bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole-genome sequencing of 1,171 elderly admixed individuals from the largest Latin American metropolis (São Paulo, Brazil)
Authors: Naslavsky Michel , Scliar Marilia , Yamamoto Guilherme , Wang Jaqueline , Zverinova Stepanka , Karp Tatiana , Nunes Kelly , Ceroni José Ricardo , Carvalho Diego , Simões Cerlos Eduardo , Bozoklian Daniel , Nonaka Ricardo , Silva Nayane , Souza Andreia , Andrade Heloísa , Passos Marília , Castro Camila , Mendes-Junior Celso , Mercuri Rafael , Miller Thiago , Buzzo José , Rego Fernanda , Araújo Nathalia , Magalhaes Wagner , Mingroni-Netto Regina , Borda Vctor , Guio Heinner , Barreto Maurício , Lima-Costa Maria , Horta Bernardo , Tarazona-Santos Eduardo , Meyer Diogo , Galante Pedro , Consortium Genome of the Netherlands , Castelli Erick , Duarte Yeda , Passos-Bueno Maria Rita , Zatz Mayana 
Published: October 2020

Abstract
As whole-genome sequencing (WGS) becomes the gold standard tool for studying population genomics and medical applications, data on diverse non-European and admixed individuals are still scarce. Here, we present a high-coverage WGS dataset of 1,171 highly admixed elderly Brazilians from a census-based cohort, providing over 76 million variants, of which ~ 2 million are absent from large public databases. WGS enabled identifying ~ 2,000 novel mobile element insertions, nearly 5 Mb of genomic segments absent from human genome reference, and over 140 novel alleles from HLA genes. We reclassified and curated nearly four hundred variant's pathogenicity assertions in genes associated with dominantly inherited Mendelian disorders and calculated the incidence for selected recessive disorders, demonstrating the clinical usefulness of the present study. Finally, we observed that whole-genome and HLA imputation could be significantly improved compared to available datasets since rare variation represents the largest proportion of input from WGS. These results demonstrate that even smaller sample sizes of underrepresented populations bring relevant data for genomic studies, especially when exploring analyses allowed only by WGS.
LINC00680 Enhances Hepatocellular Carcinoma Stemness Behavior and Chemoresistance by Sponging miR-568 to Upregulate AKT3
Authors: Shu Gege , Su Huizhao , Wang Zhiqian , Lai Shihui , Wang Yan , Liu Xiaomeng , Dai Luo , Bi Yin , Chen Wei , Huang Weiyu , Zhou Ziyan , He Songqing , Dai Hongliang , Tang Bo 
Published: October 2020

Abstract
Background: Hepatocellular carcinoma (HCC) has an extremely poor prognosis due to the development of chemoresistance, coupled with inherently increased stemness properties. Long non-coding RNAs (LncRNAs) are key regulators for tumor cell stemness and chemosensitivity. Currently the relevance between LINC00680 and tumor progression was still largely unknown, with only one study showing its significance in glioblastoma. The study herein was aimed at identifying the role of LINC00680 in the regulation HCC stemness and chemosensitivity. Methods: QRT-PCR was used to detect the expression of LINC00680, miR-568 and AKT3 in tissue specimen and cell lines. Gain- or loss-of function assays were applied to access the function of LINC00680 in HCC cells, including cell proliferation and stemness properties. HCC stemness and chemosensitivity were determined by sphere formation, cell viability and colony formation. Luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull down assays were performed to examine the interaction between LINC00680 and miR-568 as well as that between miR-568 and AKT3. A nude mouse xenograft model was established for the in vivo study.Results: We found that LINC00680 was remarkably upregulated both in HCC tissue and cell lines. Patients with high level of LINC00680 had poorer prognosis. LINC00680 overexpression significantly enhanced HCC cell stemness and decreased in vitro and in vivo chemosensitivity to 5-fluorouracil (5-Fu), whereas LINC00680 knockdown led to opposite results. Mechanism study revealed that LINC00680 regulated HCC stemness and chemosensitivity through sponging miR-568, thereby expediting the expression of AKT3, which further activated its downstream signaling molecules, including mTOR, elF4EBP1, and p70S6K.Conclusion: LINC00680 promotes HCC stemness properties and decreases chemosensitivity through sponging miR-568 to activate AKT3, suggesting that LINC00680 might be a potentially important HCC diagnosis marker and therapeutic target.
Clinical relevance of CD70 expression in resected pancreatic cancer: prognostic value and therapeutic potential
Authors: Nakamura Kota , Sho Masayuki , Akahori Takahiro , Nishiwada Satoshi , Kunishige Tomohiro , Nakagawa Kenji , Nagai Minako , Takagi Tadataka , Terai Taichi , Ikeda Naoya 
Published: October 2020

Abstract
BackgroundAberrant expression of CD70 in several malignancies is potentially associated with poor patient prognosis and could serve as a therapeutic target. However, the clinical relevance of CD70 expression in pancreatic cancer has not been thoroughly explored.MethodsWe evaluated CD70 expression in 166 surgical specimens obtained from human patients with pancreatic cancer. We analyzed the function of CD70 in proliferation and migration using pancreatic cancer cell lines with silenced CD70 expression.ResultsCD70 expression was positively stained in 42 patients (25%). In the whole cohort, high CD70 expression was not associated with overall survival (OS: 33.1 vs. 40.8 months, P = 0.256), although it was significantly associated with inferior OS in a population of patients that completed adjuvant chemotherapy (P = 0.027). Moreover, the incidence of hematogenous metastasis was significantly higher in patients with high CD70 expression than in those with low CD70 expression (P = 0.020). This finding was also statistically significant in multivariate analyses (P = 0.001). In vitro experiments demonstrated that CD70 expression contributed to cancer cell proliferation independently of gemcitabine treatment as well as cell migration. Furthermore, real-time polymerase chain reaction analysis of frozen surgical tissues showed a correlation between the expression of CD70 and mesenchymal markers.ConclusionsCD70 expression in pancreatic cancer might be involved in hematogenous metastasis. Furthermore, our results imply that CD70 overexpression can serve as a novel prognostic factor and a potential therapeutic target in patients who have completed adjuvant chemotherapy.
A positive feedback loop between TAZ and miR-942-3p modulates proliferation, migration, epithelial-mesenchymal transition process and glycometabolism in human bladder cancer
Authors: Wang Feifan , Fan Mengjing , Zhou Xuejian , Yu Yanlan , Cai Yueshu , Wu Hongshen , Zhang Yan , Liu Jiaxin , Huang Shihan , He Ning , Hu Zhenghui , Ding Guoqing , Jin Xiaodong 
Published: October 2020

Abstract
Background: Transcriptional co-activator with PDZ-binding motif (TAZ) has been reported to involve in tumor progression, epithelial-mesenchymal transition (EMT) process and glycometabolism modulation. Herein, the underlying molecular mechanisms of TAZ-induced biological effects in bladder cancer were discovered; Methods: qRT-PCR, western blot and immunohistochemistry were performed to determine the level of TAZ in bladder cancer cells and tissues; CCK-8 assay, Colony formation assay, wound healing assay and Transwell assay were performed to evaluate the functions of TAZ, miR-942-3p and GAS1. qRT-PCR and western blot were used to determine the expression levels of related genes. Chromatin immunoprecipitation and dual-luciferase reporter assay confirmed the interaction between TAZ and miR-942. In vivo tumorigenesis assay and colorimetric assay of glycolysis were also conducted; Results: We determined the upregulation and vital roles of TAZ in bladder cancer. TAZ-induced upregulation of miR-942-3p amplified upstream signaling by inhibiting the expression of large tumor suppressor 2 (LATS2, a TAZ inhibitor). MiR-942-3p attenuated the suppression of cell proliferation, EMT process and glycolysis induced by TAZ knockdown. Further, miR-942-3p resulted in restrained expression of growth arrest-specific 1 (GAS1) to modulate biological functions; Conclusion: Our study identified a novel positive feedback loop between TAZ and miR-942-3p that regulates biological functions in bladder cancer cells via GAS1 expression, and illustrated that TAZ and miR-942-3p might be potential therapeutic targets for bladder cancer treatment.
Stretching and Shearing Contamination Analysis for Liutex and Other Vortex Identification Methods
Authors: Shrestha Phushpa , Nottage Charles , Yu Yifei , Alvarez Oscar , Liu Chaoqun 
Published: October 2020

Abstract
The newly developed vortex-identification method, Liutex, has provided a new systematic description of the local fluid rotation, which includes scalar, vector, and tensor forms. However, the advantages of Liutex over the other widely used vortex-identification methods such as Q, Δ, λ2 , and λci have not been realized. These traditional methods count on shearing and stretching as a part of vortex strength. But, in the real flow, shearing and stretching do not contribute to fluid rotation. In this paper, the decomposition of the velocity gradient tensor is conducted in the Principal Coordinate for uniqueness. Then the contamination effects of stretching and shearing of the traditional methods are investigated and compared with the Liutex method in terms of mathematical analysis and numerical calculations. The results show that the Liutex method is the only method that is not affected by either stretching or shear, as it represents only the local fluid rigid rotation. These results provide supporting evidence that Liutex is the superior method over others.
Genome-wide association study reveals the genetic architecture of 27 yield-related traits in tomato
Authors: Ye Jie , Wang Xin , Wang Wenqian , Yu Huiyang , Ai Guo , Li Changxing , Sun Pengya , Wang Xianyu , Li Hanxia , Ouyang Bo , Zhang Jun-Hong , Zhang Yuyang , Giovannoni James , Fei Zhangjun , Ye Zhibiao 
Published: October 2020

Abstract
Tomato (Solanum lycopersicum) is a highly valuable vegetable crop and yield is one of the most important traits. Uncovering the genetic architecture of yield-related traits in tomato is critical for the management of vegetative and reproductive development, thereby enhancing yield. Here we perform a comprehensive genome-wide association study for 27 yield-related traits in tomato. A total of 239 significant associations corresponding to 129 loci, harboring many reported and novel genes related to vegetative and reproductive development, were identified, and these loci explained an average of ~8.8% of the phenotypic variance. A total of 51 loci associated with 25 traits have been under selection, especially during tomato improvement. Furthermore, a candidate gene, SlALMT15 that encodes an aluminum-activated malate transporter, was functionally characterized and shown to act as a pivotal regulator of leaf stomata formation through increasing photosynthesis and drought resistance. This study provides valuable information for tomato genetic research and breeding.
Facing COVID-19 via anti-inflammatory mechanism of action: Molecular docking and Pharmacokinetic studies of six anti-inflammatory compounds derived from Passiflora edulis
Authors: Matondo Aristote , Kilembe Jason T , Mwanangombo Domaine T , Nsimba Beaudrique M , Gbolo Benjamin Z , Bongo Gedeon N , Ngbolua Koto-te-Nyiwa , Tshilanda Dorothée D , Tshibangu Damien S T , Mudogo Virima , Mpiana Pius T 
Published: October 2020

Abstract
SARS-CoV-2 is the causative agent of the COVID-19 disease. Pathophysiologically, high levels of proinflammatory cytokines in the serum of SARS-CoV-2 patients are reported, which is so-called the cytokine storm. In this study, molecular docking calculations of six bioactive compounds from Passiflora edulis with anti-inflammatory activity in interaction with the main protease of SARS-CoV-2 were performed, and their pharmacokinetic properties were predicted. The results of their molecular simulations and the ADME-T profiles of each ligand (Absorption, Distribution, Metabolism, Excretion and Toxicity) suggest their use as potential treatment for SARS-CoV-2. Among the six investigated compounds in which four flavonoids and two alkaloids, the best docked ligands are quercetin (-8.2 kcal/mol), chrysin (-8.0 kcal/mol), kaempferol (-7.9 kcal/mol) and luteolin (-7.7 kcal/mol), both flavonoids compounds. Their pharmacokinetic studies using SwissADME, preADMET and pkCSM Web servers establish the good ADMET profile for each ligand.
Universal health care access for all residents reduce mortality in COVID-19 patients in Abu Dhabi, UAE: A retrospective multicenter cohort study
Authors: kaabi Nawal Al , Nuaimi Asma Al , Harbi Mariam Al , Abdalla Jehad , Khan Tehmina , Gasmelseed Huda , Khan Asad , Hamdoun Osama , Weber Stefan 
Published: October 2020

Abstract
Background: SARS‐CoV‐2 was first reported in December 2019. The severity of COVID-19 infection ranges from being asymptomatic to severe infection leading to death. The aim of the study is to describe the clinical characteristics and outcomes of hospitalized COVID-19 patients within the largest government healthcare facilities in the Emirate of Abu Dhabi, the capital of UAE. Methods: This paper is a retrospective cross-sectional study of all patients admitted to Abu Dhabi Healthcare services facilities (SEHA) between the period of March 1st until May 31st with a laboratory-confirmed test of SARS-CoV2, known as Coronavirus disease (COVID19). Variation in characteristics, comorbidities, laboratory values, length of hospital stay, treatment received and outcomes were examined. Data was collected from electronic health records available at SEHA health information system.Results: There were 9390 patients included; patients were divided into severe and non-severe groups. 721 (7.68%) patients required intensive care while the remaining majority (92.32 %) were mild-moderate cases. The mean age (41.8 years) is less than the mean age reported globally. Our population had a male predominance and variable representation of different nationalities. Three major comorbidities were noted, hypertension, diabetes mellitus and chronic kidney disease. The laboratory tests that were significantly different between the severe and the non-severe groups were LDH, Ferritin, CRP, neutrophil count, IL6 and creatinine level. The major antiviral therapies the patients have received were a combination of hydroxychloroquine and favipiravir. The overall in hospital mortality was 1.63% while severe group mortality rate was 19.56 %. The Death rate in the adults younger than 30 years was noted to be higher compared to elderly patients above 60 years, 2.3% and 0.9 % respectively. Conclusion: our analysis suggests that Abu Dhabi had a relatively low morbidity and mortality rate and a high recovery rate compared to published rates in China, Italy and The United States. The demographic of the population is younger and has an international representation. The country had the highest testing rate in relation to the population volume. We believe the early identification and younger demographic had affected the favorable comparative outcome in general with early identification of cases leading to a lower mortality rate.
Long-term cognitively challenging experiences modulate metabolite concentrations in the healthy brain: the case of bilingualism
Authors: Pliatsikas Christos , DeLuca Vincent , Soares Sergio Pereira , Voits Toms , Rothman Jason 
Published: October 2020

Abstract
Cognitively demanding experiences, including complex skills acquisition and processing, have been shown to induce brain adaptations, at least at the macroscopic level, e.g. on brain volume and/or functional connectivity. However, the neurobiological bases of these adaptations, including at the microstructural cellular level, remain poorly understood. Here we use bilingualism as a case study to investigate the microscopic correlates of experience-based brain adaptations. We employ Magnetic Resonance Spectroscopy to measure concentrations of metabolites in the ventral striatum, a region critical to language control which is reshaped by bilingualism. Our results revealed increased concentration of myo-Inositol in bilinguals compared to monolinguals. This metabolite is linked to synaptic pruning, a process underlying experience-based brain restructuring. Crucially, concentration was predicted by relative amount of bilingual engagement. Our results suggest that (degree of) long-term cognitive experiences have measurable effects at the microcellular level, which might accompany, if not drive, the observed macroscopic brain adaptations.
Phylogenetic analysis of variable and conserved genomic regions in severe acute respiratory syndrome coronavirus 2 (COVID-19)
Authors: Nahas Abeer F. El , Elkatatny Nasema M. , Abo-Al-Ela Haitham G. 
Published: October 2020

Abstract
SARS-CoV-2 has rapidly spread around the world. Several mutations have been detected in its genome, but they do not seem to affect the abilities of the virus to spread or infect. We aimed to explore the conserved genomic regions in coronavirus that could contain the key strengths of the virus. SARS-CoV-2 sequence data were retrieved from Genbank from the period of December 2019 to March 2020. Phylogenetic analyses were conducted for 207 sequences using MEGAX compared with the reference sequence (MN908947.3- CHN-Wuhan Dec-2019). The analysis included seven important genomic regions, the ORF1ab gene (21,290 bp), S gene (3,822 bp), Orf3a gene (827 bp), E gene (227 bp), M gene (669 bp), and N gene (1,259 bp), which play critical roles in virus invasion and replication. Furthermore, the variant nucleotides and amino acids were detected by MEGAX and BLAST. Through the phylogenetic analysis and amino acid substitution, the ORF1ab gene showed 11 conserved regions and also several variable sites. The E and M genes were mainly conserved, and all sequences were included in one clade, with one or two amino acid variants. Orf3a and the N gene have four conserved sites distributed along the genes. The S gene has 12 mutations and four main large conserved regionsWe conclude that the favored occurrence of mutations at the ORFab and Orf3a genes during the SARS-CoV epidemic is an important mechanism for virus pathogenesis. The E and M proteins have an almost conserved structure, whereas the S and N genes have many conserved regions, which could serve as possible targets for vaccine design for SARS-CoV.
Internal doses to the public in the Fukushima prefecture from the Fukushima Daiichi NPP accident
Authors: Zvonova I. A. 
Published: October 2020

The article is devoted to the analysis of internal dosimetry in residents of Fukushima Prefecture due to the accident at the Fukushima-Daiichi NPP. On March 24-30, 2011, screening studies were conducted on measurements of 131I content in thyroid gland of children in those municipalities where the Japanese program for assessing the radiological consequences of the radiation accident “SPEEDI” predicted doses in the thyroid of one-year children from 100 to 500 mSv. Among 1080 children measured, 55% had results below the background, and the maximum estimate of the equivalent dose in the thyroid was 43 mSv. Measurements of several dozen inhabitants with other instruments and methods confirmed low levels of 131I in the thyroid. In total, the 131I thyroid direct measurement database of Fukushima residents contains approximately 1300 individuals. 75% quartile of individual thyroid dose distributions was below 10 mSv, the median was from 0 to 3.7 mSv among children aged from 0 to 15 years in the five examined municipalities. The contribution of short-lived iodine radionuclides was estimated as 15% of the dose from 131I for the main radioactive release on March 15. The effective dose of internal exposure to cesium radionuclides (134Cs + 137Cs), estimated from 10 thousand whole body measurements for the first year after the accident, was below 0.1 mSv in 90% of the examined people. Whole body measurements of children 6-15 years old in the second year after the accident confirmed the values of the effective dose of internal exposure less than 0.1 mSv, while the estimates of the effective dose of external exposure in the same children with using individual dosimeters determined the median distribution as 0.66 mSv with a maximum value of 3.45 mSv . The measurement results do not provide any basis to expect a future increase in the incidence of thyroid cancer and other radiogenic diseases among the Fukushima residents. Preventive evacuation of the population before the radioactive release, stay in enclosed dwellings, strict radiation control of food products have effectively reduced the expected doses of internal exposure to residents. In the predictions of the radiological consequences of the accident, it is necessary to take into account the actually implemented measures to protect the population, and local characteristics of the style of life and living.
Proteomic Analysis of Huntington’s Disease
Authors: Kumar Shobhit , Singh Priyanka , Sharma Shrestha , Ali Javed , Baboota Sanjula , Pottoo Faheem Hyder 
Published: October 2020

:
Huntington’s disease (HD) is a neurodegenerative disease that is genetically inherited
through an autosomal dominant gene located on chromosome 4. HD is caused by DNA mutation
(generally 37 or more repetition of CAG nucleotides) that leads to an excessive stretch of glutamine
residues. However, the main pathogenesis pathway resulted by polyglutamine expansion in
mutant HD is unknown. The characteristics of this disease mostly appear in adults. Patients who
suffer from this disease have shown an inability to control physical movements, emotional
problems, speech disturbance, dementia, loss of thinking ability and death occurs between 15-20
years from the time of symptomatic onset. This review article suggested that investigation of mutation
in the HD gene can be done by proteomic analysis such as mass spectroscopy, gel electrophoresis,
western blotting, chromatographic based technology, and X-ray crystallography. The primary
aim of proteomics is to focus on the molecular changes occurring in HD, there by enhancing the effectiveness
of treatment.
The Association between Polygenic Hazard and Markers of Alzheimer’s Disease Following Stratification for APOE Genotype
Authors: De Marco Matteo , Manca Riccardo , Kirby Janine , Hautbergue Guillaume M. , Blackburn Daniel J. , Wharton Stephen B. , Venneri Annalena , Alzheimer’s Disease Neuroimaging Initiative  
Published: October 2020

Background:Research indicates that polygenic indices of risk of Alzheimer’s disease are linked to clinical profiles.Objective:Given the “genetic centrality” of the APOE gene, we tested whether this held true for both APOE-ε4 carriers and non-carriers.Methods:A polygenic hazard score (PHS) was extracted from 784 non-demented participants recruited in the Alzheimer’s Disease Neuroimaging Initiative and stratified by APOE ε4 status. Datasets were split into sub-cohorts defined by clinical (unimpaired/MCI) and amyloid status (Aβ+/Aβ-). Linear models were devised in each sub-cohort and for each APOE-ε4 status to test the association between PHS and memory, executive functioning and grey-matter volumetric maps.Results:PHS predicted memory and executive functioning in ε4ε3 MCI patients, memory in ε3ε3 MCI patients, and memory in ε4ε3 Aβ+ participants. PHS also predicted volume in sensorimotor regions in ε3ε3 Aβ+ participants.Conclusion:The link between polygenic hazard and neurocognitive variables varies depending on APOE-ε4 allele status. This suggests that clinical phenotypes might be influenced by complex genetic interactions.