bluuebunny/crossref_metadata_2025 huggingface dataset:
An evaluation of postmarketing reports of hyperglycaemia associated with dolutegravir for treatment of HIV in Eswatini
Authors: Duga Alemayehu L. , Magongo Sibongile , Nhlabatsi Siphesihle , Ladwar Denis O. , Härmark Linda , Rolfes Leàn
Published: April 2022

Background: Dolutegravir (DTG) is an Integrase Strand Transfer Inhibitor (INSTI) indicated in combination with other antiretroviral agents for the treatment of HIV infection. It is available in a number of pharmaceutical preparations including the fixed-dose combination (TLD)containing tenofovir (300mg) + lamivudine ( 300mg) + dolutegravir (50mg). In 2018, Eswatini adopted TLD as the preferred first-line HIV treatment regimen for adults and adolescents as per WHO recommendations. From March 2019 to March 2020, the National Pharmacovigilance Center (NPC) in Eswatini received eight reports of hyperglycaemia associated with the use of DTG. Method: A review and analysis of Pharmacovigilance reports identified from the Eswatini national pharmacovigilance database from March 2019 (introduction of DTG) to March 2020. All reports with DTG containing regimen and suspected Adverse Event of hyperglycaemia in the period of March 2019 to March 2020 were included in the study.Results: Seven of the reports were serious (resulted in hospitalization and one case concerned optic neuritis, leading to blindness). Two patients had a medical history of diabetes while the rest of the patients had never experienced hyperglycaemia before. For all the reports, the time to onset of hyperglycaemia ranges from 2-5 months after the initiation of DTG. None of the patients discontinued the use of DTG. All the patients were treated with oral hypoglycaemic medication. In severe cases, patients were treated with intravenous normal saline and ringer lactate as well as rapid-acting insulins. All patients are currently stable on oral hypoglycaemic drugs. Conclusion: Based on these findings it is recommended that healthcare professionals (HCPs) actively screen all patients for risk factors of hyperglycaemia before DTG initiation. In addition, it is important that HCPs are aware of the possible association between DTG and hyperglycaemia.
Citation analysis of the 100 top-cited articles on diskectomy via endoscopy since 2011 using Alluvial diagrams: Bibliometric analysis
Authors: Yeh Chao-Hung , Chien Tsair-Wei , Chou Po-Hsin
Published: April 2022

Background
Percutaneous endoscopic lumbar discectomy (PELD) is synonymous with percutaneous endoscopic transforaminal discectomy (PETD) and percutaneous endoscopic interlaminar discectomy (PEID). PEID has gained increasing recognition for its small incision, quick recovery, short hospital stay, and equivalent clinical outcome to open surgery. Numerous articles related to PEID have been published in the literature. However, which countries, journals, subject categories, and articles have ultimate influence remains unknown. The study aimed to (1) display influential entities in 100 top-cited PEID-related articles (T100PEID) on the Alluvial diagram and (2) investigate whether medical subject headings (i.e., MeSH terms) can be used to predict article citations.
Methods
T100PEID data can be found since 2011 in the PubMed and Web of Science (WOS) databases. Using Alluvial diagrams, citation analysis was conducted to compare the dominant entities. We used social network analysis (SNA) to classify MeSH terms and research areas extracted from PubMed and WOS. The difference in article citations across subject categories and the predictive power of MeSH terms on article citations in T100 PEID were examined using one-way analysis of variance (ANOVA) and regression analysis.
Results
A total of 81% of T100PEID is occupied by the top three countries (the US, China, and South Korea). There was an overall T100PEID impact factor of 41.3 (IF = citations/100). Articles were published in Spine (Phila Pa 1976) (23%; IF = 41.3). Six subject categories were classified using the SNA. The most cited article authored by D Scott Kreiner from Ahwatukee Sports and Spine in the US state of Phoenix had 123 citations in PubMed. The network characteristics of T100PEID are displayed on the Alluvial diagram. No difference was found in article citations among subject categories (F = 0.813, p = 0.543). The most frequently occurring MeSH term was surgery. MeSH terms were evident in the prediction power of the number of article citations (F =15.21; p <0 .001).
Conclusion
We achieved a breakthrough by displaying the T100PEID network characteristics on the Alluvial Plateau. The MeSH terms can be used to classify article subject categories and predict T100PEID citations. The Alluvial diagram can be applied to bibliometrics on 100 top-cited articles in future studies.
Comprehensive analysis reveals a CTHRC1-based fourteen-gene signature for prognosis prediction in colon cancer
Authors: Jianwei Wang , Xu Miaorong , Mu Jiayi , Chen Yiquan , Mu Yali , Ye Xun , Zhou Qin
Published: April 2022

Background: Colon cancer is a malignant gastrointestinal tumor and is still a worldwide leading cause of cancer-related mortality. Owing to the development of high-throughput sequencing technologies, large-scale data have become available in public databases. We devoted to construct and validate a gene signature that can predict patients’ outcomes for colon cancer using bioinformatics methods. Methods: We integrated GSE44076 and GSE39582 to identify differentially expressed genes (DEGs). Timer 2.0 was used to analysis CTHRC1 expression in various types of cancer. The relationship of clinicopathological features and CTHRC1 expression was explored based on TCGA database. Hub genes were identified by String database and Cytoscape software. The gene prognostic signature was established based on the Cox regression analysis.Results: We obtained 170 common DEGs and confirmed CTHRC1 was significantly overexpressed in colon cancer samples (P < 0.001). High CTHRC1 level was associated with advanced stage and shorter overall survival (OS) time and relapse-free survival (RFS) time in colon cancer patients. We identified thirteen hub genes among 516 genes co-expressed with CTHRC1 and subsequently constructed a 14-gene risk signature, which associated advanced stage and poor OS (log-rank test p < 0.01). Multivariate Cox regression indicated that high risk score was an independent risk factor for poor prognosis (p < 0.01). Finally, Receiver operating characteristic curve analysis was performed to further confirm the validity of the signature. Conclusions: We confirmed the important role of CTHRC1 in colon cancer and further constructed a 14-gene risk signature with promising prognostic accuracy for colon cancer patients.
A prospective study of Daikenchuto on superior mesenteric artery and portal venous blood flows in extremely low birthweight infants
Authors: Watanabe Shunsuke , Inoue Mikihiro , Miyata Masafumi , Boda Hiroko
Published: April 2022

Background: Focal intestinal perforation (FIP) is a devastating complication of prematurity, and extremely low birthweight (ELBW) infants are at highest risk. The aim of this study was to evaluate the relationship between superior mesenteric artery (SMA) and portal venous (PV) blood flow velocities to investigate the association between FIP and intestinal blood flow. In addition, Daikenchuto (TJ-100) is expected to have the effect of improving intestinal blood flow disorders, so we evaluated the effect.Methods: We conducted a prospective cohort study of 15 ELBW infants from January 2020 to August 2021.15 infants were divided the non-surgery group (Group I; 6), the surgery group with FIP (Group II; 4), and the TJ-100 administration group (Group III; 5). Main outcome parameters included SMA blood flow velocity and PV blood flow velocity.Results: A statistically significant difference was observed between the Group I and Group III on gestational age (p = 0.03). On the longitudinal evaluation of SMA and PV blood flow, statistically significant differences were found in SMA of Group I, and SMA and PV of Group III (p < 0.01, p = 0.01 and p = 0.0.4, respectively). And there was a correlation between SMA and PV in Group III (p = 0.03).Conclusion: TJ-100 may increase SMA and PV blood flow, and improve intestinal blood flow in ELBW infants at the risk of FIP. Therefore, we will continue to study the effect of TJ-100.
Differential gene screening and bioinformatics analysis of epidermal stem cells and dermal fibrblasts during skin aging
Authors: Hu Weisheng , Jing Yuan , Yu Qingqian , Huang Ning
Published: April 2022

Objective
To explore the differentially expressed genes (DEGs) and potential therapeutic targets of skin aging in GEO database by bioinformatics methods.
Methods
Dermal fibroblasts and skin aging related data sets GSE110978 and GSE117763 were downloaded from GEO database, and epidermal stem cells and skin aging related data sets GSE137176 were downloaded. GEO2R was used to screen DEGs of candidate samples from the three microarrays, GO function analysis and KEGG pathway analysis were performed. Protein interaction network was constructed using String database, and hub gene was obtained by Cytoscape. NetworkAnalys was used to analyze the coregulatory network of DEGs and MicroRNA (miRNA), interaction with TF, and protein-chemical interactions of DEGs. Finally, DSigDB was used to determine candidate drugs for DEGs.
Results
Six DEGs were obtained. It mainly involves the cytological processes such as response to iron ion, and is enriched in mineral absorption and other signal pathways. Ten genes were screened by PPI analysis. Gene-miRNA coregulatory network found that Peg3 and mmu-miR-1931 in DEGs were related to each other, and Cybrd1 was related to mmu-miR-290a-5p and mmu-miR-3082-5p. TF-gene interactions found that the transcription factor UBTF co-regulated two genes, Arhgap24 and Mpzl1. Protein-chemical Interactionsa analysis and identification of candidate drugs show results for candidate drugs.
Conclusion
Try to explore the mechanism of hub gene action in skin aging progression, and to discover the key signaling pathways leading to skin aging, which may be a high risk of skin aging.
Efficacy of risk-stratified indicators for adjuvant chemotherapy with fluorouracil and oxaliplatin after hepatectomy for colorectal cancer liver metastasis Running title: Risk-stratified indication for doublet AC after hepatectomy for CRLM
Authors: Tominaga Tetsuro , Maruyama Keizaburo , Nonaka Takashi , Moriyama Masaaki , Oyama Shosaburo , Ishii Mitsutoshi , Sawai Terumitsu , Nagayasu Takeshi
Published: April 2022

Background: The recurrence rate after hepatectomy for colorectal cancer liver metastasis (CRLM) is high, and there is no consensus regarding the effect of adjuvant chemotherapy (AC) using oxaliplatin (doublet AC) in these patients.Methods: The present study included 91 patients who underwent hepatectomy for complete resection at our hospitals between 2008 and 2018. Based on whether or not they had undergone doublet AC, patients were divided into AC (n=35) and non-AC (n=56) groups. Recurrent risk was evaluated by Memorial Sloan Kettering Cancer Center clinical risk score (MSKCC-CRS).Results: The number of females and median age were higher in the AC group (51.4% vs 25.0%, p=0.010 and 67 vs 61 years, p=0.012, respectively). Doublet AC was an independent prognostic factor for 5-year relapse-free survival (hazard ratio, 0.225; 95%CI, 0.097–0.522; p<0.001) and for 5-year overall survival (hazard ratio, 0.165; 95%CI, 0.057–0.476; p<0.001) in multivariate analysis. In patients with high risk of recurrence (MSKCC-CRS 3–5), 5-year relapse-free survival and 5-year overall survival was higher in the doublet AC group than in the non-AC group (p<0.01). In low-risk patients (MSKCC-CRS 0–2), 5-year relapse-free survival and 5-year overall survival were similar between the groups.Conclusions: Doublet AC could have a positive effect on prognosis after curative resection of CRLM, especially in high-risk patients. Selection of patients and AC regimen should take into consideration the risk of recurrence.
On springtails (Hexapoda: Collembola): A morphofunctional study of the jumping apparatus
Authors: Oliveira Fábio G. L.
Published: April 2022

Background
Springtails (Hexapoda: Collembola) are tiny organisms that lead a hidden life, mostly occuring deep in the soil and on leaf litter. They have a variety of interesting body morphology patterns, the most famous of which is the catapult-like structure that enables them to jump and flee from predators. This highly specialized jumping apparatus consists of a mobile furca, which when at rest fits into a trigger, "the retinaculum" on the ventral side of the abdomen. Despite the many studies that have attempted to investigate the jumping apparatus, the actual mechanisms involved in the jump, for example the way in which the furca is released by the retinaculum, how and where the mechanisms of spring and hydrostatic pressure originate, are still not properly understood. The morphology of the jumping apparatus of Orchesella cincta was investigated in detail using confocal laser scanning microscopy and MicroCT techniques for 3D reconstruction.
Results
The morphology of O. cincta with both flexed and extended furca is analysed and described. The abdominal musculature involved in the jumping mechanism and relevant structures of the exoskeleton of retinaculum and furca are described in detail. With the data obtained in this study, hypotheses can be made about 1) where and how the spring and hydrostatic pressure mechanisms originate; 2) which muscles act on the extension and flexion of the furca; 3) which muscles act on the retinaculum and 4) how the retinaculum is released from the furca.
Conclusions
The comparative morphological study proved informative, and shows how springtail jumping involves mechanisms unique to this taxon. Hydrostatic pressure regulation possibly varies between animals with distinct segmentation, and those with fused segmentation. Interesting cuticular characters were revealed, such as basal plates and sclerites related to the construction of the spring mechanism. The present study establishes itself as a model option for future morphofunctional studies on springtails' jumping. Analysis of videos and images using a high speed camera will be useful for understanding how the jump develops through take-off, aerial and landing phases.
Utilization of nanoparticles for sustainable biogas production: process stability and effluent quality
Authors: Abdelwahab Taha Abdelfattah Mohammed , Fodah Ahmed Elsayed Mahmoud
Published: April 2022

One of the most important techniques for converting complex organic waste into renewable energy in the form of biogas and effluent is anaerobic digestion (AD). Several issues have been raised related to the effectiveness of the AD process in recent years. Hence nanoparticles (NPs) have been used widely in AD process for converting organic wastes into useful biogas and effluent in an effective way. This review addresses the knowledge gaps and summarizes recent researchers’ findings concentrating on the stability and effluent quality of the cattle manure AD process using various NPs (e.g., Fe, Ni, Co, and metal oxides). In summary, the utilization of NPs have beneficial effects on methane generation, process optimization, and effluent quality. Their function, as key nutrient providers, aid in the synthesis of key enzymes and co-enzymes, and thus stimulate anaerobic microorganism activities when present at an optimum concentration (e.g., Fe NPs 100 mg/L; Ni NPs 2 mg/L; Co NPs 1 mg/L). Furthermore, utilizing Fe NPs at concentrations higher than 100 mg/L is more effective at reducing hydrogen sulfide production than increasing methane, whereas Ni NPs and Co NPs at concentrations greater than 2 mg/L and 1 mg/L, respectively, reduce methane production. Effluent with Fe and Ni NPs showed stronger fertilizer values more than Co NPs.
Biotransformation of antibiotic norfloxacin by marine-derived fungi
Authors: Morais Aline Teixeira do Brasil , Barreiro Juliana Cristina , Porto André Luiz Meleiro Porto
Published: April 2022

The occurrence of drugs in the environment has called attention due to the adverse effects on the biotic community. Norfloxacin (NOR) is a compound widely used for treatment of serious bacterial infections in human and animals, therefore its monitoring and toxicological effects have been investigated, mainly in aquatic environment. In this study the biotransformation/biodegradation of NOR was followed in the presence of marine-derived fungi for 35 days and the products was identified by LC-MS/MS, based on the similarity between experimental and theoretical exact mass. An analytical method was developed and validated to determine the percentage of NOR biodegradation in the presence of fungi Penicillium raistrickii CBMAI 931 (34.07%), Aspergillus sydowii CBMAI 1241 (58.91%), fungal consortium (57.05%) and in a mineral medium (59.35%).
WITHDRAWN: Analysis of prognostic factors for recurrence and metastasis sites of high-grade upper tract urothelial carcinoma
Authors: Ding Dexin , Gao Jianing , Wang Huan , Li Hao
Published: April 2022

Purpose: Metastatic recurrence takes place in more than 21.7% of patients with UTUC underwent RNU. Although metastatic recurrence suggested a poor prognosis, the effect of the specific recurrence site on prognosis is still to be discussed.Methods: According to a retrospective analysis on 355 patients who underwent RNU for high-grade, node-negative upper urothelial carcinoma in our hospital from 2010 to 2020. The result showed that no one received neoadjuvant or adjuvant chemotherapy. So, Univariate and multivariate Cox regression analyses were then performed to assess predictors of metastatic recurrence as well as site-specific prognosis. In addition, Kaplan-Meier method and log-rank test were adopted for the estimation and comparison of the recurrence site-specific survival probabilities after metastatic recurrence.Results: Of 355 patients, 77 recurred during a median follow-up of 17 months. In multivariate analysis, IVR, tumor size, and pT-stage were significant predictors of metastatic recurrence. Metastatic recurrence was most common in bone and multiple sites, with less median survival time for liver recurrence and multiple site recurrence.Conclusion: A majority of patients with high-grade UTUC suffered from systematical recurrence after RNU. IVR, tumor size, and pT-stage are predictors of metastasis and recurrence. Besides, prevention of IVR after RNU may help improve the prognosis of patients with UTUC. Poor prognosis showed compared with other sites, liver, bone and multiple sites relapse relatively quickly. These findings are of great likelihood to contribute to the development of future site-specific treatment plans for recurrence. Plus, studying the genetic association of UTUC and elucidating the underlying mechanism of metastasis recurrence must be of paramount importance.
An 8-week Exercise Study to Improve CRF and Quality of Life Among African-American Breast Cancer Patients During Radiation Treatment: A Pilot Randomized Clinical Trial
Authors: Adams-Campbell Lucile L. , Mills Mary , Hicks Jennifer , Randolph-Jackson Pamela , Isaacs Claudine , Makambi Kepher , Dash Chiranjeev
Published: April 2022

Background
Cancer related fatigue (CRF) is one of the most debilitating side effects of adjuvant radiation therapy (RT). Several studies have found that physical activity (PA) may be an effective intervention to decrease fatigue and enhance QOL in cancer survivors.
Purpose
The primary objective of the PEDLAR study is to test the efficacy of an easily administered 8-week structured moderate-intensity PA intervention, delivered concurrently with RT, in reducing CRF and improving health-related QOL among AA breast cancer patients. This study is also designed to provide pilot data on the acceptability and adherence of PA interventions in AA women with breast cancer.
Methods
It is a prospective, 2-arm, 8-week feasibility trial. Participants are randomized to either a structured, moderate-intensity aerobic training exercise regimen concurrent with radiotherapy or a control group.
Results
Participants in intervention group reported high satisfaction with exercise and adherence was > 75% for exercise sessions.
Conclusions
African-American breast cancer patients in a moderate-intensity 75 min/wk aerobic exercise intervention had marginally lower fatigue at 8-wk follow-up compared to baseline. The control group participants had marginally higher fatigue at 8-wk follow-up compared to baseline. Participants in the intervention group reported slightly better quality of life at 8-wk follow-up compared to baseline (P = 0.06).
Revealing the mechanism of Salvia miltiorrhiza Bunge and Carthamus tinctorius L herb pair in treating myocardial ischemia by combined network pharmacology and experimental verification
Authors: Du Shao Bing , Zhou Hui Hui , Xue Zhi Peng , Li Jing , Wang Peng Fei , Wang Xiaoping , Bai Jiqing , Li Na , Gao Su
Published: April 2022

The present work was aimed to gain more insight into the molecular mechanisms of Salvia miltiorrhiza Bunge and Carthamus tinctorius L herb pair (SMCTHP) in treating myocardial ischemia (MI) through network pharmacology and in vivo experiments. Firstly, various electronic databases and literatures-mining were utilized to acquire and screen out the bioactive compounds of SMCTHP and potential therapeutic targets of myocardial ischemia (MI). Subsequently, functional enrichment analysis was carried out to obtain a more radical understanding of SMCTHP against MI via the DAVID database. PPI network was established and analyzed to determine the hub targets. Finally, we used the acute myocardial ischemia (AMI) rat model to evaluate the cardioprotective effects of SMCTHP, and TUNEL assay and Western blotting analysis were used to measure the apoptotic rate and validated the hub targets and key pathways, respectively. A total of 92 bioactive compounds of SMCTHP and 245 overlapping targets between SMCTHP and MI were identified from these databases. By performing functional enrichment analysis, the anti-MI targets of SMCTHP were highly correlated with the apoptosis process, and the key functional pathways may be the PI3K/AKT and NF-κB pathways. Then, the hub targets of the PPI network contained AKT1, IL6, TNF, VEGFA, MAPK1, STAT3, RELA, MMP9, CASP3, and TLR4. In vivo experiment demonstrated that SMCTHP significantly improved myocardial ischemic injury, reduced cardiomyocyte apoptosis in ischemic rat myocardium. In addition, SMCTHP could markedly upregulate the expression of phosphorylated (p)-AKT, and obviously downregulated the expressions of TLR4 and p-NF-κBp65 in the myocardial tissue of AMI rats. This study revealed that SMCTHP may ameliorate ISO-induced myocardial ischemic injury via exhibiting the anti-apoptotic effects potentially be regulating the AKT and TLR4/NF-κB pathways.
Factors Driving the Adoption of Organic Tea Farming Practices by the Farmers in Panchagarh District of Bangladesh
Authors: Prodhan Foyez Ahmed , Afrad Md. Safiul Islam , Haque Md. Enamul , Hoque Muhammad Ziaul , Rokonuzzaman Mohammed , Mohana Hasiba Pervin , Pervez A.K.M. Kanak
Published: April 2022

Tea is a regular export item for Bangladesh, but due to slow growth in production, the country's tea exports have declined. However, organic tea has a great future in this regard. Understanding the status and underlying factors of organic tea farming adoption has great potential to further enhance organic tea production and contribute to sustainable development. Therefore, our main objective was to identify factors influencing tea growers’ attitude, perception and adoption of organic tea farming in the Panchagarh district of Bangladesh. Factors affecting the farmers' belief in the adoption of organic farming were measured based on control factors (marketing factors and cost and benefit factors), attitude towards organic farming and social factors (extension factors) through a binary logistic regression model. This study showed that attitudes towards organic farming and perceptions on different dimensions are the major factors that bring about the adoption of organic farming. We also observed that organic growers had more favorable perception and it was significantly difference than non-organic growers reading various factors on organic farming. Our results demonstrated Education and knowledge greatly influence the farmers to form a highly favorable attitude towards organic tea farming. Moreover, attitudes towards organic farming and cost and benefit factors were indicated as the significant contributors to the adoption of organic tea farming practices. Finally, we suggested a participatory extension program by the Bangladesh Tea Board to change the attitudes and knowledge of the growers towards organic tea farming.
Using Prescribed Fire and Biosolids Applications as Grassland Management Tools: Do Wildlife Respond?
Authors: Washburn Brian E. , Begier Michael J.
Published: April 2022

Prescribed burning is a management tool commonly used in forested ecosystems in the southeastern United States, but the influence of this method on grassland vegetation and wildlife in this geographic region are unknown. During 2009–2015, we conducted a study to determine if the application of prescribed burning and/or long-term biosolids applications have altered plant communities and/or wildlife use of grassland areas at Marine Corps Air Station Cherry Point, Havelock, NC. We monitored vegetation growth, measured plant community composition, and documented wildlife activity in four study plots for 3 year after the implementation of annual winter prescribed burns. Prescribed burning reduced the amount of litter, increased bare ground during spring and altered the plant community composition relative to areas that were not burned. We observed similar (P = 0.55) total birds per 3-min survey using prescribed burn treatment plots (5.6 ± 0.6 birds; x¯ ± SE) and unburned (5.0 ± 0.5 birds) plots. Few species-specific differences in avian use of prescribed burned and unburned grasslands were found. In contrast, white-tailed deer (Odocoileus virginianus) use of areas that were burned in winter, as well as the adjacent unburned areas, was drastically reduced. Winter prescribed burning appeared to remove forage plants at the time of year deer would use them the most. Our findings suggest that prescribed burning, with and without biosolids, might be a viable grassland management tool to alter wildlife use of grassland areas, specifically white-tailed deer; however, similar research at additional locations should be conducted.
Safe delivery of radiation therapy in a patient with Implanted Cardiac Pacemaker - Tips and Pitfalls
Authors: Sidhique Sharief K , B Swathi , Babu Ebenezer Suman , Sebastian Patricia , Backianathan Selvamani , Manickavasagam Anand , Roshan John , Balakrishnan Rajesh
Published: April 2022

Background: There are clinical scenarios when it is required to deliver Radiotherapy (RT) to patients who have implanted pacemakers and it is challenging when treatment portals are close to pacemaker. The cumulative dose to the pacemaker needs to be less than 2 to 5 Gy as per the current recommendations.Aim and Methods: To describe the steps undertaken for safe delivery of mediastinal radiotherapy for a patient with Hodgkin’s lymphoma and implanted pacemaker. Case presentation: Sixty-year-old gentleman who had implanted dual-chamber rate adaptive (DDDR), magnetic resonance imaging (MRI) compatible, permanent pacemaker for complete heart block presented with lymphadenopathy and was diagnosed with Classical Hodgkin’s Lymphoma stage IV. He received consolidation RT (30 Gy in 15 fractions) to the mediastinum after completion of chemotherapy. An algorithm was developed based on AAPM (The American Association of Physicists) report for necessary steps to be taken at various stages of radiotherapy planning and treatment delivery. This approach made it possible to reduce cumulative dose to the pacemaker to < 2Gy.Conclusion: RT can be safely delivered to the patients with cardiac pacemakers. Close follow-up of the patients in conjunction with the Cardiologist, before, during and after radiation is essential for the patient’s safety.
Gene signature of m6A-related targets to predict prognosis and immunotherapy response in ovarian cancer
Authors: Tan Wei , Liu Shiyi , Deng Zhimin , Dai Fangfang , Yuan Mengqin , Hu Wei , Cheng Yanxiang
Published: April 2022

Background: According to cancer statistics for 2021, ovarian cancer is the fifth leading cause of mortality among adult women. M6A regulators played a nonnegligible role in cancers by acting on downstream target genes. The aim of the study was to construct a risk score model based on m6A-related targets to predict overall survival and immunotherapy response in ovarian cancer.Methods: The gene expression profiles of 24 m6A regulators were extracted from The Cancer Genome Atlas (TCGA) and GSE140082. Survival analysis screened 9 prognostic m6A regulators. Next, consensus clustering analysis was applied to identify clusters of ovarian cancer patients. Furthermore, 47 phenotype-related differentially expressed genes, strongly correlated with 9 prognostic m6A regulators, were screened and subjected to univariate and the least absolute shrinkage and selection operator (LASSO) cox regression. Ultimately, a nomogram was constructed which presented a strong ability to predict overall survival in ovarian cancer.Results: CBLL1, FTO, HNRNPC, METTL3, METTL14, WTAP, ZC3H13, RBM15B and YTHDC2 were associated with worse overall survival (OS) in ovarian cancer. Three m6A clusters were identified, which were highly consistent with the three immune phenotypes, including immune rejection, immune inflammation, and immune desert. What’s more, a risk model based on seven m6A-related targets was constructed with distinct prognosis. And the low-risk group are the best candidate population for immunotherapy. Ultimately, integrating other clinical features, a nomogram was constructed, which showed good predictive ability at 1, 3 and 5-year overall survivals (1-year AUC = 0.679, 3-year AUC = 0.661, 5-year AUC = 0.624). Conclusions: We comprehensively analyzed the m6A modification landscape of ovarian cancer and detected seven m6A-related targets as an independent prognostic biomarker for predicting survival. Furthermore, we divided patients into high- and low- risk groups with distinct prognosis and select the optimum population which may benefit from immunotherapy and constructed a nomogram to precisely predict ovarian cancer patients’ survival time and visualize the prediction results.
Insecticidal effects of some selected plant extracts against Anopheles stephensi Liston (Culicidae: Diptera)
Authors: Muhammed Merdya , Dugassa Sisay , Belina Merga , Zohdy Sarah , Irish Seth R. , Gebresilassie Araya
Published: April 2022

Background: The use of synthetic insecticides against mosquitoes may lead to resistance development and potential health hazards in humans and the environment. In connection to these adverse effects, a paradigm needs to shift towards the alternative use of botanical insecticides that could strengthen an insecticide resistance management program. This study aimed to assess the insecticidal effects of crude leaf solvent extracts of Calpurnia aurea, Momordica foetida, and Zehneria scabra on an insectary colony of Anopheles stephensi larvae and adults. Methods: Fresh leaves were collected and dried, then separately ground to powder. Powdered leaves of test plants were extracted using sonication with aqueous, hexane, and methanol solvents. The extracts were concentrated, and a stock solution was prepared. For comparison, temephos (Synthetic larvicide) and control solutions (a mixture of water and emulsifier) were used as the positive and negative controls, respectively. A range of test concentrations for the larvae and the adults were prepared and tested according to WHO (2005) and CDC (2010) guidelines to determine lethal concentration (LC) values. Mortality was observed after 24 hrs exposure. The statistical analyses were performed using Statistical Package for the Social Sciences (SPSS) software (Kruskal-Wallis test) and R software (a generalized linear model was used to determine LC50 and LC90 values of the extracts). Results: The lowest LC50 values were observed in aqueous M. foetida extract, followed by Z. scabra and C. aurea at 34.61, 35.85, and 38.69 ppm, respectively, against the larvae. Larval mortality was not observed from the hexane and negative control, while the standard larvicide (temephos) achieved 100% mortality. In addition, the adulticidal efficacy was greatest for aqueous Z. scabra extract with LC50 = 176.20 ppm followed by aqueous C. aurea (LC50 = 297.75 ppm). Conclusions: The results suggest that the leaf extracts of the three test plants have the potential of being used for the control of vector An. stephensi larvae and adult instead of synthetic mosquitocides. Further studies need to be conducted to identify the active ingredients and their mode of action.
Nucleotide Sugar Transporter SLC35A2 Is Involved In Promoting Metastatic Potential Of Hepatocellular Carcinoma
Authors: Cheng Hongxia , Wang Sikai , Yu Kangkang , Li Miaomiao , Zhang Jubo , Guo Kun
Published: April 2022

Purpose
Recently, aberrant glycosylation has been recognized to be relate to malignant behaviors of cancer and outcomes of patients in various cancers. SLC35A2 serves as a nucleotide sugar transporter and plays an indispensable role on glycosylation. However, effects of SLC35A2 on malignant behaviors of cancer cells and alteration of cancer cells surface glycosylation profile are still not fully understood, particularly in liver cancer. Hence, from an glycosylation prospective, we assessed the effects of SLC35A2 on malignant behaviors including metastatic potential of liver cancer cells.
Methods
SLC35A2 expression in HCC cells was examined by Western blot and quantitative PCR and was regulated by RNA interference or vectors-mediated transfection. Effects of SLC35A2 expression alteration on malignant behaviors and membrane glycan profile of HCC cells by using respectively invasion, migration, cell adhesion assay and lectins microarray. Co-location among proteins in HCC cells was observed by fluorescence microscope and detected by an in vitro co-immunoprecipitation assay.
Results
SLC35A2 was upregulated in HCC, and associated with poor prognosis of patients. SLC35A2 knockdown led to the decrese of invasion, adhesion, metastasis and the alteration of membrane glycan profile as well as the dysregulated expressions or glycosylation of cell adhesion-related molecules in HCC. Mechanistically, delivery of B4GalT1 to Golgi apparatus required the involvement of SLC35A2 in HCC cells and the site G266 was critical in maintaining the intact activity of B4GalT1.
Conclusion
SLC35A2 plays important roles in promoting HCC metastasis by regulating glycosylation modification on HCC cell surface and inducing cell adhesive ability.
Isolation and Characterization of Halophilic Plant Growth Promoting Rhizobacteria From Marine Sediment, Water, and Coastal Sanddune Plant and It’s Screening for Plant Growth Regulators
Authors: A Mugip Rahaman , Palaniyandi Thirunavukkarasu , Wyson John , Viswanathan Sandhiya , Basker Gomathy , Ranganathan Mohan
Published: April 2022

Plant Growth Promoting Rhizobacteria (PGPR) is beneficial bacteria that are colonizing in the plant root and enhance into the plant growth. The use of PGPR is steadily increasing in agriculture and offers an attractive way to replace chemical fertilizers and pesticides. In this present study, PGPR were isolated from marine sediment, marine water and coastal sand dune plants. From that, 480 different bacterial strains were isolated. Antimicrobial activity and screening of enzyme producing bacteria from the aquatic and terrestrial environment acted as plant growth inducer. Among 480 strains, the 14 strains of Pseudomonas sp exhibited the production of Indole Acetic Acid (IAA), Extracellular polysaccharides (EPS) and antimicrobial activity. This study concluded that PGPR from marine environment can be used as plant growth promoters in agricultural crops.
Vascular endothelial growth factor I/D variant and postmenopausal osteoporosis risk
Authors: Yigit Serbulent , Nursal Ayse Feyda , Nacar Mehmet Can , Tural Ercan , Bahrikarehmi Laleh
Published: April 2022

Introduction: Postmenopausal osteoporosis (PMOP) is a common metabolic bone disorder manifested by low bone mineral density and increased fracture risks in postmenopausal women. Vascular endothelial growth factor (VEGF) plays an essential role in bone formation. In this study, we have investigated the potential association between VEGF insertion/deletion (I/D) variant and PMOP in a cohort consisting of Turkish females. Methods: One hundred and fifty females with PMOP and 150 age, and ethnicity matched females were enrolled in this study. -2549 I/D variant of VEGF was analyzed by PCR method. The results of the analysis were evaluated for statistical significance. Results: The frequency of the II, ID and DD genotype was 7.34% versus 6.66%; 67.33% versus 65.34%; and 25.33% versus 28%, in patients and the control group, respectively. The allele frequencies were I: 41% (patients) and 39.4% (controls); D: 59% (patients) and 60.66% (controls). There were no statistically significant differences in the distribution of VEGF -2549 I/D variant genotypes and alleles between patients with PMOP and control subjects. Conclusion: In conclusion, this study demonstrates first time that the VEGF -2549 I/D variant might not contribute to the development of PMOP among Turkish population. These findings need confirmation in other ethnic populations.
Transcriptome-wide N6-methyladenosine methylome profiling of Bombyx mori reveals a potential mechanism of epigenetic regulation on diapause
Authors: Chen Yan-Hua , Jiang Tao , Fan Bing-Yan , Zhu Juan , Wang Mei-Xian , Shen Xing-Jia , YaSen AYiNuEr
Published: April 2022

Background
Epigenetic regulation may be one of the potential determinants of diapause, which is a strategy for insects to cope with adverse environments and evolution. Epigenetic regulation is multi-dimensional and synergistic, how this combination responds to diapause induced environmental signals and how epigenetic regulation induced by environmental signals precisely regulates insect diapause ware still remain unknown. m6A methylation is one of the most common internal modifications of mRNA, but its regulation on diapause is rarely reported.
Results
In this study, based on fluorescence immunoassay technology, the m6A abundance of total RNA in the pupal stage of bivoltine silkworm (Bombyx mori) QiuFeng, QFHT (incubated at a normal temperature after HCl acid treatment to produce diapause eggs) and QFLT (incubated at 16.5℃,a low temperature after HCl acid treatment to produce non-diapause eggs) were detected to explore the effects of m6A methylation modification on the diapause traits of the silkworm. The results showed that there were 1563 m6A peaks in QFLT and 659 m6A peaks in QFHT, and together 1,984 m6A peaks. The distribution and enrichment of m6A peak in gene functional elements were significantly different between the two groups. In each signaling pathway of QFLT, the gene transcripts with m6A modification were more diverse, and the methylation level was higher than that of QFHT. The period of epigenetic response to diapause-induced environmental signals was much earlier than the period of diapause phenotype formation, and the epigenetic signals undergo multiple accumulation, transmission and transformation, which may be accompanied by the metamorphosis development and transgenerational regulation of B. mori.
Conclusions
m6A methylation modification may be one of the molecular markers of diapause regulation or developmental decision, and its specific role in diapause regulation is of great importance for understanding of insect diapause mechanism.
Comparison of short-term efficiency of endoscopic biliary drainage and percutaneous transhepatic biliary drainage in the treatment of obstructive jaundice caused by hilar cholangiocarcinoma: a propensity score matching analysis
Authors: Zhu Dalong , Zayier Musitafa , Tulahong Alimu , Abuduhelili Abuduhaiwaier , Lu Fashun , Ran Bo , Jiang Tiemin , Shao Yingmei , Aji Tuerganaili
Published: April 2022

Background: For patients with obstructive jaundice caused by cholangiocarcinoma (CCA), drainage methods, including endoscopic biliary drainage (EBD) and percutaneous suprahepatic biliary drainage (PTBD), may be applied. Here, this study aims to compare short-term efficiency of primary EBD and PTBD during the treatment process of obstructive jaundice caused by hilar cholangiocarcinoma (HCCA).Methods: Clinical data of 114 patients with obstructive jaundice caused by HCCA were retrospectively analyzed form January 2016 to December 2020. According to treatment options, the patients were divided into EBD group (n=37) and PTBD group (n=77), and 19 pairs of patients were obtained after propensity score matching (PSM) analysis. Liver function, technical success rate, postoperative complications and hospitalization expenses were compared between groups.Results: After PSM analysis all baseline parameters were comparable . Among PTBD group patients, technical success was observed in 75 cases (97.40%), which was found in 26 cases in EBD group (70.27%). The difference in technical success rate between groups was significant (P<0.001). Compared with EBD group, postoperative total bilirubin was significantly decreased in PTBD group (P=0.019), and there was significant difference in the decrease degree between groups (P=0.041). The incidence of postoperative complications (P=0.049) and acute pancreatitis ( P=0.046) in EBD group were higher than those in PTBD group.Conclusion: Compared with EBD, PTBD had higher success rate, greater decrease in total bilirubin level and lower incidence rate of overall postoperative complications and acute pancreatitis. Therefore, PTBD may be given priority in the treatment of obstructive jaundice caused by HCCA.
Prediction of COVID-19 Patients from X-Rays using Ensemble Deep Transfer Learning Techniques
Authors: Kumar Dinesh , Kumar Vijay , Gupta Rahul
Published: April 2022

Deep learning is very effectively used in the medical field to predict diseases such as pneumonia classification , cancer, and so on. Convolutional Neural Network (CNN) is used to classify the chest X-rays of humans in normal and COVID-19 infected cases. To build a model, pre-trained models and transfer learning is used. In this paper, four pre-trained models VGG16, VGG19, ResNet50, and InceptionV3 are ensemble and build a new ensemble model. To train and test a model, a dataset of as many as 720 X-ray images has been used. Less number of images makes us apply image augmentation. The ensemble models such as VGG19 and ResNet50, VGG16 and ResNet50, VGG16 and InceptionV3, and VGG19 and InceptionV3 yield 96.53%, 98.61%, 99.31%, and 100% accuracy respectively.
Model Informed Development of SIM0295 in Gout Patients with Hyperuricemia and Healthy Volunteers Using a Population Pharmacokinetics/pharmacodynamics Approach
Authors: Chen Yueting , Yang Yang , Xu Shansen , Wang Chenyu , Shu Pan , Zhang Xiaoyu , Huang Qin , Kim Jin Sook , Huang Yue , Jiao Zheng
Published: April 2022

Objective:
To develop population pharmacokinetic (PopPK) and pharmacodynamics (PopPD) models of SIM0295 and explore potential covariates to inform dosing regimen.
Methods:
Data from four phase I studies, including healthy Korean and Chinese subjects, and two phase IIa studies, including Korean gout patients with hyperuricemia. PopPK and popPD models of SIM0295 were developed using nonlinear mixed effects modeling.
Results:
A total of 195 subjects and 5852 plasma concentrations of SIM0295 were included to perform the PopPK model, and 147 subjects and 3781 concentrations of serum uric acid (sUA) samples were included in the PopPK/PD study. SIM0295 pharmacokinetic was described by the two-compartment model with a four transit compartments absorption and linear elimination, in which the PK parameters were corrected with body weight via an empirical allometric model. Food and food types were identified as factors that significantly affect the absorption rate. PopPK/PD study shown that the final model was investigated using an Emax model with a semi-mechanism of inhibition of sUA reabsorption. The subject status was found significantly influence the volume of distribution of serum uric acid (VU). Compared to healthy subjects, patients have a half lower VU, 246.54L and 144.72L respectively. Monte Carlo simulations demonstrated that food and food types had no significant influence on the efficacy of SIM0295 in patients.
Conclusion:
The popPK/PD model quantified characterization of the dose-exposure-response relationship for SIM0295 in patient and healthy subjects. The model may be used to inform dose selection and design of subsequent studies that aim to define SIM0295 safety and efficacy in patients.
Salvianolic acid B inhibits RAW264.7 cell polarization towards M1 type by inhibiting NF-κB and Akt/mTOR pathways
Authors: Zou Tao , Gao Shan , Yu Zhaolan , Zhang Fuyong , Yao Lan , Xu Mengyao , Li Junxin , Wu Zhigui , Huang Yilan , Wang Shurong
Published: April 2022

M1 macrophages can secrete a large number of pro-inflammatory factor and promote the expansion of atherosclerosis plaque and process. Salvianolic acid B (Sal B) has anti-inflammatory, anti-tumor and other effects, but there is no study on whether Sal B can regulate the polarization of macrophages to exert anti-atherosclerosis effect. Therefore, the present study is investigating the inhibition of Sal B in the process of M1 macrophages polarization and its underlying mechanism. The effects of different treatments on cell viability, expression and secretion of related proteins, phenotypic markers and cytokines were detected by MTT, Western blot assay, RT-qPCR and ELISA. The cell viability was no significantly change when the concentration of Sal B is under 200 µM, and LPS (100 ng/mL) + IFN-γ (2.5 ng/mL) successfully induced M1 polarization. RT-qPCR and ELISA results indicated that Sal B can down-regulate the M1 markers (iNOS, TNF-α, and IL-6), and upregulate the M2 markers (Arg-1 and IL-10). Western blot was used to detect the expression of NF-κB, p-Akt, p-mTOR, LC3-II, Beclin-1, and p62, which suggested that Sal B inhibits RAW264.7 macrophages to M1 polarization by promoting autophagy in nuclear factor-κB (NF-κB) signaling pathway. The present study indicated that Sal B inhibits macrophages to M1 polarization by inhibiting the NF-κB signaling pathway and down-regulating Akt/mTOR to promote autophagy.