bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk and predictors of in-hospital mortality from COVID-19 in patients with diabetes and cardiovascular disease
Authors: Rastad Hadith , Karim Hossein , Ejtahed Hanieh-Sadat , Tajbakhsh Ramin , Noorisepehr Mohammad , Babaei Mehrdad , Azimzadeh Mehdi , Soleimani Alireza , Inanloo Seyed Hasan , Hassani Neda Shafiabadi , Rasanezhad Fariba , Shahrestanaki Ehsan , Khodaparast Zeinab , Golami Hossein , Qorbani Mostafa
Published: June 2020

Background: Diabetes mellitus (DM) and cardiovascular disease (CVD) are present in a large number of patients with novel Coronavirus disease 2019 (COVID-19). We aimed to determine the risk and predictors of in-hospital mortality from COVID-19 in patients with DM and CVD.Methods: This retrospective cohort study included hospitalized patients aged ≥ 18 years with confirmed COVID-19 in Alborz province, Iran, from 20 February 2020 to 25 March 2020. Data on demographic, clinical and outcome (in-hospital mortality) data were obtained from electronic medical records. Self-reported comorbidities were classified into the following groups: “DM” (having DM with or without other comorbidities), “only DM” (having DM without other comorbidities), “CVD” (having CVD with or without other comorbidities), “only CVD” (having CVD without other comorbidities), and “having any comorbidity”. Multivariate logistic regression models were fitted to quantify the risk and predictors of in-hospital mortality from COVID-19 in patients with these comorbidities.Results: Among 2957 patients with COVID-19, 2656 were discharged as cured, and 301 died. In multivariate model, DM (OR: 1.62 (95%CI: 1.14-2.30)) and only DM (1.69 (1.05-2.74)) increased the risk of death from COVID-19; but, both CVD and only CVD showed non-significant associations (p>0.05). Moreover, “having any comorbidities” increased the risk of in-hospital mortality from COVID-19 (OR: 2.66 (95%CI: 2.09 -3.40)). Significant predictors of mortality from COVID-19 in patients with DM were lymphocyte count, creatinine and C-reactive protein (CRP) level (all P- values < 0.05).Conclusions: Our findings suggest that diabetic patients have an increased risk of in-hospital mortality following COVID-19; also, lymphocyte count, creatinine and CRP concentrations could be considered as significant predictors for the death of COVID-19 in these patients.
LncRNA BANCR Facilitates Melanoma Cells Growth, Migration and Invasion by Inhibiting miR-206 and miR-571 to Induce G6PD Expression
Authors: Yang Yuye , Yang Huixin , Yi Zihan , Yang Lijuan , Ni Yueli , Zhou Meiling , Xiong Guohang , AGBANA Yannick Luther , Zhao Lei , Yang Zhe , Zhang Qiao , Kuang Yingmin , Zhu Yuechun
Published: June 2020

Background Here, we evaluated the roles of LncRNA BANCR in facilitating melanoma cells growth, migration, invasion. Moreover, we examined the molecular mechanisms of BANCR in promoting melanoma development.Methods Here, we measured BANCR expression by quantitative PCR. By transwell assay, we detected the cancer cell migration and invasion. The melanoma growth and migration induced by BANCR was detected by colony formation assay and in xenograft nude mice model. By Western blotting and luciferase assay, we evaluated the molecular mechanism of BANCR in inhibiting miR-206 and miR-571 to induce G6PD expression. Results We found BANCR was overexpressed in melanoma cells and tissues. In addition, we showed that BANCR promoted melanoma cells growth in vitro and in vivo. Moreover, BANCR promotes cancer cell migration and invasion in vitro, and induced melanoma metastasis in nude mice model. The migration and invasion induced by BANCR in melanoma cells were involved in upregulation of matrix metalloproteinases (MMPs) MMP2 and MMP9. Mechanismly, we indicated BANCR promoted melanoma cell growth and migration by suppressing miR-206 and miR-571 expression to activate glucose metabolism pathway and induce G6PD expression. Furthermore, miR-206 and miR-571 inhibited G6PD expression by directly binding the 3’UTR of G6PD. We also showed miR-206 and miR-571 inhibited the proliferation of melanoma cells.Conclusion Our findings indicated that BANCR contributed to melanoma development, which might provide novel insights into the function of lncRNA-driven carcinogenesis in melanoma.
Determining Causes of Gully Erosion and Associated Rates of Change in South-east Nigeria, Using a Remote Sensing and GIS Methodology
Authors: Iro Sylvanus Ibeabuchi
Published: June 2020

In this work a study of gully erosion in southeast Nigeria is presented. The study of gully development on a regional scale is currently undermined by the inherent costs associated with consistent field monitoring and the lack of historic measurements to perform time series analysis. The analysis of study area topography at 30m resolution reveals 85% of the surveyed gullies develop on concave slopes with high values of 6 plan curvatures and >50 inclines. Results also reveal high association with ferralsols soils. Statistical analysis to determine significance of variables on the proportional yearly gully change in metre squared per square metre were conducted via principle component analysis. The analysis of this work was restricted to the time periods 2006/7, 2009/10, and 2014/15. The approach did not report any existence of one singular driver of erosion across the studied years and multiple sites confirming the complexity of gullies. The PCA showed that the level of variance explained in the yearly gully change variable was most similar in PC1 (representing the component with the highest eigenvalue) to Vegetation loss, Vegetation loss and slope in the respective years.The study offers a method of monitoring gully development from early stage to maturity and exemplifies the complexity and variability of erosion drivers in the SE Nigeria region. It presents a verified approach to local and regional monitoring of gullies, enacted through use of low budget/computing cost remote sensing and classification technologies, and serves to embolden civilian and governmental efforts to manage the societal and environmental menace of gully erosion.
Mapping Regional Forest Management Units: A Road-based Framework in Southeastern Coastal Plain and Piedmont
Authors: Yang Di , Fu Chiung-Shiuan
Published: June 2020

Management practices are one of the most important factors affecting forest structure and function. Landowners in southern United States manage forests using appropriately sized areas, to meet management objectives that include economic return, sustainability, and esthetic enjoyment. Road networks spatially designate the socio-environmental elements for the forests, which represented and aggregated as forest management units. Road networks are widely used for managing forests by setting logging roads and firebreaks. We propose that common types of forest management are practiced in road-delineated units that can be determined by remote sensing satellite imagery coupled with crowd-sourced road network datasets. Satellite sensors do not always capture road-caused canopy openings, so it is difficult to delineate ecologically relevant units based only on satellite data. By integrating citizen-based road networks with the National Land Cover Database, we mapped road-delineated management units across the regional landscape and analyzed the size frequency distribution of management units. We found the road-delineated units smaller than 0.5 Ha comprised 64% of the number of units, but only 0.98% of the total forest area. We also applied a statistical similarity test (Warren’s I) to access the equivalency of road-delineated units with forest disturbances by simulating a serious of neutral landscapes. The outputs showed that the whole southeastern U.S. has the probability of road-delineated unit of 0.44 and production forests overlapped significantly with disturbance areas with an average probability of 0.50.
Associations between substandard housing and depression: Insights from the Korea Welfare Panel Study
Authors: KIM Selin , Jeong Wonjeong , Jang Bich Na , Park Eun-Cheol , Jang Sungin
Published: June 2020

Background
Housing is an important social determinant of health. Poor housing conditions are associated with a wide range of health conditions, including mental health. The study aimed to investigate the association between substandard housing and depression.
Methods
We used panel data collected by the Korea Welfare Panel Study and a sample drawn from waves 11 (2016) to 13 (2018). Substandard housing was defined via three criteria: the minimum residential area and number of rooms by application, essential facility standards, and environmental standards. Depression was measured with the CESD-11. A generalized estimating equation model was used to investigate associations between substandard housing and CESD-11 scores.
Results
Participants living in substandard housing have higher depression scores (male: β = 0.63, female: β = 0.40) than participants who do not live in substandard housing. Participants who do not meet environmental standards have higher depression scores (male: β = 0.85, female: β = 0.66) than participants who do not live in substandard housing; the findings are seen in both men and women.
Conclusion
This study identified an association between substandard housing and depression by gender, and the results were significant. We found that among the three criteria, environmental standards are most likely to be associated with depression. In practical terms, we should consider improving environmental factors of housing to mitigate mental health issues related to substandard housing.
Multi-model seascape genomics identifies distinct environmental drivers of selection among sympatric marine species
Authors: Nielsen Erica , Henriques Romina , Beger Maria , Toonen Robert , Heyden Sophie von der
Published: June 2020

Background: As global change and anthropogenic pressures continue to increase, conservation and management increasingly needs to consider species’ potential to adapt to novel environmental conditions. Therefore, it is imperative to characterise the main selective forces acting on ecosystems, and how these may influence the evolutionary potential of populations and species. Using a multi-model seascape genomics approach, we compare the dominant environmental drivers of selection in three sympatric southern African marine invertebrates with contrasting ecology and life histories: Cape urchin ( Parechinus angulosus ), Common shore crab ( Cyclograpsus punctatu s), and Granular limpet ( Scutellastra granularis ). Results: Using pooled (Pool-seq), restriction-site associated DNA sequencing (RAD-seq), and seven outlier detection methods, we characterise genomic variation between populations along a strong biogeographical gradient. Of the three species, only S. granularis showed significant isolation-by-distance, and isolation-by-environment driven by sea surface temperatures (SST). In contrast, sea surface salinity (SSS) and range in air temperature correlated more strongly with genomic variation in C. punctatus and P. angulosus . Differences were also found in genomic structuring between the three species, with outlier loci contributing to two clusters in the East and West Coasts for S. granularis and P. angulosus , but not for C. punctatus . Conclusion: The findings illustrate distinct evolutionary potential across species, suggesting that species-specific habitat requirements and responses to environmental stresses better predict evolutionary patterns than the strong environmental gradients within the region. We also found large discrepancies between outlier detection methodologies, and thus offer a novel multi-model approach to identifying the principal environmental selection forces acting on species. Overall, this work highlights how adding a comparative approach to seascape genomics (both with multiple models and species) can elucidate the intricate evolutionary responses of ecosystems to global change.
Clinical Characteristics and prognostic implications of BRCA-Associated Tumors in Males: A Pan-tumor Survey
Authors: Sun Peng , Li Yue , Chao Xue , Li Jibin , Luo Rongzhen , Li Mei , He Jiehua
Published: June 2020

PurposeBRCA mutations (BRCAm) in males have been reported to confer a higher risk in the development of various tumors. However, little is known about the characteristics and prognosis of BRCA-associated tumors in males.DesignWe conducted a pan-tumor survey on BRCA-associated tumors in males (n=346). Comparative analyses with female BRCAm carriers (n=349) and male non-BRCAm carriers (n=4577) were proceed.ResultsSimilar BRCAm incidence and diagnostic age were observed in male and female patients. Carcinomas of lung (19.4%), bladder (15.6%), stomach (11.9%), and cutaneous melanoma (16.3%) were the frequent tumors demonstrating BRCAm in males. The majority were stage II/III diseases with a higher frequency of BRCA2 mutation (65.6%). A total of 127 BRCA1 and 311 BRCA2 mutations were identified in males, of which 21.8% and 28.6% were deleterious, respectively. Deleterious variants were commonly identified in cancer of breast, colorectum, prostate, and stomach. Recurrent BRCA2 mutations at P606L/S, E832K/G, and T3033Lfs*29 were detected in males, while N1784K/Tfs*3 were frequently observed in both males and females. BRCAm in males was associated with a decrease OS and PFS than in females, as well as an increased OS than in non-BRCAm carriers. Subgroup analysis demonstrated that BRCAm was associated with increased OS in gastric and bladder cancer, decreased PFS in cancer of prostate, esophagus, head and neck, and a decreased OS in glioma/glioblastoma in males.ConclusionOur findings provide an overview of the distinct characteristics and clinical outcomes in BRCA-associated tumors in males, suggesting the importance of further BRCA testing in males.
Genomic signatures in pediatric advanced stage Burkitt lymphoma/ leukemia in Chinese population by next generation sequencing
Authors: Lei Xiaoying , Yin Nange , Guo Yuxia , Song Ling , Zhu Jin , Xiao Jianwen
Published: June 2020

Background: Burkitt lymphoma/leukemia (BL/BAL) is the most common lymphoma in chidren and sporadic subtype is dominant in Chinese population. MYC gene translocation is essential for sporadic BL/BAL (sBL/BAL), whereas other gene mutations also play important roles in the development of sBL/BAL. Methods: The clinical data of ten Chinese children with sBL/BAL were collected; next generation sequencing of tumor tissues were detected. BL and diffused large B cell lymphoma (DLBCL) database was also collected and bioinformatics analyzed was done.Results: Nine male and one female were enrolled in the study, including six BL patients (stage III) and four BAL patients (stage IV). Average age at diagnosis was 100.10±13.39mon; overexpression of CD20 was detectable, MYC rearrangement were confirmed. The patients received combination treatment of chemotherapy and Rituximab, complete remission was achieved and all the patients survived. Germline causal gene mutations were detected in four (40%) patients by whole exome sequencing (WES); ID3, BRCA2, ARID1A and SMARCA4 mutations, except MYC mutation, were the most common somatic mutations. The gene functions in pathopoiesis were differ from BL to DLBCL in dataset. These identified mutated genes were enriched and connected by GO or KEGG pathway, it seemed that PI3K-Akt signaling pathway or EGFR-TKI resistance pathway play important roles in the pathopoiesis of sBL/BAL. Conclusion: sBL/BAL is a highly aggressive but curable lymphoma; the pathophysiolopoiesis is still in research. The molecular hallmark of sBL/BAL is MYC translocation, whereas additional chromosomal abnormalities and gene mutations also occur and play roles in the progression of the disease. PI3K-Akt signaling pathway seems play important roles in the pathopoiesis of sBL/BAL, and sBL/BAL may be inhibited by such signaling pathway; EGFR-TKI resistance pathway was also analyzed in sBL/BAL patients, it reveals that EGFR-TKI treatment is invalid. Further research is needed for the hypothesis and possible mechanisms.
Low-level expression of necroptosis factors indicative of a poor prognosis of squamous cell carcinoma subtype of non-small-cell lung cancer
Authors: Lim Jun Hyeok , Oh Sekyung , Kim Lucia , Suh Young Ju , Ha Yu-Jin , Kim Jung Soo , Kim Hyun-Jung , Park Mi Hwa , Kim Young Sam , Cho Yunjung , Kwak Seung Min , Lee Hong Lyeol , Kim You-Sun , Ryu Jeong-Seon
Published: June 2020

Background

A programmed cell death pathway, necroptosis may synergize with DNA damage response (DDR) in opposing tumor progression. While our basic mechanistic understanding of necroptotic cell death advances rapidly, its prognostic implications have not been thoroughly examined in cancer.
Methods

We measured expression level of nine proteins involved in necroptosis and DDR in primary stage I non-small-cell lung carcinoma (NSCLC) samples from 394 patients using a tissue microarray.
Results

We find that low-level expression of the necroptosis markers RIPK3 and PELI1 is associated with increased risk of patient death and that high-level expression of the key DDR factor p53 enhances this risk. These effects appear to be specific to squamous cell carcinoma (SCC) subtype of NSCLC patients but not observable in non-SCC patients.
Conclusions

Low-level expression of such necroptosis factors as RIPK3 and PELI1 in combination with high-level expression of the DDR factor p53 can serve as a critical indicator in predicting survival of patients with stage I SCC.
Energy Replenishment Diversification Under Marine Spatial Planning Connects Big Data, Artificial Intelligence, Internet of Things for Coastal Community Sustainability
Authors: Liao Victor Te Cheng
Published: June 2020

Background Controversial coal power plant restart and non-nuke policy were rejected by referendum in Taiwan on 24 Nov 2018. Outcomes affecting energy replenishment and undermining economic stability are criticized politicization because coal energy is detrimental but no nuke beneficial for the environment. These policies could be contradictory. Problem No autonomous energy puts the country into extreme risk and is controlled by foreigners. Developing energy faces a traditional tradeoff between economic development and environmental protection. Purpose The assumption an innovative energy diversification linking Big Data, artificial intelligence (AI), and the Internet of Things (IoT) is encouraged. The paper investigates upgrading liquified petroleum gas (LPG) to liquified natural gas (LNG) under marine spatial planning (MSP) for energy replenishment and creating an energy diversification framework through integrated coastal zone management (ICZM) linking Big Data, IoT, AI whether are supported. Results Online sampling investigation results, enhancing LPG to LNG at the ecologically biologically significant area (EBSA) under MSP was less encouraged but linking Big Data, IoT, AI innovation through ICZM was overwhelmingly supported and consistent with goalkeepers interview. Research finding gender, the environment, age revealed no significant difference from LNG through MSP and AI under ICZM. Males more support LNG energy replenishment and energy diversification. Energy deficiency, environmental protection, and economic development were interrelated. Conclusion The results LPG to LNG revealed less encouraging and implicates many coastal communities in favor of tangible stable electricity without blackout is important than the intangible slogan EBSA protection, or perhaps renewable energy is an alternative approach. An autonomous energy diversification framework through ICZM links Big Data, IoT, AI for sustainable coastal community development (SCCD) indicating no significant difference from gender, environment, age, and is consistent with the goalkeepers' interview results supporting energy diversification. The finding males more support LNG and energy diversification. Finally, the study suggests that legislative enforcement establishment designate expertise teamwork to coordinate administration, integrate programs of energy replenishment, creating an autonomous energy diversification framework for monitoring energy demand, supplies, replenishment, and connect Big Data, IoT, AI innovation for SCCD.
NMR Elucidation of Non-productive Binding Sites of 13C-Labeled Lignin Models with Carbohydrate Binding Module of Cellobiohydrolase I for Efficient Biomass Conversion
Authors: Tokunaga Yuki , Nagata Takashi , Kondo Keiko , Katahira Masato , Watanabe Takashi
Published: June 2020

Background: Highly efficient enzymatic saccharification of pretreated lignocellulose is a primary key step in achieving lignocellulosic biorefinery. Cellobiohydrolase I (Cel7A) secreted by Trichoderma reesei is an industrially used cellulase possessing carbohydrate binding module 1 (TrCBM1) as the C-terminal domain. Non-productive binding of TrCBM1 to lignin significantly decreases enzymatic saccharification efficiency and enhance cost of biomass conversion due to required additional enzymes. Understanding of the interaction mechanism between lignin and TrCBM1 is essentially required to realize cost-effective biofuels production, but the binding sites in lignin have not been clearly elucidated. Results: Three types of 13C-labeled b-O-4 lignin oligomer models were synthesized and characterized. The 2D 1H-13C HSQC spectra of the 13C-labeled lignin models exhibited that 13C-labels were correctly incorporated in the (1) aromatic rings and b positions, (2) a positions, and (3) methoxy groups, respectively. The TrCBM1 binding sites in lignin were analyzed by observing NMR chemical shift perturbations (CSPs) using the synthetic 13C-labeled b-O-4 lignin oligomer models. Obvious CSPs were observed in signals from the aromatic regions in oligomers bound to TrCBM1, whereas perturbations in the signals from aliphatic regions and methoxy groups were insignificant. This indicated that hydrophobic interactions and p–p stacking were dominating factors in non-productive binding. The synthetic lignin models have two configurations whose terminal units were differently aligned and donated C(I) and C(II). The C(I) ring showed remarkable perturbation compared with C(II), which indicated that binding of TrCBM1 is evidently affected by configuration of lignin models. Long-chain lignins (DP 4.16–4.70) clearly bound to TrCBM1. Interactions with short-chain lignins (DP 2.64–3.12) were insignificant, indicating that a DP greater than 4 was necessary for TrCBM1 binding. Conclusion: The CSP analysis using 13C-labeled b-O-4 lignin oligomer models enabled us to identify TrCBM1 binding sites in lignin at the atomic level. This specific interaction analysis will lead to new molecular design of cellulase having controlled affinity to cellulose and lignin for cost-effective biorefinery process.
Impact of negative energy balance on transcriptomic profiles of three endometrial cell types isolated by laser capture microdissection in postpartum dairy cows
Authors: Chankeaw Wiruntita , Lignier Sandra , Richard Christophe , Ntallaris Theodoros , Raliou Mariam , Guo Yongzhi , Plassard Damien , Bevilacqua Claudia , Sandra Olivier , Andersson Goran , Humblot Patrice , Charpigny Gilles
Published: June 2020

Background: In postpartum dairy cows, the energy needs to satisfy high milk production induces a more or less pronounced Negative Energy Balance (NEB) status. NEB associated with fat mobilization impairs reproductive function. This study investigated the specific impact of NEB on gene expression in the three main types of endometrial cells at time planned for insemination and implantation. Endometrial cell types (stromal, glandular and luminal epithelial cells) were isolated by laser micro-dissection allowing the study of constitutive gene expression and their specific response to NEB. Methods: Nine Swedish Red cows receiving a control diet or a mild restricted diet to induce differences of energy balance were categorized into mild (MNEB, n = 5) and severe negative energy balance (SNEB, n = 4). The three endometrial cell types: luminal (LE), glandular (GE) epithelium and stroma (ST) were collected by laser microdissection from endometrial biopsies performed at 80 days postpartum. Results: Transcriptome profiles obtained by RNA sequencing revealed differences in constitutive gene expression between the three cells types and also differences in specific responses related to the severity of NEB. Number of differentially expressed genes between SNEB and MNEB cows was higher in ST than in LE and GE, respectively. SNEB was associated with differential expression of genes related to metabolic processes and embryo-maternal interactions in ST. Under-expression of genes related to cell structure was found in GE whereas genes related to pro-inflammatory pathways were over-expressed. Genes associated to adaptive immunity were under-expressed in LE. Conclusion: The three different main cells types of the endometrium, have very different patterns of gene expression. The severity of NEB after calving is associated with changes in gene expression at time of breeding. Specific alterations in GEs are associated with activation of pro-inflammatory mechanisms. Concomitantly, changes in the expression of genes related to cell to cell interactions and maternal recognition of pregnancy takes place in ST. The combination of these effects possibly altering the uterine environment and embryo maternal interactions may negatively influence the establishment of pregnancy.
Contribution to a Mixed Assessment of Patient Safety Culture
Authors: Fourar Youcef Oussama , Djebabra Mebarek , Benhassine Wissal , Boubaker Leila
Published: June 2020

The authors have withdrawn this preprint due to author disagreement.
Understanding the Physiological Functions of the Host Xenobiotic-sensing Nuclear Receptors PXR and CAR on the Gut Microbiome using Genetically Modified Mice
Authors: Little Mallory , Dutta Moumita , Li Hao , Matson Adam , Shi Xiaojian , Gu Haiwei , Mani Sridhar , Cui Julia Yue
Published: June 2020

Background: Pharmacological activation of the host xenobiotic-sensing nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) is well-known to increase drug metabolism and reduce inflammation. Little is known regarding the physiological functions of PXR and CAR on the gut microbiome, which is an important regulator for the host immune surveillance and bile acid (BA) metabolism. We examined the gut microbiome composition and BA metabolites in high vs. low PXR/CAR-expressing mice, and in mice that are deficient in PXR, CAR, or both, at two developmental ages. We also utilized humanized PXR transgenic (hPXR-TG) mice to compare the species-specific effect of PXR on the gut microbiome. Results: We discovered bivalent hormetic functions of PXR and CAR in modulating the richness of the gut microbiome and inflammatory biomarkers: the high PXR/CAR expressers had higher microbial richness, pro-inflammatory bacteria (distinct taxa in Helicobacteraceae and Helicobacter), and fecal pro-inflammatory cytokines, suggesting higher immune surveillance to prevent the colonization of harmful bacteria. Interestingly, the absence of PXR or CAR also increased the microbial richness, and absence of both receptors synergistically increased the microbial richness. PXR and CAR deficiency increased the pro-inflammatory bacteria (Helicobacteraceae and Helicobacter). Most notably, deficiency in both PXR and CAR markedly increased the relative abundance of Lactobacillus, which is capable of bile salt hydrolase (BSH) activity. This corresponded to a decrease in major primary taurine-conjugated bile acids (BAs) in feces, which may lead to higher internal burden of taurine and unconjugated BAs, both of which are linked to inflammation, oxidative stress, and cytotoxicity. hPXR-TG mice had a distinct microbial profile as compared to wild-type mice, including a higher representation of Prevotella. hPXR-TG mice also had higher 12-OH BAs but lower 6-OH BAs, suggesting PXR’s species-specific role in modulating host hepatic BA synthesis. Conclusions: This study is the first to show that the host PXR and CAR profoundly influence the composition of the gut microbiome and its BA metabolites, with a bivalent hormetic relationship between PXR/CAR levels and microbial richness, unveiling the involvement of PXR/CAR-microbiome interactions in host immune surveillance and BA metabolism.
Clinicopathological and prognostic significance of Fusobacterium nucleatum infection in colorectal cancer: a meta-analysis
Authors: Huangfu Shuchen , Zhang Wen-bin , Zhang haoran , Li Yang , Zhang Yiran , Chu Xiaodong , Nie Jinling , Chen Changshun , Jiang Hai-ping , Pan Jing-hua
Published: June 2020

Background: Accumulating evidences about the association between Fusobacterium nucleatum (F. nucleatum) and colorectal cancer (CRC) has been reported in various studies. However, the definite relationship between abundance of F. nucleatum with clinical characteristics and prognosis of CRC is still controversial. Methods: PubMed, Embase and Web of Science were searched for relevant articles up to April 7, 2020. Outcomes of interest included clinical characteristics, molecular characteristic and survival analysis. HR (OR), odds ratios (OR) and 95% confidence interval (CI) were calculated to explore the prognostic value and relationship of clinical characteristics of Fusobacterium nucleatum in CRC.Results: A total of 3626 patients with CRC from 13 eligible studies were included. High abundance of F. nucleatum was associated with worse prognosis on overall survival (OS) (HR= 1.40, P < 0.0001), disease-free survival (DFS) (HR = 1.71, P = 0.0002) and cancer-specific survival (OR= 1.93, P <0.0001). In addition, F. nucleatum abundance was related with T (T3-T4) stage(OR = 2.20, P < 0.00001), M (M1) stage (OR = 2.11, P = 0.005), poor tumor differentation(OR = 1.83, P =0.02), microsatellite instability (MSI) -high (OR = 2.53, P = 0.0003) and KRAS mutation (OR =1.27, P=0.05).Conclusion: The present evidences revealed that high abundance of F. nucleatum is inclined to indicate worse prognosis and is associated with tumor growth, distant Impact: This study highlights the risk factor of F. nucleatum for worse prognosis of CRC.
Comparative genomic analysis of head and body/tail of pancreatic ductal adenocarcinoma at early and late stages
Authors: Zhang Xueyou , Feng Shi , Wang Qian , Huang Haitao , Xie Qinfen , Zhang Wu , Wang Aodi , Zhang Shuirong , Wang Lingjian , Yao Ming , Ling Qi
Published: June 2020

Background

Pancreatic ductal adenocarcinoma (PDAC), one of the most lethal human cancers, can be divided into head and body/tail cancers according to the anatomy. We previously reported a prognostic relevance of tumor location in resectable PDAC. This study is aimed to further explore the mechanism underlying the molecular diversity between the head and body/tail of PDACs.
Methods

We detected tumor genomes in 154 resectable (surgery) and non-resectable (biopsy) PDACs using a next-generation sequencing panel. Wilcoxon rank test or Fisher exact test was used for evaluating associations between clinical characteristics, mutation frequency, and survival probability between the two cohorts.
Results

Compared with pancreatic head cancers, pancreatic body/tail cancers showed significantly more enriched genomic alterations in KRAS (97.1% vs. 82.4%, p = 0.004) and SMAD4 (42.0% vs. 21.2%, p = 0.008). At early stages (I-II), the SMAD4 mutation rate was significantly higher in pancreatic body/tail cancers than pancreatic head cancers (56.0% vs. 26.5%, p = 0.021). At late stages (III-IV), pancreatic body/tail cancers presented significantly higher KRAS mutation rate (100.0% vs. 75.8%, p = 0.001), higher frequency of MAPK pathway mutation (100% vs. 87.8%, p = 0.040) and lower rates of druggable genomic alterations (30.8% vs. 57.6%, p = 0.030) than pancreatic head cancers.
Conclusions

The molecular diversity exists between pancreatic head and body/tail cancers in both tumor initiation and progression. Pancreatic body/tail cancer seems to be more malignant than pancreatic head cancer at late stages.
A 3-Week Dynamic Differences of Immunological Parameters in Severe and Non-severe COVID-19
Authors: Li Qiang , Xu Wei , Li Weixia , Huang Chenglu , Chen Liang
Published: June 2020

Objective We aimed to compare the dynamic differences of immunological parameters in severe and non-severe COVID-19. Methods In this study, the cytokine profiles and lymphocyte subsets of 70 patients (31 severe COVID-19 and 39 non-severe COVID-19) were longitudinally analyzed. Results Compared with non-severe cases, severe cases had higher age (64 vs 36 years, p<0.001), more common comorbidities (74.2% vs 15.4%, p<0.001), and more frequently lymphopenia (0.7 vs 1.6×109/L, p<0.001). Severe cases had markedly higher levels of IL-6, IL-8, and IL-10 than non-severe cases from baseline to 3 weeks after admission (p<0.001). No significant differences were observed in the levels of IL-1β, IL-2, IL-4, IL-5, IL-12P70, IL-17, TNF-α, IFN-α, and IFN-γ between the two groups during the follow-up (p > 0.05). The absolute numbers of CD3+, CD4+, CD8+, and CD45+ T cells were markedly lower in severe cases compared with that in non-severe cases from baseline to 3 weeks after admission (p<0.001). The decrease of T lymphocyte subsets reached its peak from day 1 to 3 after admission, and gradually increased from day 4 to 21 in the non-severe group; however, reached its peak from day 4 to 7 after admission, and sustained at a low levels in the severe group. Conclusion The dynamic changes of cytokine profiles and T lymphocyte subsets are related with the disease severity of patients with COVID-19.
Potential causes and consequences of rapid mitochondrial genome evolution in thermoacidophilic Galdieria (Rhodophyta)
Authors: Cho Chung Hyun , Park Seung In , Ciniglia Claudia , Yang Eun Chan , Graf Louis , Bhattacharya Debashish , Yoon Hwan Su
Published: June 2020

The Cyanidiophyceae is an early-diverged red algal class that thrives in extreme conditions around acidic hot springs. Although this lineage has been highlighted as a model for understanding the biology of extremophilic eukaryotes, little is known about the evolutionary history of their mitochondrial genomes. To fill this knowledge gap, we sequenced five mitogenomes from representative clades of Cyanidiophyceae and identified two major groups, here referred to as Galdieria-type (G-type) and Cyanidium-type (C-type). G-type mitogenomes exhibit the following three features: (i) reduction in genome size and gene inventory, (ii) evolution of unique protein properties including charge, hydropathy, stability, amino acid composition, and protein size, and (iii) distinctive GC-content and skewness of nucleotides. Based on GC-skew-associated characteristics, we postulate that unidirectional DNA replication may have resulted in the rapid evolution of G-type mitogenomes. This high divergence was likely driven by natural selection in the multiple extreme environments Galdieria species inhabit, their highly flexible heterotrophic metabolism, and the impacts of population size reduction. We speculate that the interplay between mitogenome divergence and adaptation may help explain the dominance of Galdieria species in diverse extreme habitats.
Global Optimization of a Numerical Two-layer Model Using Observed Data: A Case Study of the 2018 Sunda Strait Tsunami
Authors: Pakoksung Kwanchai , Suppasri Anawat , Abdul Muhari , Syamsidik Syamsidik , Imamura Fumihiko
Published: June 2020

Following the eruption of Anak Krakatoa, aconsiderable landslide occurred on the southwestern part of the volcano and, upon entering the sea, generated a large tsunami within the Sunda Strait, Indonesia, on 22 December 2018. This tsunami traveled ~5 km across the strait basin and inundated the shorelines of Sumatra and Java with a vertical runupreaching 13 m. Following the event, observed field data, GPS measurements of the inundation, and multibeam echo soundings of the bathymetry within the strait were collected and publicly provided. Using this dataset, numerical modeling of the tsunami was conducted using the two-layer (soil and water) TUNAMI-N2 model based on a combination of landslidesources and bathymetry data. The two-layer model was implemented to nest the grid system using a finest grid size of 20 m. To constrain the unknown landslide parameters, the differential evolution (DE) global optimization algorithm was applied, which resulted in a parameter set that minimized the deviation from the measured bathymetry after the event. The DE global optimization procedure was effective at determining the landslide parameters for the model with the minimum deviation from the measured seafloor. The lowest deviation from the measured bathymetry was obtained for the best-fitting parameters:a maximum landslide thickness of 301.2 m and a landslide time of 10.8 minutes. The landslide volume of 0.182 km3 estimated by the best-fitting parameters shows that the tsunami flow depth could have reached 3-10 m along the shore with a K value of0.89, although thesimulated flow depths were underestimatedin comparison with the observation data. According to the waveforms, the general wave pattern was well reproduced at tide gauges during the event. A large number of objective function evaluations were necessary to locate the minimum with the DE procedure to fix the grid cell size to 20 m;this limited the accuracy of the obtained parameter values for the two-layer model. Moreover, considering the generalizations in the modeling of landslide movements, the impact landslide time and thickness must be carefully calculated to obtain a suitable accuracy.
Attenuation of The Protective Effect of Honey On Alcohol Induced Hepatotoxicity By Kolanut In Male Albino Rats
Authors: Saka Adeoye Waheed , Kehinde Busuyi David , Akintola Adebola Olayemi , Oyekanmi Samuel Seyi , Oyewande Ajoke Esther , Ogwumu Murphy Dumbiri
Published: June 2020

Background: The excessive use of alcohol can lead to alcohol liver damage. However, natural compounds such as honey and kolanut have been investigated to have hepatoprotective activities against liver damage. Objectives: The possible protective effects of aqueous extract of kolanut and honey and the combination of both on alcohol induced hepatotoxicity of male rats were investigated.Materials and Methods: The rats were randomly divided into five equal groups (n=6). Group A was allowed access to water; Group B received ethanol (45% at 3g/kg) once for 21 days, Group C, D and E received alcohol an hour before treated with 50mg/kg of Cola nitida, 2.5g/kg of honey and combination of both respectively. Histopathological analysis and measurement of serum alanine aminotransferase (ALT), aspartate amino transferase (AST), alkaline phosphatase (ALP), malondialdehyde (MDA) and catalase (CAT).Results: Administration of ethanol (45%) at 3g/kg to rats resulted in significant (P < 0.05) increase in the activities of hepatic markers enzymes (ALT, AST, ALP) as compared with control. Pretreatment of rats with kolanut (50 mg/kg) and honey (2.5g/kg) separately caused significant reduction in ALT, AST and ALP activities while pretreatment with combination of both was not better than the decrease observed when pretreated separately as compared to alcohol-induced group. Conversely, the results of oxidative stress and histological findings took a different pattern in all the pretreated groups.Conclusion: The result showed that the combination of honey and kolanut does not work synergistically in alcohol-induced hepatic damage.
Inhibition of the Mammalian Target of Rapamycin Pathway Stimulates Osteoblast Proliferation and Differentiation Through Autophagy in MC3T3-E1 Cells
Authors: Li Xining , Li Xi-Ning , Zhao Yu , Zhou Zhi-Gang , Zhou Hong-Chang , Min Ji-Kang
Published: June 2020

Background: OP(Osteoporosis) is a common bone metabolic disorder in the elderly characterized by loss of bone mass and a tendency to fracture. The mammalian target of rapamycin (mTOR) pathway in autophagy plays an indispensable role in maintaining the stability of the intracellular environment and ensuring the normal physiological functions of cells. Methods: In this study, different concentrations(20, 40, 60, 80, 100, 120, 140, 160, 180 and 200nM) of rapamycin were used to act on MC3T3-E1 osteoblasts for different time lengths(6, 12, 24, 36 and 48 hours). CCK8 was used to detect the proliferative activity of cells and screen suitable rapamycin concentration for subsequent experiments. Western blot and real-time quantitative PCR were used to detect the expression changes of phosphorylated mTOR, upstream and downstream mTOR pathway, autophagy and osteogenic differentiation markers. The expression of LC3 was observed by immunofluorescence. The differentiation ability of osteoblasts was observed by alizarin red and alkaline phosphatase staining.Results: The results showed that the induction of proliferation activity of osteoblasts from 20 nM to 200 nM presented a parabolic feature. After the action time of 50 μM rapamycin exceeded 12 hours, the proportion of S stage cells was significantly increased. The results of gene and protein analysis showed that rapamycin significantly inhibited the phosphorylation of mTOR, and the phosphorylation of the downstream factors of mTOR, 4E-BP1(eIF4E-binding protein 1) and S6K1(p70 ribosomal S6 kinase 1) also decreased. Rapamycin significantly increased the expression of LC3 II (microtubule associated protein 1 light chain 3-α), significantly increased the ratio of LC3II/LC3I, and significantly decreased the expression of p62(sequestosome-1). Rapamycin significantly induced the expression of ALP(Alkaline phosphatase), Runx2(Runt-related transcription factor 2) and osterix. Conclusions: This study confirmed that rapamycin stimulates the autophagy of osteoblasts by inhibiting mTOR and promotes their proliferation and differentiation, suggesting that mTOR may be a potential therapeutic target for osteoporosis.
Phosphorylation of Pit-1 by Cyclin-Dependent Kinase 5 at Serine 126 is Associated with Cell Proliferation and Poor Prognosis in Prolactinomas
Authors: Fang Qiuyue , Li Chuzhong , Gong Lei , Guo Jing , Xie Weiyan , Zhang Yazhuo
Published: June 2020

Background Pit-1 is a POU-homeodomain transcription factor, and cyclin-dependent kinase 5 (CDK5) is a protein kinase that can phosphorylate many key transcription factors, but the mechanism by which CDK5 phosphorylates Pit-1 is unclear.Methods We generated an antibody that specifically recognizes phosphorylated the serine at position 126 of Pit-1 (Ser126-Pit-1); we used western blotting to detect the level of Pit-1 phosphorylation and observed the proliferation and apoptosis of GH3 cells with different levels of Pit-1 phosphorylation by clone formation experiments, cell viability assays, and flow cytometry. ELISA was used to measure the level of prolactin (PRL) in the supernatant of GH3 cells. Tissue microarrays and immunohistochemistry (IHC) were used to evaluate the expression of the phosphorylation level of Ser126-Pit-1 (pSer126-Pit-1) in prolactinomas. Results Our data indicated that Ser126-Pit-1 is specifically phosphorylated by CDK5. pSer-126-Pit-1 can promote cell proliferation and PRL secretion. Besides, a higher level of pSer-126-Pit-1 correlates with a worse prognosis in patients with prolactinoma. Conclusions CDK5 mediated Ser126-Pit-1 phosphorylation regulates prolactinoma progression and PRL secretion.
Necessity for Detection of SARS-CoV-2 RNA in Multiple Types of Specimens for the Discharge of the Patients with COVID-19
Authors: Tong Yongqing , Bao Anyu , Chen Hongbing , Huang Jingtao , Lv Zhihua , Feng Lina , Cheng Yun , Wang Youna , Bai Li , Rao Wenlong , Zheng Hongyun , Wu Zegang , Qiao Bin , Zhao Zhijun , Wang Huiming , Li Yan
Published: June 2020

Background The SARS-CoV-2 RNA was detected positive again after discharged from hospital in some COVID-19 patients, with or without clinical symptoms such as fever or dry cough. Methods 1008 severe COVID-19 patients, with SARS-CoV-2 RNA positive detected with the mixed specimen of nasopharyngeal swab and oropharyngeal swab by real-time fluorescence quantitative PCR (RT-qPCR), were selected to monitor SARS-CoV-2 RNA with the 12 types of specimens by RT-qPCR during hospitalization. All of 20 discharged cases with COVID-19 were selected to detect SARS-CoV-2 RNA in isolation period with 7 types of specimens by RT-qPCR before releasing the isolation period.Results Of the enrolled 1008 severe patients, the nasopharyngeal swab specimens showed the highest positive rate of SARS-CoV-2 RNA (71.06%), followed by alveolar lavage fluid (66.67%), oropharyngeal swab (30.77%), sputum (28.53%), urine (16.30%), blood (12.5%), stool (12.21%), anal swab (11.22%) and corneal secretion (2.99%), and SARS-CoV-2 RNA couldn’t be detected in other types of specimen in this study. Of the 20 discharged cases, the positive rate of SARS-CoV-2 RNA was 30% (6/20); 2 cases were positive in sputum at day 8 and day 9, 1 case was positive in nasopharynx swab at day 6, 1 case was positive in anal swab at day 8, and 1 case was positive in 3 specimens (nasopharynx swab, oropharynx swab and sputum) simultaneously at day4; no positive SARS-CoV-2 RNA was detected in other specimens including stool, urine and blood at the discharged patients.Conclusions SARS-CoV-2 RNA should be detected in multiple specimens, such as nasopharynx swab, oropharynx swab, sputum, and if necessary, stool and anal anal swab specimens should be performed simultaneously at discharge when the patients were considered for clinical cure and before releasing the isolation period.
IL-6R protective variant rs7529229 reduces interleukin-6 signaling and contributes to decreased ischemic stroke risk
Authors: Zhang Haihua , Zhao Wenbo , Liu Bian , Wang Tao , Han Zhifa , Ji Xunming , Liu Guiyou
Published: June 2020

BackgroundInterleukin-6 (IL-6) signaling is associated with the increased risk of coronary artery disease (CAD) and ischemic stroke (IS). Growing evidence shows that the minor allele of IL-6R rs7529229 variant could significantly increase the soluble IL-6 receptor levels and reduce CAD risk. However, it is largely unknown about the role of rs7529229 in IS, which promotes us to perform a comprehensive analysis. MethodsIn stage 1, we performed a meta-analysis of three GWAS datasets from MEGASTROKE, UK Biobank, and Million Veteran Program to evaluate the association of rs7529229 with IS. In stage 2, we conducted an expression quantitative trait loci analysis to examine the effects of rs7529229 on IL-6R expression in neuropathologically normal individuals from UK Brain Expression Consortium, GTEx project and eQTLGen Consortium. In stage 3, a tissue-specific gene expression analysis is used to evaluate the potential difference of IL-6R expression across the human tissues using gene expression data from GTEx. In stage 4, a case-control gene expression analysis is used to explore the potentially differential expression of IL-6R in IS and healthy controls in whole blood. ResultsOur results show that (1) rs7529229 minor allele could significantly reduce the risk of IS (OR=0.97, 95% CI 0.95-0.99, P=2.30E-03); (2) rs7529229 minor allele could significantly reduce IL-6R expression in relevant tissues especially in blood vessels and whole blood; (3) IL-6R is mainly expressed in skeletal muscle and whole blood; (4) expression of IL-6R is significantly reduced in healthy controls compared with IS cases in whole blood. Importantly, the biological senses in stage 1-4 are all convergent. ConclusionsCollectively, these findings indicate that rs7529229 minor allele may first reduce IL-6R expression in relevant tissues, further reduce IL-6 signaling, and eventually reduce the IS risk. Hence, IL-6R may be a potential therapeutic target, and blocking IL-6 signaling might be effective in treatment of IS.