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Correlation-Based Analysis of COVID-19 Virus Genome Versus Other Fatal Virus Genomes.
Purohit, S, Satapathy, SC, Sibi Chakkaravarthy, S, Zhang, YD
Arabian journal for science and engineering. 2021;:1-13
Abstract
Virus attacks have had devastating effects on mankind. The prominent viruses such as Ebola virus (2012), SARS-CoV or Severe acute respiratory syndrome, Middle East respiratory syndrome-related coronavirus called as the MERS (EMC/2012), Spanish flu (H1N1 virus-1918) and the most recent COVID-19(SARS-CoV-2) are the ones that have created a difficult situation for the survival of the human race. Currently, throughout the world, a global pandemic situation has put economy, livelihood and human existence in a very pathetic situation. Most of the above-mentioned viruses exhibit some similar characteristics and genetic pattern. Analysing such characteristics and genetic pattern can help the researchers to get a deeper insight into the viruses and helps in finding appropriate medicine or cure. To address these issues, this paper proposes an experimental analysis of the above-mentioned viruses data using correlation methods. The virus data considered for the experimental analysis include the distribution of various amino acids, protein sequences, 3D modelling of viruses, pairwise alignment of proteins that comprise the DNA genome of the viruses. Furthermore, this comparative analysis can be used by the researchers and organizations like WHO(World Health Organization), computational biologists, genetic engineers to frame a layout for studying the DNA sequence distribution, percentage of GC (guanine-cytosine) protein which determines the heat stability of viruses. We have used the Biopython to illustrate the gene study of prominent viruses and have derived results and insights in the form of 3D modelling. The experimental results are more promising with an accuracy rate of 96% in overall virus relationship calculation.
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2.
MTHFR C677T and A1298C Polymorphisms in Breast Cancer, Gliomas and Gastric Cancer: A Review.
Petrone, I, Bernardo, PS, Dos Santos, EC, Abdelhay, E
Genes. 2021;(4)
Abstract
Folate (vitamin B9) is found in some water-soluble foods or as a synthetic form of folic acid and is involved in many essential biochemical processes. Dietary folate is converted into tetrahydrofolate, a vital methyl donor for most methylation reactions, including DNA methylation. 5,10-methylene tetrahydrofolate reductase (MTHFR) is a critical enzyme in the folate metabolism pathway that converts 5,10-methylenetetrahydrofolate into 5-methyltetrahydrofolate, which produces a methyl donor for the remethylation of homocysteine to methionine. MTHFR polymorphisms result in reduced enzyme activity and altered levels of DNA methylation and synthesis. MTHFR polymorphisms have been linked to increased risks of several pathologies, including cancer. Breast cancer, gliomas and gastric cancer are highly heterogeneous and aggressive diseases associated with high mortality rates. The impact of MTHFR polymorphisms on these tumors remains controversial in the literature. This review discusses the relationship between the MTHFR C677T and A1298C polymorphisms and the increased risk of breast cancer, gliomas, and gastric cancer. Additionally, we highlight the relevance of ethnic and dietary aspects of population-based studies and histological stratification of highly heterogeneous tumors. Finally, this review discusses these aspects as potential factors responsible for the controversial literature concerning MTHFR polymorphisms.
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Dietary fibre to reduce colon cancer risk in Alaska Native people: the Alaska FIRST randomised clinical trial protocol.
Koller, KR, Wilson, A, Normolle, DP, Nicholson, JK, Li, JV, Kinross, J, Lee, FR, Flanagan, CA, Merculieff, ZT, Iyer, P, et al
BMJ open. 2021;(8):e047162
Abstract
INTRODUCTION Diet, shown to impact colorectal cancer (CRC) risk, is a modifiable environmental factor. Fibre foods fermented by gut microbiota produce metabolites that not only provide food for the colonic epithelium but also exert regulatory effects on colonic mucosal inflammation and proliferation. We describe methods used in a double-blinded, randomised, controlled trial with Alaska Native (AN) people to determine if dietary fibre supplementation can substantially reduce CRC risk among people with the highest reported CRC incidence worldwide. METHODS AND ANALYSES Eligible patients undergoing routine screening colonoscopy consent to baseline assessments and specimen/data collection (blood, urine, stool, saliva, breath and colon mucosal biopsies) at the time of colonoscopy. Following an 8-week stabilisation period to re-establish normal gut microbiota post colonoscopy, study personnel randomise participants to either a high fibre supplement (resistant starch, n=30) or placebo (digestible starch, n=30) condition, repeating stool sample collection. During the 28-day supplement trial, each participant consumes their usual diet plus their supplement under direct observation. On day 29, participants undergo a flexible sigmoidoscopy to obtain mucosal biopsy samples to measure the effect of the supplement on inflammatory and proliferative biomarkers of cancer risk, with follow-up assessments and data/specimen collection similar to baseline. Secondary outcome measures include the impact of a high fibre supplement on the oral and colonic microbiome and biofluid metabolome. ETHICS AND DISSEMINATION Approvals were obtained from the Alaska Area and University of Pittsburgh Institutional Review Boards and Alaska Native Tribal Health Consortium and Southcentral Foundation research review bodies. A data safety monitoring board, material transfer agreements and weekly study team meetings provide regular oversight throughout the study. Study findings will first be shared with AN tribal leaders, health administrators, providers and community members. Peer-reviewed journal articles and conference presentations will be forthcoming once approved by tribal review bodies. TRIAL REGISTRATION NUMBER NCT03028831.
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Conventional transarterial chemoembolization combined with systemic therapy versus systemic therapy alone as second-line treatment for unresectable colorectal liver metastases: randomized clinical trial.
Liu, Y, Chang, W, Zhou, B, Wei, Y, Tang, W, Liang, F, Chen, Y, Yan, Z, Lv, M, Ren, L, et al
The British journal of surgery. 2021;(4):373-379
Abstract
BACKGROUND The combination of conventional transarterial chemoembolization (cTACE) and systemic therapy has the potential to treat chemotherapy-refractory unresectable colorectal liver metastases (CRLMs). This study aimed to compare survival after this combined treatment versus systemic chemotherapy alone. METHODS This single-centre RCT included patients with unresectable CRLMs that progressed after first-line treatment. Patients were randomized on a 1 : 1 basis to either systemic chemotherapy with or without cTACE, without further stratification. The primary outcome was progression-free survival (PFS). Secondary outcomes were overall response rate, disease control rate, conversion rate to liver resection, overall survival, and adverse events. RESULTS Of 180 patients recruited, 168 were randomized. Eighty-five patients in arm A received systemic chemotherapy plus cTACE and 83 in arm B received systemic chemotherapy alone. Median PFS was longer in arm A than B (6.7 versus 3.8 months; hazard ratio (HR) 0.67, 95 per cent c.i. 0.49 to 0.91; P = 0.009), but did not translate into prolonged median overall survival (18.4 versus 14.8 months; HR = 0.92, 0.62 to 1.36; P = 0.669). Overall response rates (20 versus 22 per cent; P = 0.788) and conversion rate to liver resection (18 versus 16 per cent; P = 0.730) were no different between arms A and B. The disease control rate was higher in arm A than arm B (67 versus 51 per cent; P = 0.030). No adverse event higher than grade 3 according to the Common Terminology Criteria for Adverse Events was observed during treatment. CONCLUSION Systemic chemotherapy plus cTACE is a safe option as second-line treatment for unresectable colorectal liver metastases, with a modest effect on PFS. Registration number: NCT03783559 (http://www.clinicaltrials.gov).
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5.
Evaluation and management of the critically ill adult asthmatic in the emergency department setting.
Long, B, Lentz, S, Koyfman, A, Gottlieb, M
The American journal of emergency medicine. 2021;:441-451
Abstract
INTRODUCTION Asthma is a common reason for presentation to the Emergency Department and is associated with significant morbidity and mortality. While patients may have a relatively benign course, there is a subset of patients who present in a critical state and require emergent management. OBJECTIVE This narrative review provides evidence-based recommendations for the assessment and management of patients with severe asthma. DISCUSSION It is important to consider a broad differential diagnosis for the cause and potential mimics of asthma exacerbation. Once the diagnosis is determined, the majority of the assessment is based upon the clinical examination. First line therapies for severe exacerbations include inhaled short-acting beta agonists, inhaled anticholinergics, intravenous steroids, and magnesium. Additional therapies for refractory cases include parenteral epinephrine or terbutaline, helium‑oxygen mixture, and consideration of ketamine. Intravenous fluids should be administered, as many of these patients are dehydrated and at risk for hypotension if they receive positive pressure ventilatory support. Noninvasive positive pressure ventilation may prevent the need for endotracheal intubation. If mechanical ventilation is required, it is important to avoid breath stacking by setting a low respiratory rate and allowing permissive hypercapnia. Patients with severe asthma exacerbations will require intensive care unit admission. CONCLUSIONS This review provides evidence-based recommendations for the assessment and management of severe asthma with a focus on the emergency clinician.
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6.
Glucose and Amino Acid Metabolic Dependencies Linked to Stemness and Metastasis in Different Aggressive Cancer Types.
Chisari, A, Golán, I, Campisano, S, Gélabert, C, Moustakas, A, Sancho, P, Caja, L
Frontiers in pharmacology. 2021;:723798
Abstract
Malignant cells are commonly characterised by being capable of invading tissue, growing self-sufficiently and uncontrollably, being insensitive to apoptosis induction and controlling their environment, for example inducing angiogenesis. Amongst them, a subpopulation of cancer cells, called cancer stem cells (CSCs) shows sustained replicative potential, tumor-initiating properties and chemoresistance. These characteristics make CSCs responsible for therapy resistance, tumor relapse and growth in distant organs, causing metastatic dissemination. For these reasons, eliminating CSCs is necessary in order to achieve long-term survival of cancer patients. New insights in cancer metabolism have revealed that cellular metabolism in tumors is highly heterogeneous and that CSCs show specific metabolic traits supporting their unique functionality. Indeed, CSCs adapt differently to the deprivation of specific nutrients that represent potentially targetable vulnerabilities. This review focuses on three of the most aggressive tumor types: pancreatic ductal adenocarcinoma (PDAC), hepatocellular carcinoma (HCC) and glioblastoma (GBM). The aim is to prove whether CSCs from different tumour types share common metabolic requirements and responses to nutrient starvation, by outlining the diverse roles of glucose and amino acids within tumour cells and in the tumour microenvironment, as well as the consequences of their deprivation. Beyond their role in biosynthesis, they serve as energy sources and help maintain redox balance. In addition, glucose and amino acid derivatives contribute to immune responses linked to tumourigenesis and metastasis. Furthermore, potential metabolic liabilities are identified and discussed as targets for therapeutic intervention.
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7.
Visual Cortex Transcranial Direct Current Stimulation for Proliferative Diabetic Retinopathy Patients: A Double-Blinded Randomized Exploratory Trial.
de Venecia, ABF, Fresnoza, SM
Brain sciences. 2021;(2)
Abstract
Proliferative diabetic retinopathy (PDR) is a severe complication of diabetes. PDR-related retinal hemorrhages often lead to severe vision loss. The main goals of management are to prevent visual impairment progression and improve residual vision. We explored the potential of transcranial direct current stimulation (tDCS) to enhance residual vision. tDCS applied to the primary visual cortex (V1) may improve visual input processing from PDR patients' retinas. Eleven PDR patients received cathodal tDCS stimulation of V1 (1 mA for 10 min), and another eleven patients received sham stimulation (1 mA for 30 s). Visual acuity (logarithm of the minimum angle of resolution (LogMAR) scores) and number acuity (reaction times (RTs) and accuracy rates (ARs)) were measured before and immediately after stimulation. The LogMAR scores and the RTs of patients who received cathodal tDCS decreased significantly after stimulation. Cathodal tDCS has no significant effect on ARs. There were no significant changes in the LogMAR scores, RTs, and ARs of PDR patients who received sham stimulation. The results are compatible with our proposal that neuronal noise aggravates impaired visual function in PDR. The therapeutic effect indicates the potential of tDCS as a safe and effective vision rehabilitation tool for PDR patients.
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8.
Anthropometric Parameters and Mediterranean Diet Adherence in Preschool Children in Split-Dalmatia County, Croatia-Are They Related?
Bučan Nenadić, D, Kolak, E, Selak, M, Smoljo, M, Radić, J, Vučković, M, Dropuljić, B, Pijerov, T, Babić Cikoš, D
Nutrients. 2021;(12)
Abstract
Obesity is a rapidly growing problem in European countries, Croatia being among them. According to the latest CroCOSI data, every third child in Croatia aged 8.0-8.9 years is overweight or obese. The Mediterranean diet (MeDi) and its impact on nutritional status and health has been the focus of recent research. Therefore, the aim of this cross-sectional, observational study was to determine the nutritional status and adherence to the MeDi of preschool children in Split, Croatia. We included 598 preschool children aged 3 to 7 years and, for each child, parents completed a lifestyle questionnaire and the Mediterranean Diet Quality Index (KIDMED) in order to assess adherence to the MeDi. The anthropometric assessment included the measurement of weight, height, mid-upper arm circumference (MUAC), waist circumference (WC) and the z-score was calculated. According to the z-score, 420 (70.2%) children had a healthy body weight with 54 (9%) underweight and 124 (20.8%) overweight or obese children. Almost half (49%) of the study participants had a low KIDMED index score, indicating a low MeDi adherence, 37% had an average score, while only 14% had high MeDi compliance. Statistically significant negative correlations between MUAC and WC and the consumption of a second daily serving of fruit (p = 0.04) as well as a daily serving of vegetables (p = 0.03) were found. In conclusion, low compliance to the MeDi principles in preschool children is concerning. Considering the beneficial effects of the MeDi on overall health, further education, and the adoption of healthy eating habits in preschool children in this Mediterranean region are required.
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9.
Pulmonary Functional Imaging: Part 1-State-of-the-Art Technical and Physiologic Underpinnings.
Ohno, Y, Seo, JB, Parraga, G, Lee, KS, Gefter, WB, Fain, SB, Schiebler, ML, Hatabu, H
Radiology. 2021;(3):508-523
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Abstract
Over the past few decades, pulmonary imaging technologies have advanced from chest radiography and nuclear medicine methods to high-spatial-resolution or low-dose chest CT and MRI. It is currently possible to identify and measure pulmonary pathologic changes before these are obvious even to patients or depicted on conventional morphologic images. Here, key technological advances are described, including multiparametric CT image processing methods, inhaled hyperpolarized and fluorinated gas MRI, and four-dimensional free-breathing CT and MRI methods to measure regional ventilation, perfusion, gas exchange, and biomechanics. The basic anatomic and physiologic underpinnings of these pulmonary functional imaging techniques are explained. In addition, advances in image analysis and computational and artificial intelligence (machine learning) methods pertinent to functional lung imaging are discussed. The clinical applications of pulmonary functional imaging, including both the opportunities and challenges for clinical translation and deployment, will be discussed in part 2 of this review. Given the technical advances in these sophisticated imaging methods and the wealth of information they can provide, it is anticipated that pulmonary functional imaging will be increasingly used in the care of patients with lung disease. © RSNA, 2021 Online supplemental material is available for this article.
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10.
Network pharmacology and experimental investigation of Rhizoma polygonati extract targeted kinase with herbzyme activity for potent drug delivery.
Xie, Y, Mu, C, Kazybay, B, Sun, Q, Kutzhanova, A, Nazarbek, G, Xu, N, Nurtay, L, Wang, Q, Amin, A, et al
Drug delivery. 2021;(1):2187-2197
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Abstract
Rhizoma polygonati (Huangjing, RP) has been used for a long history with many chemical components in inducing anti-cancer, anti-aging, anti-diabetes, anti-fatigue, and more prevention of diseases or acts as nutrition sources in food. Here we investigated RP extract combination with kinase inhibitors in anti-cell growth and blockade in pathways targeting kinases. Experimental investigation and network pharmacology analysis were applied to test the potent kinase-mediated signaling. Herbzyme activity was determined by substrate with optical density measurement. Extract of processed RP inhibits cell growth in a much greater manner than alone when applied in combination with inhibitors of mTOR or EGFR. Moreover, processing methods of RP from Mount Tai (RP-Mount Tai) play essential roles in herbzyme activity of phosphatase suggesting the interface is also essential, in addition to the chemical component. The network pharmacology analysis showed the chemical component and target networks involving AKT and mTOR, which is consistent with experimental validation. Finally, EGFR inhibitor could be associated with nano-extract of RP-Mount Tai but not significantly affects the phosphatase herbzyme activity in vitro. Thus the processed extract of RP-Mount Tai may play a dual role in the inhibition of cell proliferation signaling by both chemical component and nanoscale herbzyme of phosphatase activity to inhibit kinases including mTOR/AKT in potent drug delivery of kinase inhibitors.