Search results for: locally advanced rectal cancer

Authors: Yong Zhang

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Light has proven to be useful in a wide range of biomedical applications such as fluorescence imaging, photoacoustic imaging, optogenetics, photodynamic therapy, photothermal therapy, and light controlled drug/gene delivery. Taking photodynamic therapy (PDT) as an example, PDT has been proven clinically effective in early lung cancer, bladder cancer, head, and neck cancer and is the primary treatment for skin cancer as well. However, clinical use of PDT is severely constrained by the low penetration depth of visible light through thick tissue, limiting its use to target regions only a few millimeters deep. One way to enhance the range is to use invisible near-infrared (NIR) light within the optical window (700–1100nm) for biological tissues, extending the depth up to 1cm with no observable damage to the intervening tissue. We have demonstrated use of NIR-to-visible upconversion fluorescent nanoparticles (UCNPs), emitting visible fluorescence when excited by a NIR light at 980nm, as a nanotransducer for PDT to convert deep tissue-penetrating NIR light to visible light suitable for activating photosensitizers. The unique optical properties of UCNPs enable the upconversion wavelength to be tuned and matched to the activation absorption wavelength of the photosensitizer. At depths beyond 1cm, however, tissue remains inaccessible to light even within the NIR window, and this critical depth limitation renders existing phototherapy ineffective against most deep-seated cancers. We have demonstrated some new treatment modalities for deep-seated cancers based on UCNP hydrogel implants and miniaturized, wirelessly powered optoelectronic devices for light delivery to deep tissues.

Keywords: upconversion, fluorescent, nanoparticle, bioimaging, photodynamic therapy

Procedia PDF Downloads 160

Authors: K. Żak, S. Przetocka, R. Kitel, K. Guzik, B. Musielak, S. Malicki, G. Dubin, T. A. Holak

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Studies on tumor genesis revealed a number of factors that may potentially serve as molecular targets for immunotherapies. One of such promising targets are PD1 and PDL1 proteins. PD1 (Programmed cell death protein 1) is expressed by activated T cells and plays a critical role in modulation of the host's immune response. One of the PD1 ligands -PDL1- is expressed by macrophages, monocytes and cancer cells which exploit it to avoid immune attack. The notion of the mechanisms used by cancer cells to block the immune system response was utilized in the development of therapies blocking PD1-PDL1 interaction. Up to date, human PD1-PDL1 complex has not been crystallized and structure of the mouse-human complex does not provide a complete view of the molecular basis of PD1-PDL1 interactions. The purpose of this study is to obtain crystal structure of the human PD1-PDL1 complex which shall allow rational design of small molecule inhibitors of the interaction. In addition, the study presents results of binding small-molecules to PD1 and fragment docking towards PD1 protein which will facilitate the design and development of small–molecule inhibitors of PD1-PDL1 interaction.

Keywords: PD1, PDL1, cancer, small molecule, drug discovery

Procedia PDF Downloads 394

Authors: Deepak Singh, Rail Kuliev

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This research article explores the significance of advanced data visualization techniques in enhancing decision-making processes within the oil and gas exploration and production domain. With the oil and gas industry facing numerous challenges, effective interpretation and analysis of vast and diverse datasets are crucial for optimizing exploration strategies, production operations, and risk assessment. The article highlights the importance of data visualization in managing big data, aiding the decision-making process, and facilitating communication with stakeholders. Various advanced data visualization techniques, including 3D visualization, augmented reality (AR), virtual reality (VR), interactive dashboards, and geospatial visualization, are discussed in detail, showcasing their applications and benefits in the oil and gas sector. The article presents case studies demonstrating the successful use of these techniques in optimizing well placement, real-time operations monitoring, and virtual reality training. Additionally, the article addresses the challenges of data integration and scalability, emphasizing the need for future developments in AI-driven visualization. In conclusion, this research emphasizes the immense potential of advanced data visualization in revolutionizing decision-making processes, fostering data-driven strategies, and promoting sustainable growth and improved operational efficiency within the oil and gas exploration and production industry.

Keywords: augmented reality (AR), virtual reality (VR), interactive dashboards, real-time operations monitoring

Procedia PDF Downloads 86

Authors: Robin L. Rohrer

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Introduction: Pre-natal or early childhood exposure to the medical radiation used in diagnosis or treatment is an identified risk for childhood cancers but can be difficult to document. The author developed a family questionnaire/interview form to identify possible exposures. Aims: This retrospective study examines pre-natal and early childhood medical radiation exposure in a cohort of children diagnosed with a solid tumor including brain tumors from 1985-2015 at the Children’s Hospital of Pittsburgh (CHP). The hospital is a tri-state regional referral center which treats about 150-180 new cases of cancer in children per year. About 70% are diagnosed with a solid tumor. Methods: Each consented family so far (approximately 50% of the cohort) has been interviewed in person or by the phone call. Medical staff and psycho- social staff referred patient families for the interview with the author. Results: Among the families interviewed to date at least one medical radiation exposure has been identified (pre-conception, pre-natal or early childhood) in over 70% of diagnosed children. These exposures have included pre-conception sinus or chest CT or X-ray in either parent, sinus CT or X-ray in the mother or diagnostic radiation of chest or abdomen in children. Conclusions: Exposures to medical radiation for a child later diagnosed with cancer may occur at several critical junctures. These exposures may well contribute to a ‘perfect storm’ in the still elusive causes of childhood cancer. The author plans to expand the study from 1975 to present to hopefully further document these junctures.

Keywords: pediatric, solid tumors, medical radiation, cancer

Procedia PDF Downloads 264

Authors: Ashhar Ahmed Shaikh, Ayush Tandon

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The swift reduction of fossil fuels from nature has crucial need for alternative energy sources to cater vital demand. It is essential to boost alternative energy sources to cover the continuously increasing demand for energy while minimizing the negative environmental impacts. Solar energy is one of the reliable sources that can generate energy. Solar energy is freely available in nature and is completely eco-friendly, and they are considered as the most promising power generating sources due to their easy availability and other advantages for the local power generation. This paper is to review the implementation of power electronic devices through Solar Energy Grid Integration System (SEGIS) to increase the efficiency. This paper will also concentrate on the future grid infrastructure and various other applications in order to make the grid smart. Development and implementation of a power electronic devices such as PV inverters and power controllers play an important role in power supply in the modern energy economy. Solar Energy Grid Integration System (SEGIS) opens pathways for promising solutions for new electronic and electrical components such as advanced innovative inverter/controller topologies and their functions, economical energy management systems, innovative energy storage systems with equipped advanced control algorithms, advanced maximum-power-point tracking (MPPT) suited for all PV technologies, protocols and the associated communications. In addition to advanced grid interconnection capabilities and features, the new hardware design results in small size, less maintenance, and higher reliability. The SEGIS systems will make the 'advanced integrated system' and 'smart grid' evolutionary processes to run in a better way. Since the last few years, there was a major development in the field of power electronics which led to more efficient systems and reduction of the cost per Kilo-watt. The inverters became more efficient and had reached efficiencies in excess of 98%, and commercial solar modules have reached almost 21% efficiency.

Keywords: solar energy grid integration systems, smart grid, advanced integrated system, power electronics

Procedia PDF Downloads 184

Authors: Itee Chowdhury, Shikha Modi

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Introduction: Cancer is beginning to outpace cardiovascular disease as a cause of death affecting every major organ system with profound implications for perioperative management. Breast cancer is the most common cancer in women in India, accounting for 27% of all cancers. The small changes in analgesic management of cancer patients can greatly improve prognosis and reduce the risk of postsurgical cancer recurrence as opioid-based analgesia has a deleterious effect on cancer outcomes. Shortened postsurgical recovery time facilitates earlier return to intended oncological therapy maximising the chance of successful treatment. Literature reveals that the role of BIS since FDA approval has been assessed in various types of surgeries, but clinical data on its use in oncosurgical patients are scanty. Our study focuses on the role of BIS-guided anaesthesia for breast cancer surgery patients. Methods: A prospective randomized controlled study in patients aged 36-55years scheduled for modified radical mastectomy was conducted in 51 patients in each group who met the inclusion and exclusion criteria, and randomization was done by sealed envelope technique. In BIS guided anaesthesia group (B), sevoflurane was titrated to keep the BIS value 45-60, and thereafter if the patient showed hypertension/tachycardia, an opioid was given. In standard anaesthesia care (group C), sevoflurane was titrated to keep MAC in the range of 0.8-1, and fentanyl was given if the patient showed hypertension/tachycardia. Intraoperative opioid consumption was calculated. Postsurgery recovery characteristics, including Aldrete score, were assessed. Patients were questioned for pain, PONV, and recall of the intraoperative event. A comparison of age, BMI, ASA, recovery characteristics, opioid, and VAS score was made using the non-parametric Mann-Whitney U test. Categorical data like intraoperative awareness of surgery and PONV was studied using the Chi-square test. A comparison of heart rate and MAP was made by an independent sample t-test. #ggplot2 package was used to show the trend of the BIS index for all intraoperative time points for each patient. For a statistical test of significance, the cut-off p-value was set as <0.05. Conclusions: BIS monitoring led to reduced opioid consumption and early recovery from anaesthesia in breast cancer patients undergoing MRM resulting in less postoperative nausea and vomiting and less pain intensity in the immediate postoperative period without any recall of the intraoperative event. Thus, the use of a Bispectral index monitor allows for tailoring of anaesthesia administration with a good outcome.

Keywords: bispectral index, depth of anaesthesia, recovery, opioid consumption

Procedia PDF Downloads 127

Authors: Ognen Kostovski, Svetozar Antovic, Rubens Jovanovic, Irena Kostovska, Nikola Jankulovski

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Introduction:Colorectal carcinoma (CRC) is one of the most common malignancies in the world. The cancer stem cell (CSC) markers are associated with aggressive cancer types and poor prognosis. The aim of study was to determine whether the expression of colorectal cancer stem cell markers CD133 and CD44 could be significant in prediction of clinically aggressive form of CRC. Materials and methods: Our study included ninety patients (n=90) with CRC. Patients were divided into two subgroups: with metatstatic CRC and non-metastatic CRC. Tumor samples were analyzed with standard histopathological methods, than was performed immunohistochemical analysis with monoclonal antibodies against CD133 and CD44 stem cell markers. Results: High coexpression of CD133 and CD44 was observed in 71.4% of patients with metastatic disease, compared to 37.9% in patients without metastases. Discordant expression of both markers was found in 8% of the subgroup with metastatic CRC, and in 13.4% of the subgroup without metastatic CRC. Statistical analyses showed a significant association of increased expression of CD133 and CD44 with the disease stage, T - category and N - nodal status. With multiple regression analysis the stage of disease was designate as a factor with the greatest statistically significant influence on expression of CD133 (p <0.0001) and CD44 (p <0.0001). Conclusion: Our results suggest that the coexpression of CD133 and CD44 have an important role in prediction of clinically aggressive form of CRC. Both stem cell markers can be routinely implemented in standard pathohistological diagnostics and can be useful markers for pre-therapeutic oncology screening.

Keywords: colorectal carcinoma, stem cells, CD133+, CD44+

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Authors: Ella Tyuryumina, Alexey Neznanov

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This study is an attempt to obtain reliable data on the natural history of breast cancer growth. We analyze the opportunities for using classical mathematical models (exponential and logistic tumor growth models, Gompertz and von Bertalanffy tumor growth models) to try to describe growth of the primary tumor and the secondary distant metastases of human breast cancer. The research aim is to improve predicting accuracy of breast cancer progression using an original mathematical model referred to CoMPaS and corresponding software. We are interested in: 1) modelling the whole natural history of the primary tumor and the secondary distant metastases; 2) developing adequate and precise CoMPaS which reflects relations between the primary tumor and the secondary distant metastases; 3) analyzing the CoMPaS scope of application; 4) implementing the model as a software tool. The foundation of the CoMPaS is the exponential tumor growth model, which is described by determinate nonlinear and linear equations. The CoMPaS corresponds to TNM classification. It allows to calculate different growth periods of the primary tumor and the secondary distant metastases: 1) ‘non-visible period’ for the primary tumor; 2) ‘non-visible period’ for the secondary distant metastases; 3) ‘visible period’ for the secondary distant metastases. The CoMPaS is validated on clinical data of 10-years and 15-years survival depending on the tumor stage and diameter of the primary tumor. The new predictive tool: 1) is a solid foundation to develop future studies of breast cancer growth models; 2) does not require any expensive diagnostic tests; 3) is the first predictor which makes forecast using only current patient data, the others are based on the additional statistical data. The CoMPaS model and predictive software: a) fit to clinical trials data; b) detect different growth periods of the primary tumor and the secondary distant metastases; c) make forecast of the period of the secondary distant metastases appearance; d) have higher average prediction accuracy than the other tools; e) can improve forecasts on survival of breast cancer and facilitate optimization of diagnostic tests. The following are calculated by CoMPaS: the number of doublings for ‘non-visible’ and ‘visible’ growth period of the secondary distant metastases; tumor volume doubling time (days) for ‘non-visible’ and ‘visible’ growth period of the secondary distant metastases. The CoMPaS enables, for the first time, to predict ‘whole natural history’ of the primary tumor and the secondary distant metastases growth on each stage (pT1, pT2, pT3, pT4) relying only on the primary tumor sizes. Summarizing: a) CoMPaS describes correctly the primary tumor growth of IA, IIA, IIB, IIIB (T1-4N0M0) stages without metastases in lymph nodes (N0); b) facilitates the understanding of the appearance period and inception of the secondary distant metastases.

Keywords: breast cancer, exponential growth model, mathematical model, metastases in lymph nodes, primary tumor, survival

Procedia PDF Downloads 341

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

Procedia PDF Downloads 188

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

Procedia PDF Downloads 444

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

Abstract:

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: 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

Abstract:

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: Pooja Kumari, Anandkumar Tengli

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Aurora kinase enzyme, a protein on overexpression, leads to metastasis and is extremely important for women’s health in terms of prevention or treatment. While creating a targeted technique, the aim of the work is to design purine molecules that inhibit in aurora kinase enzyme and helps to suppress breast cancer. Purine molecules attached to an amino acid in DNA block protein synthesis or halt the replication and metastasis caused by the aurora kinase enzyme. Various protein related to the overexpression of aurora protein was docked with purine molecule using Biovia Drug Discovery, the perpetual software. Various parameters like X-ray crystallographic structure, presence of ligand, Ramachandran plot, resolution, etc., were taken into consideration for selecting the target protein. A higher negative binding scored molecule has been taken for simulation studies. According to the available research and computational analyses, purine compounds may be powerful enough to demonstrate a greater affinity for the aurora target. Despite being clinically effective now, purines were originally meant to fight breast cancer by inhibiting the aurora kinase enzyme. In in-silico studies, it is observed that purine compounds have a moderate to high potency compared to other molecules, and our research into the literature revealed that purine molecules have a lower risk of side effects. The research involves the design, synthesis, and identification of active purine molecules against breast cancer. Purines are structurally similar to the normal metabolites of adenine and guanine; hence interfere/compete with protein synthesis and suppress the abnormal proliferation of cells/tissues. As a result, purine target metastasis cells and stop the growth of kinase; purine derivatives bind with DNA and aurora protein which may stop the growth of protein or inhibits replication and stop metastasis of overexpressed aurora kinase enzyme.

Keywords: aurora kinases, in silico studies, medicinal chemistry, combination therapies, chronic cancer, clinical translation

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Authors: Muhammad Usman

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Pattern extraction has been done in past to extract hidden and interesting patterns from large datasets. Recently, advancements are being made in these techniques by providing the ability of multi-level mining, effective dimension reduction, advanced evaluation and visualization support. This paper focuses on reviewing the current techniques in literature on the basis of these parameters. Literature review suggests that most of the techniques which provide multi-level mining and dimension reduction, do not handle mixed-type data during the process. Patterns are not extracted using advanced algorithms for large datasets. Moreover, the evaluation of patterns is not done using advanced measures which are suited for high-dimensional data. Techniques which provide visualization support are unable to handle a large number of rules in a small space. We present a theoretical model to handle these issues. The implementation of the model is beyond the scope of this paper.

Keywords: association rule mining, data mining, data warehouses, visualization of association rules

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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

Abstract:

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: 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: Zoliana Bawitlung, P. C. Rohmingliana, L. Z. Chhangte, Remlal Siama, Hming Chungnunga, Vanram Lawma, L. Hnamte, B. K. Sahoo, B. K. Sapra, J. Malsawma

Abstract:

Mizoram state has the highest lung cancer incidence rate in India due to its high-level consumption of tobacco and its products which is supplemented by the food habits. While smoking is mainly responsible for this incidence, the effect of inhalation of indoor radon gas cannot be discarded as the hazardous nature of this radioactive gas and its progenies on human population have been well-established worldwide where the radiation damage to bronchial cells eventually can be the second leading cause of lung cancer next to smoking. It is also known that the effect of radiation, however, small may be the concentration, cannot be neglected as they can bring about the risk of cancer incidence. Hence, estimation of indoor radon concentration is important to give a useful reference against radiation effects as well as establishing its safety measures and to create a baseline for further case-control studies. The indoor radon/thoron concentrations in Mizoram had been measured in 41 dwellings selected on the basis of spot gamma background radiation and construction type of the houses during 2015-2016. The dwellings were monitored for one year, in 4 months cycles to indicate seasonal variations, for the indoor concentration of radon gas and its progenies, outdoor gamma dose, and indoor gamma dose respectively. A time-integrated method using Solid State Nuclear Track Detector (SSNTD) based single entry pin-hole dosimeters were used for measurement of indoor Radon/Thoron concentration. Gamma dose measurements for indoor as well as outdoor were carried out using Geiger Muller survey meters. Seasonal variation of indoor radon/ thoron concentration was monitored. The results show that the annual average radon concentrations varied from 54.07 – 144.72 Bq/m³ with an average of 90.20 Bq/m³ and the annual average thoron concentration varied from 17.39 – 54.19 Bq/m³ with an average of 35.91 Bq/m³ which are below the permissible limit. The spot survey of gamma background radiation level varies between 9 to 24 µR/h inside and outside the dwellings throughout Mizoram which are all within acceptable limits. From the above results, there is no direct indication that radon/thoron is responsible for the high lung cancer incidence in the area. In order to find epidemiological evidence of natural radiations to high cancer incidence in the area, one may need to conduct a case-control study which is beyond this scope. However, the derived data of measurement will provide baseline data for further studies.

Keywords: background gamma radiation, indoor radon/thoron, lung cancer, seasonal variation

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Authors: Naz Najma, Grace T. M. Dal Sasso, Maria de Lourdes de Souza

Abstract:

The development of information and communication technologies and the accessibility of mobile devices has increased the possibilities of the teaching and learning process anywhere and anytime. Mobile and web application allows the production of constructive teaching and learning models in various educational settings, showing the potential for active learning in nursing. The objective of this study was to present the development of an educational technology (Savinglife®, an app) for learning cardiopulmonary resuscitation and advanced cardiovascular life support training. Savinglife® is a technological production, based on the concept of virtual learning and problem-based learning approach. The study was developed from January 2016 to November 2016, using five phases (analyze, design, develop, implement, evaluate) of the instructional systems development process. The technology presented 10 scenarios and 12 simulations, covering different aspects of basic and advanced cardiac life support. The contents can be accessed in a non-linear way leaving the students free to build their knowledge based on their previous experience. Each scenario is presented through interactive tools such as scenario description, assessment, diagnose, intervention and reevaluation. Animated ECG rhythms, text documents, images and videos are provided to support procedural and active learning considering real life situation. Accessible equally on small to large devices with or without an internet connection, Savinglife® offers a dynamic, interactive and flexible tool, placing students at the center of the learning process. Savinglife® can contribute to the student’s learning in the assessment and management of basic and advanced cardiac life support in a safe and ethical way.

Keywords: problem-based learning, cardiopulmonary resuscitation, nursing education, advanced cardiac life support, educational technology

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Authors: Caroline Mendes, Mary McNamara, Orla Howe

Abstract:

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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Authors: M. R. Vijayakumar, Sanjay Kumar Singh, Lakshmi, Hithesh Dewangan, Sanjay Singh

Abstract:

Trans resveratrol (RES) is a natural molecule proved for cancer preventive and therapeutic activities devoid of any potential side effects. However, the therapeutic application of RES in disease management is limited because of its rapid elimination from blood circulation thereby low biological half life in mammals. Therefore, the main objective of this study is to enhance the circulation as well as therapeutic efficacy using PEGylated liposomes. D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) is applied as steric surface decorating agent to prepare RES liposomes by thin film hydration method. The prepared nanoparticles were evaluated by various state of the art techniques such as dynamic light scattering (DLS) technique for particle size and zeta potential, TEM for shape, differential scanning calorimetry (DSC) for interaction analysis and XRD for crystalline changes of drug. Encapsulation efficiency and invitro drug release were determined by dialysis bag method. Cancer cell viability studies were performed by MTT assay, respectively. Pharmacokinetic studies were performed in sprague dawley rats. The prepared liposomes were found to be spherical in shape. Particle size and zeta potential of prepared formulations varied from 64.5±3.16 to 262.3±7.45 nm and -2.1 to 1.76 mV, respectively. DSC study revealed absence of potential interaction. XRD study revealed presence of amorphous form in liposomes. Entrapment efficiency was found to be 87.45±2.14 % and the drug release was found to be controlled up to 24 hours. Minimized MEC in MTT assay and tremendous enhancement in circulation time of RES PEGylated liposomes than its pristine form revealed that the stearic stabilized PEGylated liposomes can be an alternative tool to commercialize this molecule for chemopreventive and therapeutic applications in cancer.

Keywords: trans resveratrol, cancer nanotechnology, long circulating liposomes, bioavailability enhancement, liposomes for cancer therapy, PEGylated liposomes

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Authors: Hritwik Ghosh, Irfan Sadiq Rahat, Sachi Nandan Mohanty, J. V. R. Ravindra

Abstract:

In the rapidly evolving landscape of medical diagnostics, the early detection and accurate classification of skin cancer remain paramount for effective treatment outcomes. This research delves into the transformative potential of Artificial Intelligence (AI), specifically Deep Learning (DL), as a tool for discerning and categorizing various skin conditions. Utilizing a diverse dataset of 3,000 images representing nine distinct skin conditions, we confront the inherent challenge of class imbalance. This imbalance, where conditions like melanomas are over-represented, is addressed by incorporating class weights during the model training phase, ensuring an equitable representation of all conditions in the learning process. Our pioneering approach introduces a hybrid model, amalgamating the strengths of two renowned Convolutional Neural Networks (CNNs), VGG16 and ResNet50. These networks, pre-trained on the ImageNet dataset, are adept at extracting intricate features from images. By synergizing these models, our research aims to capture a holistic set of features, thereby bolstering classification performance. Preliminary findings underscore the hybrid model's superiority over individual models, showcasing its prowess in feature extraction and classification. Moreover, the research emphasizes the significance of rigorous data pre-processing, including image resizing, color normalization, and segmentation, in ensuring data quality and model reliability. In essence, this study illuminates the promising role of AI and DL in revolutionizing skin cancer diagnostics, offering insights into its potential applications in broader medical domains.

Keywords: artificial intelligence, machine learning, deep learning, skin cancer, dermatology, convolutional neural networks, image classification, computer vision, healthcare technology, cancer detection, medical imaging

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Authors: Zahra Solgi, Hossein Rassi

Abstract:

Colorectal cancer (CRC) is a multi-step disease, and chronic gastric infection with H. pylori could play a role in one or more of the steps in this pathogenic process. Polymorphisms in several miRNAs are considered to increase the risk for the development of CRC by controlling proliferation, apoptosis and H. pylori pathogenesis. Therefore, the aim of this study was to investigate miRNA146a rs2910164 polymorphism and Helicobacter pylori infection in CRC. A total of 65 patients with CRC were divided into 2 groups: 28 patients < 50 years of age and 37 patients ≥ 50 years of age. DNA was extracted from all samples by a standard method and H. pylori cagA and miRNA146a rs2910164 genotypes were determined by PCR method. The results show that there was no significant difference in the frequency of H. pylori cagA gene between the two groups but there was a significant difference in the distribution of rs2910164 genotypes in patients < 50 years of age with the p-value of 0.05 and odds ratio equal to 2.69. On other hand, patients < 50 years of age with genotype CC of miRNA146a showed a significant difference in CRC risk. Furthermore, there was a significant correlation between rs2910164 CC genotype with Helicobacter pylori infection in patients < 50 years of age. The present study suggests that the CC genotype of miRNA146a in combination with H. pylori infection can be effective as risk factors and molecular markers for early diagnosis and treatment of CRC.

Keywords: colorectal cancer, Helicobacter pylori, miRNA146a, rs2910164 polymorphism

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Authors: B. Engel, H. Hassan

Abstract:

Rotary draw bending is a method which is being used in tube forming. In the tube bending process, the neutral axis moves towards the inner arc and the wall thickness distribution changes for tube’s cross section. Thinning takes place in the outer arc of the tube (extrados) due to the stretching of the material, whereas thickening occurs in the inner arc of the tube (intrados) due to the comparison of the material. The calculations of the wall thickness distribution, neutral axis shifting, and strain distribution have not been accurate enough, so far. The previous model (the geometrical model) describes the neutral axis shifting and wall thickness distribution. The geometrical of the tube, bending radius and bending angle are considered in the geometrical model, while the influence of the material properties of the tube forming are ignored. The advanced model is a modification of the previous model using material properties that depends on the correction factor. The correction factor is a purely empirically determined factor. The advanced model was compared with the Finite element simulation (FE simulation) using a different bending factor (Bf=bending radius/ diameter of the tube), wall thickness (Wf=diameter of the tube/ wall thickness), and material properties (strain hardening exponent). Finite element model of rotary draw bending has been performed in PAM-TUBE program (version: 2012). Results from the advanced model resemble the FE simulation and the experimental test.

Keywords: rotary draw bending, material properties, neutral axis shifting, wall thickness distribution

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Authors: Sunpetch Angkititrakul, Seree Klaengair, Dusadee Phongaran, Arunee Ritthipanun

Abstract:

The objective of this study is to determine the prevalence and antimicrobial resistance pattern of Salmonella spp. isolated from pigs at slaughterhouses in the northeast of Thailand. During 2015-2016, all samples were isolated and identified by ISO 6579:2002. A total of 699 samples of rectal swab were collected and isolated for the presence of Salmonella. Salmonella was detected in 275 of 699 (39.34%) samples. 24 serovars were identified in the 275 isolates. The most prevalent serovars were rissen (36.97%), S. enterica ser.4,5,12:i: (25.35%) and typhimurium (21.33%). In this study, 76.30% of the isolates were resistant to at least one antimicrobial drug and 38.39% were multidrug resistant. The highest resistances were found in ampicillin (69.20%), tetracycline (66.35%), sulfamethoxazole/trimethoprim (35.55%) and chloramphenicol (9.00%) The results showed high prevalence of Salmonella spp. in pigs and high antimicrobial resistance among the isolates, and indicated the need for monitoring program to control Salmonella contamination and reduce the dissemination of antimicrobial resistance in pig supply chain.

Keywords: prevalence, antimicrobial resistance, Salmonella spp., pig

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Authors: Eunhye Cho, Hyuk-Hoon Kim, Sieun Lee, Minjung Kathy Chae

Abstract:

Introduction: I-gel is a commonly used supraglottic advanced airway device in prehospital out-of-hospital cardiac arrest (OHCA) allowing for minimal interruption of continuous chest compression. However, previous studies have shown that prehospital supraglottic airway had inferior neurologic outcomes and survival compared to no advanced prehospital airway with conventional bag mask ventilation. We hypothesize that continuous compression with i-gel as an advanced airway may cause insufficient ventilation compared to 30:2 chest compression with conventional BVM. Therefore, we investigated the ventilation efficacy of i-gel with the initial arterial blood gas analysis in OHCA patients visiting our ER. Material and Method: Demographics, arrest parameters including i-gel insertion, initial arterial blood gas analysis was retrospectively analysed for 119 transported OHCA patients that visited our ER. Linear regression was done to investigate the association with i-gel insertion and initial pCO2 as a surrogate of prehospital ventilation. Result: A total of 52 patients were analysed for the study. Of the patients who visited the ER during OHCA, 24 patients had i-gel insertion and 28 patients had BVM as airway management in the prehospital phase. Prehospital i-gel insertion was associated with the initial pCO2 level (B coefficient 29.9, SE 10.1, p<0.01) after adjusting for bystander CPR, cardiogenic cause of arrest, EMS call to arrival. Conclusion: Despite many limitations to the study, prehospital insertion of i-gel was associated with high initial pCO2 values in OHCA patients visiting our ER, possibly indicating insufficient ventilation with prehospital i-gel as an advanced airway and continuous chest compressions.

Keywords: arrest, I-gel, prehospital, ventilation

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Authors: Nathen A. Spitz, Dennis Martin Kivlighan III, Arwa Aburizik

Abstract:

Background and Purpose: Presently, there is a paucity of naturalistic studies that directly compare the effectiveness of psychotherapy versus concurrent psychotherapy and psychiatric care for the treatment of depression and anxiety in cancer patients. Informed by previous clinical trials examining the efficacy of concurrent approaches, this study sought to test the hypothesis that a combined approach would result in the greatest reduction of depression and anxiety symptoms. Methods: Data for this study consisted of 433 adult cancer patients, with 252 receiving only psychotherapy and 181 receiving concurrent psychotherapy and psychiatric care at the University of Iowa Hospitals and Clinics. Longitudinal PHQ9 and GAD7 data were analyzed between both groups using latent growth curve analyses. Results: After controlling for treatment length and provider effects, results indicated that concurrent care was more effective than psychotherapy alone for depressive symptoms (γ₁₂ = -0.12, p = .037). Specifically, the simple slope for concurrent care was -0.25 (p = .022), and the simple slope for psychotherapy alone was -0.13 (p = .006), suggesting that patients receiving concurrent care experienced a greater reduction in depressive symptoms compared to patients receiving psychotherapy alone. In contrast, there were no significant differences between psychotherapy alone and concurrent psychotherapy and psychiatric care in the reduction of anxious symptoms. Conclusions: Overall, as both psychotherapy and psychiatric care may address unique aspects of mental health conditions, in addition to potentially providing synergetic support to each other, a combinatorial approach to mental healthcare for cancer patients may improve outcomes.

Keywords: psychiatry, psychology, psycho-oncology, combined care, psychotherapy, behavioral psychology

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Authors: Feng-Sheng Wang, Chao-Ting Cheng

Abstract:

Developing a drug from conception to launch is costly and time-consuming. Computer-aided methods can reduce research costs and accelerate the development process during the early drug discovery and development stages. This study developed a fuzzy multi-objective hierarchical optimization framework for identifying potential anticancer targets in a metabolic model. First, RNA-seq expression data of colorectal cancer samples and their healthy counterparts were used to reconstruct tissue-specific genome-scale metabolic models. The aim of the optimization framework was to identify anticancer targets that lead to cancer cell death and evaluate metabolic flux perturbations in normal cells that have been caused by cancer treatment. Four objectives were established in the optimization framework to evaluate the mortality of cancer cells for treatment and to minimize side effects causing toxicity-induced tumorigenesis on normal cells and smaller metabolic perturbations. Through fuzzy set theory, a multiobjective optimization problem was converted into a trilevel maximizing decision-making (MDM) problem. The applied nested hybrid differential evolution was applied to solve the trilevel MDM problem using two nutrient media to identify anticancer targets in the genome-scale metabolic model of colorectal cancer, respectively. Using Dulbecco’s Modified Eagle Medium (DMEM), the computational results reveal that the identified anticancer targets were mostly involved in cholesterol biosynthesis, pyrimidine and purine metabolisms, glycerophospholipid biosynthetic pathway and sphingolipid pathway. However, using Ham’s medium, the genes involved in cholesterol biosynthesis were unidentifiable. A comparison of the uptake reactions for the DMEM and Ham’s medium revealed that no cholesterol uptake reaction was included in DMEM. Two additional media, i.e., a cholesterol uptake reaction was included in DMEM and excluded in HAM, were respectively used to investigate the relationship of tumor cell growth with nutrient components and anticancer target genes. The genes involved in the cholesterol biosynthesis were also revealed to be determinable if a cholesterol uptake reaction was not induced when the cells were in the culture medium. However, the genes involved in cholesterol biosynthesis became unidentifiable if such a reaction was induced.

Keywords: Cancer metabolism, genome-scale metabolic model, constraint-based model, multilevel optimization, fuzzy optimization, hybrid differential evolution

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