bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Diagnostic Accuracy of Fecal Protein Biomarkers for Colorectal Advanced Neoplasms: A Systematic Review and Meta-Analysis
Authors: Kansestani Atefeh Nasir , Zare Mohammad Erfan , Tong Qingchao , Zhang Jun 
Published: July 2021

Abstract
Early diagnosis of colorectal advanced neoplasms (AN), including colorectal cancer (CRC) and advanced adenoma (AA), has positive effect on survival rate. As the first attempt, the aim of this meta-analysis was to compare the diagnostic accuracy of fecal protein biomarkers for detection of colorectal neoplasms with consideration of wide range covariates.Until Jun 10, 2021, a systematic literature search was performed on Web of Sciences, Scopus and PubMed. The diagnostic accuracies were calculated using the bivariate/hierarchical random effect model. Biomarkers were determined clinically applicable (CA) if they had area under the curves> 0.70, positive and negative likelihood ratio >2 and <0.5, respectively. A total of 47059 test results were extracted from 16 Immunochemical fecal occult blood test (iFOBT), 26 Pyruvate Kinase-M2 (PK-M2) and 23 Fecal Calprotectin (FC) studies. Only iFOBT, PK-M2 and FC for CRC plus iFOBT and PK-M2 for AN were CA. iFOBT had significantly superior accuracy (P= 0.02 versus PK-M2 and P< 0.01 versus FC for CRC; P< 0.01 versus PK-M2 for AN). Regarding covariates, lateral flow method of PK-M2 measurement increased its accuracy for CRC detection compared to enzyme-linked immunosorbent assay (P< 0.01). Briefly, iFOBT is the most accurate fecal biomarker for diagnosis of CRC and AN.
WITHDRAWN: miR-99a-3p Targeting EIF4EBP1 Affects B Lymphocytes Function Through Autophagy and Aggravates SLE Disease Progression
Authors: yang meng , Danqi Deng 
Published: July 2021

Abstract
Background:Overactivation of immune cells plays a key role in the pathogenesis of systemic lupus erythematosus (SLE). The regulation of immune cells by miRNA is a research hotspot.In this study, the second-generation high-throughput sequencing found that the expression of miR-99a-3p in SLE decreased, but the specific mechanism is still unclear.The purpose of this study is to explore the potential target genes, target cells of miR-99a-3p and their potential mechanisms affecting the progression of SLE.Methods: Isolate PBMC from healthy individulas and SLE patients, transfect Ball-1, Jurkat, THP-1 and K562 cells with miR-99a-3p agomir and antagomir,detect miR-99a-3p, predict target genes and autophagy pathway mRNA and protein expression by RT-qPCR and Western blotting.CCK-8 method detects cell proliferation, PI method detects cell cycle, flow cytometry detects cell apoptosis, and luciferase reporter gene experiment determines miR-99a-3p target genes.With C57BL/6J mice as control,construct miR-99a-3p overexpression and interference model based on MRL/lpr mice,ELISA detects plasma ANA, dsDNA, IgE, IgM, IL-6, IL-10, BLyS.Pathological analysis of HE staining and C3 immunofluorescence(IF) deposition in mouse kidney tissue,Immunohistochemistry(IHC) detects changes in target genes and pathway proteins in kidney tissue,isolate B cells to verify the differential expression of miR-99a-3p, target genes, pathway mRNA and protein.Results: Compared with healthy individulas, miR-99a-3p in SLE was down-regulated, while EIF4EBP1, LC3II, LAMP-2A mRNA and protein expression were up-regulated.After Ball-1 was transfected with miR-99a-3p agomir, cell proliferation decreased and apoptosis increased.After transfected with miR-99a-3p antagomir, the effect was opposite;Luciferase reporter gene detection proved that miR-99a-3p directly targets EIF4EBP1. Rescue experiments confirmed the interaction model between miR-99a-3p and EIF4EBP1. Clinical, in vitro, and in vivo experiments further confirmed that miR-99a-3p agomir can reduce the expression of EIF4EBP1, LC3-Ⅱ, and LAMP-2A, while miR-99a-3p antagomir had the opposite effect.In vivo experiment antagomir group mice serum ANA, dsDNA, IgE, IgM, IL-6, IL-10, BLyS were higher than those in the MRL/lpr group, EIF4EBP1, LC3-Ⅱ, LAMP-2A mRNA, protein and IHC levels also increased, and the urinary protein and C3 IF deposition of mice in the antagomir group were increased, and the related indexes of mice in the agomir group were lower than those in the MRL/lpr group.Conclusion:The expression of miR-99a-3p in SLE PBMC was down-regulated. Up-regulation of miR-99a-3p by transfection can protect B cells from autophagy mediated by EIF4EBP1.The down-regulation of miR-99a-3p induces autophagy by regulating the autophagy signaling pathway mediated by EIF4EBP1 in SLE B cells. These results indicate that miR-99a-3p and EIF4EBP1 may be potential targets of SLE.
A Genome-Wide Association Study for Melatonin Secretion
Authors: Liu Pi-Hua , Chuang Gwo-Tsann , Hsiung Chia-Ni , Yang Wei-Shun , Ku Hsiao-Chia , Lin Yi-Ching , Chen Yi-Shun , Huang Yu-Yao , Lin Chia-Hung , Lin Jou-Wei , Hsu Chih-Neng , Hwang Juey-Jen , Hsieh Meng-Lun , Lee Hsiao-Lin , Shen Chen-Yang , Chang Yi-Cheng 
Published: July 2021

Abstract
SummaryPurpose: Melatonin exerts a wide range of effects among various tissues and organs. However, there is currently no study to investigate the genetic determinants of melatonin secretion. Here, we conducted a genome-wide association study (GWAS) for melatonin secretion using morning urine 6-hydroxymelatonin sulfate-to-creatinine ratio (UMCR). Methods: We initially enrolled 5,000 participants from Taiwan Biobank in this study. After excluding individuals that did not have their urine collected in the morning and those who failed to pass quality control, association of single nucleotide polymorphisms with log-transformed UMCR adjusted for age, sex and principal components of ancestry were analyzed. A second model additionally adjusted for estimated glomerular filtration rate (eGFR). Results: A total of 2,504 participants underwent the genome-wide analysis. Six candidate loci associated with log UMCR (P value ranging from 7.54 x 10-7 to 4.65 x 10-6) encompassing GALNT15, ZFHX3, NKAIN2, MME and NBPF22P were identified. Similar results were yielded with further adjustment for eGFR. Interestingly, the identified genes are associated with central nervous system function and clinical condition such as Alzheimer's disease or sleep disorders.Conclusions: We conducted the first GWAS for melatonin secretion and identified six candidate genetic loci associated with melatonin level. Replication and functional studies are needed in the future.
In Silico Design, Synthesis, Anti-Microbial and Anti-Tubercular Evaluation of New Series of Benzothiazinone Derivatives Containing Triazolo Thiadiazole Moiety
Authors: Jaiswal Paridhi , Kawathekar Neha , Jain Gourav , Jain Sanjay 
Published: July 2021

Abstract
Tuberculosis has proved harmful to the entire history of mankind from past several decades. Among the strategies for the development of new anti-tubercular lead compounds, Benzothiazinone (BTZ) were studied, with highly selective mechanism of action on DprE1 (Decaprenyl phosphoryl-b-D-ribose 2-epimerase) flavoenzyme. DprE1 is a vital enzyme for cell wall synthesis, plays a crucial role in the formation of D-arabinofuranose, a component of lipo-arabinomannan and arabinogalactam. Formation of covalent and non covalent bond by the interacting ligand with the enzyme causes loss of its catalytic activity which ultimately leads to death of the mycobacterium. The Benzothiazinone derivatives kill the mycobacterium by inhibiting the essential flavoenzyme DprE1. This study involves designing of a series of 16 Benzothiazinone derivatives that binds non covalently to DprE1. These derivatives were subjected to energy minimization and molecular docking studies with Schrodinger software, from which the binding free energy calculations showed that the suggested compounds had better binding affinity with DprE1. Ten compounds were selected for synthesis on the basis of docking score. The synthesized compounds were characterized and evaluated for their antimicrobial and anti-tubercular activity against different strains. Out of 5 evaluated compounds 3 compounds exhibited potent activity against microbial (Staphylococcus Aureus and Escherichia Coli) and tubercular (H37RV) strains. BTZ4 and BTZ10 has shown good activity against anti-microbial strain and BTZ8 has shown good activity against anti-tubercular strain. On the basis of docking results, we concluded that the selected new series of Benzothiazinone hybrid derivatives BTZ4, BTZ7, BTZ8, BTZ9, BTZ10 act on the Enzyme DprE1, against tuberculosis binding protein with PDB ID: 4NCR, as they may have better binding sites and better energy values, when compared with the standard drugs Ampicillin, Isoniazid and Rifampicin. So these derivatives (BTZ4, BTZ8, BTZ10) can be taken as best hit molecule and it could be useful for development of more new antimicrobial and anti-tubercular agents, blocking the mycobacterial cell wall formation.
Seroprevalence of Newcastle Disease Virus in Slaughtered Pigeons from Selected Markets in Zaria, Kaduna State Nigeria
Authors: Ibrahim Abdulhamid Burour , Wada Yusuf , Kamardeen Shamsudeen 
Published: July 2021

Abstract
Newcastle disease (ND) outbreak even in the face of vaccination is a common problem in Nigeria. Three Newcastle disease (ND) panzootic were recorded in the past and one of such was caused by feral pigeon fecal contamination of poultry feed materials. The study was designed to investigate the presence of ND antibodies in pigeons slaughtered in three markets in Zaria Nigeria. A total of 1500 Pigeons sera samples were tested across the selected markets, namely: Sabon-gari, Samaru and Tudun-wada markets. Five hundred blood samples were collected from each market. An overall seroprevalence of 22.33% (335/1500) was recorded in this study. Hemagglutination inhibition test revealed that pigeons from Sabon-gari market had the highest seroprevalence of 29% (145/500). Female pigeons had higher seroprevalence of 27.66% (130/470) compared to male pigeons 19.90% (205/1030). Younger pigeons of < 10 weeks old are more prone to ND infection with a seroprevalence of 34.21% (52/152) compared to pigeons > 10 weeks old 20.99% (238/1348). Also, only in Samaru market was there a significant association between ages (P = 0.00) and sexes (P = 0.00) of pigeons and seroprevalence of ND. Therefore, free routine ND vaccination campaign should be launched in the study areas with more emphases targeting the market species in order to mitigate the epidemic cycle of the virus. Moreover, market poultry farmers should be enlightened on the economic significance of the disease and the need to maintain strict biosecurity measures on their market farms.
Models Comparison And Validation With the Experimental Nano- Scale Silicon Substrate Based Annealed Pt/HfO2/Pt Resistive Random Access Memory Cell
Authors: A Napolean , NM Sivamangai , N Nithya , R Naveenkumar 
Published: July 2021

Abstract
Metal oxide resistive random access memory (RRAM) is a novel device that provides an alternate solution for existing CMOS memory devices. In RRAM, correlate the experimental result with a simulated result by a unique model is a critical task. This work focused on the validation of silicon substrate-based fabricated single layer annealed and electroformed at 80oC ambient temperature (A-80) RRAM cell. The experimental result concludes that the proposed Pt/HfO2/Pt device provides the forming voltage of 3.8 V, Vset = 1.7 V, and Vreset=-0.8 V. Switching results are compared with the simulated result which is working based on non-linear ion drift, Yakopcic and voltage threshold adaptive memristor (VTEAM) models. VTEAM model gives a closure relationship with experimental data and well suited for our fabricated device. Further, the VTEAM model is modified to contribute accurate results and one of the standard model metrics, accuracy is analysed for a modified VTEAM model. Statistical analysis proves that, the mean error percentage of modified VTEAM and VTEAM models against experimental outcomes are 21.4% and 25.3 % respectively
Bromodomain containing 4 (BRD4) as a potential prognostic marker in a pan-cancer analysis of human tumors
Authors: He Yi , Zhang Xudong , Zhu Chunfu , Qin Xihu 
Published: July 2021

Abstract
There is some evidence supporting an association between Bromodomain containing 4 (BRD4) and cancer, but no research using pan-cancer analysis has been conducted previously. We therefore investigated the oncogenic role of BRD4 in 33 tumors from the Gene Expression Omnibus and The Cancer Genome Atlas databases. BRD4 is highly expressed in many tumors, and the prognosis of certain cancers is vitally linked with BRD4 expression. BRD4 expression is associated with CD8+ T-cell infiltration levels in testicular germ cell tumors and head and neck squamous cell carcinomas, and we observed a positive relationship between BRD4 and Tcm (T central memory) and Th(T helper) cells, and a negative relationship pDC (plasmacytoid DC). BRD4 had negative associations with marophages, iDC, Treg, cytotoxic cells, and Th17 cells in multiple tumors. The top 100 genes that are most strongly related to BRD4 were identified, and enrichment analysis indicated that the biological process with the closest relationship was chromatin modifying enzymes, related pathways included the signaling pathways of intracellular receptor, cytokine Signaling in Immune system and regulation of TP53 activity through acetylation. BRD4 is related to biological cell behaviors such as DNA-templated transcription, regulation of histone modification, protein modification by small protein removal and mitotic sister chromatid segregation. As the first study to perform a pan-cancer analysis of BRD4, the present findings will improve the understanding of the oncogenic role of BRD4 in different tumors.
Characterization of Potential Candidate Genes for Grain Size in Wild Emmer Wheat Triticum Dicoccoides
Authors: Shinde Sanket , Dhillon Guriqbal Singh , Kaur Amandeep , Chhuneja Parveen , Sharma Achla , Kaur Satinder 
Published: July 2021

Abstract
There is an incessant need to address food security in staple crops, and the crop yield is positively correlated with grain weight. Grain size, determined by grain length and width, is an essential component of final grain weight in cereals. Wheat wild relatives are the goldmine to harness any trait of interest, including the component traits of grain size. It is crucial to understand the detailed mechanism of grain size formation and unravel underlying genes controlling grain size in these species for their proper utilization in wheat improvement. In this study, gene expression analysis was performed on developing grain in wild tetraploid progenitor Triticum dicoccoides (AABB) to identify candidate genes involved in determining grain size. Four T. dicoccoides accessions were selected, two (pau5228 and pau5322) with higher grain length and weight and two (pau14703 and pau14756) with comparatively smaller grains.Six genes out of the eight genes selected for expression study, viz., GL7, TaGL3, TaGS5, GS3, SRS3, and TaGASR7, were upregulated from 8 days post-anthesis (DPA) to 20 DPA in both the large grain accessions, while TaGW2 gene was upregulated in both small grain accessions. TGW6 was downregulated in all the accessions at all stages of grain development. The results indicated that the selected genes play an essential role in grain size formation by controlling individual morphometric components of grain length and width. Targeted introgression genes controlling grain size components will eventually aid in improving grains yield.
Synergy of nanodiamond-doxorubicin conjugates and PD-L1 blockade effectively turns tumor associated macrophages against tumor cells
Authors: Xu Huazhen , Li Tongfei , Wang Chao , Ma Yan , Liu Yan , Zheng Meiyan , Liu Zhang Jun Yan , Chen Jinbo , Li Ke , Sun Shikuan , Komatsu Naoki , Xu Yonghong , Zhao Li , CHEN XIAO 
Published: July 2021

Abstract
Background: Tumor-associated macrophages (TAM) are the most abundant stromal cells in the tumor microenvironment. Turning the TAM against their host tumor cells is an intriguing therapeutic strategy particularly attractive for patients with immunologically “cold” tumors. This concept was mechanistically demonstrated on in vitro human and murine lung cancer cells and their corresponding TAM models through combinatorial use of nanodiamond-doxorubicin conjugates (Nano-DOX) and a PD-L1 blocking agent BMS-1. Nano-DOX are an agent previously proved to be able to stimulate tumor cells’ immunogenicity and thereby reactivate the TAM into the anti-tumor M1 phenotype. Results: Nano-DOX were first shown to stimulate the tumor cells and the TAM to release the cytokine HMGB1 which, regardless of its source, acted through the RAGE/NF-κB pathway to induce PD-L1 in the tumor cells and PD-L1/PD-1 in the TAM. Interestingly, Nano-DOX also induced NF-κB-dependent RAGE expression in the tumor cells and thus reinforced HMGB1’s action thereon. Then, BMS-1 was shown to enhance Nano-DOX-stimulated M1-type activation of TAM both by blocking Nano-DOX-induced PD-L1 in the TAM and by blocking tumor cell PD-L1 ligation with TAM PD-1. The TAM with enhanced M1-type repolarization both killed the tumor cells and suppressed their growth. BMS-1 could also potentiate Nano-DOX’s action to suppress tumor cell growth via blocking of Nano-DOX-induced PD-L1 therein. Finally, Nano-DOX and BMS-1 achieved synergistic therapeutic efficacy against in vivo tumor grafts in a TAM-dependent manner. Conclusions: PD-L1/PD-1 upregulation mediated by autocrine and paracrine activation of the HMGB1/RAGE/NF-κB signaling is a key response of lung cancer cells and their TAM to stress, which can be induced by Nano-DOX. Blockade of Nano-DOX-induced PD-L1, both in the cancer cells and the TAM, achieves enhanced activation of TAM-mediated anti-tumor response.
Evaluation on the characteristics of gut microbiome in polycystic ovary syndrome rats induced by dihydrotestosterone or letrozole
Authors: Zheng Yan-hua , Xu Ying , Ma Hong-xia , Liang Cheng-jie , Yang Tong 
Published: July 2021

Abstract
Background: Etiology of polycystic ovary syndrome (PCOS) is unclear. Recent reports indicated that gut microbiota regulates metabolism and plays a major role in the development of PCOS. The present study aimed to investigate and compare the effects of dihydrotestosterone or letrozole on the gut microbiome in rats.Methods: We used dihydrotestosterone (DHT) or letrozole (LET) to induce PCOS model rats. At the end of the experiment, ovarian morphology, hormonal and metabolic status were investigated in all rats. We analyzed the gut microbiome of rats by deep sequencing the 16S rDNA V3-V4 hypervariable regions. Predictive metagenomics profiling using PICRUST revealed functional alternation of the KEGG pathways in rats.Result: Rats induced by letrozole exhibited endocrine and reproductive characteristics, such as hyperandrogenism, abnormal oestrus cycles or complete acyclic, polycystic ovaries, and obesity. DHT-induced rats were obesity, irregular oestrus cycles, polycystic ovaries, with lower level of HDL-C and lower activity of SOD than controls. The bacterial diversity (Chao1 and Ace) of DHT group was decreased compared with the control group. Furthermore, principal coordinates analysis revealed that DHT and control groups could be distinguished from each other. The DHT group exhibited increased numbers of Firmicutes, Cyanobacteria, Actinobacteria and Saccharibacteria, and decreased Bacteroidetes compared with the control group at the phylum level. Moreover, PICRUST-predicted KEGG pathways related to Carbohydrate metabolism, Amino acid metabolism, Metabolism of terpenoids and polyketides, Metabolism of other amino acids, Replication and repair, Lipid metabolism and Energy metabolism, Translation, Folding, sorting and degradation and Xenobiotics biodegradation and metabolism were significantly elevated in the DHT group. And pathways related to Metabolism of terpenoids and polyketides, Replication and repair, Xenobiotics biodegradation and metabolism, Nucleotide metabolism, Infectious diseases and Excretory system were significantly elevated in the LET group.Conclusion: The findings of the present study indicated that DHT affected the composition and diversity of gut microbial community, and leads to the gut dysbiosis. KEGG function profiles calculated by PICRUST suggested that DHT may affect metabolism of the gut microbiota more directly than letrozle.
EFEITOS DO MÉTODO DE REEQUILÍBRIO TORACOABDOMINAL SOBRE A FUNÇÃO CARDIORRESPIRATÓRIA DE PREMATUROS COM SÍNDROME DO DESCONFORTO RESPIRATÓRIO
Authors: Carvalho Andreza Marques , Zimpel Sandra Adriana , Costa Cinthia Maria Xavier , Teixeira Raphaela Farias 
Published: July 2021

Resumo
Objetivo: Avaliar os efeitos do método de reequilíbrio tóraco-abdominal sobre a função cardiorrespiratória de prematuros com Síndrome do Desconforto Respiratório. Métodos: Ensaio clínico não randomizado. Os recém-nascidos participantes do estudo foram divididos em dois grupos. O grupo 1 recebeu os manuseios do método de reequilíbrio tóraco-abdominal: apoio no espaço íleo-costal, apoio abdominal inferior e apoio tóraco-abdominal. O grupo 2 recebeu o tratamento que consistiu no alongamento dos músculos acessórios da respiração e mobilização da cintura escapular. Ambos os grupos foram avaliados antes e após o tratamento. A avaliação foi composta pela verificação da saturação periférica de oxigênio, frequência cardíaca, frequência respiratória e grau de desconforto respiratório a partir do Boletim de Silverman-Andersen. Resultados: Participaram do estudo 14 recém-nascidos. Foi verificado aumento significativo da saturação periférica de oxigênio nos recém-nascidos submetidos ao reequilíbrio tóraco-abdominal (p-valor = 0,04) e aumento significativo da frequência cardíaca nos recém-nascidos que receberam o tratamento de controle (p-valor = 0,01). Não houve diferença estatística na relação intergrupos e nos demais fatores avaliados na análise intragrupos. Conclusão: O método de reequilíbrio tóraco-abdominal produziu efeitos positivos sobre a saturação periférica de oxigênio de recém-nascidos diagnosticados com Síndrome do Desconforto Respiratório, não influenciando nos parâmetros de frequência cardíaca, frequência respiratória e grau de desconforto respiratório. O reequilíbrio tóraco-abdominal não demonstrou superioridade ao tratamento de controle exceto pela saturação periférica de oxigênio.