Nepal Jharana , Paudel Sudip , Chand Mohan Bahadur , Qaisar Faizan Ur Rehman , Pal Khadka Bahadur , Thapa Lal B , Wang Guanxing 
Published: April 2021

Abstract
To explore the seasonal variability and associated health risks of dissolved trace elements (TEs), a total of 45 water samples (15 samples in each season) were collected from the Seti River Basin during pre-monsoon, monsoon, and post-monsoon seasons. A total of 15 (TEs) were analysed and the results revealed that Arsenic (As), Chromium (Cr), and Nickel (Ni) were primarily controlled by lithogenic sources, whereas, Cadmium (Cd), Cobalt (Co), Cesium (Cs), Cupper (Cu), Manganese (Mn), Lead (Pb), and Zinc (Zn) were derived from both anthropic and geogenic origin. Additionally, the concentration of Zn was markedly high, especially during the post-monsoon season nearby the landfill site, indicating the anthropic signatures. The hazard index and cancer index were found to be < 1.00 and 10− 6-10− 4, respectively indicating minimum health impacts. The water quality index was < 50 throughout the sampling periods, with better water quality during the monsoon. This study could help to formulate the necessary policies for the sustainability of the Himalayan River Basins.
Comparative transcriptome provides strategy for phylogenetic analysis and SSR marker development in Chaenomeles
Authors: Shao Wenhao , Huang Shiqing , Zhang Yongzhi , Jiang Jingmin , Li Hui 
Published: April 2021

Abstract
The genus Chaenomeles has long been considered as an important ornamental, herbal and cash plant and widely cultivated in East Asian. Traditional researches of Chaenomeles mainly focus on evolutionary relationships on phenotypic level. In this study, we conducted RNA-seq for 10 Chaenomeles germplasms supplemented with one related species Docynia delavayi (D. delavay) by Illumina HiSeq2500 platform. After de novo assemblies, we have generated unigenes for each germplasm with numbers from 40 084 to 48 487. By pairwise comparison of the orthologous sequences, 9 659 othologus within the 11 germplasms were obtained, with 6 154 othologous genes identified as single-copy genes. The phylogenetic tree was visualized to reveal evolutionary relationship for these 11 germplasms. GO and KEGG analyses were performed for these common single-copy genes to compare the functional similarities and differences. Selective pressure analysis based on 6 154 common single-copy genes reveals that 45 genes were under positive pressure selection. Most of them involved in plant disease defense system building process. 292 genes containing simple sequence repeats (SSRs) were used to develop SSR markers and compare their function in secondary metabolism pathways. Finally, 10 primers were chosen as SSR markers candidates for Chaenomeles germplasms by comprehensive screening. Our research provides new methodology and reference for future related research in Chaemomeles and is also useful for improvement, breeding and selection project in other related species.
Inulin-Niacin Conjugates: Preparation, Characterization, Kinetic and in vitro Release Studies
Authors: Ganie Showkat Ali , Ali Akbar , Mir Tariq Ahmad , Mazumdar Nasreen 
Published: April 2021

Abstract
Niacin, an essential B-complex vitamin, used in the treatment of nonalcoholic fatty liver disease is the first perceived lipid regulating medication, inhibits and reverses hepatic steatosis and inflammation in animals and liver cell cultures. Niacin shows beneficial effects on adiposity. Niacin plays an important role in DNA repair, electron transfer, one-carbon metabolism and fatty acid synthesis in cells. Natural polysaccharides with desirable chemical modifications can be combined with vitamins for developing the supplement treatment for vitamin deficiency disorders. Modification of inulin was carried out by tosylation, amination and then conjugated with niacin. Structural elucidation of the derivatives and conjugates was carried out by FT-IR, 1H NMR and SEM. Thermal behavior was investigated by TGA and DSC techniques. The release and kinetics of niacin, from the conjugate, at different pH was studied. The release was observed to be pH dependent, showing a greater release at higher pH following Korsmeyer-Peppas kinetic model. Polysaccharide based approach was used for the preparation of stable niacin-inulin conjugates with controllable and prolonged release of niacin. These types of conjugates may be useful as vitamin delivery systems for vitamin deficiency disorders.
Human Mobility and Droplet-transmissible Pediatric Infectious Diseases During the Coronavirus Disease-2019 Pandemic
Authors: Ae Ryusuke , Shibata Yoshihide , Furuno Toshiki , Sasahara Teppei , Nakamura Yosikazu , Hamada Hiromichi 
Published: April 2021

Abstract
Background: The number of children with common pediatric infectious diseases (PIDs) other than coronavirus disease-2019 (COVID-19) decreased in 2020 compared with those in previous years worldwide. The present study tested the hypothesis that human mobility may be a potential factor contributing to reductions in PIDs that can be transmitted by droplets among children.Methods: An ecological study was conducted using two publicly available datasets: surveillance on infectious diseases collected by the Japanese government and COVID-19 community mobility reports presented by Google. Among common PIDs, we focused on focused on respiratory syncytial virus (RSV) infection, pharyngoconjunctival fever (PCF), group A streptococcal (GAS) pharyngitis, hand-foot-and-mouth disease (HFMD), and herpangina because of their nature as droplet-transmissible PIDs. The COVID-19 community mobility reports demonstrated percent decreases in the movement of people over time in groceries and pharmacies, parks, and transit stations. We compared the weekly trends in numbers of patients with PIDs identified in 2020 with those identified in the previous years 2015–2019. We then determined the associations between numbers of patients with PIDs and percentage decreases in human mobility during 2020 using Pearson correlation analysis.Results: Despite experiencing their peak seasons, dramatic reductions were observed in the numbers of patients with PCF and GAS pharyngitis after the 10th week in 2020. Beyond the 20th week, no seasonal peaks were observed in the numbers of patients with all PIDs identified in 2020. Significant correlations were found between percentage decreases in human mobility in transit stations and numbers of patients with HFMD (Pearson correlation coefficient [95% confidence interval]: 0.65 [0.44–0.79]), PCF (0.47 [0.21–0.67]), RSV infection (0.45 [0.19–0.66]), and GAS pharyngitis (0.34 [0.06–0.58]). No significant correlations were found between numbers of patients with PIDs and human mobility in parks.Conclusions: The highest correlations were found for the associations between numbers of patients with PIDs and human mobility in transit stations, suggesting that adult-to-child transmission may be a primary factor associated with increased numbers of patients with PIDs, rather than cross-transmission among children. A reduction in human mobility for adults may contribute toward decreases in the numbers of children with droplet-transmissible PIDs.
Response to Foliar Micronutrients Application: Oil Content, Fatty Acid Profiling, Growth and Yield Attributes in Sunflower Hybrids
Authors: Mehmood Ayaz , Ahmed Junaid , Rukh Shah , Shahzad Khurram , Rafique Mazhar , Imran Muhammad , Khan Ahmad , Qayyum Abdul , Ahmad Waseem , Gurmani Ali , Shah Zahid , Alghabari Fahad , Chung Gyuhwa 
Published: April 2021

Abstract
Micronutrient deficiency is widespread in alkaline soils of Pakistan which ultimately affect the yield and quality of sunflower oil. The current study was designed to investigate the combined as well as the sole effect of micronutrient application on the growth and yield attributes, and fatty acids profiling of selected sunflower hybrids. A field trial was conducted in sub-humid climatic conditions and two sunflower hybrids (FMC-1 and Parsun-3) were grown at the University of Haripur’s research farm. Micronutrients were applied through the foliar application at the start of the bud growing stage and before the flowering stage i.e., after 30 and 55 days of sowing. The application of micronutrients resulted in significant variation in agronomic parameters of sunflower hybrids. Molybdenum among the sole application and in combination treatments Zn, B, and Mo increased the growth traits of sunflower genotypes, while application of Zn and Mo (among sole application), and combination of Zn, B, and Mo increased the yield attributes. Oil content was highest in the combination of three micronutrients (Zn, B, and Mo) application followed by the Zn and B application individually. Sole micronutrients application also increased oil contents in both hybrids. Zinc application resulted in an increase of unsaturated fatty acids and a decrease in saturated fatty acids, while the B increased the oleic acid and stearic acid content and decreased the linoleic acid and palmitic acid contents. Among the varieties, FMC-1 has significantly achieved a higher yield than the Parsun-3. It is concluded from the research that Zn application increased the beneficial (poly- and mono-unsaturated) fatty acids and decreased the harmful (saturated) fatty acids. Zinc application @ 2 kg ha1 is recommended for good quality oil production.