bluuebunny/crossref_metadata_2025_split huggingface dataset:
In-Utero Mother-to-Child SARS-CoV-2 Transmission: Viral Detection and Fetal Immune Response
Authors: Fenizia Claudio , Biasin Mara , Cetin Irene , Vergani Patrizia , Mileto Davide , Spinillo Arsenio , Gismondo Maria Rita , Perrotti Francesca , Callegari Clelia , Mancon Alessandro , Cammarata Selene , Beretta Ilaria , Nebuloni Manuela , Trabattoni Daria , Clerici Mario , Savasi Valeria 
Published: July 2020

Abstract
Pregnancy is known to increase the risk of severe illnesses in response to viral infections. Therefore, the impact of SARS-CoV-2 infection during gestational ages might be detrimental and the potential vertical transmission should be thoroughly studied.Herein, we investigated whether SARS-CoV-2 vertical transmission is possible and, in case, whether this results in a fetal involvement. Additionally, we analyzed the role of the antibody and the inflammatory responses in placenta and plasma from SARS-CoV-2-positive pregnant women and fetuses.31 SARS-CoV-2 pregnant women were enrolled. Real-time PCR was performed to detect the virus on maternal and newborns’ nasopharyngeal swabs, vaginal swabs, maternal and umbilical cord plasma, placenta and umbilical cord biopsies, amniotic fluids and milk. Maternal and umbilical cord plasma, and milk were tested for specific anti-SARS-CoV-2 antibodies. RNA expression quantification of genes involved in the inflammatory response was performed on four selected placentas. On maternal and umbilical cord plasma of the same subjects, secreted cytokines/chemokines were quantified.SARS-CoV-2 is found in at-term placentae and in the umbilical cord blood, in the vaginal mucosa of pregnant women and in milk. Furthermore, we report the presence of specific anti-SARS-CoV-2 IgM and IgG antibodies in the umbilical cord blood of pregnant women, as well as in milk specimens. Finally, a specific inflammatory response is triggered by SARS-CoV-2 infection in pregnant women at both systemic and placental level, and in umbilical cord blood plasma.Our data strongly support the hypothesis that in-utero vertical transmission is possible in SARS-CoV-2 positive pregnant women. This is essential for defining proper obstetric management of COVID-19 pregnant women, or putative indications for mode and timing of delivery.
Rational Engineering of Saccharomyces Cerevisiae Towards Improved Tolerance to Multiple Inhibitors in Lignocellulose Fermentations
Authors: Brandt Bianca A. , García-Aparicio Maria D.P. , Görgens Johann F. , Zyl Willem Heber Van 
Published: July 2020

Abstract
Background: The fermentation of lignocellulose hydrolysates to ethanol require robust xylose capable Saccharomyces cerevisiae strains able to operate in the presence of microbial inhibitory stresses. This study aimed at developing industrial S. cerevisiae strains with enhanced tolerance towards pretreatment-derived microbial inhibitors, by identifying novel gene combinations that confer resistance to multiple inhibitors (thus cumulative inhibitor resistance phenotype) with minimum impact on the xylose fermentation ability. The strategy consisted of multiple sequential delta-integrations of double gene cassettes containing one gene conferring broad inhibitor tolerance (ARI1, PAD1 or TAL1) coupled with an inhibitor specific gene (ADH6, FDH1 or ICT1). The performances of the transformants were compared with the parental strain in terms of biomass growth, ethanol yields and productivity, as well as detoxification capacities in a synthetic inhibitor cocktail, sugarcane bagasse hydrolysate as well as hardwood spent sulphite liquor.Results: The first and second round of delta-integrated transformants exhibited a trade-off between biomass and ethanol yield. Transformants showed increased inhibitor resistance phenotypes relative to parental controls specifically in fermentations with concentrated spent sulphite liquors at 40% and 80% v/v concentrations in 2% SC media. Unexpectedly, the xylose fermentation capacity of the transformants was reduced compared to the parental control, but certain combinations of genes had a minor impact (e.g. TAL1 + FDH1). The TAL1+ ICT1 combination negatively impacted on both biomass growth and ethanol yield, which could be linked to the ICT1 protein increasing transformant susceptibility to weak acids and temperature due to cell membrane changes. Conclusions: The integration of the selected genes was proven to increase tolerance to pretreatment inhibitors in synthetic or industrial hydrolysates, but they were limited to the fermentation of glucose. However, some genes combination sequences had a reduced impact on xylose conversion.
Using exosomal miRNAs extracted from follicular fluid to investigate their role in porcine oocyte development
Authors: Hu Junhe , Dong Jinyi , Zeng Zhi , Wu Juan , Tan Xiansheng , Tang Tao , Yan Jiao , Jin Chenzhong 
Published: July 2020

Abstract
Follicular development is crucial to normal oocyte maturation, with follicular size closely related to oocyte maturation. To better understand the molecular mechanisms behind porcine oocyte maturation, we obtained exosomal miRNA from porcine follicular fluid (PFF). These miRNA samples were then sequenced and analyzed regarding their different follicular sizes, as described in the methods section. First, these results showed that this process successfully isolated PFF exosomes. Nearly all valid reads from the PFF exosomal sequencing data were successfully mapped to the porcine genome database. Second, we used hierarchical clustering methods to determine that significantly expressed miRNAs were clustered into A, B, C, and D groups in our heatmap according to different follicle sizes. These results allowed for the targeting of potential mRNAs genes related to porcine oocyte development. Third, we chose ten, significantly expressed miRNAs and predicted their target genes for further GO analysis. These results showed that the expression levels of neurotransmitter secretion genes were greatly changed, as were many target genes involved in the regulation of FSH secretion. Notably, these are genes that are very closely related to oocyte maturation in growing follicles. We then used pathway analysis for these targeted genes based on the originally selected ten miRNAs. Results indicated that the pathways were mainly related to the biosynthesis of TGF-beta and its signaling pathway, which are very closely related to reproductive system functions. Finally, these exosomal miRNAs obtained from PFF may provide a valuable addition to our understanding of the mechanism of porcine oocyte maturation. It is also likely that these exosomal miRNAs could function as molecular biomarkers to choose high-quality oocytes and allow for in vitro porcine embryo production.
Prognostic Role of MicroRNA Let-7 in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis
Authors: Zhang Xiaoting , Kang Huaning , Chen Guihong , Li Xiaofeng 
Published: July 2020

Abstract
BackgroundRecent studies have shown that MicroRNAs can be used as potential biomarkers to the prognosis in non-small cell lung cancer (NSCLC). Hence, we conducted this meta-analysis to evaluate the prognostic role of microRNA let-7 in NSCLC patients.MethodsPubMed, Web of Science, Medline and the Cochrane Library were searched for relevant studies. Eligible studies were met specific inclusion and exclusion criteria. Stata 15.1 was used to calculate the pooled parameters.ResultsA total of 11 studies involving 2278 NSCLC patients were included in this meta-analysis. Subgroup analyses established that the heterogeneity was connected with ethnicity and follow-up time. The results suggested that the low expression of microRNA let-7 indicates a poor overall survival rate, with a hazard ratio value of 0.99 (95% CI: 0.64-1.34, P <0.05).ConclusionsLow expression of microRNA let-7 is closely related to the poor prognosis of NSCLC, so microRNA let-7 may become a new biomarker to evaluate the prognosis of NSCLC patients.
IL-19 Induced by IL-13/IL-17A in the Nasal Epithelium of Patients with Chronic Rhinosinusitis Upregulates MMP-9 Expression via ERK/NF-kB Signaling Pathway
Authors: Li Xia , Huang Jiancong , Chen Xiaohong , Lai Xiaoping , Huang Zizhen , Li Yue , Li Shuaixiang , Chang Lihong , Zhang Gehua 
Published: July 2020

Abstract
Background

Tissue remodeling is a crucial characteristic of chronic rhinosinusitis (CRS). Imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) is crucial for the pathologic tissue remodeling in CRS. Elevation of interleukin (IL)-19 or MMP-9 levels in patients with CRS had been proven in previous studies. Here, we aimed to investigate the role of IL-19 in mediating MMP-9 expression in CRS.
Methods

Nasal tissue samples were collected from individuals having chronic rhinosinusitis with nasal polyps (CRSwNP), CRS without nasal polyps (CRSsNP), and controls. Expression of IL-19, its receptors (IL-20R1/IL-20R2), and MMP-9 were investigated. Human nasal epithelial cells (HNECs) were stimulated by IL-19; ERK phosphorylation, NF-κB pathway activation, and MMP-9 level were detected. We also explored the effect of type1/2/3 cytokines on IL-19 production.
Results

Expression levels of IL-19, its receptors (IL-20R1/IL-20R2), and MMP-9 were increased in nasal tissues from individuals with CRSwNP compared to those with CRSsNP as well as the controls. IL-19 significantly elevated the production of MMP-9 in HNECs. Furthermore, IL-19 could activate the ERK and NF-κB pathways, accompanied by increased MMP-9 production in HNECs. Conversely, both ERK and NF-κB inhibitors significantly attenuated the role of IL-19 in MMP-9 production. siRNA knockdown of IL-20R1 suppressed ERK and NF-κB pathway activation, thereby decreasing MMP-9 expression. IL-13 and IL-17A were found to stimulate IL-19 production in HNECs.
Conclusion

IL-19, promoted by IL-13 and IL-17A, contributes to the upregulation of secretion of the tissue remodeling factor MMP-9 in patients with CRS.
Runx2 deficiency in osteoblasts promotes myeloma resistance to bortezomib by increasing thrombospondin 1-mediated TGF-ß1 activation and suppression immunity in the bone marrow
Authors: Zhang Chao , Xu Xiaoxuan , Trotter Timothy N. , Gowda Pramod S. , Lu Yun , Suto Mark J. , Javed Amjad , Murphy-Ullrich Joanne E. , Li Juan , Yang Yang 
Published: July 2020

Abstract
Background: Multiple myeloma (MM) is a plasma cell malignancy that thrives in the bone marrow (BM). Although the proteasome inhibitor bortezomib (BTZ) is one of the most effective front-line chemotherapeutic drugs for MM, 15–20% of high-risk patients do not respond to this drug or become resistant to treatment. The mechanisms driving this chemoresistance remain unclear. Previous studies showed that the tumor microenvironment contributes to cancer chemoresistance. Our recent studies demonstrated that Runt-related transcription factor 2 (Runx2) deficiency in osteoblasts (OBs) creates a cytokine-rich and immunosuppressive microenvironment in the BM and promotes MM progression. However, the impact of Runx2 deficiency in OBs on the efficacy of BTZ in treatment of MM is still unknown. Methods: We assessed the effects of OB-Runx2 deficiency on the outcome of BTZ treatment in OB-Runx2 +/+ and OB-Runx2 -/- mouse models with MM using bioluminescence imaging, ELISA and flow cytometry. In addition, we used a co-culturing in vitro system to explore the mechanism of BTZ resistance and assessed this system by MTT assays and Western blot analysis. Results: We discovered that OB-Runx2 deficiency induces MM cells resistance to BTZ via the suppression of immunity and increased active TGF-β1 in the BM. We further demonstrated that depletion of myeloid-derived suppressor cells (MDSCs) by gemcitabine or inhibition of TGF-ß1 activity by SRI31277, a compound that blocks thrombospondin 1 (TSP1)-mediated TGF-ß1 activation, restores anti-tumor immunity in the BM and overcomes BTZ resistance induced by OB-Runx2 deficiency. In addition, SRI31277 also directly inhibits the activity of canonical (Smad2/3) and non-canonical (Erk1/2) signaling pathways of TGF-ß1 in 5TGM1-Luc MM cells and sensitizes MM cells to BTZ, resulting in increased apoptosis of MM cells. Conclusions: OB-Runx2 deficiency promotes BTZ resistance in MM cells through the regulations of MDSCs and TSP1-mediated TGF-ß1 activation in the BM. These data identify novel mechanisms of BTZ resistance in MM and suggest new strategies to overcome BTZ resistance in treatment of MM.
Severe Pneumonia with and without Adenovirus Infection in Children Under the Age of 5 in Guangzhou, 2009-2019: A Retrospective Cohort Study
Authors: Zheng Lingling , Liao Weiyao , Li Kuanrong , Li Ling , Liang Feng , Liang Huiying 
Published: July 2020

Abstract
Background: To identify the differences of epidemiology, clinical features, laboratory findings and clinical outcomes of severe pneumonia children under 5 years old among with and without ADV infection.Methods: A retrospective cohort study was conducted in three pediatric hospitals in Guangzhou, China. All children under the age of 5 for sever pneumonia and admitting ICU during 1 January 2009 and 31 December 2019. Demographics, complications, the first routine laboratory findings, therapeutic records and clinical outcome were collected from electronic medical records. We compared characteristics of children with and without ADV infection.Results: ADV were detected in 75 (4.7%) of 1595 severe pneumonia children. Cases with ADV infection were more likely to be male, older than one year old, combined other microbial infections, but less likely to have mixed virus infections and combined with cardiovascular disease, and had more abnormal laboratory results than cases without ADV infection. Antiviral therapy was rarely used in children with severe pneumonia, but antibiotic therapy was commonly used in severe pneumonia children, especially cases with ADV infection (91.9%). Children infected with ADV were also hospitalized longer and had a higher mortality within 30 days of hospitalization.Conclusions: Severe pneumonia children under 5 years old with ADV infection had more abnormal laboratory findings and more severe clinical outcomes than cases without ADV infection. More attention should be focused on the harm caused by ADV infection.
Whether CAR-T cell bridging to allo-HSCT increases the incidence of graft-versus-host disease in patients with high-risk chronic lymphocytic leukemia
Authors: Gong Jiaojiao , Wang Qian , Su Yan , Ai Hao , Han Lu , Fu Yuewen , Wei Xudong , Song Yongping , Yin Qingsong 
Published: July 2020

Abstract
Background The TP53 aberration[both del(17p) and TP53 mutations], a high-risk prognostic factor in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), is closely related to drug-resistance, rapid disease progression, and short-term survival. Although novel agents, such as ibrutinib, idelalisib, as well as venetoclax, have shown good responses, allogenic hematopoietic stem cell transplantation (allo-HSCT) has been considered the only approach offered with curative intent.Case presentation We reported a case of young high-risk CLL/SLL patient with Ritcher’s transformation received ibrutinib plus CAR-T cells after the BCL-2 inhibitor venetoclax resistance, and then bridging to allo-HSCT when she had a complete remission (CR). Unfortunately, the patients died on day + 99 after transplantation due to intestinal grade IV acute graft-versus-host-disease (aGVHD) which could not be reversed by intensified immunosuppressive agents, including high-dose glucocorticoid, anti-CD25 monoclonal antibody basiliximab, and small-molecular inhibitors ruxolitinib, ibrutinib, as well as fecal microbiota transplantation (FMT).Conclusion TP53 aberrations in CLL/SLL patients are prone to large cell transformation, and have a poor prognosis, especially in venetoclax-resistant patients. Ibrutinib combined with CAR-T cells offered a treatment option, but whether bridging allo-HSCT following CAR-T cells increased severe aGVHD remained unclear.
Relationship of Common Variants in Krüppel-like Factor 7 Gene With Susceptibility and Prognosis of Oral Squamous Cell Carcinoma
Authors: Wang Lili , Song Hongguang , Yang Shiming 
Published: July 2020

Abstract
Background: The aim of this study was to assess the prognostic value of Krüppel-like factor 7 (KLF7) for patients with oral squamous cell carcinoma(OSCC).Methods: The expression of KLF7 was detected by quantitative real-time polymerase chain reaction (qRT-PCR) in pairs of tumor tissues and adjacent non-tumor tissues of OSCC. Chi-square (χ2) test was applied to evaluate the association of KLF7 expression with clinicopathological characteristics of OSCC patients. Overall survival was estimated using the Kaplan-Meier method with log rank test. The cox proportional hazards model was used for univariate and multivariate analyses.Results: The expression of KLF7 was remarkably increased in OSCC tissues compared with adjacent non-tumor tissues (P<0.001). KLF7 expression was related to TNM stage (P=0.006), tumor size (P=0.010), smoking (P=0.006) and drinking (P=0.000). Kaplan-Meier analysis showed that OSCC patients with high KLF7 expression had a poorer overall survival than those with low expression (log rank test, P=0.018). Moreover, multivariate analyses showed that KLF7 was an independent prognostic factor for OSCC (P=0.002 HR=2.645 95%CI: 1.426-4.906).Conclusion: Decreased expression of KLF7 may be a potential unfavorable prognostic factor for patients with OSCC.
Relationship of Common Variants in PRL-3 Gene With Susceptibility and Prognosis of Prostate Cancer
Authors: Cao Shuangqing , Zheng Lei 
Published: July 2020

Abstract
Background: Phosphatase of regenerating liver-3 (PRL-3) was involved in a variety of malignancies. In this study, we investigated the expression pattern of PRL-3 and its prognostic significance in prostate cancer (PCa).Methods: The expression profiles of PRL-3 in 126 pairs PCa tissues and adjacent normal specimens were analyzed by quantitative rreal-time polymerase chain reaction (qRT-PCR). Chi-square test was used to estimate the association of PRL-3 level with clinicopathological factors. Survival analysis was performed by Kaplan-Meier method with log rank test. Prognosis analysis was carried out using Cox proportional hazard models.Results: PRL-3 expression was significantly up-regulated in PCa tissues compared to that in normal controls (P<0.001). Moreover, the expression of PRL-3 was positively associated with lymph node metastasis (P=0.038), Gleason score (P=0.003) and lymphovascular invasion (P=0.013). High PRL-3 expression predicted poor overall survival (OS) (log rank test, P=0.019) and dismal BCR-free survival (log rank test, P=0.021) for PCa patients. PRL-3 was an independent prognostic factor for OS (HR=2.619, 95%CI=1.129-6.076, P=0.025) and BCR-free survival (HR=2.120, 95%CI=1.095-4.105, P=0.026) in PCa.Conclusions: PRL-3 expression is elevated in PCa, and exhibits positive association with malignant tumor progression. PRL-3 may serve as a prognostic biomarker for patients with PCa.
Accelerated repurposing and drug development of pulmonary hypertension therapies for COVID-19 treatment using an AI-integrated biosimulation platform
Authors: Chakravarty Kaushik , Antontsev Victor , Jagarapu Aditya , Bundey Yogesh , Hou Hypatia , Maharao Neha , Varshney Jyotika 
Published: July 2020

Abstract
A World Health Organization-declared pandemic, COVID-19, has affected more than 4 million people worldwide with over 100,000 deaths and growing in the United States. Due to the fast-spreading and multi-targeted nature of the virus, it is clear that drugs and/or vaccines need to be developed at an accelerated rate, and a combinatorial approach may stand to be more successful than a single drug therapy. Among several targets and pathways that are under investigation, the renin-angiotensin system (RAS) and specifically Angiotensin converting enzyme (ACE), and Ca2+ -mediated SARS-CoV-2 cellular entry and replication are noteworthy. A combination of ACE inhibitors (e.g. benazepril) and calcium channel blockers (CCB, e.g. amlodipine), a critical line of therapy for pulmonary hypertension, has shown therapeutic relevance in COVID-19 when investigated independently. To that end, we conducted in silico modeling using BIOiSIM, an AI-integrated mechanistic modeling platform by utilizing known preclinical in vitro and in vivo datasets to accurately simulate systemic therapy disposition and site-of-action penetration of the CCB and ACEI compounds to tissues implicated in COVID-19 pathogenesis.
Bioinformatic analysis of the inner heterogeneity within MYCN non-amplified pediatric neuroblastoma sub-group
Authors: Wang Haiwei , Wang Xinrui , Xu Liangpu , Zhang Ji , Cao Hua 
Published: July 2020

Abstract
Background: Pediatric neuroblastoma is divided into MYCN amplified and MYCN non-amplified sub-groups. However, the extent of heterogeneity within MYCN amplified or non-amplified pediatric neuroblastoma is unclear.Methods: The prognostic significance of age and MYCN amplification was determined through multivariate cox regression and Kaplan-Meier survival analysis. MYCN non-amplified pediatric neuroblastoma patients were divided into different sub-consensuses using non-negative matrix factorization (NMF) based on the gene expression profiling. Genes particularly expressed in MYCN non-amplified young neuroblastoma patients were identified using Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) datasets. The prognostic effects of ALCAM, CACNA2D3, DST, EPB41L4A and KIFIB in MYCN non-amplified pediatric neuroblastoma patients were determined by Kaplan-Meier survival.Results: Age and MYCN amplification were independent prognostic factors in pediatric neuroblastoma. MYCN non-amplified pediatric neuroblastoma comprised young and old two distinct sub-groups. Compared with MYCN non-amplified old neuroblastoma patients, MYCN non-amplified young neuroblastoma patients had better clinical outcomes. MYCN non-amplified pediatric neuroblastoma was divided into three sub-consensuses through NMF assay and each sub-consensus was with significantly different clinical outcomes. However, MYCN amplified pediatric neuroblastoma was relatively homogeneous, and could not divide into sub-groups with different clinical outcomes by age or by NMF assay. ALCAM, CACNA2D3, DST, EPB41L4A and KIFIB were highly expressed in MYCN non-amplified young neuroblastoma patients. Moreover, the high expression levels of ALCAM, CACNA2D3, DST, EPB41L4A or KIFIB were associated with the favorable prognosis of MYCN non-amplified neuroblastoma patients. We also found that DST was an independent prognostic factor in MYCN non-amplified neuroblastoma patients and MYCN non-amplified neuroblastoma young patients with high DST expression levels had the best clinical overall survival.Conclusions: MYCN non-amplified neuroblastoma was a heterogeneous disease and could be divided into sub-groups based on age or the expression levels of ALCAM, CACNA2D3, DST, EPB41L4A or KIFIB. MYCN non-amplified neuroblastoma young patients with high DST expression levels had the best clinical overall survival.