Search results for: signet ring cell cancer

Authors: Sara Ataei, Molouk Hadjibabaie, Shirinsadat Badri, Amirhossein Moslehi, Iman Karimzadeh, Ardeshir Ghavamzadeh

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Purpose: To assess the pattern and probable risk factors for moderate and major drug–drug interactions in a referral hematology-oncology ward in Iran. Methods: All patients admitted to hematology–oncology ward of Dr. Shariati Hospital during a 6-month period and received at least two anti-cancer or non-anti-cancer medications simultaneously were included. All being scheduled anti-cancer and non-anti-cancer medications both prescribed and administered during ward stay were considered for drug–drug interaction screening by Lexi-Interact On- Desktop software. Results: One hundred and eighty-five drug–drug interactions with moderate or major severity were detected from 83 patients. Most of drug–drug interactions (69.73 %) were classified as pharmacokinetics. Fluconazole (25.95 %) was the most commonly offending medication in drug–drug interactions. Interaction of sulfamethoxazole-trimethoprim with fluconazole was the most common drug–drug interaction (27.27 %). Vincristine with imatinib was the only identified interaction between two anti-cancer agents. The number of administered medications during ward stay was considered as an independent risk factor for developing a drug–drug interaction. Conclusions: Potential moderate or major drug–drug interactions occur frequently in patients with hematological malignancies or related diseases. Performing larger standard studies are required to assess the real clinical and economical effects of drug–drug interactions on patients with hematological and non-hematological malignancies.

Keywords: drug–drug interactions, hematology–oncology ward, hematological malignancies

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Authors: Harish K. Chandrawanshi, Mithun S. Rajput, Neelima Choure, Purnima Dey Sarkar, Shailesh Jain

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The present research study aimed to fabricate and evaluate biodegradable nanoparticles of aromatase inhibitor letrozole, intended for breast cancer therapy. Letrozole loaded poly(D,L-lactide-co-glycolide acid) nanoparticles were prepared by solvent evaporation method using dichlorometane as solvent (oil phase) and polyvinyl alcohol (PVA) as aqueous phase. Prepared nanoparticles were characterized by particle size, infrared spectra, drug loading efficiency, drug entrapment efficiency and in vitro release and also evaluated for in vivo anticancer activity. The high speed homogenizer was used to produce stable nanoparticles of mean size range 198.35 ± 0.04 nm with high entrapment efficiency (69.86 ± 2.78%). Percentage of drug and homogenization speed significantly influenced the particle size, entrapment efficiency and release (p<0.05). The nanoparticles show significant in vivo anticancer activity against Ehrlich ascites carcinoma in mice. The significant system sustained the release of letrozole drug effectively and further investigation could exhibit its potential usefulness in breast cancer therapy.

Keywords: breast cancer/therapy, letrozole, nanoparticles, PLGA

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Authors: Anna Bak-Klimek, Emily Spencer, Siew Lee, Karen Campbell, Wendy McInally

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Background & Significance: Over half of Teenagers and Young Adults (TYAs) say that they experience psychological distress after cancer diagnosis and TYAs with cancer are at higher risk of developing distress compared to other age groups. Despite this there are no age-appropriate interventions to help TYAs manage distress and there is a lack of conceptual understanding of what causes distress in this population group. This makes it difficult to design a targeted, developmentally appropriate intervention. This review aims to identify the key determinants of distress in TYAs affected by cancer and to propose an integrative model of cancer-related distress for TYAs. Method: A literature search was performed in Cochrane Database of Systematic Reviews, MEDLINE, PsycINFO, CINAHL, EMBASE and PsycArticles in May-June, 2022. Quantitative literature was systematically reviewed on the relationship between psychological distress experienced by TYAs affected by cancer and a wide range of factors i.e. individual (demographic, psychological, developmental, and clinical factors) and contextual (social/environmental) factors. Evidence was synthesized and correlates were categorized using the Biopsychosocial Model. The full protocol is available from PROSPERO (CRD42022322069) Results: Thirty eligible quantitative studies met criteria for the review. A total of twenty-six studies were cross-sectional, three were longitudinal and one study was a case control study. The evidence on the relationship between the socio-demographic, illness and treatment-related factors and psychological distress is inconsistent and unclear. There is however consistent evidence on the link between psychological factors and psychological distress. For instance, the use of cognitive and defence coping, negative meta-cognitive beliefs, less optimism, a lack of sense of meaning and lower resilience levels were significantly associated with higher psychological distress. Furthermore, developmental factors such as poor self-image, identity issues and perceived conflict were strongly associated with higher distress levels. Conclusions: The current review suggests that psychological and developmental factors such as ineffective coping strategies, poor self-image and identity issues may play a key role in the development of psychological distress in TYAs affected by cancer. The review proposes a Positive Developmental Psychology Model of Distress for Teenagers and Young Adults affected by cancer. The review highlights that implementation of psychological interventions that foster optimism, improve resilience and address self-image may result in reduced distress in TYA’s with cancer.

Keywords: cancer, determinant, psychological distress, teenager and young adult, theoretical model

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Authors: Kriyapa lairungruang, Arunporn Itharat

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Limonia acidissima L. (LA) (Common name: wood apple, Thai name: ma-khwit) is a medicinal plant which has long been used in Thai traditional medicine. Its bark is used for treatment of diarrhea, abscess, wound healing and inflammation and it is also used in oral cancer. Thus, this research aimed to investigate antioxidant and cytotoxic activities of the LA bark extracts produced by various extraction methods. Different extraction procedures were used to extract LA bark for biological activity testing: boiling in water, maceration with 95% ethanol, maceration with 50% ethanol and water boiling of each the 95% and the 50% ethanolic residues. All extracts were tested for antioxidant activity using DPPH radical scavenging assay, cytotoxic activity against human laryngeal epidermoid carcinoma (HEp-2) cells and human oral epidermoid carcinoma (KB) cells using sulforhodamine B (SRB) assay. The results found that the 95% ethanolic extract of LA bark showed the highest antioxidant activity with EC50 values of 29.76±1.88 µg/ml. For cytotoxic activity, the 50% ethanolic extract showed the best cytotoxic activity against HEp-2 and KB cells with IC50 values of 9.55±1.68 and 18.90±0.86 µg/ml, respectively. This study demonstrated that the 95% ethanolic extract of LA bark showed moderate antioxidant activity and the 50% ethanolic extract provided potent cytotoxic activity against HEp-2 and KB cells. These results confirm the traditional use of LA for the treatment of oral cancer and laryngeal cancer, and also support its ongoing use.

Keywords: antioxidant activity, cytotoxic activity, Laryngeal epidermoid carcinoma, Limonia acidissima L., oral epidermoid carcinoma

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Authors: Lakmali Anthony, Madeline Gillies

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Background Breast cancer (BC) is usually managed with surgical resection. Many outcomes traditionally used to define successful operative management, such as resection margin, do not adequately reflect patients’ experience. Patient-reported outcomes (PRO) such as Health-Related Quality of life (HRQoL) provide a means by which the impact of surgery for cancer can be reported in a patient-centered way. This exploratory cross-sectional study aims to; (1) describe postoperative HRQoL in patients who underwent primary resection in a regional Australian hospital; (2) describe the prevalence of anxiety, depression and clinically significant fear of cancer recurrence (FCR) in this population; and (3) identify demographic, psychosocial, disease and treatment factors associated with poorer self-reported HRQoL. Methods Patients who had resection of BC in a regional Australian hospital between 2015 and 2022 were eligible. Participants were asked to complete a survey designed to assess HRQoL, as well as validated instruments that assess several other psychosocial PROs hypothesized to be associated with HRQoL; emotional distress, fear of cancer recurrence, social support, dispositional optimism, body image and spirituality. Results Forty-six patients completed the survey. Clinically significant levels of FCR and emotional distress were present in this group. Many domains of HRQoL were significantly worse than an Australian reference population for BC. Demographic and disease factors associated with poor HRQoL included smoking and ongoing adjuvant systemic therapy. The primary operation was not associated with HRQoL for breast cancer. All psychosocial factors measured were associated with HRQoL. Conclusion HRQoL is an important outcome in surgery for both research and clinical practice. This study provides an overview of the quality of life in a regional Australian population of postoperative breast cancer patients and the factors that affect it. Understanding HRQoL and awareness of patients particularly vulnerable to poor outcomes should be used to aid the informed consent and shared decision-making process between surgeon and patient.

Keywords: breast cancer, surgery, quality of life, regional population

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Authors: Zakaria Mowafy Emam Mowafy, Hamed Abd Allah Hamed, Marwa Mahmoud Abd-Elmotalb, Andrew Anis Fakhray Mosaad

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The purpose of this paper is to determine the efficacy of polarized light therapy for chemotherapy-treated cancer patients who have oral mucositis. Methods of evaluation are the measurement of the WHO oral mucositis scale and the common toxicity criteria scale. Methods: Thirty cancer patients receiving chemotherapy (males and females) who had oral mucositis and ulceration pain, and their ages ranged from 30 to 55 years, were divided into two groups. Group (A), composed of 15 patients, received the Bioptron light therapy (BLT) in addition to the routine medical care of oral mucositis. Group (B) received only the routine medical care of oral mucositis; the duration of the BLT application was 10 minutes applied daily for 30 days. Results and conclusion: Results showed that the application of the BLT had valuable healing effects on oral mucositis in cancer patients receiving chemotherapy, as evidenced by the high decreases of the WHO oral mucositis scale and the common toxicity criteria scale.

Keywords: Bioptron light therapy, oral mucositis, WHO oral mucositis scale, common toxicity criteria scale

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Authors: Milica Karadzic, Lidija Jevric, Sanja Podunavac-Kuzmanovic, Strahinja Kovacevic, Sinisa Markov, Aleksandar Okljesa, Andrea Nikolic, Marija Sakac, Katarina Penov Gasi

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This study considered the microbiological activity determination and molecular docking study for selected steroid derivatives of biomedical importance. Minimal inhibitory concentration (MIC) was determined for steroid derivatives against Staphylococcus aureus using macrodilution method. Some of the investigated steroid derivatives express bacteriostatic effect against Staphylococcus aureus. Molecular docking approaches are the most widely used techniques for predicting the binding mode of a ligand. Molecular docking study was done for steroid derivatives for androgen receptor negative prostate cancer cell line (PC-3) toward Human Cytochrome P450 CYP17A1. The molecules that had the smallest experimental IC50 values confirmed their ability to dock into active place using suitable molecular docking procedure. The binding disposition of those molecules was thoroughly investigated. Microbiological analysis and molecular docking study were conducted with aim to additionally characterize selected steroid derivatives for future investigation regarding their biological activity and to estimate the binding-affinities of investigated derivatives. This article is based upon work from COST Action (TD1305), supported by COST (European Cooperation and Science and Technology).

Keywords: binding affinity, minimal inhibitory concentration, molecular docking, pc-3 cell line, staphylococcus aureus, steroids

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Authors: Dimitrie Marinceu, Alan Murchison

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The Canadian Used Fuel Container (UFC) is a mid-size hemispherical headed copper coated steel container measuring 2.5 meters in length and 0.5 meters in diameter containing 48 used fuel bundles. The contained used fuel produces significant gamma radiation requiring automated assembly processes to complete the assembly. The design throughput of 2,500 UFCs per year places constraints on equipment and hot cell design for repeatability, speed of processing, robustness and recovery from upset conditions. After UFC assembly, the UFC is inserted into a Buffer Box (BB). The BB is made from adequately pre-shaped blocks (lower and upper block) and Highly Compacted Bentonite (HCB) material. The blocks are practically ‘sandwiching’ the UFC between them after assembly. This paper identifies one possible approach for the BB automatic assembly cell and processes. Automation of the BB assembly will have a significant positive impact on nuclear safety, quality, productivity, and reliability.

Keywords: used fuel packing plant, automatic assembly cell, used fuel container, buffer box, deep geological repository

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Authors: Benoit Jauniaux, Azzam Ismail

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Objectives: The aims were to identify all incident adult cases of idiopathic inflammatory myopathies (IIMs) in the City of Leeds, UK, and to estimate the risk of cancer in IIMs as compared with the general population. Methods: Cases of IIMs were ascertained by review of all muscle biopsy reports from the Neuropathology Laboratory. A review of medical records was undertaken for each case to review the clinical diagnosis and collect epidemiological data such as age, ethnicity, sex, and comorbidities, including cancer. Leeds denominator population numbers were publicly obtainable. Results: Two hundred and six biopsy reports were identified, and after review, 50 incident cases were included in the study between June 2010 and January 2021. Out of the 50 cases, 27 were male, and 23 were female. The mean incidence rate of IIMs in Leeds throughout the study period was 7.42/1 000 000 person years. The proportion of IIMs cases with a confirmed malignancy was 22%. Compared to the general population, the relative risk of cancer was significantly greater in the IIMs population(31.56, P < 0.01). Conclusions: The incidence rate of IIMs in Leeds was consistent with data from previous literature, however, disagreement exists between different methods of IIMs case inclusion due to varying clinical criteria and definitions. IIMs are associated with increased risk of cancer however, the pathogenesis of this relationship still requires investigating. This study supports the practice of malignancy screening and long-term surveillance in patients with IIMs.

Keywords: idiopathic inflammatory myopathies, myositis, polymyositis, dermatomyositis, malignancy, epidemiology, incidence rate, relative risk

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Authors: Mansha Kotwani

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The specific spatio-temporal calcium concentration patterns are required by the fibroblasts to maintain its structure and functions. Thus, calcium concentration is regulated in cell at different levels in various activities of the cell. The variations in cytosolic calcium concentration largely depend on the buffers present in cytosol and influx of calcium into cytosol from ER through IP3Rs or Raynodine receptors followed by reuptake of calcium into ER through sarcoplasmic/endoplasmic reticulum ATPs (SERCA) pump. In order to understand the mechanisms of wound repair, tissue remodeling and growth performed by fibroblasts, it is of crucial importance to understand the mechanisms of calcium concentration regulation in fibroblasts. In this paper, a model has been developed to study calcium distribution in NRK fibroblast in the presence of buffers and ER flux with SERCA pump. The model has been developed for two dimensional unsteady state case. Appropriate initial and boundary conditions have been framed along with physiology of the cell. Finite element technique has been employed to obtain the solution. The numerical results have been used to study the effect of buffers, ER flux and source amplitude on calcium distribution in fibroblast cell.

Keywords: buffers, IP3R, ER flux, SERCA pump, source amplitude

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Authors: Asghar Ebrahimi, Elyas Lakzian

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For the analysis of flow inside micro geometries, classical CFD methods can not accurately predict the behavior of flow. Alternatively, the gas flow through micro geometries can be investigated precisely using the direct simulation Monte Carlo (DSMC) method. In the present paper, a pressure boundary condition is utilized to simulate a gaseous flow inside a micro channel using the DSMC method. Accuracy of simulation is guaranteed by choosing proper cell dimension and number of particle per cell analysis. Also, results of simulation are compared with the results of reliable references. Good agreement with results certifies the correctness of new boundary condition implemented on the micro channel.

Keywords: pressure boundary condition, DSMC, micro channel, cell dimension, particle per cell

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Authors: Ahlam Ali, Katrina Lappin, Jaine Blayney, Ken Mills

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Leukaemia is the most frequently (30%) occurring type of paediatric cancer. Of these, approximately 80% are acute lymphoblastic leukaemia (ALL) with acute myeloid leukaemia (AML) cases making up the remaining 20% alongside other leukaemias. Unfortunately, children with AML do not have promising prognosis with only 60% surviving 5 years or longer. It has been highlighted recently the need for age-specific therapies for AML patients, with paediatric AML cases having a different mutational landscape compared with AML diagnosed in adult patients. Drug Repurposing is a recognized strategy in drug discovery and development where an already approved drug is used for diseases other than originally indicated. We aim to identify novel combination therapies with the promise of providing alternative more effective and less toxic induction therapy options. Our in-silico analysis highlighted ‘cell death and survival’ as an aberrant, potentially targetable pathway in paediatric AML patients. On this basis, 83 apoptotic inducing compounds were screened. A preliminary single agent screen was also performed to eliminate potentially toxic chemicals, then drugs were constructed into a pooled library with 10 drugs per well over 160 wells, with 45 possible pairs and 120 triples in each well. Seven cell lines were used during this study to represent the clonality of AML in paediatric patients (Kasumi-1, CMK, CMS, MV11-14, PL21, THP1, MOLM-13). Cytotoxicity was assessed up to 72 hours using CellTox™ Green reagent. Fluorescence readings were normalized to a DMSO control. Z-Score was assigned to each well based on the mean and standard deviation of all the data. Combinations with a Z-Score <2 were eliminated and the remaining wells were taken forward for further analysis. A well was considered ‘successful’ if each drug individually demonstrated a Z-Score <2, while the combination exhibited a Z-Score >2. Each of the ten compounds in one well (155) had minimal or no effect as single agents on cell viability however, a combination of two or more of the compounds resulted in a substantial increase in cell death, therefore the ten compounds were de-convoluted to identify a possible synergistic pair/triple combinations. The screen identified two possible ‘novel’ drug pairing, with BCL2 inhibitor ABT-737, combined with either a CDK inhibitor Purvalanol A, or AKT/ PI3K inhibitor LY294002. (ABT-737- 100 nM+ Purvalanol A- 1 µM) (ABT-737- 100 nM+ LY294002- 2 µM). Three possible triple combinations were identified (LY2409881+Akti-1/2+Purvalanol A, SU9516+Akti-1/2+Purvalanol A, and ABT-737+LY2409881+Purvalanol A), which will be taken forward for examining their efficacy at varying concentrations and dosing schedules, across multiple paediatric AML cell lines for optimisation of maximum synergy. We believe that our combination screening approach has potential for future use with a larger cohort of drugs including FDA approved compounds and patient material.

Keywords: AML, drug repurposing, ABT-737, apoptosis

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Authors: Kyriaki Hatziagapiou, Konstantinos Bethanis, Olti Nikola, Elias Christoforides, Eleni Koniari, Eleni Kakouri, George Lambrou, Christina Kanaka-Gantenbein

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Glioblastoma multiforme (GBM) remains a serious health challenge, as current therapeutic modalities continue to yield unsatisfactory results, with the average survival rarely exceeding 1-2 years. Natural compounds still provide some of the most promising approaches for discovering new drugs. The non-psychotropic cannabidiol (CBD) deriving from Cannabis sativa L. provides such promise. CBD is endowed with anticancer, antioxidant, and genoprotective properties as established in vitro and in in vivo experiments. CBD’s selectivity towards cancer cells and its safe profile suggest its usage in cancer therapies. However, the bioavailability of oral CBD is low due to poor aqueous solubility, erratic gastrointestinal absorption, and significant first-pass metabolism, hampering its therapeutic potential and resulting in a variable pharmacokinetic profile. In this context, CBD can take great advantage of nanomedicine-based formulation strategies. Cyclodextrins (CDs) are cyclic oligosaccharides used in the pharmaceutical industry to incorporate apolar molecules inside their hydrophobic cavity, increasing their stability, water solubility, and bioavailability or decreasing their side effects. CBD-inclusion complexes with CDs could be a good strategy to improve its properties, like solubility and stability to harness its full therapeutic potential. The current research aims to study the potential cytotoxic effect of CBD and CBD-CDs complexes CBD-RMβCD (randomly methylated β-cyclodextrin) and CBD-HPβCD (hydroxypropyl-b-CD) on the A172 glioblastoma cell line. CBD is diluted in 10% DMSO, and CBD/CDs solutions are prepared by mixing solid CBD, solid CDs, and dH2O. For the biological assays, A172 cells are incubated at a range of concentrations of CBD, CBD-RMβCD and CBD-HPβCD, RMβCD, and HPβCD (0,03125-4 mg/ml) at 24, 48, and 72 hours. Analysis of cell viability after incubation with the compounds is performed with Alamar Blue viability assay. CBD’s dilution to DMSO 10% was inadequate, as crystals are observed; thus cytotoxicity experiments are not assessed. CBD’s solubility is enhanced in the presence of both CDs. CBD/CDs exert significant cytotoxicity in a dose and time-dependent manner (p < 0.005 for exposed cells to any concentration at 48, 72, and 96 hours versus cells not exposed); as their concentration and time of exposure increases, the reduction of resazurin to resofurin decreases, indicating a reduction in cell viability. The cytotoxic effect is more pronounced in cells exposed to CBD-HPβCD for all concentrations and time-points. RMβCD and HPβCD at the highest concentration of 4 mg/ml also exerted antitumor action per se since manifesting cell growth inhibition. The results of our study could afford the basis of research regarding the use of natural products and their inclusion complexes as anticancer agents and the shift to targeted therapy with higher efficacy and limited toxicity. Acknowledgments: The research is partly funded by ΙΚΥ (State Scholarships Foundation) – Post-doc Scholarships-Partnership Agreement 2014-2020.

Keywords: cannabidiol, cyclodextrins, glioblastoma, hydroxypropyl-b-Cyclodextrin, randomly-methylated-β-cyclodextrin

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Authors: Jeet Chakraborty, Sanjay Dutta

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Antibiotic resistance by bacteria has proved to be a severe threat to mankind in recent times, and this fortifies an urgency to design and develop potent antibacterial small molecules/compounds with nonconventional mechanisms than the conventional ones. DNA carries the genetic signature of any organism, and bacteria maintain their genomic DNA inside the cell in a well-regulated compact form with the help of various nucleoid associated proteins like HU, HNS, etc. These proteins control various fundamental processes like gene expression, replication, etc., inside the cell. Alteration of the native DNA structure of bacteria can lead to severe consequences in cellular processes inside the bacterial cell that ultimately result in the death of the organism. The change in the global DNA structure by small molecules initiates a plethora of cellular responses that have not been very well investigated. Echinomycin and Triostin-A are biologically active Quinoxaline small molecules that typically consist of a quinoxaline chromophore attached with an octadepsipeptide ring. They bind to double-stranded DNA in a sequence-specific way and have high activity against a wide variety of bacteria, mainly against Gram-positive ones. To date, few synthetic quinoxaline scaffolds were synthesized, displaying antibacterial potential against a broad scale of pathogenic bacteria. QNOs (Quinoxaline N-oxides) are known to target DNA and instigate reactive oxygen species (ROS) production in bacteria, thereby exhibiting antibacterial properties. The divergent role of Quinoxaline small molecules in medicinal research qualifies them for the evaluation of their antimicrobial properties as a potential candidate. The previous study from our lab has given new insights on a 6-nitroquinoxaline derivative 1d as an intercalator of DNA, which induces conformational changes in DNA upon binding.7 The binding event observed was dependent on the presence of a crucial benzyl substituent on the quinoxaline moiety. This was associated with a large induced CD (ICD) appearing in a sigmoidal pattern upon the interaction of 1d with dsDNA. The induction of DNA superstructures by 1d at high Drug:DNA ratios was observed that ultimately led to DNA condensation. Eviction of invitro-assembled nucleosome upon treatment with a high dose of 1d was also observed. In this work, monoquinoxaline derivatives of 1d were synthesized by various modifications of the 1d scaffold. The set of synthesized 6-nitroquinoxaline derivatives along with 1d were all subjected to antibacterial evaluation across five different bacteria species. Among the compound set, 3a displayed potent antibacterial activity against Staphylococcus aureus bacteria. 3a was further subjected to various biophysical studies to check whether the DNA structural alteration potential was still intact. The biological response of S. aureus cells upon treatment with 3a was studied using various cell biology processes, which led to the conclusion that 3d can initiate DNA damage in the S. aureus cells. Finally, the potential of 3a in disrupting preformed S.aureus and S.epidermidis biofilms was also studied.

Keywords: DNA structural change, antibacterial, intercalator, DNA superstructures, biofilms

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Authors: Kkochorong Park, Keun Cheon Kim, Hyoban Lee, Eun Ju Lee, Bongsoo Kim

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Introduction of biomaterials such as DNA, RNA, proteins is important for many research areas. There are many methods to introduce biomaterials into living organisms like tissue and cells. To introduce biomaterials, several indirect methods including virus‐mediated delivery, chemical reagent (i.e., lipofectamine), electrophoresis have been used. Such methods are passive delivery using an endocytosis process of cell, reducing an efficiency of delivery. Unlike the indirect delivery method, it has been reported that a direct delivery of exogenous biomolecules into nucleus have been more efficient to expression or integration of biomolecules. Nano-sized material is beneficial for detect signal from cell or deliver stimuli/materials into the cell at cellular and molecular levels, due to its similar physical scale. Especially, because 1 dimensional (1D) nanomaterials such as nanotube, nanorod and nanowire with high‐aspect ratio have nanoscale geometry and excellent mechanical, electrical, and chemical properties, they could play an important role in molecular and cellular biology. In this study, by using single crystalline 1D noble metal nanowire, we fabricated nano-sized 1D injector which can successfully interface with living cells and directly deliver biomolecules into several types of cell line (i.e., stem cell, mammalian embryo) without inducing detrimental damages on living cell. This nano-bio technology could be a promising and robust tool for introducing exogenous biomaterials into living organism.

Keywords: DNA, gene delivery, nanoinjector, nanowire

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Authors: Niousha Bagheri Khulenjani, Mohammad Saniee Abadeh

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Learning from very big datasets is a significant problem for most present data mining and machine learning algorithms. MicroRNA (miRNA) is one of the important big genomic and non-coding datasets presenting the genome sequences. In this paper, a hybrid method for the classification of the miRNA data is proposed. Due to the variety of cancers and high number of genes, analyzing the miRNA dataset has been a challenging problem for researchers. The number of features corresponding to the number of samples is high and the data suffer from being imbalanced. The feature selection method has been used to select features having more ability to distinguish classes and eliminating obscures features. Afterward, a Convolutional Neural Network (CNN) classifier for classification of cancer types is utilized, which employs a Genetic Algorithm to highlight optimized hyper-parameters of CNN. In order to make the process of classification by CNN faster, Graphics Processing Unit (GPU) is recommended for calculating the mathematic equation in a parallel way. The proposed method is tested on a real-world dataset with 8,129 patients, 29 different types of tumors, and 1,046 miRNA biomarkers, taken from The Cancer Genome Atlas (TCGA) database.

Keywords: cancer classification, feature selection, deep learning, genetic algorithm

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Authors: Debabrata Auddya, Bradley J. Roth

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The mechanical bidomain model is used to describe a colony of cells growing on a substrate. Analytical expressions are derived for the intracellular and extracellular displacements. Mechanotransduction events are driven by the difference between the displacements in the two spaces, corresponding to the force acting on integrins. The equation for the displacement consists of two terms: one proportional to the radius that is the same in the intracellular and extracellular spaces (the monodomain term) and one that is proportional to a modified Bessel function that is responsible for mechanotransduction (the bidomain term). The model predicts that mechanotransduction occurs within a few length constants of the colony’s edge, and an expression for the length constant contains the intracellular and extracellular shear moduli and the spring constant of the integrins coupling the two spaces. The model predictions are qualitatively consistent with experiments on human embryonic stem cell colonies, in which differentiation is localized near the edge.

Keywords: cell colony, integrin, mechanical bidomain model, stem cell, stress-strain, traction force

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Authors: Lakmali Anthony, Madeline Gillies

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Purpose: Long-term survivorship in colorectal cancer (CRC) is increasing as mortality decreases, leading to increased focus on patient-reported outcomes such as quality of life (QoL). CRC patients often have decreased QoL even after treatment is complete. This systematic review of the literature aims to identify psychosocial factors associated with decreased QoL in post-treatment CRC patients. Methodology: This systematic review was performed in accordance with the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. The search was conducted in MEDLINE, EMBASE, and PsychINFO using MeSH headings. The two authors screened studies for relevance and extracted data. Results: Seventeen studies were identified, including 6,272 total participants (mean = 392, 58% male) with a mean age of 60.6 years. The European Organisation for Research and Treatment of Cancer QLQ-C30 was the most common measure of QoL (n=14, 82.3%). Most studies (n=15, 88.2%) found that emotional distress correlated with poor global QoL. This was most commonly measured with the Hospital Anxiety & Depression Scale (n=11, 64.7%). Other psychosocial factors associated with QoL were lack of social support, body image, and financial difficulties. Clinicopathologic determinants included presence of stoma and metastasis. Conclusion: This systematic review provides a summary of the psychosocial determinants of poor QoL in post-treatment CRC patients, as well as the most commonly reported measures of these. An understanding of these potentially modifiable determinants of poor outcome is pivotal to the provision of quality, patient-centred care in surgical oncology.

Keywords: colorectal cancer, cancer surgery, quality of life, oncology, social determinants

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Authors: Yemima Dani Riani, Anggraini Barlian

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Green turtle (Chelonia mydas) is one of well known long-lived turtle. Its age can reach 100 years old. Senescence in green turtle is an interesting process to study because until now no clear explanation has been established about senescence at cellular or molecular level in this species. Since 1999, green turtle announced as an endangered species. Hence, establishment of fibroblast skin cell culture of green turtle may be material for future study of senescence. One common marker used for detecting senescence is telomere shortening. Reduced telomerase activity, the reverse transcriptase enzyme which adds TTAGGG DNA sequence to telomere end, may also cause senescence. The purpose of this research are establish and identify green turtle fibroblast skin cell culture and also compare telomere length and telomerase activity from passage 5 and 14. Primary cell culture made with primary explant method then cultured in Leibovitz-15 (Sigma) supplemented by 10% Fetal Bovine Serum (Sigma) and 100 U/mL Penicillin/Streptomycin (Sigma) at 30 ± 1oC. Cells identified with Rabbit Anti-Vimentin Polyclonal Antibody (Abcam) and Goat Polyclonal Antibody (Abcam) using confocal microscope (Zeiss LSM 170). Telomere length obtained using TeloTAGGG Telomere Length Assay (Roche) while telomerase activity obtained using TeloTAGGG Telomerase PCR ElisaPlus (Roche). Primary cell culture from green turtle skin had fibroblastic morphology and immunocytochemistry test with vimentin antibody proved the culture was fibroblast cell. Measurement of telomere length and telomerase activity showed that telomere length and telomerase activity of passage 14 was greater than passage 5. However, based on morphology, green turtle fibroblast skin cell culture showed senescent morphology. Based on the analysis of telomere length and telomerase activity, suspected fibroblast skin cell culture of green turtles is not undergo aging through telomere shortening.

Keywords: cell culture, chelonia mydas, telomerase, telomere, senescence

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Authors: Wissem Abdaoui, Nizar M. Mhaidat, Ilhem Mokhtari, Adel Gouri

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Colorectal cancer (CRC) is one of the most common tumors all over the world. Obesity, considered a risk factor of CRC, is characterized by a high level of secreted cytokines from adipose tissue. Among these inflammatory molecules, leptin is considered the key mediator for CRC cancer development and progression by activation of mitogenic and anti apoptotic signaling pathways. Gene expression can be significantly modulated by alterations in DNA methylation patterns. The aim of this study is to investigate the impact of leptin gene methylation on CRC prognosis and sensitivity to chemotherapy. The study involved 70 CRC tissue samples collected from King Abdullah University Hospital (KAUH) from which only 53 was analyzed because of bisulfate fragmentation and low yield of DNA extracted from FFPE tissues. A total of 22 blood samples were collected from healthy volunteers and enrolled as a control group. Leptin promoter methylation was analyzed by methylation specific PCR after bisulfate conversion. Results revealed that the incidence of leptin gene methylation was significantly higher in CRC patients in comparison to that of controls (P < 0.05). The correlation between patient’s demographics and leptin gene methylation was not significant (P < 0.05). However, a significant correlation between leptin gene methylation status and early cancer stages (I, II and III) was found in male but not in female (p < 0.05). Moreover, a significant correlation was found between leptin promoter methylation and early tumor localization T1-2 (p < 0.05). The correlation between epigenetic regulation of leptin and chemosensitivity was not significant. Taken together, these results suggest the possibility to use leptin gene methylation as a biomarker for the evaluation of CRC prognosis and metastasis.

Keywords: colorectal cancer, obesity, leptin, DNA methylation, disease prognosis, bisulfate conversion, chemoresistance

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Authors: Kim Kennedy, Daren Gibson, Stephanie Flukes, Chandra Diwakarla, Lisa Spalding, Leanne Pilkington, Andrew Redfern

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Introduction: Head and neck cancer and treatments are known for their profound effect on nutrition and tube feeding is a common requirement to maintain nutrition. Aim: We aimed to evaluate the frequency of tube feeding in Aboriginal and non-Aboriginal patients, and to examine the relapse and survival outcomes in patients who require enteral tube feeding. Methods: We performed a retrospective cohort analysis of 320 head and neck cancer patients from a single centre in Western Australia, identifying 80 Aboriginal patients and 240 non-Aboriginal patients matched on a 1:3 ratio by site, histology, rurality, and age. Data collected included patient demographics, tumour features, treatment details, and cancer and survival outcomes. Results: Aboriginal and non-Aboriginal patients required feeding tubes at similar rates (42.5% vs 46.2% respectively), however Aboriginal patients were far more likely to fail to return to oral nutrition, with 26.3% requiring long-term tube feeding versus only 15% of non-Aboriginal patients. In the overall study population, 27.5% required short-term tube feeding, 17.8% required long-term enteral tube nutrition, and 45.3% of patients did not have a feeding tube at any point. Relapse was more common in patients who required tube feeding, with relapses in 42.1% of the patients requiring long-term tube feeding, 31.8% in those requiring a short-term tube, versus 18.9% in the ‘no tube’ group. Survival outcomes for patients who required a long-term tube were also significantly poorer when compared to patients who only required a short-term tube, or not at all. Long-term tube-requiring patients were half as likely to survive (29.8%) compared to patients requiring a short-term tube (62.5%) or no tube at all (63.5%). Patients requiring a long-term tube were twice as likely to die with active disease (59.6%) as patients with no tube (28%), or a short term tube (33%). This may suggest an increased relapse risk in patients who require long-term feeding, due to consequences of malnutrition on cancer and treatment outcomes, although may simply reflect that patients with recurrent disease were more likely to have longer-term swallowing dysfunction due to recurrent disease and salvage treatments. Interestingly long-term tube patients were also more likely to die with no active disease (10.5%) (compared with short-term tube requiring patients (4.6%), or patients with no tube (8%)), which is likely reflective of the increased mortality associated with long-term aspiration and malnutrition issues. Conclusions: Requirement for tube feeding was associated with a higher rate of cancer relapse, and in particular, long-term tube feeding was associated with a higher likelihood of dying from head and neck cancer, but also a higher risk of dying from other causes without cancer relapse. This data reflects the complex effect of head and neck cancer and its treatments on swallowing and nutrition, and ultimately, the effects of malnutrition, swallowing dysfunction, and aspiration on overall cancer and survival outcomes. Tube feeding was seen at similar rates in Aboriginal and non-Aboriginal patient, however failure to return to oral intake with a requirement for a long-term feeding tube was seen far more commonly in the Aboriginal population.

Keywords: head and neck cancer, enteral tube feeding, malnutrition, survival, relapse, aboriginal patients

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Authors: Irshad U. Khan, Tanmay Paul, Murali Mohan Seepana

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This paper presents a study on synthesizing and characterizing a Copper oxide doped Carbon (CuO-C) electrocatalyst for the negative half-cell reactions of Vanadium Redox Flow Battery (VRFB). The CuO was synthesized using a microreactor. The electrocatalyst was characterized using X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), and Field Emission Scanning Electron Microscopy (SEM). The electrochemical performance was assessed by linear sweep voltammetry (LSV). The findings suggest that the synthesized CuO exhibited favorable crystallinity, morphology, and surface area, which reflects improved cell performance.

Keywords: ECSA, electrocatalyst, energy storage, Tafel

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Authors: Yingjeng James Li, Chiao-Chih Hu

Abstract:

Membrane electrode assemblies (MEAs) for proton exchange membrane fuel cell (PEMFC) applications were prepared by using 10 and 15 um PEMs. Except for different membrane thicknesses, these MEAs were prepared by the same conditions. They were prepared by using catalyst coated membrane (CCM) process. The catalyst employed is 40% Pt/C, and the Pt loading is 0.5mg/cm² for the sum of anode and cathode. Active area of the MEAs employed in this study is 5cm*5cm=25cm². In polarization measurements, the flow rates were always set at 1.2 stoic for anode and 3.0 stoic for cathode. The outlets were in open-end mode. The flow filed is tri-serpentine design. The cell temperatures and the humidification conditions were varied for the purpose of MEA performance observations. It was found that the performance of these two types of MEAs is about the same at fully or partially humidified operation conditions; however, 10um MEA exhibits higher current density in dry or low humidified conditions. For example, at 70C cell, 100% RH, and 0.6V condition, both MEAs have similar current density which is 1320 and 1342mA/cm² for 15um and 10um product, respectively. However, when in operation without external humidification, 10um MEA can produce 1085mA/cm²; whereas 15um MEA produces only 720mA/cm².

Keywords: fuel cell, membrane electrode assembly, PEFC, PEMFC, proton exchange membrane

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Authors: A. Hamieh, Z. Olama, H. Holail

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Drinking Water Distribution Systems provide opportunities for microorganisms that enter the drinking water to develop into biofilms. Antimicrobial agents, mainly chlorine, are used to disinfect drinking water, however, there are not yet standardized disinfection strategies with reliable efficacy and development of novel anti-biofilm strategies is still of major concern. In the present study the ability of Lactobacillus acidophilus and Streptomyces sp. cell free supernatants to inhibit the bacterial biofilm formation in Drinking Water Distribution System in Lebanon was investigated. Treatment with cell free supernatants of Lactobacillus acidophilus and Streptomyces sp. at 20% concentration resulted in average biofilm inhibition (52.89 and 39.66% respectively). A preliminary investigation about the mode of action of biofilm inhibition revealed that cell free supernatants showed no bacteriostatic or bactericidal activity against all the tested isolates. Pre-coating wells with supernatants revealed that Lactobacillus acidophilus cell free supernatant inhibited average biofilm formation (62.53%) by altering the adhesion of bacterial isolates to the surface, preventing the initial attachment step, which is important for biofilm production.

Keywords: biofilm, cell free supernatant, distribution system, drinking water, lactobacillus acidophilus, streptomyces sp, adhesion

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Authors: Tamara Jimah, Priscilla Kehoe, Pamela Pimentel, Amir Rahmani, Nikil Dutt, Yuqing Guo

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Ensuring equitable access to maternal health care is critical for public health. Particularly for underserved women, community health workers (CHWs) have been invaluable in providing support through health education and strategies for improved maternal self-care management. Our research aimed to assess the acceptance of technology by CHWs and perinatal women to promote healthy pregnancy and postpartum wellness. This pilot study was conducted at a local community organization in Orange County, California, where CHWs play an important role in supporting low-income women through home visitations. Questionnaires were administered to 14 CHWs and 114 pregnant and postpartum women, literate in English and/or Spanish. CHWs tested two wearable devices (Galaxy watch and Oura ring) and shared their user experience, including potential reception by the perinatal women they served. In addition, perinatal women provided information on access to a smart phone and the internet, as well as their interest in using wearable devices to self-monitor personal health with guidance from a CHW. Over 85% of CHWs agreed that it was useful to track pregnancy with the smart watch and ring. The majority of perinatal women owned a smartphone (97.4%), had access to the internet (80%) and unlimited data plans (78%), expressed interest in using the smart wearable devices to self-monitor health, and were open to receiving guidance from a CHW (87%). Community health workers and perinatal women embraced the use of wearable technology to monitor maternal health. These preliminary findings have formed the basis of an ongoing research study that integrates CHW guidance and technology (i.e., smart watch, smart ring, and a mobile phone app) to promote self-efficacy and self-management among underserved perinatal women.

Keywords: community health workers, health promotion and education, health equity, maternal and child health, technology

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Authors: Katerina Balounova, Jiri Pacha, Peter Ergang, Martin Vodicka, Pavlina Kvapilova

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MicroRNAs are small non-coding RNAs involved in a wide range of physiological processes. Post-transcriptional regulation of gene expression by microRNAs gives the organism a further level of control of the gene-expression program and the disruption of this microRNA regulatory mechanism seems to increase the risk of various pathophysiological conditions including tumorigenesis. To the present day, microRNAs were shown to participate in the mayor signalization pathways leading to tumorigenesis, including proliferation, cell cycle, apoptosis and metastasis formation. In addition, microRNAs have been found to play important roles in the generation and maintenance of circadian clock. These clocks generate circadian rhythms, which participate in a number of regulatory pathways. Disruption of the circadian signals seems to be associated with the development and the progression of tumours including colorectal cancer. We investigated therefore whether the diurnal profiles of miRNAs linked to tumorigenesis and regulation of circadian clock are changed during tumorigenesis. Based on published data we chose 10 microRNAs linked to tumorigenesis or circadian clock (let-7b-5p, miR 1 3p, miR 106b 5p, miR 141 3p, miR 191 5p, miR 20a 5p, miR 25 3p, miR 29a 3p, miR 34a 5p and miR 93 5p) and compared their 24-hr expression profiles in healthy and in chemically induces primary colorectal tumours of 52week-old mice. Using RT-qPCR we proved circadian rhythmicity in let-7b-5p, miR 106b 5p, miR 141 3p, miR 191 5p, miR 20a 5p, miR 25 3p, miR 29a 3p and miR 93 5p in healthy colon but not in tumours. The acrophases of miR 106b 5p, miR 141 3p, miR 191 5p, miR 20a 5p, miR 25 3p and miR 93 5p were reached around CT 24, the acrophases of let-7b-5p and miR-29a-3p were slightly shifted and reached around CT 21. In summary, our results show that circadian regulation of some colonic microRNAs is greatly affected by neoplastic transformation.

Keywords: circadian rhythm, colon, colorectal cancer, microRNA, tumorigenesis

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Authors: S. Cheragh Dar, M. Saljooghi, A. Babrgir

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In the last couple of decades researchers' attitudes were focused on developing and enhancing heat transfer processes by using new components or cellular solids that divide into stochastic structures and periodic structures. Open-cell metal foams are part of stochastic structures families that they can be considered as an avant-garde technology and they have unique properties, this porous media can have tremendous achievements in thermal processes. This paper argues and surveys postulating possible in industrial thermal issues which include: compact electronic cooling, heat exchanger, aerospace, fines, turbo machinery, automobiles, crygen tanks, biomechanics, high temperature filters and etc. Recently, by surveying exponential rate of publications in thermal open-cell metal foams, all can be demonstrated in a holistic view which can lead researchers to a new level of understanding in different industrial thermal sections.

Keywords: heat transfer, industrial thermal, cellular solids, open cell metal foam

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Authors: Seyede Sanaz Seyedebrahimi, Shima Rahimi, Shohreh Fakhari, Ali Jalili

Abstract:

Background: CXCR4, as a chemokine receptor, plays well-known roles in various types of cancers. Several studies have been conducted to overcome CXCR4 axis acts in multiple myeloma (MM) pathogenesis and progression. Dexamethasone, a standard treatment for multiple myeloma, has been shown to increase CXCR4 levels in multiple myeloma cell lines. Herein, we focused on the effects of metformin and dexamethasone on CXCR4 at the cellular level and the migration rate of cell lines after exposure to a combination compared to single-agent models. Materials and Method: Multiple myeloma cell lines (U266 and RPMI8226) were cultured with different metformin and dexamethasone concentrations in single-agent and combination models. The simultaneous combination doses were calculated by CompuSyn software. Cell surface and mRNA expression of CXCR4 were determined using flow cytometry and the quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay, respectively. The Transwell cell migration assay evaluated the migration ability. Results: In concurred with previous studies, our results showed a dexamethasone up-regulation effect on CXCR4 in a dose-dependent manner. Although, the metformin single-agent model could reduce CXCR4 expression of U266 and RPMI8226 in cell surface and mRNA expression level. Moreover, the administration of metformin and dexamethasone simultaneously exerted a higher suppression effect on CXCR4 expression than the metformin single-agent model. The migration rate through the combination model's matrigel membrane was remarkably lower than the metformin and dexamethasone single-agent model. Discussion: According to our findings, the combination of metformin and dexamethasone effectively inhibited dexamethasone-induced CXCR4 expression in multiple myeloma cell lines. As a result, metformin may be counted as an alternative medicine combined with other chemotherapies to combat multiple myeloma. However, more research is required.

Keywords: CXCR4, dexamethasone, metformin, migration, multiple myeloma

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Authors: A. C. Khor, M. R. Mohamed, M. H. Sulaiman, M. R. Daud

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Packaging for vanadium redox flow battery is one of the key elements for successful implementation of flow battery in the electrical energy storage system. Usually the bulky battery size and low energy densities make this technology not available for mobility application. Therefore RFB with improved packaging size and energy capacity are highly desirable. This paper focuses on the study of packaging improvement for unit cell V-RFB to the application on Series Hybrid Electric Vehicle. Two different designs of 25 cm2 and 100 cm2 unit cell V-RFB at same current density are used for the sample in this investigation. Further suggestions on packaging improvement are highlighted.

Keywords: electric vehicle, redox flow battery, packaging, vanadium

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Authors: Idris Garba, Aisha Rabiu Abdullahi, Mansur Yahuza, Akintade Dare

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Background: CT urography (CTU) is efficient radiological examination for the evaluation of the urinary system disorders. However, patients are exposed to a significant radiation dose which is in a way associated with increased cancer risks. Objectives: To determine Computed Tomography Dose Index following CTU, and to evaluate organs equivalent doses. Materials and Methods: A prospective cohort study was carried at a tertiary institution located in Kano northwestern. Ethical clearance was sought and obtained from the research ethics board of the institution. Demographic, scan parameters and CT radiation dose data were obtained from patients that had CTU procedure. Effective dose, organ equivalent doses, and cancer risks were estimated using SPSS statistical software version 16 and CT dose calculator software. Result: A total of 56 patients were included in the study, consisting of 29 males and 27 females. The common indication for CTU examination was found to be renal cyst seen commonly among young adults (15-44yrs). CT radiation dose values in DLP, CTDI and effective dose for CTU were 2320 mGy cm, CTDIw 9.67 mGy and 35.04 mSv respectively. The probability of cancer risks was estimated to be 600 per a million CTU examinations. Conclusion: In this study, the radiation dose for CTU is considered significantly high, with increase in cancer risks probability. Wide radiation dose variations between patient doses suggest that optimization is not fulfilled yet. Patient radiation dose estimate should be taken into consideration when imaging protocols are established for CT urography.

Keywords: CT urography, cancer risks, effective dose, radiation exposure

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