Search results for: cancer risk

Authors: Kieren Wilson, Gulnaz Majeed

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NHS constitution gives rights to the patient with suspected cancer to be seen by a cancer specialist within 2 weeks of referral. Guys and St Thomas Hospital (GSTT) is one of the largest cancer centres in London. NICE guidelines have provided guidance for health professionals to refer patients appropriately to RAC. In GSTT suspected gynae cancer referrals are mostly by NHS e-Referral Service with some fax, emails as well as paper referrals. The objective of this study was to evaluate compliance with 2-week referral pathway with emphasis on one stop diagnostic service with supporting efficient pathways. A prospective evaluation over 3 months (1 Jan 2017 to 31 Mar 2017) was undertaken. There were 26 clinics, 761 patients were booked in the clinics with a DNA rate of 13% (n=101) hence 606 patients were seen. Majority of referrals were for post menopausal bleeding (PMB) 25% (n=194) followed by cervical, vaginal, vulval reasons 23% (n=179) (abnormal cytology excluded as patients directly referred to colposcopy unit in GSTT), ovarian 7% (n=54) and endometrial 5% (n=41). Women with new or previous established diagnosis of cancer were 24, cervical (n=17), vulva (n=6) and vagina (n=1). Multifocal preinvasive disease vulva (VIN), vagina (VAIN) and cervix (CIN) was confirmed in twenty-six patients 4% (high prevalence in HIV patients). Majority of cervical referrals: PCB (n=14), cervical erosion (n=7), polyps (n=9) and cervical cyst were benign. However, two women with PMB had cervical cancer. Only 2 out of 13 referrals with vaginal concerns had VAIN. One case with non-cervical glandular cytology was confirmed to have endometrial cancer. One stop service based on the diagnostic support of ultrasound, colposcopy and hysteroscopy was achieved in 54% (n=359). Patients were discharged to GP, benign gynaecology, endometriosis, combined vulval/dermatology clinic or gynae oncology. 33% (n=202) required a second visit, 12% (n=70) third visit, 3% (n=19) fourth visit, 1% (n=4) fifth visit and 1% (n=6) sixth visit. Main reasons for follow ups were the unavailability of diagnostic slots, patient choice, need for interpreters, the discussion following gynae MDM review for triage to benign gynae, delay in availability of diagnostic results like histology/MRI/CT. Recommendations following this study are multi disciplinary review of pathways with the availability of additional diagnostic procedure slots to aim for one stop service. Furthermore, establishment of virtual and telephone consultations to reduce follow ups.

Keywords: multifocal disease, post menopausal bleeding, preinvasive disease, rapid access clinic

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Authors: Noraziah Nordin, Najihah Mohd Hashim, Nazia Abdul Majid, Mashitoh Abdul Rahman, Hamed Karimian, Hapipah Mohd Ali

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Enicosanthellum pulchrum belongs to family Annonaceae is also known as family of 'mempisang' in Malaysia. Liriodenine was isolated by prep-HPLC method. This method was first technique used for the isolation of this compound. The structure of the liriodenine was elucidated by 1D and 2D spectroscopy techniques. Liriodenine was tested on ovarian cancer cells line (CAOV-3) for MTT, AO/PI and cytotoxicity 3 assays. The MTT assay was performed to determine the cytotoxicity effect of lirodenine on CAOV-3 cells. The morphological changes on CAOV-3 cells were observed by AO/PI assay for the early and late stage of apoptosis, as well as necrosis. Meanwhile, the measurement of cell loss, nuclear morphology, DNA content, cell membrane permeability, mitochondrial membrane potential changes and cytochrome c release from mitochondria were detected through cytotoxicity 3 assay. The IC50 results showed liriodenine inhibits the growth of CAOV-3 cells after 24 h of treatment at 10.25 ± 1.06 µg/mL. After 48 and 72 h of treatments, the IC50 values were decreased to 7.65 ± 0:07 and 6.35 ± 1.62 µg/mL, respectively. The morphology changes can be seen on CAOV-3 with a production of cell membrane blebbing, cromatin condensation and apoptotic bodies with increasing time of treatment from 24 to 72 h. Evaluation of cytotoxicity 3 on CAOV-3 cells after treated with liriodenine, resulting loss of mitochondrial membrane potential and release of cytochrome c from mitochondria. The results demonstrated the capability of liriodenine as a promising anticancer agent, particularly on human ovarian cancer.

Keywords: Enicosanthellum pulchrum, ovarian cancer, apoptosis, cytotoxicity

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Authors: Ilzira A. Minigalieva

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Assessment of cumulative health risks associated with the widely observed combined exposures to two or more metals and their compounds on the organism in industrial or general environment, as well as respective regulatory and technical risk management decision-making have presumably the theoretical and experimental toxicology of mixtures as their reliable scientific basis. Analysis of relevant literature and our own experience proves, however, that there is no full match between these different practices. Moreover, some of the contradictions between them are of a fundamental nature. This unsatisfactory state of things may be explained not only by unavoidable simplifications characteristic of the methodologies of risk assessment and permissible exposure standards setting but also by the extreme intrinsic complexity of the combined toxicity theory, the most essential issues of which are considered and briefly discussed in this paper.

Keywords: toxic metals, nanoparticles, typology of combined toxicity, mathematical modeling, health risk assessment and management

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Authors: Md. Fazlul Karim, Ashik Sharfaraz, Aysha Ferdoushi

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Background: Computational medicinal chemistry approaches are used for designing and identifying new drug-like molecules, predicting properties and pharmacological activities, and optimizing lead compounds in drug development. SIRT7, a nicotinamide adenine dinucleotide (NAD+)-dependent deacylase which regulates aging, is an emerging target for cancer therapy with mounting evidence that SIRT7 downregulation plays important roles in reversing cancer phenotypes and suppressing tumor growth. Activation or altered expression of SIRT7 is associated with the progression and invasion of various cancers, including liver, breast, gastric, prostate, and non-small cell lung cancer. Objectives: The goal of this work was to identify potent and selective bioactive candidate inhibitors of SIRT7 by in silico screening of small molecule compounds obtained from Nigella sativa (N. sativa). Methods: SIRT7 structure was retrieved from The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), and its active site was identified using CASTp and metaPocket. Molecular docking simulation was performed with PyRx 0.8 virtual screening software. Drug-likeness properties were tested using SwissADME and pkCSM. In silico toxicity was evaluated by Osiris Property Explorer. Bioactivity was predicted by Molinspiration software. Antitumor activity was screened for Prediction of Activity Spectra for Substances (PASS) using Way2Drug web server. Molecular dynamics (MD) simulation was carried out by Desmond v3.6 package. Results: A total of 159 bioactive compounds from the N. Sativa were screened against the SIRT7 enzyme. Five bioactive compounds: chrysin (CID:5281607), pinocembrin (CID:68071), nigellidine (CID:136828302), nigellicine (CID:11402337), and epicatechin (CID:72276) were identified as potent SIRT7 anti-cancer candidates after docking score evaluation and applying Lipinski's Rule of Five. Finally, MD simulation identified Chrysin as the top SIRT7 anti-cancer candidate molecule. Conclusion: Chrysin, which shows a potential inhibitory effect against SIRT7, can act as a possible anti-cancer drug candidate. This inhibitor warrants further evaluation to check its pharmacokinetics and pharmacodynamics properties both in vitro and in vivo.

Keywords: SIRT7, antitumor, molecular docking, molecular dynamics simulation

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Authors: Yujie Yuan, Yiyang Fan, Hong Fan

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Objective: The RNA methylation recognition protein Aly/REF export factor (ALYREF) is considered one type of “reader” protein acting as a recognition protein of m5C, has been reported involved in several biological progresses including cancer initiation and progression. 5-methylcytosine (m5C) is a conserved and prevalent RNA modification in all species, as accumulating evidence suggests its role in the promotion of tumorigenesis. It has been claimed that ALYREF mediates nuclear export of mRNA with m5C modification and regulates biological effects of cancer cells. However, the systematical regulatory pathways of ALYREF in cancer tissues have not been clarified, yet. Methods: The expression level of ALYREF in pan-cancer and their normal tissues was compared through the data acquired from The Cancer Genome Atlas (TCGA). The University of Alabama at Birmingham Cancer data analysis Portal UALCAN was used to analyze the relationship between ALYREF and clinical pathological features. The relationship between the expression level of ALYREF and prognosis of pan-cancer, and the correlation genes of ALYREF were figured out by using Gene Expression Correlation Analysis database GEPIA. Immune related genes were obtained from TISIDB (an integrated repository portal for tumor-immune system interactions). Immune-related research was conducted by using Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) and TIMER. Results: Based on the data acquired from TCGA, ALYREF has an obviously higher-level expression in various types of cancers compared with relevant normal tissues excluding thyroid carcinoma and kidney chromophobe. The immunohistochemical images on The Human Protein Atlas showed that ALYREF can be detected in cytoplasm, membrane, but mainly located in nuclear. In addition, a higher expression level of ALYREF in tumor tissue generates a poor prognosis in majority of cancers. According to the above results, cancers with a higher expression level of ALYREF compared with normal tissues and a significant correlation between ALYREF and prognosis were selected for further analysis. By using TISIDB, we found that portion of ALYREF co-expression genes (such as BIRC5, H2AFZ, CCDC137, TK1, and PPM1G) with high Pearson correlation coefficient (PCC) were involved in anti-tumor immunity or affect resistance or sensitivity to T cell-mediated killing. Furthermore, based on the results acquired from GEPIA, there was significant correlation between ALYREF and PD-L1. It was exposed that there is a negative correlation between the expression level of ALYREF and ESTIMATE score. Conclusion: The present study indicated that ALYREF plays a vital and universal role in cancer initiation and progression of pan-cancer through regulating mitotic progression, DNA synthesis and metabolic process, and RNA processing. The correlation between ALYREF and PD-L1 implied ALYREF may affect the therapeutic effect of immunotherapy of tumor. More evidence revealed that ALYREF may play an important role in tumor immunomodulation. The correlation between ALYREF and immune cell infiltration level indicated that ALYREF can be a potential therapeutic target. Exploring the regulatory mechanism of ALYREF in tumor tissues may expose the reason for poor efficacy of immunotherapy and offer more directions of tumor treatment.

Keywords: ALYREF, pan-cancer, immunotherapy, PD-L1

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Authors: Maryam Hajrezaie, Mahmood Ameen Abdulla, Nazia Abdul Majid, Hapipa Mohd Ali, Pouya Hassandarvish, Maryam Zahedi Fard

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Background: Colon cancer is one of the most prevalent cancers in the world and is the third leading cause of death among cancers in both males and females. The incidence of colon cancer is ranked fourth among all cancers but varies in different parts of the world. Cancer chemoprevention is defined as the use of natural or synthetic compounds capable of inducing biological mechanisms necessary to preserve genomic fidelity. Andrographolide is the major labdane diterpenoidal constituent of the plant Andrographis paniculata (family Acanthaceae), used extensively in the traditional medicine. Extracts of the plant and their constituents are reported to exhibit a wide spectrum of biological activities of therapeutic importance. Laboratory animal model studies have provided evidence that Andrographolide play a role in inhibiting the risk of certain cancers. Objective: Our aim was to evaluate the chemopreventive efficacy of the Andrographolide in the AOM induced rat model. Methods: To evaluate inhibitory properties of andrographolide on colonic aberrant crypt foci (ACF), five groups of 7-week-old male rats were used. Group 1 (control group) were fed with 10% Tween 20 once a day, Group 2 (cancer control) rats were intra-peritoneally injected with 15 mg/kg Azoxymethan, Gropu 3 (drug control) rats were injected with 15 mg/kg azoxymethan and 5-Flourouracil, Group 4 and 5 (experimental groups) were fed with 10 and 20 mg/kg andrographolide each once a day. After 1 week, the treatment group rats received subcutaneous injections of azoxymethane, 15 mg/kg body weight, once weekly for 2 weeks. Control rats were continued on Tween 20 feeding once a day and experimental groups 10 and 20 mg/kg andrographolide feeding once a day for 8 weeks. All rats were sacrificed 8 weeks after the azoxymethane treatment. Colons were evaluated grossly and histopathologically for ACF. Results: Administration of 10 mg/kg and 20 mg/kg andrographolide were found to be effectively chemoprotective, as evidenced microscopily and biochemically. Andrographolide suppressed total colonic ACF formation up to 40% to 60%, respectively, when compared with control group. Pre-treatment with andrographolide, significantly reduced the impact of AOM toxicity on plasma protein and urea levels as well as on plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and gamma-glutamyl transpeptidase (GGT) activities. Grossly, colorectal specimens revealed that andrographolide treatments decreased the mean score of number of crypts in AOM-treated rats. Importantly, rats fed andrographolide showed 75% inhibition of foci containing four or more aberrant crypts. The results also showed a significant increase in glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO), and Prostaglandin E2 (PGE2) activities and a decrease in malondialdehyde (MDA) level. Histologically all treatment groups showed a significant decrease of dysplasia as compared to control group. Immunohistochemical staining showed up-regulation of Hsp70 and down-regulation of Bax proteins. Conclusion: The current study demonstrated that Andrographolide reduce the number of ACF. According to these data, Andrographolide might be a promising chemoprotective activity, in a model of AOM-induced in ACF.

Keywords: chemopreventive, andrographolide, colon cancer, aberrant crypt foci (ACF)

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Authors: Renata Checiches, Thierry Coche, Nicolas F. Delahaye, Albert Linder, Fernando Ulloa Montoya, Olivier Gruselle, Karen Langfeld, An de Creus, Bart Spiessens, Vincent G. Brichard, Jamila Louahed, Frédéric F. Lehmann

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Background: The RNA-expression levels of cancer-testis antigens MAGE A3 and PRAME were determined in resected tissue from patients with primary non-small-cell lung cancer (NSCLC) and related to clinical outcome. EGFR, KRAS and BRAF mutation status was determined in a subset to investigate associations with MAGE A3 and PRAME expression. Methods: We conducted a single-centre, uncontrolled, retrospective study of 1260 tissue-bank samples from stage IA-III resected NSCLC. The prognostic value of antigen expression (qRT-PCR) was determined by hazard-ratio and Kaplan-Meier curves. Results: Thirty-seven percent (314/844) of tumours expressed MAGE-A3, 66% (723/1092) expressed PRAME and 31% (239/839) expressed both. Respective frequencies in squamous-cell tumours and adenocarcinomas were 43%/30% for MAGE A3 and 80%/44% for PRAME. No correlation with stage, tumour size or patient age was found. Overall, no prognostic value was identified for either antigen. A trend to poorer overall survival was associated with MAGE-A3 in stage IIIB and with PRAME in stage IB. EGFR and KRAS mutations were found in 10.1% (28/311) and 33.8% (97/311) of tumours, respectively. EGFR (but not KRAS) mutation status was negatively associated with PRAME expression. Conclusion: No clear prognostic value for either PRAME or MAGE A3 was observed in the overall population, although some observed trends may warrant further investigation.

Keywords: MAGE A3, PRAME, cancer-testis gene, NSCLC, survival, EGFR

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Authors: Sarah Holdren, Laura Crook, Anne Drapkin Lyerly

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Objective: The COVID-19 Pandemic has drawn new attention to long-existing bioethical questions around pregnancy, childbirth, and parenthood. Due to the increased risk of severe COVID-19, pregnant individuals may experience anxiety regarding medical decision-making. Especially in the case of hospital births, questions around the ethics of bringing healthy pregnant individuals into a high-risk environment for viral transmission illuminate gaps in the American maternal and child healthcare system. Limited research has sought to understand the experiences of those who gave birth outside hospitals during this time. This study aims to understand pregnant individuals’ conceptualization of risk during the COVID-19 pandemic. Methods: Individuals who gave birth after March 2020 were recruited through advertisements on social media. Participants completed a 1-hour semi-structured interview and a demographic questionnaire. Interviews were transcribed and coded by members of the research team using thematic narrative analysis. Results: A total of 18 participants were interviewed and completed the demographic questionnaire. The language of risk was utilized in birth narratives in three different ways, which highlighted the multileveled and nuanced ways in which risk is understood and mitigated by pregnant and birthing individuals. These included: 1. The risk of contracting COVID-19 before, during, and after birth, 2. The risk of birth complications requiring medical interventions dependent on selected birthing space (home, birthing center, hospital), and 3. The overall risk of creating life in the middle of a pandemic. The risk of contracting COVID-19 and risk of birth complications were often weighed in paradoxical ways throughout each individual’s pregnancy, while phrases such as “pandemic baby” and “apocalypse” appeared throughout narratives and highlighted the broader implications of pregnancy and childbirth during this momentous time. Conclusions: Healthcare professionals should consider the variety of ways that pregnant and birthing individuals understand the risk when counseling patients on healthcare decisions, especially during times of healthcare crisis such as COVID-19. Future work should look to understand how the language of risk fits into a broader understanding of the human experience of growing life in times of crisis.

Keywords: maternal and child health, thematic narrative analysis, COVID-19, risk mitigation

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Authors: Omar Amoudi, Latifa Al Brashdi

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Construction projects are always subject to risks and uncertainties due to its unique and dynamic nature, outdoor work environment, the wide range of skills employed, various parties involved in addition to situation of construction business environment at large. Altogether, these risks and uncertainties affect projects objectives and lead to cost overruns, delay, and poor quality. Construction projects in Oman often experience cost overruns and delay. Managing these risks and reducing their impacts on construction cost requires firstly identifying these risks, and then analyzing their severity on project cost to obtain deep understanding about these risks. This in turn will assist construction managers in managing and tacking these risks. This paper aims to investigate the main risk factors that affect construction projects cost in the Sultanate of Oman. In order to achieve the main aim, literature review was carried out to identify the main risk factors affecting construction cost. Thirty-three risk factors were identified from the literature. Then, a questionnaire survey was designed and distributed among construction professionals (i.e., client, contractor and consultant) to obtain their opinion toward the probability of occurrence for each risk factor and its possible impact on construction project cost. The collected data was analyzed based on qualitative aspects and in several ways. The severity of each risk factor was obtained by multiplying the probability occurrence of a risk factor with its impact. The findings of this study reveal that the most significant risk factors that have high severity impact on construction project cost are: Change of Oil Price, Delay of Materials and Equipment Delivery, Changes in Laws and Regulations, Improper Budgeting, and Contingencies, Lack of Skilled Workforce and Personnel, Delays Caused by Contractor, Delays of Owner Payments, Delays Caused by Client, and Funding Risk. The results can be used as a basis for construction managers to make informed decisions and produce risk response procedures and strategies to tackle these risks and reduce their negative impacts on construction project cost.

Keywords: construction cost, construction projects, Oman, risk factors, risk management

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Authors: Cameron Truong, Mikhail Bhatia, Yangyang Chen, Viet Nga Cao

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Using a sample of U.S. firms between 1996 and 2011, this paper documents a positive association between options trading volume and future stock price crash risk. This relation is evidently more pronounced among firms with higher information asymmetry, business uncertainty, and short-sale constraints. In a dichotomous cross-sectional setting, we also document that firms with options trading have higher future crash risk than firms without options trading. We further show in a difference-in-difference analysis that firms experience an increase in crash risk immediately after the listing of options. The results suggest that options traders are able of identifying bad news hoarding by management and choose to trade in a liquid options market in anticipation of future crashes.

Keywords: bad news hoarding, cross-sectional setting, options trading, stock price crash

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Authors: hassan gheisari

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Ferro silicate calcium nano particles are prepared through the sol-gel method using polyvinyl alcohol (PVA) as a chelating agent. The powder, as prepared, is annealed at three different temperatures (900 ºC, 1000 ºC, and 1100 ºC) for 3 h. The XRD patterns of the samples indicate broad peaks, and the full width at half maximum decreased with increasing annealing temperature. FTIR spectra of the samples confirm the presence of metal - oxygen complexes within the structure. The average particle size obtained from PSA curve demonstrates ultrafine particles. SEM micrographs indicate the particles synthesized have spherical morphology. The saturation magnetization (Ms) and remnant magnetization (Mr) of the samples show dependence on particle size and crystallinity of the samples. The highest saturation magnetization is achieved for the sample annealed at 1100 ºC having maximum average particle size. The high saturation magnetization of the samples suggests the present method is suitable for obtaining nano particles magnetic ferro bioceramic, which is desirable for practical applications such as hyperthermia bone cancer therapy.

Keywords: hyperthermia, bone cancer, bio ceramic; magnetic materials; sol– gel, silicate calcium

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Authors: Hassan Gheisari

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Ferro silicate calcium nano particles are prepared through the sol-gel method using polyvinyl alcohol (PVA) as a chelating agent. The powder as prepared is annealed at three different temperatures (900 ºC, 1000 ºC and 1100 ºC) for 3 h. The XRD patterns of the samples indicate broad peaks and the full width at half maximum decreased with increasing annealing temperature. FTIR spectra of the samples confirm the presence of metal - oxygen complexes within the structure. The average particle size obtained from PSA curve demonstrates ultrafine particles. SEM micrographs indicate the particles synthesized have spherical morphology. The saturation magnetization (Ms) and remnant magnetization (Mr) of the samples show dependence on particle size and crystallinity of the samples. The highest saturation magnetization is achieved for the sample annealed at 1100 ºC having maximum average particle size. The high saturation magnetization of the samples suggests the present method is suitable for obtaining nano particles magnetic ferro bioceramic which is desirable for practical applications such as hyperthermia bone cancer therapy.

Keywords: hyperthermia, bone cancer, bio ceramic, magnetic materials, sol– gel, silicate calcium

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Authors: Nourhan G. Sahly, Ahmed Moustafa, Mohamed S. Zaghloul, Tamer Z. Salem

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The gut microbiome plays important roles in the human body that includes but not limited to digestion, immunity, homeostasis and response to some drugs such as chemotherapy and immunotherapy. Its role has also been linked to radiotherapy and associated gastrointestinal injuries, where the microbial dysbiosis could be the driving force for dose determination or the complete suspension of the treatment protocol. Linking the gut microbiota alterations to different cancer treatment protocols is not easy especially in humans. However, enormous effort was exerted to understand this complex relationship. In the current study, we described the gut microbiota dysbiosis in pediatric sarcoma patients, in the pelvic region, with regards to radiotherapy and antibiotics. Fecal samples were collected as a source of microbial DNA for which the gene encoding for V3-V5 regions of 16S rRNA was sequenced. Two of the three patients understudy had experienced an increase in alpha diversity post exposure to 50.4 Gy. Although phylum Firmicutes overall relative abundance has generally decreased, six of its taxa increased in all patients. Our results may indicate the possibility of radiosensitivity or enrichment of the antibiotic resistance of the elevated taxa. Further studies are needed to describe the extent of radiosensitivity with regards to antibiotic resistance.

Keywords: combined radiotherapy and chemotherapy, gut microbiome, pediatric cancer, radiosensitivity

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Authors: Ogbuagu Josephat Okechukwu, Okeke Abuchi Princewill, Arinze Rosemary Uche, Tabugbo Ifeyinwa Blessing, Ogbuagu Adaora Stellamaris

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Phthalates or Phthalate esters (PAEs), categorized as an endocrine disruptor and persistent organic pollutants, are known for their environmental contamination and toxicological effects. In this study, the concentration of selected phthalates was determined across the sampling site to investigate their occurrence and the ecological and health risk assessment they pose to the environment. Water and sediment samples were collected following standard procedures. Solid phase and ultrasonic methods were used to extract seven different PAEs, which were analyzed by Gas Chromatography with Mass Detector (GCMS). The analytical average recovery was found to be within the range of 83.4% ± 2.3%. The results showed that PAEs were detected in six out of seven samples with a high percentage of detection rate in water. Di-n-butyl phthalate (DPB) and disobutyl phthalates (DiBP) showed a greater detection rate compared to other PAE monomers. The concentration of PEs was found to be higher in sediment samples compared to water samples due to the fact that sediments serve as a sink for most persistent organic pollutants. The concentrations of PAEs in water samples and sediments ranged from 0.00 to 0.23 mg/kg and 0.00 to 0.028 mg/l, respectively. Ecological risk assessment using the risk quotient method (RQ) reveals that the estimated environmental risk caused by phthalates lies within the moderate level as RQ ranges from 0.1 to 1.0, whereas the health risk assessment caused by phthalates on estimating the average daily dose reveals that the ingestion of phthalates was found to be approaching permissible limit which can cause serious carcinogenic occurrence in the human system with time due to excess accumulation.

Keywords: phthalates, endocrine disruptor, risk assessment, ecological risk, health risk

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Authors: Zahra Shokrolahi, Mohammad Reza Atashzar

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The goals of treating patients with breast cancer are to cure the disease, prolong survival, and improve quality of life. Immune cells in the tumor microenvironment have an important role in regulating tumor progression. The term of cellular immunotherapy refers to the administration of living cells to a patient; this type of immunotherapy can be active, such as a dendritic cell (DC) vaccine, in that the cells can stimulate an anti-tumour response in the patient, or the therapy can be passive, whereby the cells have intrinsic anti-tumour activity; this is known as adoptive cell transfer (ACT) and includes the use of autologous or allogeneic lymphocytes that may, or may not, be modified. The most important breast cancer cellular immunotherapies involving the use of T cells and natural killer (NK) cells in adoptive cell transfer, as well as dendritic cells vaccines. T cell-based therapies including tumour-infiltrating lymphocytes (TILs), engineered TCR-T cells, chimeric antigen receptor (CAR T cell), Gamma-delta (γδ) T cells, natural killer T (NKT) cells. NK cell-based therapies including lymphokine-activated killers (LAK), cytokine-induced killer (CIK) cells, CAR-NK cells. Adoptive cell therapy has some advantages and disadvantages some. TILs cell strictly directed against tumor-specific antigens but are inactive against tumor changes due to immunoediting. CIK cell have MHC-independent cytotoxic effect and also need concurrent high dose IL-2 administration. CAR T cell are MHC-independent; overcome tumor MHC molecule downregulation; potent in recognizing any cell surface antigen (protein, carbohydrate or glycolipid); applicable to a broad range of patients and T cell populations; production of large numbers of tumor-specific cells in a moderately short period of time. Meanwhile CAR T cells capable of targeting only cell surface antigens; lethal toxicity due to cytokine storm reported. Here we present the most popular cancer cellular immunotherapy approaches and discuss their clinical relevance referring to data acquired from clinical trials .To date, clinical experience and efficacy suggest that combining more than one immunotherapy interventions, in conjunction with other treatment options like chemotherapy, radiotherapy and targeted or epigenetic therapy, should guide the way to cancer cure.

Keywords: breast cancer , cell therapy , CAR T cell , CIK cells

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Authors: Hyeon-Kyo Lim, Hyunjung Kim, Kune-Woo Lee

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Decommissioning process of nuclear facilities can be said to consist of a sequence of problem solving activities, partly because there may exist working environments contaminated by radiological exposure, and partly because there may also exist industrial hazards such as fire, explosions, toxic materials, and electrical and physical hazards. As for an individual hazard factor, risk assessment techniques are getting known to industrial workers with advance of safety technology, but the way how to integrate those results is not. Furthermore, there are few workers who experienced decommissioning operations a lot in the past. Therefore, not a few countries in the world have been trying to develop appropriate counter techniques in order to guarantee safety and efficiency of the process. In spite of that, there still exists neither domestic nor international standard since nuclear facilities are too diverse and unique. In the consequence, it is quite inevitable to imagine and assess the whole risk in the situation anticipated one by one. This paper aimed to find out an appropriate technique to integrate individual risk assessment results from the viewpoint of experts. Thus, on one hand the whole risk assessment activity for decommissioning operations was modeled as a sequence of individual risk assessment steps, and on the other, a hierarchical risk structure was developed. Then, risk assessment procedure that can elicit individual hazard factors one by one were introduced with reference to the standard operation procedure (SOP) and hierarchical task analysis (HTA). With an assumption of quantification and normalization of individual risks, a technique to estimate relative weight factors was tried by using the conventional Analytic Hierarchical Process (AHP) and its result was reviewed with reference to judgment of experts. Besides, taking the ambiguity of human judgment into consideration, debates based upon fuzzy inference was added with a mathematical case study.

Keywords: decommissioning, risk assessment, analytic hierarchical process (AHP), fuzzy inference

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Authors: Lily Ingsrisawang, Tasanee Nacharoen

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Introduction: The problems of unbalanced data sets generally appear in real world applications. Due to unequal class distribution, many research papers found that the performance of existing classifier tends to be biased towards the majority class. The k -nearest neighbors’ nonparametric discriminant analysis is one method that was proposed for classifying unbalanced classes with good performance. Hence, the methods of discriminant analysis are of interest to us in investigating misclassification error rates for class-imbalanced data of three diabetes risk groups. Objective: The purpose of this study was to compare the classification performance between parametric discriminant analysis and nonparametric discriminant analysis in a three-class classification application of class-imbalanced data of diabetes risk groups. Methods: Data from a healthy project for 599 staffs in a government hospital in Bangkok were obtained for the classification problem. The staffs were diagnosed into one of three diabetes risk groups: non-risk (90%), risk (5%), and diabetic (5%). The original data along with the variables; diabetes risk group, age, gender, cholesterol, and BMI was analyzed and bootstrapped up to 50 and 100 samples, 599 observations per sample, for additional estimation of misclassification error rate. Each data set was explored for the departure of multivariate normality and the equality of covariance matrices of the three risk groups. Both the original data and the bootstrap samples show non-normality and unequal covariance matrices. The parametric linear discriminant function, quadratic discriminant function, and the nonparametric k-nearest neighbors’ discriminant function were performed over 50 and 100 bootstrap samples and applied to the original data. In finding the optimal classification rule, the choices of prior probabilities were set up for both equal proportions (0.33: 0.33: 0.33) and unequal proportions with three choices of (0.90:0.05:0.05), (0.80: 0.10: 0.10) or (0.70, 0.15, 0.15). Results: The results from 50 and 100 bootstrap samples indicated that the k-nearest neighbors approach when k = 3 or k = 4 and the prior probabilities of {non-risk:risk:diabetic} as {0.90:0.05:0.05} or {0.80:0.10:0.10} gave the smallest error rate of misclassification. Conclusion: The k-nearest neighbors approach would be suggested for classifying a three-class-imbalanced data of diabetes risk groups.

Keywords: error rate, bootstrap, diabetes risk groups, k-nearest neighbors

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Authors: Armenia Nazar, Sally M. J. Anggelya, Rose Dinda

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Hypertension prevalence in Indonesian has increased from time to time since 2013, especially in women. This cross-sectional analysis study was made to observe the incidence of hypertension on the reproductive women (20-49 years old) with several risk factors who use contraceptive pills. Data was collected from June - October 2016 in the Andalas Public Health Center, East Padang District, Indonesia. An amount of 167 respondents who were taken using consecutive sampling technique were participate in this study. Data of social demography, contraceptive used, duration of use, hypertension risk factors (age, family history, central obesity, body mass index, physical activity, and stress) were collected and analyzed statistically using Chi-Square analysis. Significant was taken at p < 0.05. Results showed that the woman with contraceptive pill was tent to get hypertension (OR = 3,90 and p < 0,001). In addition, woman with a family history OR of 6,77 (p = 0,09), mild physical activity OR of 3,67 (p = 0,33), moderate physical activity OR of 3,33 (p = 0,16), and stressed OR of 5.11 (p = 0.18). These indicated that the contraceptive pill user is 3.9 times more risk to develop hypertension than non-users, especially one with a family history of hypertension. Other risk factors were not associated with hypertension risk in these sex productive women.

Keywords: hypertension, oral contraceptive, sex productive woman, risk factors

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Authors: Xiaoyu Shen, Fang Fang, Chujun Qiu

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Herewith we present a Fourier method for credit risk quantification and allocation in the factor-copula model framework. The key insight is that, compared to directly computing the cumulative distribution function of the portfolio loss via Monte Carlo simulation, it is, in fact, more efficient to calculate the transformation of the distribution function in the Fourier domain instead and inverting back to the real domain can be done in just one step and semi-analytically, thanks to the popular COS method (with some adjustments). We also show that the Euler risk allocation problem can be solved in the same way since it can be transformed into the problem of evaluating a conditional cumulative distribution function. Once the conditional or unconditional cumulative distribution function is known, one can easily calculate various risk metrics. The proposed method not only fills the niche in literature, to the best of our knowledge, of accurate numerical methods for risk allocation but may also serve as a much faster alternative to the Monte Carlo simulation method for risk quantification in general. It can cope with various factor-copula model choices, which we demonstrate via examples of a two-factor Gaussian copula and a two-factor Gaussian-t hybrid copula. The fast error convergence is proved mathematically and then verified by numerical experiments, in which Value-at-Risk, Expected Shortfall, and conditional Expected Shortfall are taken as examples of commonly used risk metrics. The calculation speed and accuracy are tested to be significantly superior to the MC simulation for real-sized portfolios. The computational complexity is, by design, primarily driven by the number of factors instead of the number of obligors, as in the case of Monte Carlo simulation. The limitation of this method lies in the "curse of dimension" that is intrinsic to multi-dimensional numerical integration, which, however, can be relaxed with the help of dimension reduction techniques and/or parallel computing, as we will demonstrate in a separate paper. The potential application of this method has a wide range: from credit derivatives pricing to economic capital calculation of the banking book, default risk charge and incremental risk charge computation of the trading book, and even to other risk types than credit risk.

Keywords: credit portfolio, risk allocation, factor copula model, the COS method, Fourier method

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Authors: A. D. Abdellatif, A. N. Ahmed, M. E. Abdelaziz

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The main purpose of this paper is to design a double acceptance sampling plan under the time truncated life test when the product lifetime follows an exponentiated transmuted Weibull distribution. Here, the motive is to meet both the consumer’s risk and producer’s risk simultaneously at the specified quality levels, while the termination time is specified. A comparison between the results of the double and single acceptance sampling plans is conducted. We demonstrate the applicability of our results to real data sets.

Keywords: double sampling plan, single sampling plan, producer’s risk, consumer’s risk, exponentiated transmuted weibull distribution, time truncated experiment, single, double, Marshal-Olkin

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Authors: Mamiza Haq

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This paper examines the relevance of bank capital and charter value on bank insolvency and liquidity risks. Using an unbalanced panel of 2,111 unique local banks across 22 countries over 1998-2012, we find that both bank capital and charter value lower insolvency and liquidity risks, but this effect varies among conventional, Islamic, and Islamic-window banks. The risk constraining effect of bank capital becomes more prominent in the post 2007-2008 global financial crisis. Moreover, the relationships vary when conditioned upon other key bank-specific characteristics. For instance, the effect of capital on risk-reduction diminishes in the presence of high charter value for conventional-G7 and Islamic-window banks, during-GFC and pre-GFC period; respectively. Our findings have important policy implications related to bank safety. The results are robust to a range of robustness tests.

Keywords: bank capital, charter value, risk, financial crisis

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Authors: Mohammad Ghavami, Reza S. Dilmaghani

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This paper presents an adaptive framework for modelling financial markets using equity risk premiums, risk free rates and volatilities. The recorded economic factors are initially used to train four adaptive filters for a certain limited period of time in the past. Once the systems are trained, the adjusted coefficients are used for modelling and prediction of an important financial market index. Two different approaches based on least mean squares (LMS) and recursive least squares (RLS) algorithms are investigated. Performance analysis of each method in terms of the mean squared error (MSE) is presented and the results are discussed. Computer simulations carried out using recorded data show MSEs of 4% and 3.4% for the next month prediction using LMS and RLS adaptive algorithms, respectively. In terms of twelve months prediction, RLS method shows a better tendency estimation compared to the LMS algorithm.

Keywords: adaptive methods, LSE, MSE, prediction of financial Markets

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Authors: Maria Debora Braga, Luigi Riso, Maria Grazia Zoia

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Risk-based approaches to asset allocation are portfolio construction methods that do not rely on the input of expected returns for the asset classes in the investment universe and only use risk information. They include the Minimum Variance Strategy (MV strategy), the traditional (volatility-based) Risk Parity Strategy (SRP strategy), the Most Diversified Portfolio Strategy (MDP strategy) and, for many, the Equally Weighted Strategy (EW strategy). All the mentioned approaches were based on portfolio volatility as a reference risk measure but in 2023, the Kurtosis-based Risk Parity strategy (KRP strategy) and the Minimum Kurtosis strategy (MK strategy) were introduced. Understandably, they used the fourth root of the portfolio-fourth moment as a proxy for portfolio kurtosis to work with a homogeneous function of degree one. This paper contributes mainly theoretically and methodologically to the framework of risk-based asset allocation approaches with two steps forward. First, a new and more flexible objective function considering a linear combination (with positive coefficients that sum to one) of portfolio volatility and portfolio kurtosis is used to alternatively serve a risk minimization goal or a homogeneous risk distribution goal. Hence, the new basic idea consists in extending the achievement of typical risk-based approaches’ goals to a combined risk measure. To give the rationale behind operating with such a risk measure, it is worth remembering that volatility and kurtosis are expressions of uncertainty, to be read as dispersion of returns around the mean and that both preserve adherence to a symmetric framework and consideration for the entire returns distribution as well, but also that they differ from each other in that the former captures the “normal” / “ordinary” dispersion of returns, while the latter is able to catch the huge dispersion. Therefore, the combined risk metric that uses two individual metrics focused on the same phenomena but differently sensitive to its intensity allows the asset manager to express, in the context of an objective function by varying the “relevance coefficient” associated with the individual metrics, alternatively, a wide set of plausible investment goals for the portfolio construction process while serving investors differently concerned with tail risk and traditional risk. Since this is the first study that also implements risk-based approaches using a combined risk measure, it becomes of fundamental importance to investigate the portfolio effects triggered by this innovation. The paper also offers a second contribution. Until the recent advent of the MK strategy and the KRP strategy, efforts to highlight interesting properties of risk-based approaches were inevitably directed towards the traditional MV strategy and SRP strategy. Previous literature established an increasing order in terms of portfolio volatility, starting from the MV strategy, through the SRP strategy, arriving at the EQ strategy and provided the mathematical proof for the “equalization effect” concerning marginal risks when the MV strategy is considered, and concerning risk contributions when the SRP strategy is considered. Regarding the validity of similar conclusions when referring to the MK strategy and KRP strategy, the development of a theoretical demonstration is still pending. This paper fills this gap.

Keywords: risk parity, portfolio kurtosis, risk diversification, asset allocation

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Authors: Allioua Meryem

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Similar to much of the developing world, Algeria is currently undergoing an epidemiological transition. While mal- and under-nutrition and infectious diseases used to be the main causes of poor health, today there is a higher proportion of chronic, non-communicable diseases (NCDs), including cardiovascular disease, diabetes mellitus, cancer, etc. According to estimates for Algeria from the World Health Organization (WHO), NCDs accounted for 63% of all deaths in 2010. The objective of this study was the assessment of eating habits and anthropometric characteristics in a group of youth aged 15 to 19 years in Tlemcen. This study was conducted on a total effective of 806 youth enrolled in a descriptive cross-sectional study; the classification of nutritional status has been established by international standards IOTF, youth were defined as obese if they had a BMI ≥ 95th percentile, and youth with 85th ≤ BMI ≤ 95th percentile were defined as overweight. Wc is classified by the criteria HD, Wc with moderate risk ≥ 90th percentile and Wc with high risk ≥ 95th percentile. The dietary assessment was based on a 24-hour dietary recall assisted by food records. USDA’S nutrient database for Nutrinux® program was used to analyze dietary intake. Nutrients adequacy ratio was calculated by dividing daily individual intake to dietary recommended intake DRI for each nutrient. 9% of the population was overweight, 3% was obese, 7.5% had abdominal obesity, foods eaten in moderation are chips, cookies, chocolate 1-3 times/day and increased consumption of fried foods in the week, almost half of youth consume sugary drinks more than 3 times per week, we observe a decreased intake of energy, protein (P < 0.001, P = 0.003), SFA (P = 0.018), the NAR of phosphorus, iron, magnesium, vitamin B6, vitamin E, folate, niacin, and thiamin reflecting less consumption of fruit, vegetables, milk, and milk products. Youth surveyed have eating habits at risk of developing obesity and chronic disease.

Keywords: food intake, health, anthropometric characteristics, Algeria

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Authors: Orla Muldoon, Tamaryn Nicolson, Mike Quayle, Aisling O'Donnell

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Psychology most often considers the role of experience and behaviour in shaping health at the individual level. On the other hand epidemiology has long considered risk at the wider group or structural level. Here we use the social identity approach to integrate group-level risk with individual level behaviour. Using a social identity approach we demonstrate that group or macro-level factors impact implicitly and profoundly in everyday ways at the level of individuals, via social identities. We illustrate how identities related to race, gender and inequality intersect to affect HIV/AIDS risk and AIDS treatment behaviours; how social identity processes drive stigmatising consequences of HIV and AIDS, and promote positive and effective interventions. We conclude by arguing that the social identity approach offers the field an explanatory framework that conceptualizes how social and political forces intersect with individual identity and agency to affect human health.

Keywords: social identity approach, HIV/AIDS, Africa, HIV risk, race, gender

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Authors: Rami S. Alasmari, Abdullah Al Zahrani, Hattan A. Hassani, Hattan A. Hassani, Nawwaf A. Almalky, Abdullah F. Bokhari, Alwalied A. Hafez

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Diabetes mellitus type 2 (DMT2) is a major chronic condition that is considered common among elderly people, with multiple potential complications that could contribute to falls. However, this concept is not well understood, thus, the aim of this study is to determine whether diabetes is an independent risk factor for falls in elderly. In this observational cross-sectional study, 309 diabetic patients aged 60 or more who visited the primary healthcare centers of the Ministry of National Guard Health Affairs in Jeddah were chosen via convenience sampling method. To collect the data, Semi-structured Fall Risk Assessment questionnaire and Fall Efficacy Score scale were used. The mean age of the participants was estimated to be 68.5 (SD:7.4) years. Among the participants, 48.2% experienced falling before, and 63.1% of them suffered falls in the past 12-months. The results showed that gait problems were independently associated with a higher likelihood of fall among the elderly patients (OR = 1.98, 95%CI, 1.08 to 3.62, p = 0.026. This paper suggests that diabetes mellitus is an independent fall risk factor among elderly. Therefore, identifying such patients as being at higher risk and prompt referral to a specialist falls clinic is recommended.

Keywords: diabetes, fall, elderly, risk factors

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Authors: Syue-Wen Lin

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Objective:This article reviews the care experience of a 40-year-old male patient who underwent a thoracoscopic right lower lobectomy following a COVID-19 infection. His complex medical history included multiple metastases (lungs, liver, spleen, and left kidney) and lung damage from COVID-19, which complicated the weaning process from mechanical ventilation. The care involved managing cancer treatment, postoperative pain, wound care, and palliative care. Methods:Nursing care was provided from August 16 to August 17, 2024. Challenges included difficulty with sputum clearance, which exacerbated the patient's anxiety and fear of reintubation. Pain management strategies combined analgesic drugs, non-drug methods, essential oil massages with family members, and playing the patient’s favorite music to reduce pain and anxiety. Progressive rehabilitation began with stabilizing vital signs, followed by assistance with sitting on the edge of the bed and walking within the ward. Strict sterile procedures and advanced wound care technology were used for daily dressing changes, with meticulous documentation of wound conditions and appropriate dressing selection. Holistic cancer care and palliative measures were integrated to address the patient’s physical and psychological needs. Results:The interdisciplinary care team developed a comprehensive plan addressing both physical and psychological aspects. Respiratory therapy, lung expansion exercises, and a high-frequency chest wall oscillation vest facilitated sputum expulsion and assisted in weaning from mechanical ventilation. The integration of cancer care, pain management, wound care, and palliative care led to improved quality of life and recovery. The collaborative approach between nursing staff and family ensured that the patient received compassionate and effective care. Conclusion: The complex interplay of emergency surgery, COVID-19, and advanced cancer required a multifaceted care strategy. The care team’s approach, combining critical care with tailored cancer and palliative care, effectively improved the patient’s quality of life and facilitated recovery. The comprehensive care plan, developed with family collaboration, provided both high-quality medical care and compassionate support for the terminally ill patient.

Keywords: multiple metastases, testicular cancer, palliative care, nursing experience

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Authors: Haluk Eren, Ümit Çelik

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Recent developments in unmanned aerial vehicles (UAVs) have begun to attract intense interest. UAVs started to use for many different applications from military to civilian use. Some online retailer and logistics companies are testing the UAV delivery. UAVs have great potentials to reduce cost and time of deliveries and responding to emergencies in a short time. Despite these great positive sides, just a few works have been done for routing of UAVs for package deliveries. As known, transportation of goods from one place to another may have many hazards on delivery route due to falling hazards that can be exemplified as ground objects or air obstacles. This situation refers to wide-range insurance concept. For this reason, deliveries that are made with drones get into the scope of shipping insurance. On the other hand, air traffic was taken into account in the absence of unmanned aerial vehicle. But now, it has been a reality for aerial fields. In this study, the main goal is to conduct risk analysis of package delivery services using drone, based on delivery routes.

Keywords: aerial package delivery, insurance estimation, territory risk map, unmanned aerial vehicle, route risk estimation, drone risk assessment, drone package delivery

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Authors: Loredana G. Marcu, David Marcu, Sanda M. Filip

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Advanced head and neck cancers are aggressive tumours, which require aggressive treatment. Treatment efficiency is often hindered by cancer cell repopulation during radiotherapy, which is due to various mechanisms triggered by the loss of tumour cells and involves both stem and differentiated cells. The aim of the current paper is to present in silico simulations of radiotherapy schedules on a virtual head and neck tumour grown with biologically realistic kinetic parameters. Using the linear quadratic formalism of cell survival after radiotherapy, altered fractionation schedules employing various treatment breaks for normal tissue recovery are simulated and repopulation mechanism implemented in order to evaluate the impact of various cancer cell contribution on tumour behaviour during irradiation. The model has shown that the timing of treatment breaks is an important factor influencing tumour control in rapidly proliferating tissues such as squamous cell carcinomas of the head and neck. Furthermore, not only stem cells but also differentiated cells, via the mechanism of abortive division, can contribute to malignant cell repopulation during treatment.

Keywords: radiation, tumour repopulation, squamous cell carcinoma, stem cell

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Authors: Caroline Mendes, Mary McNamara, Orla Howe

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Drug delivery systems are proposed for use in cancer treatment to specifically target cancer cells and deliver a therapeutic dose without affecting normal cells. For that purpose, the use of folate receptors (FR) can be considered a key strategy, since they are commonly over-expressed in cancer cells. In this study, cyclodextrins (CD) have being used as vehicles to target FR and deliver the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within their cavities. Here, β-CD has been modified using folic acid so as to specifically target the FR. Thus, this drug delivery system consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 15.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 16.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 10.5 for A549 and 132.6 µM ± 16.1 and 288.1 µM ± 26.3 for BEAS-2B. These results demonstrate that free MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug. The use of cell imaging by confocal microscopy has allowed visualisation of FR targeting in cancer cells, as well as the identification of the interlisation pathway of the drug. Hence, the cellular uptake and internalisation process of this drug delivery system is being addressed.

Keywords: cancer treatment, cyclodextrins, drug delivery, folate receptors, reduced folate carriers

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