bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and integrative analysis of ACLY and related gene panels associated with immune microenvironment reveal prognostic significance in hepatocellular carcinoma
Authors: Xu Yunfeng , Zhang Ze , Xu Da , Zhou Li-Na , Zhu Ying
Published: January 2021

BackgroundCumulating evidence reveals the key role of aberrant lipogenesis and immunogenomic features in hepatocellular carcinoma (HCC). However, there are still obstacles in our understanding of the complicated interaction between metabolic reprogramming and tumor immune microenvironment.MethodsWe compared metabolomic, transcriptomic and immunogenomic characteristics of portal vein tumor thrombosis (PVTT) and primary tumor to seek valuable markers. Human HCC samples with PVTT (n = 28) was analyzed through ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Transcript levels of mRNA in two cohorts from published database GEO (n = 60) and TCGA (n = 411) were downloaded to explore differentially expressed genes and functional enriched gene set. Evaluation of immune infiltration was estimated and validated from transcriptomic data in both cohorts through six immune deconvolution algorithms (TIMER, CIBERSORT, quanTIseq, xCell, MCP-counter, EPIC) and in a high-resolution mode (CIBERSORTx). Survival analysis (Kaplan-Meier and multivariable Cox regression model) was performed to examine prognostic value of ACLY, related immune checkpoints and immune infiltration levels from TCGA cohort. LASSO regression was further conducted to determine a gene panel to further predict survival outcomes associated with ACLY.ResultsWe identified a novel signature, ATP citrate lyase, through transcriptomic and metabolomic approaches. We demonstrated that the metabolism adaptations in both fatty acid and cholesterol biosynthesis triggered by ACLY oncogenic activation. We illustrated the crucial function of ACLY in lipogenesis and its potential interaction with immune microenvironment. CD276, a promising target in immune checkpoint blockade, showed correlation to ACLY and differential expression in ACLY risk classification. Combination of ACLY, CD276 and immune infiltration level and a novel ACLY-associated panel from a predictive model retrieved from published database validated the prognostic value to risk stratification in patients with HCC. According to the survival outcome and correlation analysis, ACLY blockade to counteract metabolic activation and immunosuppressive status of the tumor microenvironment highlighted attractive prospect for translational application.ConclusionsWe investigated ACLY and its indispensable role in metabolism, immune function and a prognostic gene panel in HCC. We anticipate that the multifaced role of ACLY may reveal the potential value for mechanistic research and combinational therapy, suggesting that the combination blockade of ACLY and immune checkpoints may work as a promising strategy.
RAP1GAP is a novel marker of trabecular pattern and poor sorafenib treatment response in hepatocellular carcinoma
Authors: Wen Xue , Su Kunkai , Liu Zhikun , Ling Sunbin , Lu Di , Xiong Bin , Ye Yufu , Wang Kun , Pan Binhua , Wu Weiqiang , Wei Xuyong , Zheng Shusen , Xu Xiao
Published: January 2021

Background

The trabecular pattern is one of the most common features of hepatocellular carcinoma (HCC). In this study, we aimed to identify the molecular mechanisms underlying different trabecular patterns in HCC, and their interaction with current therapies.
Methods

To screen potential biomarkers of different trabecular patterns, we first linked gene expression data to haematoxylin and eosin (H&E) images from The Cancer Genome Atlas (TCGA). The Gene Expression Omnibus (GEO) database was used to explore potential targets of sorafenib treatment. Selected candidate biomarkers were further verified by immunohistochemistry, and their relationship with sorafenib efficacy was evaluated in 107 HCC samples with trabecular patterns.
Results

Analysis of RNA sequencing data from TCGA showed that the increasing number of cells in the trabecular structure correlated with increase in the expression of related signalling pathways—Ras, Rap1, IL17, TNF, AGE-RAGE, oestrogen, toll-like receptor signalling, and ubiquitin-mediated proteolysis—and genes related to response to oxygen levels and neoangiogenesis. In contrast, the expression of bile acid and carton, tryptophan, butanoate, and lipid metabolism-related pathways was reduced. The GEO database showed that RAP1GAP, TOB1, ACO2, and SCNN1D expression levels were selectively up-regulated in sorafenib non-responders. Based on the combined analysis of the two datasets and our previous studies, two candidate biomarkers, RAP1GAP and HIF1α, were selected. Immunohistochemical staining showed that RAP1GAP and HIF1α were expressed in the tumour tissues. Interestingly, RAP1GAP was also expressed in the tumour sinusoids. Overexpression of RAP1GAP in sinusoids were associated with trabecular patterns. Multivariate analysis also showed that RAP1GAP expression in the sinusoid was an independent predictor of progressive free survival (PFS) and overall survival (OS) in response to sorafenib treatment.
Conclusions

RAP1GAP is an essential microenvironment marker in the trabecular structure of HCC and exhibits an adverse association with outcome in sorafenib treatment.
Overexpression of SMYD3 contributes to sorafenib resistance by epigenetically activating the expression of multiple cancer-promoting genes in hepatocellular carcinoma
Authors: Wang Shanshan , You Xinxin , Zhang Fengwei , Zhou Hongjuan , Shang Xuechai , Long Cai
Published: January 2021

Background

The resistance mechanism to sorafenib in hepatocellular carcinoma (HCC) remains poorly understood. Recent evidence has demonstrated the enrichment of liver cancer stem cells (CSCs) as culprit for treatment resistance. In liver cancer development, SMYD3 epigenetically activates or overexpresses JAK/STAT3 pathway, epithelial-mesenchymal transition (EMT) pathway, SOX4 and MYC oncogenes, which play crucial roles in liver CSC. In this study, we demonstrate the novel role of SMYD3 in HCC resistance to sorafenib therapy.
Methods

We used sorafenib-resistant HCC in vitro and in vivo models to study the relationship between sorafenib resistance and SMYD3 expression. Chromatin immunoprecipitation (ChIP) and quantitative real-time PCR (qRT-PCR) were used to analyze the mechanism of SMYD3 regulation. Stemness and metastatic properties were investigated after treatment with SMYD3 depletion alone or in combination with sorafenib to evaluate the therapeutic effect on sorafenib resistance by in vitro and in vivo experiments.
Result

We identified overexpression of SMYD3 and subsequent increase of histone H3K4me3 as a novel pathway of acquired resistance to sorafenib in HCC. We also found that multiple SMYD3-mediated cancer-promoting genes exhibited up-regulation in sorafenib-resistant HCC cells and tumors. Inhibition of SMYD3 by a small-molecular inhibitor BCL121 or genetic means suppressed the transcription of SMYD3 target genes via the inhibition of the recruitment of H3K4me3-midifed histone tails to the core promoter regions of these genes. Restoration of wide-type SMYD3 protein in sorafenib-resistant cells with SMYD3 knockdown partly rescued the expression of target genes, while mutant SMYD3 did not. As such, modulating SMYD3 expression or activity in vitro and in vivo models inhibited the transcription output of target genes, mainly through SOX4, MYC, JAK1 and ZEB1 genes, and suppressed activation of their associated pathways, including EMT, JAK/STAT3, SOX4 and MYC pathway, and consequently weakened the stemness and metastatic properties of sorafenib-resistant cells in vitro and suppressed the relapse and metastasis of sorafenib-resistant tumors in vivo.
Conclusion

SMYD3 conferred sorafenib-resistant cells enhanced stemness and metastatic properties in HCC by epigenetically activating the expression of multiple cancer-promoting genes. SMYD3 could be a rational target for therapeutic intervention in sorafenib-resistant HCC.
Characterization of novel natural compound derivatives with cancer-selective cytotoxicity
Authors: Nunna Suneetha , Huang Ying-Pei , Rasa Mahdi , Anna Krepelova , Annunziata Francesco , Adam Lisa , Kaeppel Sandra , Hsu Ming-Hua , Neri Francesco
Published: January 2021

BackgroundColorectal cancer (CRC) is one of the most frequent and lethal cancers in the world. The current medical treatment for CRC primarily includes combination of multiple chemotherapeutic, targeted and/or immunotherapeutic drugs. However, these approaches are still not fully successful and cause numerous and severe side effects for the patient. Therefore, there is an urgent need to discover novel and cancer-selective drugs for CRC treatment. As many other natural compounds, a-Mangostin and Paeonol possess anti-cancer properties, but both of these compounds have low solubility and low membrane permeability.Methodsa-Mangostin and Paeonol derivatives were chemically synthesized to increase cytotoxicity versus cancer cell over non-transformed cells. The anticancer properties of these compounds were investigated on human colon cancer cell lines by employing cell viability, apoptosis and cell-cycle analyses. Transcriptome of cancer cells treated with natural compounds were also analyzed by total RNA-sequencing. Finally, we investigated their effects on human colon organoids derived from healthy and cancerous tissue of the same patient.ResultsWe found the two derivative compounds (a-Mangostin-1 (aMan1) and Paeonol-1 (Pae1)) more efficiently induced cytotoxicity in HCT116, HT-29, and SW48 colorectal cancer cell lines than the parental compounds. Both, aMan1 and Pae1 arrested HCT116 cells in G1 and HT-29 and SW48 cells in G2/M phase of the cell cycle. aMan1 and Pae1 induced selective transcriptional responses in CRC cells involving genes related to metabolic stress and DNA damage response signaling pathways. Both aMan1 and Pae1 induced apoptosis in human cancer cells and organoids derived from tumor tissue without affecting the viability of human non-cancer cells and intestinal organoids derived from healthy tissue.ConclusionsOur findings increase the knowledge about natural compound derivatives as anticancer compounds and open new research options on the derivation of lead compounds aimed to the development of novel CRC chemotherapeutic drugs that selectively target cancer, but not healthy cells.
The p62/Keap1/Nrf2 axis in the control of C-2 induced human gastric cancer cell death switching between autophagy and apoptosis
Authors: Wang ZhenYa , Guo Yong , Zhang En , Ban QianHong , Wang MengLin , Wu XinXin , Yu Lu , Liu Lu , Yu HaiYang , Kim Gi-Young , Choi YungHyun , Xu YiChao , Xu HongDe , Jin Cheng-Yun
Published: January 2021

Background

Compound C-2 is a derivative of natural product Jaspine B and possesses anti-cancer activity against bladder cancer cells. However, little is known about its anti-cancer activity against gastric cancer. In this research, mechanism underlying anti-cancer effect of C-2 in gastric cancer cells was well investigated.
Methods

Anti-cancer activities of C-2 were determined by MTT, western blotting and flow cytometry. A serial of specific inhibitors, immunoprecipitation, siRNA and immunofluorescence were utilized to explore signaling pathways affected by C-2.
Results

C-2 induces apoptosis in gastric cancer cells through the internal mitochondrial pathway, and triggers autophagy in gastric cancer cells through JNK/ERK pathway. Phosphorylated JNK/ERK further activates Beclin1 via disturbing Beclin-1/Bcl-xL or Beclin-1/Bcl-2 complexes, leading to autophagy and up-regulated p62. Next, p62 competitively binds keap1 to release Nrf2, thus promoting translocation of Nrf2 from cytoplasm to nucleus and triggering expression of Nrf2 target genes. Pharmacological inhibition or knockdown of key proteins in autophagy attenuates C-2 induced cell apoptosis, indicating that autophagy antagonizes cell apoptosis induced by C-2.
Conclusion

C-2 possesses anti-tumor activity against gastric cancer cells, while C-2 triggered-autophagy antagonizes cell arrest and apoptosis induced by C-2 by upregulating Nrf2 in nucleus.
Prevalence of Neonatal Mortality and Its Associated Factor among Neonates Who Admitted In Neonatal Intensive Care Unit At Debre Tabor General Hospital, South Gondar, Amhara, Ethiopia
Authors: Demis Solomon kebede , Munye Tigabu , Munye Biniam
Published: January 2021

BackgroundNeonatal mortality is the death of newborn babies from the time of birth to 28 completed days of life which are the most vulnerable time for a child's survival. About one million of them passed away on their first day of life, and more than two thirds (38%) of the deaths were in sub-Saharan Africa where Ethiopia is one of the countries with the highest neonatal mortality in the world which accounts for 29 deaths per 1,000 live births.ObjectiveTo assess the prevalence and associated factors of neonatal mortality among neonates admitted in Debre Tabor General Hospital in South Gondar, Ethiopia.MethodsInstitutional based retrospective cross-sectional study design was conducted from November 1, 2018, up to January 30, 2019, in Debre Tabor General Hospital. A Structured interviewer-administered pre-tested questionnaire was used to collect data. The collected data were entered into Epi data version 4.2 and then exported into SPSS window version 24. Bivariate and multivariate analysis was undertaken and information was presented by using simple frequency tables, graphs, and pie charts.Resultthe prevalence of neonatal mortality was found to be 12.3%. Gestational age group 28–32 weeks (AOR = 9.5, 95% CI: 2.39–37.97), Gestational Age beyond 42 weeks (AOR = 4.6, 95% CI: 6.3–33.8), and forceps delivery (AOR = 0.18, 95% CI: 0.05–0.68) were found to be statistically significant.Conclusion and recommendationNeonatal mortality was higher than the national with independently associated factors of prematurity and post maturity while forceps delivery as a preventive factor. Therefore, this might be essential to the hospital NICU to plan for managing prematurity and post maturity in better quality as well as providing quality ANC and identifying most predisposing factors for prematurity.
Comparing the Results of Treatment Methods of Casting and Bandage of Ankle Sprain in the Patients Who Referred to the Emergency Department of Poursina Hospital in the First Half of Year 2019
Authors: Cyrus Khashayar , Khoshghalb Masoud Fallah , Asadi Kamran
Published: January 2021

Background: The purpose of this study is a comparative survey of the effect of casting and bandage treatments in ankle sprain in order to be effective in determining the more desirable method for returning the patients to work and activities as fast as possible especially in important sport activities. Methods: In this study the referents to Emergency Department of Poursina hospital whose diagnosis was ankle sprain and needed treatment have been used. The patients who have been examined, categorised based on Clanton and Mcgravey classification and the intensity of ligaments injury in type II, group II, type A. (type II: unstable ankle with positive anterior drawer test or positive talar tilt test or both, group II: athlete or high demand patient, type A: negative radiographic stress test; functional treatment). The patients who had necessary criteria to enter this study have been divided into two groups A (casting) and B (bandage) randomly. Then, they have been re-examined after 3, 6 and 12 weeks of treatment and their cast or bandage has been removed and re-examined and the results of treatment have been assessed and compared in terms of total treatment or recurrent sprain and returning to work and activities and pain intensity. Results: Pain intensity based on VAS had lower average in cast group comparing to bandage group after 3 and 6 weeks and this difference was statistically significant. AHS criterion in both groups had the same average after 3, 6 and 12 weeks. Activity restriction time was lower in cast group comparing to bandage group significantly. Conclusions: This study showed that cast therapy led to reduction of activity restriction time and consequently fast returning to work and daily activities, but in bandage group pain intensity reduced faster.
Syncytin-1 Expression is Increased in Skeletal Muscle of Humans with Obesity and is Inversely Correlated to Muscle Protein Synthesis
Authors: Ravichandran Jayachandran , Roust Lori R , Katsanos Christos
Published: January 2021

Background: Various pathophysiological conditions alter protein metabolism in skeletal muscle, with obesity being one of them. Obesity impairs regeneration of skeletal muscle, and the same biological mechanism(s) may adversely affect protein metabolism in the muscle of these individuals. Methods: We used C2C12 cell line to evaluate the effects of the anabolic hormone insulin on the expression of protein syncytin-1, which regulates regeneration of muscle, and in the presence of fatty acids whose metabolism is altered in obesity. We used muscle biopsy samples from obese humans with lower muscle protein synthesis and lean controls to evaluate expression of syncytin-1 in obesity and its correlation with protein synthesis in muscle. Results: Insulin upregulated syncytin-1 expression in C2C12 cells and this response was impaired in the presence of the fatty acid palmitate, but not oleate. Expression of the protein 4E-BP1, which signals increase in protein synthesis in muscle, showed response similar to that of syncytin-1. Humans with obesity characterized by lower muscle protein synthesis had higher expression of syncytin-1 in muscle compared to lean humans (P < 0.01). The rate of synthesis of protein in skeletal muscle across humans subjects correlated inversely (r = -0.51; P = 0.03) with the expression of syncytin-1 in muscle. Conclusions: Our studies provide novel insights in the regulation of syncytin-1 in skeletal muscle, and describe potential link between syncytin-1 expression and protein metabolism in skeletal muscle of humans. Altered syncytin-1 expression in muscle may mediate lower protein turnover in muscle of humans with obesity.
Variations in Hybrid Combinations Lead to Differences in Mitochondrial Inheritance
Authors: Luo Liming , Zou Qiting , Liang Junneng , Luo Yongju , Yin Qinglang , Li Liuqing , Zhang Xiaojin , Tan Wufang , Wei Qiyu , Han Zhuojun , Zhang Jingyi , Wang Jingjie , Zhang Xu , Xiao Jun
Published: January 2021

BackgroundWhile tilapia are the second most farmed group of fish in the world, the Oreochromis niloticus (♀) × Oreochromis aureus (♂) hybrid is one of the most frequently observed tilapia crosses in China. Based on its conservative nature and maternal inheritance pattern, mitochondrial DNA is often used in kinship analysis. Evidence of paternal inheritance has been noted in some animal species. ResultsThe mitochondrial CoI and Cytb genes, and D-loop gene regions of Oreochromis niloticus and Oreochromis aureus fish were sequenced and aligned to their orthogonal and backcrossed offspring. As evidence of paternal mitochondria DNA inheritance was found, the whole mitochondrial genome was then sequenced. Results showed that in the Oreochromis niloticus (♀) × Oreochromis aureus (♂) hybrids, certain fish shared 92.88% of the maternal mitochondria genome, and 99.86% with the paternal mitochondria genome. This implied that there was paternal mtDNA inheritance. However, all Oreochromis niloticus (♂) × Oreochromis aureus (♀) hybrids had 100% identical mitochondria genome with their female parent. ConclusionsThe study showed that while paternal mtDNA inheritance occurred in the Oreochromis niloticus (♀) × Oreochromis aureus (♂) hybrid, this did not happen in Oreochromis niloticus (♂) × Oreochromis aureus (♀) offspring. This implies that in hybrid species, different hybridization combinations might provide an explanation for paternal mtDNA inheritance pattern.
Identifying Prognostic Factors of Severe Metabolic Acidosis and Acute Kidney Injury in African Children with Severe Falciparum Malaria: A Secondary Analysis of A Randomised Trial
Authors: Mzumara Grace Wezi , Leopold Stije Stije , Marsh Kevin , Dondorp Arjen , Ohuma Eric , Mukaka Mavuto
Published: January 2021

IntroductionSevere metabolic acidosis and acute kidney injury are major causes of mortality in children with severe malaria but are often underdiagnosed in low resource settings. MethodsWe conducted a retrospective analysis of the ‘Artesunate vs Quinine in the treatment of severe falciparum malaria in African children’ (AQUAMAT) trial to identify clinical features of severe metabolic acidosis and acute kidney injury in 5425 children from nine African countries. Separate models were fitted for acute kidney injury and severe metabolic acidosis. Separate univariable and multivariable logistic regression were performed to identify prognostic factors for severe metabolic acidosis (SMA) and acute kidney injury (AKI). Both analyses adjusted for the trial arm. A forward selection approach was used for model building of the logistic models and a threshold of 5% statistical significance was used for inclusion of variables into the final logistic model. Model performance was assessed through calibration, discrimination, and internal validation with bootstrapping. ResultsThere were 2296 children identified with Severe metabolic acidosis and 1110 with Acute Kidney Injury. Prognostic features of SMA among them were: deep breathing (OR: 5.41, CI: 4.26 – 6.89), hypoglycaemia (OR: 5.22, CI: 3.80 – 7.18), AKI (OR: 3.99, CI: 3.30 – 4.81), coma ( OR: 1.79 CI: 1.36 – 2.35), respiratory distress (OR: 1.49, CI: 1.21 – 1.83), prostration (OR: 1.64 CI: 1.30 – 2.03) and severe anaemia (OR: 1.40, CI: 1.11 – 1.77). Features associated with AKI were; older children(OR: 1.20, CI: 1.15 – 1.25), coma (2.47, CI: 1.78 – 3.42), Prostration (OR: 1.52 CI: 1.14 – 2.02), decompensated shock (OR: 1.74, CI: 1.15 – 2.63), black water fever (CI: 1.81. CI: 1.22 – 2.69), jaundice (OR: 3.31 CI: 2.01 – 5.47), SMA (OR: 4.02 CI:3.30 – 4.89), mild anaemia (OR: 1.36, CI: 1.05 – 1.76), severe anaemia (OR: 1.48, CI: 1.11 – 1.96), hypoglycaemia (OR: 2.02, CI: 1.58 – 2.59), hypernatremia (OR: 5.74, CI: 2.69 – 12.26) and hyperkalaemia (OR: 5.31. CI: 4.15 – 6.80). ConclusionClinical and laboratory parameters representing contributors and consequences of severe metabolic acidosis and acute kidney injury were independently associated with these outcomes. The model can be useful for identifying patients at high risk of these complications where laboratory assessments are not routinely available.
20-Hydroxyeiscosatetraenoic Acid May Be as a Predictor of Malignant Middle Cerebral Artery Infarction in Patients With Massive Middle Cerebral Artery Infarction
Authors: Yi Xingyang , Zhou Qiang , Qing Ting , Ming Bing , Lin Jing , Li Jie , Lin Jie
Published: January 2021

BackgroundEarly identification of massive middle cerebral artery infarction (MCAI) at risk for malignant MCAI (m-MCAI) may be useful in selecting patients for aggressive therapies. The aim of this study was to determine whether CYP metabolites may help to predict impending m-MCAI.MethodsThis is a prospective, two-center observational study in 256 patients with acute massive MCAI. Plasma levels of 20-hydroxyeicosatetraenoic acid (20-HETE), epoxyeicosatrienoic acids, and dihydroxyeicosatrienoic acids were measured at admission. Brain computed tomography (CT) was performed at admission and repeated between days 3 and 7, or earlier if there was neurological deterioration. The primary outcome was m-MCAI. m-MCAI was diagnosed when follow-up brain CT detected a more than two-thirds space-occupying MCAI with midline shift, compression of the basal cisterns, and neurological worsening.ResultsAmong 256 patients, 77 (30.1%) developed m-MCAI, 60 (77.9%) patients with m-MCAI died during 3 months of stroke onset. 20-HETE level on admission was significantly higher in patients with m-MCAI than those without m-MCAI. There was an increase in the risk of m-MCAI with increase of 20-HETE levels. The third and fourth quartiles of 20-HETE levels were independent predictors of m-MCAI (OR: 2.86; 95% CI: 1.16 – 6.68; P=0.025, and OR: 4.23; 95% CI: 1.35 – 8.26; P=0.002, respectively).ConclusionsIncidence of m-MCAI was high in patients with massive MCAI and the prognosis of m-MCAI is very poor. Elevated plasma 20-HETE may be as a predictor for m-MCAI in acute massive MCAI, and it might useful in clinical practice in therapeutic decision making.
Environmental Impact of Land-use Changes and Soil Loss on Coastal Coral Reef Cover: Study Case in the Small Tropical Island, Indonesia
Authors: Mulyono Asep , Djuwansah Muhammad Rahman , Narulita Ida , Putra Risandi Dwirama , Surinati Dewi
Published: January 2021

Over 24% of coral reefs in Southeast Asia, including Indonesia, experience damage from development in coastal areas by coastal construction, land conversion, beach nourishment, and port construction. The rapid economic development activities around the coast of Bintan Island impact the extraction of natural resources and reduction of the coral reefs cover. A comprehensive study to determine the temporal change in land use and estimate the rate of soil loss and its effects on coral reef cover is needed. There has been a change in land use for five years (2014-2018) on the east coast of Bintan Island, and the average percentage of coral reef cover is in the fair category (<50%). The land-use changes have resulted in soil loss that varies each year. Apart from land-use changes, the factor of rainfall is one of the causes of soil loss. Soil loss is generated from cultivated lands due to the lack of conservation techniques. In east Bintan island, mixed garden, plantation, and bare land area with dense canopy cover contributed increasing of soil loss. The contribution of soil loss to hard coral reefs as a result of land use changes from high to low is soil erosion > soil sediment > surface run-off.
Hydrochemical Characteristics of Groundwater - Assessment of Saltwater Intrusion Along Krishna Godavari Delta Region, Andhra Pradesh, India
Authors: Rajaiah Kannan , naidu K.Appala , Kanungo Abhrankash , Murty M.V.Ramana , Ramana K.V.
Published: January 2021

The Intrusion of saltwater into a freshwater aquifer is of particular concern to the coastal community. Removal of excess groundwater from the shallow aquifers is known to be the primary cause of contamination by saltwater. In this study, groundwater samples were obtained in the 2016 and 2017 pre-monsoon and post-monsoon seasons at 105 locations from dug wells and bore wells along the coast of Andhra Pradesh in the Krishna and Godavari deltas. Groundwater samples are tested for large ions to determine the infiltration of salt water and to classify the salinity sources in the delta zone. The Various hydro-geochemical parameters such as pH, Electrical Conductivity (EC), Total Dissolved Solids (TDS), Ca2+, Mg2+, K+, Na+, CO3, HCO3-, Cl-, and SO42- are evaluated for the delineation of the intrusion of saltwater in terms of Ca2+/ Mg2+, Cl-/(CO3+ HCO3-), Na+/Cl- ratios. It is reported that the availability of fresh groundwater is 14%and 62% respectively during the pre-monsoon and post-monsoon seasons. The percentage levels of contamination in groundwater for slight, moderate, injuriously, highly, and severely categories are 43%, 22%, 12%, 8%, and 1% respectively for pre-monsoon season. However, during the post-monsoon season, the levels of contaminations in the above- mentioned categories are 22%, 9%, 4%, 1%, and 3%. The extent of contamination during the post-monsoon season is observed to be lower than during the pre-monsoon. The groundwater ratio of Na+- Cl− during pre-monsoon and post-monsoon seasons is 71%and 60% respectively. The Saltwater Mixing Index (SMI) is also measured, and extremely high is found.
Comparative Adsorption of Cd(II) and Pb(II) by MCM-48 and amine- Grafted MCM-48 in Single and Binary Component Systems
Authors: Vatandous Hadi , Younesi Habibollah , Mehraban Zahra , Heidari Ava , Khakpourd Hussein
Published: January 2021

MCM-48 were prepared using hexadecyl trimethyl ammonium bromide and TEOS and modified with N1-(3-Trimethoxy silylpropyl) diethylenetriamine by post-synthesis method, in order to develop efficient adsorbent for heavy metal adsorption. These materials were determined by X-ray diffraction, N2 adsorption–desorption measurement and Scanning Electron Microscopy. The results show that the modification of MCM-48 resulted in decrease in the Brunauer-Emmett-Teller surface area and total pore volume. Batch adsorption technique in single and multi-component system was used in this study. The influence of experimental parameters was investigated and the results indicated that amine attached MCM-48 indicated higher adsorption efficiency for metal ions than MCM-48. Langmuier and Freundlich models modeled the equilibrium data in single system; whereas two component data fitted to the extended Langmuir model. The maximum adsorption capacity (qm, single system) of NH2-NH-NH-MCM-48 for cadmium and lead was 82.7 mg g− 1 and 119.24 mg g− 1, respectively. In both adsorption systems, the affinity of NH2-NH-NH-MCM-48 for cadmium was greater than that for lead.
Acute Pancreatitis-Associated Genes Identified by Integrative Analysis of Gene Expression Data
Authors: Zeng Chunyan , Zhu Yin , Chen Youxiang
Published: January 2021

Background Acute pancreatitis (AP) is a common digestive disease. A better understanding of the biology and molecular pathogenesis of AP may provide the basis for the prevention and therapy of AP.Methods The gene expression datasets GSE109227, GSE3644 and GSE65146, which included gene expression profiles of pancreas samples from AP and control mice, were obtained from the Gene Expression Omnibus database. All differentially expressed genes (DEGs) were identified using GEO2R and annotated using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Results Thirty-eight DEGs were found to overlap among the three datasets. A protein-protein interaction (PPI) network was constructed; hub proteins were identified; and functional modules were extracted. Three genes (Cdh1, Iqgap1 and Actn4), which are involved in the adherens junction pathway, were identified using PPI analysis and may provide potential biomarkers for the diagnosis and treatment of AP.Conclusions We will further study the effects of the Cdh1, Iqgap1 and Actn4 genes on the occurrence and development of acute pancreatitis, which may provide new targets for the diagnosis and treatment of AP.
Effect of Delayed Surgical Resection of Primary Hepatocellular Carcinoma on Survival Outcomes In Elderly Patients and Prediction of Clinical Models
Authors: He Yongfei , Liang Tianyi , Mo Shutian , Chen Zijun , Zhao Shuqi , Zhou Xin , Yan Liping , Wang Xiangkun , Su Hao , Zhu Guangzhi , Han Chuangye , Peng Tao
Published: January 2021

Background: The effect of time delay from diagnosis to surgery on the prognosis of elderly patients with liver cancer is not well known. We investigated the effect of surgical timing on the prognosis of elderly hepatocellular carcinoma patients undergoing surgical resection and constructed a Nomogram model to predict the overall survival of patients.Methods: A retrospective analysis was performed on elderly patients with primary liver cancer after hepatectomy from 2012 to 2018. The effect of surgical timing on the prognosis of elderly patients with liver cancer was analyzed using the cut-off times of 18 days, 30 days, and 60 days. Cox was used to analyze the independent influencing factors of overall survival in patients, and a prognostic model was constructed.Results: A total of 232 elderly hepatocellular carcinoma patients who underwent hepatectomy were enrolled in this study. The cut-off times of 18, 30, and 60 days were used. The duration of surgery had no significant effect on overall survival. Body Mass Index, Child-Pugh classification, Tumor size Max, and Length of stay were independent influencing factors for overall survival in the elderly Liver cancer patients after surgery. These factors combined with Liver cirrhosis and Venous tumor emboli were incorporated into a Nomogram. The nomogram was validated using the clinical data of the study patients, and exhibited better prediction for 1-year, 3-year, and 5-year overall survival.Conclusion: We demonstrated that the operative time has no significant effect on delayed operation in the elderly patients with hepatocellular carcinoma, and a moderate delay may benefit some patients. The constructed Nomogram model is a good predictor of overall survival in elderly patients with hepatectomy.
Type of GI Provider Does Not Affect Rates of Vaccination Amongst Inflammatory Bowel Disease Patients
Authors: Trivedi Mehul , Malik Neena , Kwah Joann
Published: January 2021

Background:Patients with Inflammatory Bowel Disease (IBD) are at heightened risk of infection, and are often under vaccinated. At our institution, IBD patients may follow up with one of three gastroenterology (GI) providers: IBD specialists, GI Fellows and General GI providers. Aims: Our primary objective was to identify whether the type of GI provider had an effect on rates of vaccinations for IBD patients. The seven vaccines studied were listed in the American College of Gastroenterology’s 2017 Guidelines on Preventative Care in IBD, and include Influenza, Tetanus/Diphtheria/Pertussis, Hepatitis A (HAV), Hepatitis B (HBV), Pneumococcus (PCV13 and PPSV23), Meningococcus, and Human Papillomavirus (HPV).Methods:Retrospective case control study of IBD patients, looking at vaccination rates for each of the seven vaccinations listed above, and type of GI provider followed. Other data collected included patient demographics, IBD type, treatment regimen and insurance.Results:Of 338 IBD patients, 65 (19.2%) followed up with a GI fellow, 110 (32.5%) with a general GI provider, and 163 (48.2%) with an IBD specialist. HBV was the only vaccine with a significant difference in vaccination rate by type of provider. Bivariate analysis showed that patients who followed with IBD specialists and GI fellows were more likely to be vaccinated for HBV than patients who followed up with general GI provider (OR = 2.55, p = .003 and OR = 2.73, p = .007 respectively).Conclusion Type of GI provider only impacted rates of vaccination for HBV among IBD patients in this study, with IBD specialists and GI fellows outperforming general GI providers.
Association of Kawasaki Disease and COVID-19 in children
Authors: esmaeilzadeh hossein , Mortazavi Negar , Salehi Alireza , Fatemian Hossein , Vardanjani Hossein Molavi
Published: January 2021

Kawasaki Disease (KD) is most common childhood vasculitis and cause of acquired heart disease for no apparent reason. There is some evidence indicating infectious agents as possible triggers for KD. During the COVID-19 pandemic, vasculitis has been a presentation of COVID-19 in children.
Objective
We performed this study to assess the association between KD and COVID-19.
Methods and Materials
We evaluated KD hospitalized children during February to September 2020 for COVID-19 (group one) and compared their demographic, clinical, laboratory, and echocardiographic findings with KD patients from the same period of time in 2019 (group two). We also compared the same data in COVID-19 positive and COVID-19 negative KD patients in 2020 pandemic period.
Results
68% of KD patients in group one were positive for COVID-19 during the pandemic period. KD Age of onset in the group one was lower than group two (4.38 years VS 5.5 years, P-value= 0.044). There was no difference in the demographic, clinical, laboratory, and echocardiographic features of the patients during and before the COVID-19 pandemic (p-value > 0.05). Moreover, Comparing COVID-19 positive and negative patients, the incidence of rash was higher within COVID-19 positive cases (p<0.05), and coronary artery abnormalities were more prevalent in COVID-19 negative cases (p < 0.05).
Conclusion
Admission rate of KD does not have significant difference during the COVID-19 pandemic but 68% of KD admitted patient were COVID-19 positive. Age of onset for KD during the COVID-19 pandemic was lower than the same period of time in last year.
GDF11 expressed in the adult brain negatively regulates hippocampal neurogenesis
Authors: Mayweather Brittany A , Buchanan Sean M , Rubin Lee L
Published: January 2021

Growth differentiation factor 11 (GDF11) is a transforming factor-β superfamily member that functions as a negative regulator of neurogenesis during embryonic development. However, when recombinant GDF11 (rGDF11) is administered systemically in aged mice, it promotes neurogenesis, the opposite of its role during development. The goal of the present study was to reconcile this apparent discrepancy by performing the first detailed investigation into the expression of endogenous GDF11 in the adult brain and its effects on neurogenesis. Using quantitative histological analysis, we observed that Gdf11 is highly expressed in adult neurogenic niches and non-neurogenic regions within the hippocampus, choroid plexus, thalamus, habenula, and cerebellum. To investigate the role of endogenous GDF11 during adult hippocampal neurogenesis, we generated a tamoxifen inducible mouse that allowed us to reduce GDF11 levels. Depletion of Gdf11 during adulthood increased proliferation of neural progenitors and decreased the number of newborn neurons in the hippocampus, suggesting that endogenous GDF11 remains a negative regulator of hippocampal neurogenesis in adult mice. These findings further support the idea that circulating systemic GDF11 and endogenously expressed GDF11 in the adult brain have different target cells or mechanisms of action. Our data describe a role for GDF11-dependent signaling in adult neurogenesis that has implications for how GDF11 may be used to treat CNS disease.
Meta-analysis of randomized trials of ivermectin to treat SARS-CoV-2 infection
Authors: Hill Andrew , Abdulamir Ahmed , Ahmed Sabeena , Asghar Asma , Babalola Olufemi Emmanuel , Basri Rabia , Chaccour Carlos , Chachar Aijaz Zeeshan Khan , Chowdhury Abu Tauib Mohammed , Elgazzar Ahmed , Ellis Leah , Falconer Jonathan , Garratt Anna , Hany Basma , Hashim Hashim A , Haque Wasim Ul , Hayat Arshad , He Shuixiang , Jamshidian Ramin , Khan Wasif Ali , Kirti Ravi , Krolewiecki Alejandro , Lanusse Carlos , Levi Jacob , Mahmud Reaz , Mangat Sermand Ahmed , McCann Kaitlyn , Mohan Anant , Niaee Mortezza Shakshi , Okumus Nurullah , Pilkington Victoria , Podder Chinmay Saha , Qavi Ambar , Raad Houssam , Rezai Mohammaed Sadegh , Sasank Surapaneni , Spoorthi Veerapaneni , Suri Tejas , Wang Junzheng , Wentzel Hannah
Published: January 2021

Ivermectin is an antiparasitic drug being investigated for repurposing to SARS-CoV-2. In-vitro, ivermectin showed limited antiviral activity and a COVID-19 animal model demonstrated pathological benefits but no effect on viral RNA. This meta-analysis investigated ivermectin in 18 randomized clinical trials (2282 patients) identified through systematic searches of PUBMED, EMBASE, MedRxiv and trial registries. Ivermectin was associated with reduced inflammatory markers (C-Reactive Protein, d-dimer and ferritin) and faster viral clearance by PCR. Viral clearance was treatment dose- and duration-dependent. In six randomized trials of moderate or severe infection, there was a 75% reduction in mortality (Relative Risk=0.25 [95%CI 0.12-0.52]; p=0.0002); 14/650 (2.1%) deaths on ivermectin; 57/597 (9.5%) deaths in controls) with favorable clinical recovery and reduced hospitalization. Many studies included were not peer reviewed and meta-analyses are prone to confounding issues. Ivermectin should be validated in larger, appropriately controlled randomized trials before the results are sufficient for review by regulatory authorities.
Gynecological Neoplasms are the Major Cause for Malignant Effusions
Authors: Krugmann Jens , Lang-Schwarz Corinna , Sterlacci William , Nikolaev Svetlana , Ozalinskaite Agne , Steppert Claus , Adler Werner , Vieth Michael , Lermann Johannes
Published: January 2021

Background: Malignant effusions occur frequently in gynecologic neoplasms and may worsen the prognosis for these patients. Therefore a more detailed analysis for the different cavities is necessary to describe the association between the various histological subtypes and the time related occurrence of malignant effusions in gynecological malignancies. Methods: Malignant effusion specimens from patients diagnosed at Bayreuth Hospital from June 2013 to December 2018 were reevaluated retrospectively and correlated with the histolgogical subtype of primary tumors and with the clinical follow-up.Results: 435 patients with malignant effusions were analyzed, including 273 women and 162 men. 54.2% of patients developed malignant effusions in the pleural space in (54.2%) patients, in the peritoneum in (43.9%) patients and in the pericardium in (1.9%). Gynecological malignancies appear most common in (n=147, 34.0%; mean age 67.3 years) patients with predominant occurrence of ovarian carcinoma in malignant abdominal cytology in 75/191 (39.3%) patients, mostly of high-grade serous papillary subtype in 72/75 (96.1%), and only breast cancer in malignant pleural effusions in 49/236 (20.7%), frequently of 39/49 (79.6%) invasive carcinomas of no specific type. Both involvement of pleural- and peritoneal cavity in 244 female patients with gynecological-, lung- and gastrointestinal neoplasms we obtained in 37 (15.2%) patients, most common in 31/37 (83.78%) gynecological tumors and exclusively of high-grade serous papillary subtype. Malignant ascites occured in patients with lower genital tract tumors in 81/86 (94.2%) within one year after primary diagnosis, whereas breast cancer involves the peritoneum in 2/10 (20%) and the pleural cavity in 11/49 (22.4%) after 12 months. Conclusions: Gynecological neoplasms were the major cause of malignant effusions in our study. The high-grade serous papillary subtype of lower tract gynecological is most aggressive with predominant occurrence in the peritoneum and exclusive secondary involvement of the pleural cavity. Therefore, an alone/exclusive/sole involvement of the pleural cavity characterize the invasive breast carcinoma of no special type compared to predominant occurrence of the lobular subtype in malignant ascites. Breast cancer showed a statistical significant late occurrence in effusion fluids 12 months after primary diagnosis in contrast to early involvement in gynecological- as well as pulmonary- or gastrointestinal malignancies.
Feasibility Study To Assess The Delivery of A Novel Isometric Exercise Intervention For People With Stage 1 Hypertension In The NHS: Protocol For The Isofit-BP Study Including Amendments To Mitigate The Risk of COVID-19 
Authors: Wiles Jonathan , Rees-Roberts Melanie , O’Driscoll Jamie , Doulton Timothy , McInnes Douglas , Short Vanessa , Pellatt-Higgins Tracy , Saxby Katie , Gousa Katerina , West Alan , Smith Maggie , Santer Ellie , Darby John , Farmer Chris K
Published: January 2021

Background: Hypertension (HTN) affects approximately 25% of the UK population and is a leading cause of mortality. Associated annual health care costs run into billions. National treatment guidance includes initial lifestyle advice, followed by anti-hypertensive medication if blood pressure (BP) remains high. However, adoption and adherence to recommended exercise guidelines, dietary advice and anti-hypertensive medication is poor. Four short bouts of isometric exercise (IE) performed 3 days per week (d/wk) at home elicits clinically significant reductions in BP in those with normal to high-normal BP. This study will determine the feasibility of delivering personalised IE to patients with Stage 1 hypertension for whom lifestyle changes would be recommended before medication within NHS primary care.Methods: This is a randomised controlled feasibility study. Participants 18+ years, with Stage 1 hypertension, not on anti-hypertensive medication and without significant medical contraindications. Trial arms will be standard lifestyle advice (control) or isometric wall squat exercise and standard lifestyle advice. Primary outcomes include success of intervention delivery and change in BP. Secondary outcomes include accuracy of protocol delivery, execution of and adherence to protocol, recruitment rate, attrition, perception of intervention viability, cost, participant experience, and accuracy of home BP. The study will last 18 months. Sample size of 100 participants (50 per arm) allows for 20% attrition and 6.5% incomplete data, based upon 74 (37 each arm) participants (two-sided 95% confidence interval, width of 1.33 and standard deviation of 4) completing 4 weeks. Ethical approval IRAS ID: 274676.Discussion: Before the efficacy of this novel intervention to treat Stage 1 hypertension can be investigated in any large randomised controlled trial, it is necessary to ascertain if it can be delivered and carried out in a NHS primary care setting. Findings could support IE viability as a prophylactic / alternative treatment option.Trial Registration: International Standard Randomised Controlled Trial Number (ISRCTN) 13472393 registered 18 August 2020. http://www.isrctn.com/ISRCTN13472393
The climate change mitigation impacts of active travel: Evidence from a longitudinal panel study in seven European cities
Authors: Brand Christian , Goetschi Thomas , Dons Evi , Gerike Regine , Anaya-Boig Esther , Avila-Palencia Ione , Nazelle Audrey de , Gascon Mireia , Gaupp-Berghausen Mailin , Iacorossi Francesco , Kahlmeier Sonja , Panis Luc Int , Racioppi Francesca , Rojas-Rueda David , Standaert Arnout , Stigell Erik , Sulikova Simona , Wegener Sandra , Nieuwenhuijsen Mark J.
Published: January 2021

Active travel (walking or cycling for transport) is generally good for health, the environment and the economy. Yet the net effects of changes in active travel on changes in mobility-related CO2 emissions are complex and under-researched. Here we collected longitudinal data on daily travel behavior, mode choice, as well as personal and geospatial characteristics in seven European cities and derived mobility-related lifecycle CO2 emissions from daily travel activity over time and space. Fixed- and mixed-effects modelling of longitudinal panel data (n=1849) was performed to assess the associations between changes in lifecycle CO2 emissions and changes in transport mode use (primary exposure), main mode of travel, and cycling frequency (secondary exposures). Daily mobility-related lifecycle CO2 emissions were 2.8 kgCO2 per person at baseline, with car travel contributing 69% and cycling 1%. At follow-up, mobility-related lifecycle CO2 emissions were -0.52 (95%CI -0.82 to -0.21) kgCO2/day lower per additional cycling trip, -0.41 (95%CI -0.69 to -0.12) kgCO2/day lower per additional walking trip, and -2.11 (95%CI -1.78 to -2.43) kgCO2/day lower per ‘avoided’ car trip. An average person cycling 1 trip/day more and driving 1 trip/day less for 200 days a year would decrease mobility-related lifecycle CO2 emissions by about 0.5 tonnes over a year. Those who changed from ‘not cycling’ to ‘cycling’ decreased daily CO2 emissions by -2.54 (95%CI -3.90 to -1.17) kgCO2/day. Mobility-related CO2 emissions decreased by -9.28 (95%CI -11.46 to -7.11) kg/day for those who changed their ‘main mode’ from car, van or motorbike to active travel. Extensive sensitivity analyses by city, journey purpose and key personal characteristics largely confirmed our results. Active travel is shown to substitute for motorized travel, with significant climate change mitigation effects. Even if not all car trips could be substituted by active travel the potential for decreasing emissions is considerable and significant. Investing in and promoting active travel should therefore be a cornerstone of strategies to meet net zero carbon targets, particularly in urban areas, while also improving public health and quality of urban life.