bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Differentially Expressed Genes and Enriched Pathways in SARS-CoV-2/ COVID-19 using Bioinformatics Analysis
Authors: Alshabi Ali Mohamed , Shaikh Ibrahim Ahmed , Vastrad Basavaraj Mallikarjunayya , Vastrad Chanabasayya Mallikarjunayya 
Published: December 2020

Abstract
BackgroundThe exact molecular mechanisms of the progression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remain unclear. The current investigation strived to understand and functionally analyze the differentially expressed genes (DEGs) between SARS-CoV-2 infection and mock samples applying extensive bioinformatics analyses.MethodsGSE148729 dataset was downloaded from the Gene Expression Omnibus (GEO) and investigated utilising the limma package in R software to identify DEGs. Pathway and gene ontology (GO) enrichment analysis of the up and down-regulated genes were performed in ToppGene. The HIPPIE database was applied to estimate the interactions of up and down-regulated genes and to construct a protein-protein interaction (PPI) network using Cytoscape software. Receiver operating characteristic (ROC) was utilized for validation.ResultsA total of 928 DEGs (461 up-regulated genes and 467 down-regulated genes) were identified between SARS-CoV-2 infection and mock samples. The up and down-regulated genes were significantly enriched in cytokine-cytokine receptor interaction, and ascorbate and aldarate metabolism. Several significant GO terms, including the response to biotic stimulus and oxoacid metabolic process, were identified. The top hub genes and target genes included JUN, FBXO6, PCLAF, CFTR, TXNIP, PMAIP1, BRI3BP, FAHD1, PROX1, CXCL11, SERHL2 and CFI. ROC curve analysis showed that messenger RNA levels of these ten genes (DDX58, IFITM2, IRF1, PML, SAMHD1, ACSS1, CYP2U1, DDC, PNMT and UGT2A3) exhibited better diagnostic efficiency between SARS-CoV-2 infection and mock.ConclusionsThe current investigation distinguished vital genes and pathways that may be implicated in the progression of SARS-CoV-2 infection, providing a new understanding of the underlying molecular mechanisms of SARS-CoV-2 infection.
A Mutational Signature that Predicts Prognosis and Benefit of Immune Checkpoint Blockade in Colorectal Cancer
Authors: Xu Liang , Lin Yanyun , Chen Xijie , Zheng Lisheng , Cheng Yufeng , Hu Jiancong , Zheng Bin , Zhang Bin , Li Guanman , Chi Zengjie , Guo Shuang , Liu Danling , He Xiaosheng , Lan Ping 
Published: December 2020

Abstract
Background: Colorectal cancer (CRC) is characterized by broad genomic and transcriptional heterogeneity. However, the genomic basis of this variability remains poorly understood. Our pilot study identified mutated genes were associated with immune infiltration. This study aims to explore a novel mutational signature (MS) in tumor microenvironment (TME) of CRC.Methods: We integrated single nucleotide variation and transcriptome data and collected corresponding clinicopathologic information from 1,133 and 588 CRC patients of Memorial Sloan Kettering Cancer Center and The Cancer Genome Atlas databases, respectively. Single sample gene set enrichment analysis (ssGSEA) was used to identify the subtypes of CRC based on the immune genomes of 29 immune signatures. CIBERSORT was used to analyze the infiltration of 22 immune cell types in the TME and immune-related gene expression CRC tissues. Results: In the training cohort, we identified a novel MS consisting of 27 genes and generated a prognostic model that classifies patients into high- and low-risk groups. The low-risk group was associated with better survival and more tumor mutational burden, microsatellite instability, and mismatch repair deficiency. The data were all verified in the validation set. Further analysis revealed that the MS was associated with tumor immunogenicity and immunocyte infiltration, and the determined risk score (RS) could be an index for the immunity level.Conclusion: We identified a MS that could assist clinicians to select immunotherapy responsive patients and the combination of RS and TNM stage could provide comprehensive prognostic information for CRC.
Efficacy of Early Administration of Liposomal Amphotericin B in Patients with Septic Shock: A Nationwide Observational Study
Authors: Tashiro Masato , Takazono Takahiro , Ota Yuki , Wakamura Tomotaro , Takahashi Akinori , Sato Kumiko , Miyazaki Taiga , Obata Yoko , Nishino Tomoya , Izumikawa Koichi 
Published: December 2020

Abstract
To determine the most suitable time to initiate liposomal amphotericin B (L-AMB) treatment in patients with invasive fungal infections, patients with septic shock treated with L-AMB were identified from the Japanese Diagnosis Procedure Combination national database to determine their survival rates following septic shock onset, mortality during shock, and shock cessation period. We identified 141 patients administered L-AMB: 60 patients received treatment on the day of septic shock onset (early L-AMB group), whereas 81 patients received treatment after the onset (delayed L-AMB group). Survival rates after septic shock onset were higher in the early L-AMB group than in the delayed L-AMB group (4 weeks: 68.4% vs 57.9%, P=0.197; 6 weeks: 62.2% vs 44.5%, P=0.061; 12 weeks: 43.4% vs 35.0%, P=0.168, respectively). Mortality during septic shock was significantly lower in the early L-AMB group than in the delayed L-AMB group (13% vs 42%, P<0.001), with a significant difference confirmed after adjusting for confounding factors (odds ratio: 0.240, 95% confidence interval: 0.096-0.601, P=0.002). Septic shock cessation period was shorter in the early L-AMB group than in the delayed L-AMB group (7.0±7.0 days vs 16.5±15.4 days, P<0.001). L-AMB administration at septic shock onset could be associated with early shock cessation and decreased mortality.
Androgen Receptor Splice Variant 7 Detected by Immunohistochemical Is an Independent Poor Prognostic Marker in Men Receiving Adjuvant Androgen-Deprivation Therapy After Radical Prostatectomy
Authors: Ouyang Wei , Zhang Yucong , Long Gongwei , Sun Guoliang , Liu Man , Li Fan , Yang Chunguang , Zeng Xing , Yang Jun , Yu Xiao , Wang Zhihua , Liu Zheng , Guan Wei , Hu Zhiquan , Wang Shaogang , Liu Xiaming , Li Heng , Xu Hua , Ye Zhangqun 
Published: December 2020

Abstract
Background: To evaluate the predictive value of AR-V7 expression detected by immunohistochemical (IHC) in the prognosis of prostate cancer patients receiving adjuvant hormonal therapy (AHT) following by radical prostatectomy (RP).Methods: We retrospectively collected data of 110 patients with prostate cancer receiving RP, followed by AHT, from Tongji hospital. IHC analysis of AR-V7 expression was performed in a retrospective cohort. Results: In total, 110 patients were enrolled, of whom 21 patients (19.1%) were AR-V7-positive and 89 patients (80.9%) were AR-V7-negative. No significant differences in baseline characteristics were found between the two groups. AR-V7-positive patients had shorter progression‑free survival (PFS) (HR: 4.26; 95% CI, 1.55 to 11.68; P=0.003), shorter (cancer-special survival) CSS (HR: 22.47; 95% CI, 2.912 to 173.4; P=0.003) and shorter overall survival (OS ) (HR: 6.61; 95% CI, 1.40 to 31.20; P=0.017) compared to AR-V7-negative patients. In multivariate analysis, AR-V7 is an independent risk factor for shorter PFS (HR, 3.76; 95% CI, 1.63 to 8.70; P=0.002), shorter CSS (HR: 9.17; 95% CI, 1.48 to 55.56; P=0.017) and shorter OS (HR: 4.81; 95% CI, 1.28 to 17.86; P=0.020).Conclusion: The presence of AR-V7 in prostate cancer tissue is independently associated with an unfavorable prognosis for PFS, OS and CSS in patients who received AHT.
Overexpression of ID1 mediates resistance to osimertinib in T790M positive non-small cell lung cancer through epithelial-mesenchymal transition
Authors: Liu Kejun , Fang Nianxin , Wu Ligang , Chen Shiyuan , Cai Limin , Jia Jun 
Published: December 2020

Abstract
Objective

To analyzed the effect of ID1 overexpression on osimertinib resistance to T790M positive non-small cell lung cancer (NSCLC).
Methods

We established drug resistant cell line H1975/OR from osimertinib sensitive cell line H1975. Protein alterations of ID1 and Epithelial mesenchymal transition (EMT) were detected with western blot analysis. RT-PCR was used to evaluate the differences of gene mRNA. ID1 silencing and overexpression was used to investigate the effect of related gene on osimertinib resistance. Cell Counting Kit-8 (CCK8) was used to assess proliferation rate of ID1 differently expressed cells. Cell cycle and apoptosis was compared using flow cytometry.
Results

In our study, we found that in osimertinib resistant NSCLC cells, the expression level of EMT related protein E-cadherin was lower than that of sensitive cells, while the expression level of ID1 and vimentin was higher than that of sensitive cells. ID1 expression level was closely related to E-cadherin and vimentin both in osimertinib sensitive and resistant cells. Alteration of ID1 expression in H1975/OR cells could change the expression of E-cadherin. Downregulating ID1 expression of H1975/OR cells could promote the apoptosis induced by osimertinib and block cell cycle at G1/G0 stage. Our study indicated that ID1 may induce EMT in T790M positive NSCLC, which mediates drug resistance of osimertinib.
Conclusions

Our study reveal the mechanism of ID1 mediated resistance to osimertinib in T790M positive NSCLC through EMT, which may provide new ideas and methods for treatment of EGFR mutated NSCLC after osimertinib resistance.
Unwrapping the Surprisingly High Risk of Dying from Cardiovascular Disease at Christmas: The HUNT Prospective Population-based Cohort Study in Norway
Authors: Moholdt Trine , Afoakwah Clifford , Scuffham Paul , McDonald Christine , Burrell Louise , Stewart Simon 
Published: December 2020

Abstract
BackgroundAlthough it is known that winter inclusive of the Christams holiday period is associated with an increased risk of dying compared to other times of the year, very few studies have specifically examined this phenomenon within a population cohort subject to baseline profiling and prospective follow-up. In such a cohort, we sought to determine the specific characteristics of mortality occuring during the Christmas holidays. MethodsBaseline profiling and outcome data were derived from a prospective population-based cohort with longitudinal follow-up in Central Norway - the Nord-Trøndelag Health Study. From 1984-1986, 88% of the target population comprising 39,273 men and 40,353 women aged 48±18 and 50±18 years, respectively, were profiled. We examined the long-term pattern of all-cause mortality and specific causes of death according to season, month and individual days of the year to determine the number of excess (cause-specific) deaths occuring at key timepoints (including the Christmas holidays). ResultsDuring 33.5 (IQR 17.1-34.4) years follow-up, 19,879 (50.7%) men and 19,316 (49.3%) women died at age-adjusted rate of 5.3 and 4.6 deaths per 1000/annum, respectively. Each winter, there were 44 (95% CI 43-45) more all-cause deaths compared to summer, with 21 (95% CI 20-22) more deaths attributable to cardiovascular disease. Compared to any other time of the year, December 25th-27th was the deadliest; being associated with an excess of 1.3 (95% CI 1.1-1.5) all-cause and 1.0 (95% CI 0.7-1.3) cardiovascular-related deaths per day each year. Compared to the pre-Christmas/Winter period (1st-21st December), the incidence rate ratio of all-cause mortality increased to 1.22 (95% CI 1.16-1.27) and 1.17 (95% 1.11-1.22) in men and women, respectively, in the next 21 days (Christmas/New Year holiday period). All observed differences were highly significant (P<0.001). A less pronounced pattern of seasonally-linked deaths attributable to respiratory illnesses (but not cancer) was also observed.ConclusionChristmas in Central Norway is characterised by a distinctive change and increase in cardiovascular-related mortality over and above that observed between winter (more deaths) and summer (fewer deaths). This distinctive pattern contrasted with cancer-related deaths. Further research to address vulnerability to the darker consequences of winter and, more specifically Christmas, is required.
Loss of Aklotho Causes Reduced Motor Ability and Short Lifespan in Zebrafish
Authors: Ogura Yurie , Ujibe Kota , Wakamatsu Yuma , Hirata Hiromi 
Published: December 2020

Abstract
The klotho gene encodes a transmembrane protein aKlotho that interacts with a fibroblast growth factor receptor in renal tubular epithelial cells and functions as a co-receptor for FGF23, which is an osteocytes-derived hormone. It is known that this bone-to-kidney signal promotes urinary phosphate excretion. Interestingly, aKlotho-deficient mice show accelerated aging and shortened life span in addition to dysregulation of serum phosphorus. However, physiological basis of aging-related function of aklotho and its generality in animals remain unclear. The aklotho-deficient vertebrate animals other than mice have been awaited as an alternative premature aging model. We here employed zebrafish in our aklotho study and revealed that aklotho mutant zebrafish appear to be normal at 3 months postfertilization (mpf) in young adults but eventually undergo premature death by 9 mpf, while normal zebrafish is known to survive for 42 months. We also assessed motor ability of zebrafish in a forced swimming assay and found that aklotho mutant zebrafish displayed reduced swimming performance before their survival declined. A recent study also reported a similar finding that aklotho-deficient zebrafish exhibited short life span and reduced spontaneous movements. Taken together, these results suggest that aKlotho mutant zebrafish show premature aging and are useful to investigate aging in vertebrates.
Sensory Geneidentificationin the Transcriptome of the Ectoparasitoid Quadrastichus Mendeliinthe Eucalyptus Gall wasp Leptocybe Invasa
Authors: Huang You , Wang Yun , Lu Wen , Zheng Lin 
Published: December 2020

Abstract
Gall-inducing insects live within plant tissues and induce tumor-like growth that provides insects with food, shelter, and protection from natural enemies. Interestingly, these insects can be precisely targeted by parasitoids. However, the chemical mechanism of the host location by parasitoids of gall-inducing insects has not been elucidated. Empirical evidence has shown that sensory genes play a key role in the host location of parasitoids. To date, the sensory genes that regulate parasitoids to locate gall-inducing insects have not been uncovered. An obligate ectoparasitoid, Quadrastichus mendeli Kim & La Salle (Hymenoptera: Eulophidae: Tetrastichinae), is one of the most important parasitoids of Leptocybe invasa, which is a global gall-making pest in eucalyptus plantations. Therefore, Q. mendeli - L. invasa provides an ideal system to study the way that parasitoids use sensory genes in gall-making pests. In this study, we present the transcriptome of Q. mendeli using high-throughput sequencing. In total, 31820 transcripts were obtained and assembled into 26925 unigenes in Q. mendeli. Then, the major sensory genes were identified, and phylogenetic analyses were performed with these genes from Q. mendeli and other model insect species. Three chemosensory proteins (CSPs), 10 gustatory receptors (GRs), 21 ionotropic receptors (IRs), 58 odorant binding proteins (OBPs), 30 odorant receptors (ORs) and 2 sensory neuron membrane proteins (SNMPs) were identified in Q. mendeli by bioinformatics analysis. Our report is the first to obtain abundant biological information on the transcriptome of Q. mendeli that provided valuable information regarding the molecular basis of Q. mendeli perception, and it may help to understand the host location of parasitoids of gall-making pests.
Thermal Transport Investigation in AA7072 and AA7075 Aluminum Alloys Nanomaterials Based Radiative Nanofluids by Considering The Multiple Physical Flow Conditions
Authors: Abbasi Adnan , Khan Umar , Ahmed Naveed , Mohyud-Din Syed Tauseef 
Published: December 2020

Abstract
In recent time, variety of nanomaterials have been reported in scientific literature, among these Aluminum Alloys AA7072 and AA705 are significant with thermal, physical and mechanical characteristics. These extensively used in manufacturing of spacecraft, aircraft parts and building testing. Keeping in view the significance of nanoliquids, the analysis of methanol suspended by AA7072 and AA7075 alloys under the multiple physical flow conditions is reported. The model is successfully treated by coupling of RK and shooting algorithm and examined the results for the flow regimes by altering ingrained physical parameters. Then physical interpretation of the results discussed comprehensively.
The potential impacts of the COVID-19 crisis on maternal and child undernutrition in low and middle income countries
Authors: Osendarp Saskia , Akuoku Jonathan , Black Robert , Headey Derek , Ruel Marie , Scott Nick , Shekar Meera , Walker Neff , Flory Augustin , Haddad Lawrence , Laborde David , Stegmuller Angela , Thomas Milan , Heidkamp Rebecca 
Published: December 2020

Abstract
The COVID-19-related economic crisis and food- and health-system disruptions threaten to exacerbate undernutrition in low- and middle-income countries (LMIC). We used three modelling tools (MIRAGRODEP, Lives Saved Tool, and Optima Nutrition Tool) to estimate impacts on child stunting, wasting, and mortality, maternal anemia, children born to low BMI women, and future productivity losses for three scenarios across 2020–2022 (n = 118 LMICs). We also estimated the additional cost of mitigation for six nutrition interventions to maximize non-stunted and alive children. By 2022 COVID-19 could result in an additional 9.3 million wasted and 2.6 million stunted children, 168,000 additional child-deaths 2.1 million maternal anemia cases, 2.1 million children born to low BMI women and US$29.7 billion future productivity losses due to excess stunting and child mortality. An additional $1.2 billion per year is needed to mitigate these effects. Governments and donors must maintain nutrition as a priority, continue to support resilient systems, and ensure efficient use of new and existing resources.
Missed Opportunities in Tuberculosis Investigation and Associated Factors at Public Health Facilities in Uganda&nbsp;
Authors: Kakame Keith , Namuhani Noel , Kazibwe Andrew , Bongomin Felix , Baluku Joseph , Baine Sebastian 
Published: December 2020

Abstract
BackgroundThe incidence of tuberculosis (TB) is high in Uganda; yet, TB case detection is low. A recent national TB prevalence survey revealed that only 16% of presumptive TB patients seeking care at health facilities were offered sputum microscopy or chest-X ray (CXR). The objective of this study was to determine the magnitude of, and patient factors associated with missed opportunities in TB investigation at public health facilities of Wakiso District in Uganda.MethodsA facility-based cross-sectional survey was conducted at 10 high volume public health facilities offering comprehensive TB services in Wakiso, Uganda, among adults (≥18 years) with at least one symptom suggestive of TB predefined according to World Health Organisation criteria. Using exit interviews, data on demographics, TB symptoms, and clinical data relevant to TB were collected. A missed opportunity in TB investigation was defined as a patient with symptoms suggestive of TB who did not have sputum and/or CXR evaluation to rule out TB. Poisson regression analysis was performed to determine factors associated with missed opportunities in TB investigation using STATA 14.ResultsTwo hundred forty seven presumptive TB patients were recruited into this study exiting at antiretroviral therapy (ART) clinics (n=132) or general outpatient clinics (n=115) at public health facilities. Majority of participants were females (161/247, 65.2%) and the mean +SD age was 35.1 + 11.5 years. Sputum and/or CXR were not requested from 138 (55.9%) patients with symptoms suggestive of TB disease. Patients who did not inform health workers about TB related symptoms were more likely to miss a TB investigation (adjusted prevalence ratio: 1.68, 95%CI; 1.36-2.08, P<0.001). Conclusion; A large proportion of patients with symptoms suggestive of TB did not have sputum and/ or CXR requested for investigation. Patients who did not inform health workers about their TB related symptoms were more likely to miss having sputum and/ or CXR requested. We recommend studies to explore barriers and facilitators of disclosure of TB symptoms to enable formulation of effective interventions to empower people to improve likelihood of disclosing TB related symptoms.
Impact of an Intermediate Respiratory Care Unit on Clinical Outcomes of COVID-19 Patients
Authors: Suarez-Cuartin Guillermo , Gasa Merce , Bermudo Guadalupe , Ruiz-Albert Yolanda , Hernandez-Argudo Marta , Marin Alfredo , Trias-Sabria Pere , Cordoba Ana , Ariza Albert , Sabater Joan , Romero Nuria , Subirana Cristina , Molina-Molina Maria , Santos Salud 
Published: December 2020

Abstract
Background: Many severe COVID-19 patients require respiratory support and monitoring. An intermediate respiratory care unit (IMCU) may be a valuable element for optimizing patient care and limited health-care resources management. We aim to assess the impact of an IMCU in the management of severe COVID-19.Methods: Observational, retrospective study including patients admitted to the IMCU due to COVID-19 pneumonia during the months of March and April 2020. Patients were stratified based on their requirement of transfer to the intensive care unit (ICU) and on survival status at the end of follow-up. A multivariable Cox proportional hazards method was used to assess risk factors associated with mortality.Results: A total of 253 patients were included. Of them, 68% were male and median age was 65 years (IQR 18 years). Ninety-two patients (36.4%) required ICU transfer. Patients transferred to the ICU had a higher mortality rate (44.6% Vs 24.2%; p<0.001). Multivariable proportional hazards model showed that age ³65 years (HR 4.14; 95%CI 2.31-7.42; p<0.001); chronic respiratory conditions (HR 2.34; 95%CI 1.38-3.99; p=0.002) and chronic kidney disease (HR 2.96; 95%CI 1.61-5.43; p<0.001) were independently associated with mortality. High-dose systemic corticosteroids followed by progressive dose tapering showed a lower risk of death (HR 0.15; 95%CI 0.06-0.40; p<0.001). Conclusions: IMCU allow to safely and effectively manage severe COVID-19 patients requiring respiratory support and non-invasive monitoring, therefore reducing ICU burden. Older age and chronic respiratory or renal conditions are associated with worse clinical outcomes, while treatment with systemic corticosteroids may have a protective effect on mortality.