bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real Time Viral Sub-Strains Discovery in Emerging Infectious Disease Situation – The African Perspective
Authors: Ekpenyong Moses Effiong , Uzoka Faith-Michael , Edoho Mercy , Inyang Udoinyang G. , Udo Ifiok J , Uto Nseobong P. , Ekaidem Itemobong S. , Moses Anietie E. , Anwana Enoabasi D. , Tatfeng Youchou M. , Joseph Geoffery , Dan Emmanuel A. , Ndunagu Juliana 
Published: November 2020

Abstract
Background: The increased number of accessible genomes has prompted large-scale comparative studies for discerning evolutionary knowledge of infectious diseases, but challenges such as non-availability of close reference sequence(s), incompletely assembled or large number of genomes, preclude real time multiple sequence alignment and sub-strain(s) discovery. This paper introduces a cooperatively inspired open-source framework, for intelligent mining of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genomes. We situate this study within the African context, to drive advancement on state-of-the-art, towards intelligent infectious disease characterization and prediction. The outcome is an enriched Knowledge Base, sufficient to provide deep understanding of the viral sub-strains’ identification problem. We also open investigation by gender, which to the best of our knowledge has been ignored in related research. Data for the study came from the Global Initiative on Sharing All Influenza Data database (https://gisaid.org) and processed for precise discovery of viral sub-strains transmission between and within African countries. To localize the transmission route(s) of each isolate excavated and provide appropriate links to similar isolate strain(s), a cognitive solution was imposed on the genome expression patterns discovered by unsupervised self-organizing map (SOM) component planes visualization. The Freidman-Nemenyi’s test was finally performed to validate our claim. Results: Evidence of inter- and intra-genome diversity was noticed. While some isolates (or genomes) clustered differently, implying different evolutionary source (or high-diversity), others clustered closely together, indicating similar evolutionary source (or less-diversity). SOM component planes analysis revealed multiple sub-strains patterns, strongly suggesting local- or intra-community and country to country transmissions. Cognitive maps of both male and female isolates revealed multiple transmission routes. Freidman’s test results showed highly significant difference (p<0.01) among the various isolate groups. Nemenyi’s test revealed groups that differed in their isolates.Conclusion: The proposed framework offers explanations to SARS-CoV-2 diversity and provides real time identification to disease transmission routes, as well as rapid decision support for facilitating inter- and intra-country contact tracing of infected case(s). Intermediate data produced in this paper are helpful to enrich the genome datasets for intelligent characterization and prediction of COVID-19 and related pandemics, as well as the construction of intelligent device for accurate infectious disease monitoring.
Treatment of Non-small cell lung cancer with AiDi injection based on network pharmacology
Authors: Qiu Suishan , Xue Lianfang , Liu Hui , Zhong Huiting , Li Leping 
Published: November 2020

Abstract
Background: This study aimed to determine the bioactive compounds, core genes, and pharmacological mechanisms underlying the effects of Aidi injection (ADI) in non‐small cell lung cancer (NSCLC), and to provide a further research directions. Material and Methods: The bioactive compounds of ADI were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and the Traditional Chinese Medicines Integrated Database, while targets related to these bioactive compounds and NSCLC were obtained from the GEO database. Cytoscape software was used to construct ingredients–protein-targets–pathway networks. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses and network analysis were performed to investigate potential mechanisms underlying the effects of ADI on NSCLC.Results: This study screened 45 bioactive compounds and 38 major proteins of ADI as potential agents that can act against NSCLC. The results revealed the following potential therapeutic targets of ADI in the treatment of NSCLC: FOS, VEGFA, EGFR, JUN, MMP9, IL2, STAT1, CASP1, NFKBA, and CDK2. The potential mechanisms via which ADI acts against NSCLC are closely related to the inhibition of apoptosis and the activation of signaling pathways. Conclusion: This study has revealed the multicompound, multitarget, and multichannel characteristics of ADI. This provides novel insight into further research investigations of the mechanism of ADI in NSCLC treatment.
Successful Treatment of Severe Myocardial Injury Complicated With Refractory Cardiogenic Shock Caused by AOPP Using Extracorporeal Membrane Oxygenation
Authors: Li Yang , Cao ChunShui , Luo XiaoLong , Huang Liang 
Published: November 2020

Abstract
Acute organophosphorus pesticide poisoning (AOPP) is a common critical illness observed in clinical practice, and severe AOPP can cause serious cardiac toxicity. We report a case of severe myocardial injury caused by AOPP complicated with refractory cardiogenic shock that was successfully rescued with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) therapy. We suggest that for patients with severe myocardial injury complicated with cardiogenic shock following AOPP, the use of VA-ECMO therapy can improve the prognosis.
A Novel Amorphous Curcumin Preparation Improved Oral Absorption Efficiency in Healthy Volunteers: A Single-Dose, Double-Blind, Two-Way Crossover Study
Authors: Sunagawa Yoichi , Miyazaki Yusuke , Funamoto Masafumi , Shimizu Kana , Shimizu Satoshi , Nurmila Sari , Katanasaka Yasufumi , Ito Masashi , Ogawa Tatsuya , Ozawa-Umeta Hitomi , Hasegawa Koji , Morimoto Tatsuya 
Published: November 2020

Abstract
Background: Curcumin has diverse biological activities such as anti-cancer, antioxidant, and anti-inflammatory properties and is assumed to exhibit beneficial effects in the prevention and treatment of various diseases. Although curcumin is known to be safe in humans, its therapeutic efficacy is limited owing to its poor bioavailability. To overcome this problem, we prepared a novel curcumin preparation curcuRougeTM using the amorphous solid dispersion method. In this study, we aimed to investigate the oral absorption efficiency of curcuRougeTM and compare its efficiency with that of Theracurmin®, a highly absorptive curcumin preparation dispersed with colloidal submicron-particles exhibiting improved bioavailability, in rats and healthy volunteers. Methods: In the animal experiment, male Sprague–Dawley rats were orally administered curcuRougeTM or Theracurmin® (10 mg/kg of curcumin). The plasma curcumin levels were measured at 0.25, 0.5, 1, 2, 4, and 6 h after administration. In addition, we performed a single-dose, double-blind, two-way crossover study to compare plasma curcumin levels after the administration of curcuRougeTM or Theracurmin® in humans. Twelve healthy volunteers were administered curcuRougeTM or Theracurmin® containing 30 mg curcumin. The plasma curcumin concentrations at 0.5, 1, 2, 4, and 8 h after ingestion were determined. Results: The area under plasma concentration–time curve (AUC0-6 h) and maximum plasma concentration (Cmax) of curcuRougeTM in rats were 3.7- and 9.6-fold higher than those of Theracurmin®, respectively. Twelve healthy volunteers were orally administered 90 mg of curcuRougeTM or Theracurmin® in a randomized double-blind crossover study. In these volunteers, the AUC0-8 h and Cmax of curcuRougeTM were 3.4-fold and 5.4-fold higher than those of Theracurmin®, respectively. Conclusion: These findings indicate that curcuRougeTM shows better bioavailability than other highly absorptive curcumin preparations, such as Theracurmin®. Hence, curcuRougeTM is assumed to exhibit clinical efficacy for managing various diseases at a low dose.Trial registration: The trial was registered with the UMIN Clinical Trials Registry (January 8, 2020, UMIN000039083, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000044573).
Inflammatory Arthritis Complicating Galactosialidosis: A Case Report
Authors: Verkuil F. , Bosch A.M. , Struijs P.A.A. , Hemke R. , Berg J.M. van den 
Published: November 2020

Abstract
Background Galactosialidosis (GS) is a rare inherited lysosomal storage disorder (LSD) which is characterized by a defect in the lysosomal glycoprotein catabolism. We report, for the first time, the case of a child affected by GS presenting with recurrent episodes of extensive joint inflammation in both knee joints. The aim of this case-report is to describe the clinical presentation as well as the laboratory, radiologic and microscopic features of this unique presentation of GS. Furthermore, we explore inflammatory mechanisms potentially responsible for the origination of the arthritic joint pathology observed in our patient.Case presentationWe describe the rare case of a 12-year-old boy diagnosed with GS (late infantile form) who presented with multiple episodes of inflammatory arthritis involving both knees; no other joints were suspected for joint inflammation. Laboratory results did not indicate an autoimmune disorder. Synovial fluid tested negative for any bacterial infection and ruled out a malignancy and crystal induced arthritis. Microscopic examination of the synovial tissue revealed numerous foamy macrophages with extensive vacuolization, consistent with the previous diagnosis of GS. Treatment consisted of aspiration of excessive joint fluid and subsequent intra-articular injection of triamcinolonhexacetonide with excellent but transient result. Given the evidence of storage products within macrophages of the inflamed synovial tissue and the absence of other etiological clues, GS itself was considered as the primary cause for the relapsing inflammatory joint pathology. According to the restricted data on articular manifestations in GS, to date, GS cannot be linked directly to joint inflammation. Nevertheless, in several other LSDs, the accumulation of storage material has been associated with numerous osteoimmunological changes that might play a role in the pathophysiology of arthritic processes. Conclusions We hypothesize that the articular build-up of GS storage products triggered systemic as well as local inflammatory processes, resulting in the extensive inflammatory joint pathology as observed in our patient. Future identification of other patients with GS is required to corroborate the existence of an arthritic clinical phenotype of GS and to assess the underlying pathophysiology.
Platelets Count During Circulatory Assistance: Involvement in the Changes of Oxygenation Membrane
Authors: Azhari Alaa , Sawadogo Adama , D'ostrevy Nicolas , Lambert celine , Pereira Bruno , Azarnoush Kazra , CAMILLERI Lionel 
Published: November 2020

Abstract
BackgroundTo study the evolution of platelet count during patient treatment with Extra-Corporeal Membrane Oxygenation (ECMO) and the causes of Membrane Oxygenation (MO) exchange. Assessment of the morbidity and mortality rate was our secondary objective. MethodsA single center retrospective study was conducted from January 2014 to December 2015. One-hundred and thirty-nine MO exchanges were studied over 73 patients who received 66 MO exchange. Alterations in biological parameters were compared before and after each MO exchange, to study the device-related platelet count evolution. ResultsMean patient age was 56.8 ± 13.4 years. The mean duration of the MO was 5.9 ± 3.1 days, exchanged 26 times (68%) after clot formation. The median Survival After Veno-arterial ECMO score (SAVE score) was -3.5 [-4; -1] interquartile range [IQR]. The median Respiratory Extra-corporeal membrane Oxygenation Survival Prediction score (RESP score) was -1 [-3; 0] [IQR]. A significant decrease (p<0.001) in platelet count between the first and second MO exchange was observed in comparison with the baseline. Yet a steady decline was noted after the third MO exchange, afterwards, normalization was observed after ECMO weaning. During ECMO, a decrease in platelet count from the baseline was found after the first MO on day 2 (p<0.001), the delta was 58.000 ± 19.000 /µL, followed by an additional significant decrease on day 3 (p=0.001). The average platelet transfusion was 0.6 ± 1.4 units. Interestingly, the more MO was exchanged, the lesser blood products transfusion was done. The overall mortality rate was 39 %; in Veno-Arterial ECMO (VA-ECMO) it was 34.48% and 41.38 % in Veno-Venous ECMO (VV-ECMO). Conclusion﻿Clot formation is the leading cause of MO exchange during ECMO. Therefore, there is a significant decrease in platelets count starting from day 2 that indicates platelets transfusions in order to prevent complications of hemostasis.
Estimation of 18F-FDG PET Image Texture Features for Metastasis Prediction in Non-Small Cell Lung Cancer Using Epithelial Mesenchymal Transition-Related Genes
Authors: Kim Byung-Chul , Lim Ilhan , Byun Byung Hyun , Kim Jingyu , Woo Sang-Keun 
Published: November 2020

Abstract
Purpose: The aim of this study was to estimate a metastasis prediction image factor in non-small cell lung cancer by correlation next generation sequence gene expression level and fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography image features.Methods: RNA-sequencing data and 18F-FDG PET images of 63 patients with NSCLC (29 metastasis and 34 non-metastasis) from The Cancer Imaging Archive and The Cancer Genome Atlas Program databases were used in a combined analysis. Weighted correlation network analysis was performed to identify gene groups were related metastasis. Module was selected with high module significance. Genes selection was performed by gene function related metastasis and high AUC (AUC > 0.6). A total of 47 image features were extracted from PET images as radiomics. The relationship of Gene expression and image features were calculated by using a hypergeometric distribution test with the Pearson correlation method. Metastasis prediction model was validated by random forest algorithm using image texture features related gene expression.Results: 36 modules were identified by gene expression pattern with WGCNA assay. The modules had highest module significance was selected assay. 7 genes from selected module were identified to involve in the epithelial mesenchymal transition pathway that have important role in the cancer metastasis and had high AUC. Also, expression of these genes was related to quantitative of image feature (GLCM_contrast, -log10 P-value: 2.45~3.89). The AUC value (accuracy: 0.856 ± 0.06, AUC: 0.868 ± 0.05) was shown from the EMT-related gene and GLCM_contrast model and AUC value (accuracy: 0.842 ± 0.06, AUC: 0.838 ± 0.09) was shown from GLCM_contrast image texture model. Conclusion: GLCM_contrast image texture feature shows relationship with EMT related gene expression. We developed a model for predicting metastasis of non-small cell lung cancer using 18F-FDG PET image feature and evaluated its accuracy.
Far Infrared Light Irradiation Enhances Microglial Aβ Clearance and Ameliorates Cognitive Deficit in Alzheimer’s Disease-Like Mice
Authors: Li Qingyong , Wu Wensi , Lu Yanan , Wen Jing , Ren Jiaoyan , Zhao Huiying , WANG Zhi 
Published: November 2020

Abstract
BackgroundExposure to sunlight may decrease the risk of developing Alzheimer’s disease (AD). However, the wavelength of the light with this therapeutic effect and the related mechanism remain elusive. MethodWe evaluated the behaviors of AD-like mice treated by light of different wavelengths and showed that far infrared (FIR) light (λ = 3 - 25 μm) had a great potential in ameliorating cognition dysfunction. ResultsFIR light treatment promoted the recruitment of microglia to Aβ plaques, enhanced the phagocytosis of Aβ and decreased neuroinflammatory responses. Thus, FIR light treatment had a broad spectrum of beneficial effects on the brain, including alleviating the Aβ burden and neuroinflammation. Conclusions﻿As a result, FIR light treatment ameliorates the learning and memory impairment in AD-like mice. Our findings uncovered a previously unappreciated function of FIR light, suggesting that FIR light treatment may be a potential therapeutic strategy for AD.
Genetic Profiling in Heterogeneous High-Grade Adenoid Cystic Carcinoma Identifies NOTCH1 Inhibition as a Therapeutic Strategy
Authors: Wang Yu , Sun Bao , Zhang Chunye , Xia Ronghui , Wang Lizhen , Sun Jingjing , Gu Ting , Tian Zhen , Li Jiang 
Published: November 2020

Abstract
Background

High-grade adenoid cystic carcinomas (ACCs), consisting mostly of the solid type along with the occasional high-grade transformation (ACC-HGT) type, are highly aggressive and heterogeneous tumors. Because of the rarity of the tumors, therapeutic strategy guided by genetic profiles based on next generation sequencing (NGS) has been not published on these tumors.
Results

Forty-four tissues microdissected from 36 high-grade ACC cases (31 solid type ACCs and 5 ACC-HGTs) were included in our study. The solid components from the 31 solid ACCs, were enriched for mutations of genes in the NOTCH (NOTCH1, 68%; SPEN 23%) and the chromatin-remodeling pathway and were absent of the myoepithelial cell differentiation. The cases with NOTCH1 mutation exhibited strong NCID expression, which was associated with poor distant metastasis-free survival. BRCA2 mutation was observed in 23% of solid ACCs, conferring sensitivity to PARP inhibitors. From 5 of the solid ACCs, the intratumor heterogeneity was delineated between the cribriform/tubular and the solid components. NOTCH1 and FGFR2 mutations as well as NOTCH2 amplification were restricted to the solid component indicating the clonal selection within the same tumor. From 2 aggressive solid ACCs the subclones evolved in progression for local relapse and distant metastasis, although they manifested close genomic resemblance to primary tumors. Five tumors of ACC-HGTs were characterized by a loss of biphasic ductal-myoepithelial differentiation in HGT area and enriched for alterations in the NOTCH, P53 and PI3K pathways. Guided by the genetic profiles, the preclinical efficiency of a gamma-secretase inhibitor BMS-906024 was evaluated in the ACC patient-derived xenografts (PDXs) models with activating NOTCH1 mutation and it demonstrated robust antitumor effects.
Conclusion

This is the first report to describe the intratumor heterogeneity within a solid ACC as well as the intertumor evolution of clones among the primary/recurrent/metastatic tumors. Different from conventional ACCs, high-grade ACCs should be approached with a distinct therapeutic strategy particularly targeting NOTCH1 by gamma-secretase inhibitors. Microdissecting the highest grade component guided by histology is a highly recommended tumor sampling strategy and facilitates the detection of key molecular targets.
PACAP-derived peptide MPAPO impacts Adipose-derived stem cells adipogenic differentiation
Authors: Xian Wang Zi , Qian Liu , Min Liu Jian , Qiong Zheng Zi , Jia Feng , Yan Ji Chun , Xin Dai Jia , Qing Zhou Hai , Yi Ma 
Published: November 2020

Abstract
BackgroundRegenerative medicine and tissue engineering have brought new therapeutic prospects to the treatment of soft tissue defects, but the selection of seed cells is the key to treatment. Adipose-derived stem cells (ASCs) have always been a popular candidate for seed cells because of their rich sources, easy access, high plasticity, and strong value-added capabilities. The purpose of the current study is to explore the role of PACAP -derived peptide MPAPO on the adipogenic differentiation of ASCs and its molecular mechanism.MethodsThe effect of MPAPO on the proliferation of adipose-derived stem cells were detected by CCK-8 assay and PI single-staining-flow. To reveal the direct effect of MPAPO on the adipogenic differentiation of ASCs, a model of adipogenic differentiation of adipose stem cells was established. In addition, adipogenic differentiation capacity was assessed using Oil-Red-O Staining, Triglyceride (TG) assay and quantification of gene expression. Finally, the relationship between ASCs adipogenic differentiation and the ERK signaling pathway was explored by Western blot.ResultsMPAPO treatment can significantly promote the proliferation of ASCs. In addition, PACAP treatment improves the adipogenic differentiation efficiency of ASCs, including promoting the accumulation of lipid droplets and triglycerides, and the expression of adipogenic-related transcription factors PPARγ and C/EBPα. The mechanism studies showed that MPAPO selectively binds to the PAC1 receptor to promote the adipogenic differentiation of ASCs via activating the ERK signaling pathway.ConclusionsThe present study shows that MPAPO could promote the adipogenic differentiation of ASCs by activating the ERK signaling pathway, and provide relevant experimental evidence for the filling of clinical tissue defects.
Sex-dependent Gut Microbiota-brain-cognition Associations: A Multimodal MRI Study
Authors: Zhang Shujun , Cai Huanhuan , Wang Chunli , Zhang Cun , Zhao Wenming , Zhang Tingting , Zhang Biao , Chen Jingyao , Liu Siyu , Zhu Jiajia , Yu Yongqiang 
Published: November 2020

Abstract
Background: There is bidirectional communication between the gut microbiota and the brain. Empirical evidence has demonstrated sex differences in both the gut microbiome and the brain. However, the effects of sex on the gut microbiota-brain associations have yet to be determined. Methods: 157 healthy young adults underwent brain structural, perfusion, functional and diffusion MRIs to measure gray matter volume (GMV), cerebral blood flow (CBF), functional connectivity strength (FCS) and white matter integrity, respectively. Fecal samples were collected and 16S rRNA gene amplicon sequencing was utilized to assess gut microbial diversity. Correlation analyses were conducted to test for sex-dependent associations between microbial diversity and brain imaging parameters, and mediation analysis was performed to further characterize the gut microbiota-brain-cognition relationship. Results: We found that higher gut microbial diversity was associated with higher GMV in the right cerebellum Ⅵ, higher CBF in the bilateral calcarine sulcus yet lower CBF in the left superior frontal gyrus, higher FCS in the bilateral paracentral lobule, and lower diffusivity in widespread white matter regions in males. However, these associations were absent in females. Of more importance, these neuroimaging biomarkers significantly mediated the association between gut microbial diversity and behavioral inhibition in males. Conclusions: These findings highlight sex as a potential influential factor underlying the gut microbiota-brain-cognition relationship, and expose the gut microbiota as a biomarker-driven and sex-sensitive intervention target for mental disorders with abnormal behavioral inhibition.