Search results for: Difficult intubation in glottic cancer
Commenced in January 2007
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Paper Count: 4744

Search results for: Difficult intubation in glottic cancer

4024 Integrative Omics-Portrayal Disentangles Molecular Heterogeneity and Progression Mechanisms of Cancer

Authors: Binder Hans

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Cancer is no longer seen as solely a genetic disease where genetic defects such as mutations and copy number variations affect gene regulation and eventually lead to aberrant cell functioning which can be monitored by transcriptome analysis. It has become obvious that epigenetic alterations represent a further important layer of (de-)regulation of gene activity. For example, aberrant DNA methylation is a hallmark of many cancer types, and methylation patterns were successfully used to subtype cancer heterogeneity. Hence, unraveling the interplay between different omics levels such as genome, transcriptome and epigenome is inevitable for a mechanistic understanding of molecular deregulation causing complex diseases such as cancer. This objective requires powerful downstream integrative bioinformatics methods as an essential prerequisite to discover the whole genome mutational, transcriptome and epigenome landscapes of cancer specimen and to discover cancer genesis, progression and heterogeneity. Basic challenges and tasks arise ‘beyond sequencing’ because of the big size of the data, their complexity, the need to search for hidden structures in the data, for knowledge mining to discover biological function and also systems biology conceptual models to deduce developmental interrelations between different cancer states. These tasks are tightly related to cancer biology as an (epi-)genetic disease giving rise to aberrant genomic regulation under micro-environmental control and clonal evolution which leads to heterogeneous cellular states. Machine learning algorithms such as self organizing maps (SOM) represent one interesting option to tackle these bioinformatics tasks. The SOMmethod enables recognizing complex patterns in large-scale data generated by highthroughput omics technologies. It portrays molecular phenotypes by generating individualized, easy to interpret images of the data landscape in combination with comprehensive analysis options. Our image-based, reductionist machine learning methods provide one interesting perspective how to deal with massive data in the discovery of complex diseases, gliomas, melanomas and colon cancer on molecular level. As an important new challenge, we address the combined portrayal of different omics data such as genome-wide genomic, transcriptomic and methylomic ones. The integrative-omics portrayal approach is based on the joint training of the data and it provides separate personalized data portraits for each patient and data type which can be analyzed by visual inspection as one option. The new method enables an integrative genome-wide view on the omics data types and the underlying regulatory modes. It is applied to high and low-grade gliomas and to melanomas where it disentangles transversal and longitudinal molecular heterogeneity in terms of distinct molecular subtypes and progression paths with prognostic impact.

Keywords: integrative bioinformatics, machine learning, molecular mechanisms of cancer, gliomas and melanomas

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4023 Applications of AFM in 4D to Optimize the Design of Genetic Nanoparticles

Authors: Hosam Abdelhady

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Filming the behaviors of individual DNA molecules in their environment when they interact with individual medicinal nano-polymers in a molecular scale has opened the door to understand the effect of the molecular shape, size, and incubation time with nanocarriers on optimizing the design of robust genetic Nano molecules able to resist the enzymatic degradation, enter the cell, reach to the nucleus and kill individual cancer cells in their environment. To this end, we will show how we applied the 4D AFM as a guide to finetune the design of genetic nanoparticles and to film the effects of these nanoparticles on the nanomechanical and morphological profiles of individual cancer cells.

Keywords: AFM, dendrimers, nanoparticles, DNA, gene therapy, imaging

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4022 Natural Bio-Active Product from Marine Resources

Authors: S. Ahmed John

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Marine forms-bacteria, actinobacteria, cynobacteria, fungi, microalgae, seaweeds mangroves and other halophytes an extremely important oceanic resources and constituting over 90% of the oceanic biomass. The marine natural products have lead to the discovery of many compounds considered worthy for clinical applications. The marine sources have the highest probability of yielding natural products. Natural derivatives play an important role to prevent the cancer incidences as synthetic drug transformation in mangrove. 28.12% of anticancer compound extracted from the mangroves. Exchocaria agollocha has the anti cancer compounds. The present investigation reveals the potential of the Exchocaria agollocha with biotechnological applications for anti cancer, antimicrobial drug discovery, environmental remediation, and developing new resources for the industrial process. The anti-cancer activity of Exchocaria agollocha was screened from 3.906 to 1000 µg/ml of concentration with the dilution leads to 1:1 to 1:128 following methanol and chloroform extracts. The cell viability in the Exchocaria agollocha was maximum at the lower concentration where as low at the higher concentration of methanol and chloroform extracts when compare to control. At 3.906 concentration, 85.32 and 81.96 of cell viability was found at 1:128 dilution of methanol and chloroform extracts respectively. At the concentration of 31.25 following 1:16 dilution, the cell viability was 65.55 in methanol and 45.55 in chloroform extracts. However, at the higher concentration, the cell viability 22.35 and 8.12 was recorded in the extracts of methanol and chloroform. The cell viability was more in methanol when compare to chloroform extracts at lower concentration. The present findings gives current trends in screening and the activity analysis of metabolites from mangrove resources and to expose the models to bring a new sustain for tackling cancer. Bioactive compounds of Exchocaria agollocha have extensive use in treatment of many diseases and serve as a compound and templates for synthetic modification.

Keywords: bio-active product, compounds, natural products and microalgae

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4021 The Role of Volunteers in Quality Palliative Care Delivery

Authors: Aditya Manna, Lalit Kumar Khanra, Shyamal Kumar Sarkar

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Introduction: Here in India almost 75% of cancer patient die a sad death of neglect due to lack of awareness about palliative care and low economic level. Surveys in India show that two third of cancer patient do not get proper care during the terminal phase of their life. Palliative care through volunteers can make a significant difference in this respect. Objective: To identify and try to solve, to the extent possible, the main difficulties in giving palliative care to the terminal cancer patients of the area. And evaluate the impact of volunteer’s direct care of palliative patients and their families. Methods: Feedback from patients and their relatives regarding the palliative care they receive from nursing home and from volunteers and compare the two. Also feedback from volunteers regarding their positive and negative experience while delivering palliative care service. Then evaluate the data to compare and improve the quality of service. Results: We carried out two studies. One study was undertaken in nursing home palliative care and another was in home setting by volunteers. Both studies were in adult palliative care services. Since January 2015, 496 cases were studied to enquire about their experience in both home based care and nursing home care. Both the studies fulfilled our quality appraisal criteria. One found that those families and patients who received home visits from volunteers were significantly more satisfied. The study highlighted the value of the role of volunteers in better satisfaction of patients and their families. Conclusions: Further research is needed to evaluate the role of volunteers in palliative care and how it can be delivered appropriately and effectively. We also wish to compare our findings with similar studies elsewhere.

Keywords: palliative care, terminal care, cancer, home care

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4020 Antitumor Activity of Gold Nanorods against Mammary Gland and Skin Carcinoma in Dogs and Cats

Authors: Abdoon A.S., El Ashkar E.A., Kandil O.M., Wael H. Eisa, Shaban A.M., Khaled H.M., El Ashkar M.R., El Shaer M., Hussein H., Shaalan A.H., El Sayed M.

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Cancer is a major obstacle to human health and development worldwide. Conventional strategies for cancer intervention include surgery, chemotherapy, and radiation therapy. Recently, plasmon photothermal therapy (PPTT) was introduced as a promising treatment for the management of cancer and several non-cancerous diseases that are generally characterized by overgrowth of abnormal cells. The present work was conducted to evaluate the cytotoxic efficacy and toxicity of gold nanorods (AuNRs) in dogs and cats suffering from spontaneous mammary gland. AuNRs was injected intratumoral (IT, n=10, dose of 75 p.p.m/kg body weight) or by using spray method after surgical removal of cancer tissue (n=2) in dogs and cats. Then exposed to laser light after 60 min. Treated animals were observed every 2 days and the morphological changes in tumor size and shape were recorded. Blood samples were collected before and after treatment for checking CBC, liver and kidney functions. Results revealed that AuNRs successfully treat mammary gland tumor in dogs and cats (adenocarcinoma type 1 to IV). AuNRs induced sloughing of carcinogenic tissue within 5 to 15 days. AuNRs have no toxic effect on blood profile and the toxicity studies still under evaluation. Conclusion, AuNRs can be used for treatment of mammary gland carcinoma in dogs and cats.

Keywords: pet animals, mammary gland tumor, AuNRs, photothermal therapy, toxicity studies

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4019 Application of Raman Spectroscopy for Ovarian Cancer Detection: Comparative Analysis of Fresh, Formalin-Fixed, and Paraffin-Embedded Samples

Authors: Zeinab Farhat, Nicolas Errien, Romuald Wernert, Véronique Verriele, Frédéric Amiard, Philippe Daniel

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Ovarian cancer, also known as the silent killer, is the fifth most common cancer among women worldwide, and its death rate is higher than that of other gynecological cancers. The low survival rate of women with high-grade serous ovarian carcinoma highlights the critical need for the development of new methods for early detection and diagnosis of the disease. The aim of this study was to evaluate if Raman spectroscopy combined with chemometric methods such as Principal Component Analysis (PCA) could differentiate between cancerous and normal tissues from different types of samples, such as paraffin embedding, chemical deparaffinized, formalin-fixed and fresh samples of the same normal and malignant ovarian tissue. The method was applied specifically to two critical spectral regions: the signature region (860-1000 〖cm〗^(-1)) and the high-frequency region (2800-3100 〖cm〗^(-1) ). The mean spectra of paraffin-embedded in normal and malignant tissues showed almost similar intensity. On the other hand, the mean spectra of normal and cancer tissues from chemical deparaffinized, formalin-fixed, and fresh samples show significant intensity differences. These spectral differences reflect variations in the molecular composition of the tissues, particularly lipids and proteins. PCA, which was applied to distinguish between cancer and normal tissues, was performed on whole spectra and on selected regions—the PCA score plot of paraffin-embedded shows considerable overlap between the two groups. However, the PCA score of chemicals deparaffinized, formalin-fixed, and fresh samples showed a good discrimination of tissue types. Our findings were validated by analyses of a set of samples whose status (normal and cancerous) was not previously known. The results of this study suggest that Raman Spectroscopy associated with PCA methods has the capacity to provide clinically significant differentiation between normal and cancerous ovarian tissues.

Keywords: Raman spectroscopy, ovarian cancer, signal processing, Principal Component Analysis, classification

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4018 Targeted Photodynamic Therapy for Intraperitoneal Ovarian Cancer, A Way to Stimulate Anti-Tumoral Immune Response

Authors: Lea Boidin, Martha Baydoun, Bertrand Leroux, Olivier Morales, Samir Acherar, Celine Frochot, Nadira Delhem

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Ovarian cancer (OC) is one of the most defying diseases in gynecologic oncology. Even though surgery remains crucial in the therapy of patients with primary ovarian cancer, recurrent recidivism calls for the development of new therapy protocols to propose for patients dealing with this cancer. FRα is described as a tumor‐associated antigen in OC, where FRα expression is usually linked with more poorly differentiated, aggressive tumors. The Photodynamic treatment (PDT) available data have shown improvements in the uptake of small tumors and in the induction of a proper anti-tumoral immune response. In order to target specifically peritoneal metastatis, which overexpress FRα, a new-patented PS coupled with folic acid has been developed in our team. Herein we propose PDT using this new patented PS for PDT applied in an in vivo mice model. The efficacy of the treatment was evaluated in mice without and with PBMC reconstitution. Mice were divided into four groups: Non-Treated, PS, Light Only, and PDT Treated and subjected to illumination by laser set at 668nm with a duration of illumination of 45 minutes (or 1 min of illumination followed by 2 minutes of pause repeated 45 times). When mice were not reconstituted and after fractionized PDT protocol, a significant decrease in the tumor volume was noticed. An induction in the anti-tumoral cytokine IFNγ chaperoned this decrease while a subsequent inhibition in the cytokine TGFβ. Even more crucial, when mice were reconstituted and upon PDT, the fold of tumor decrease was even higher. An immune response was activated decoded with an increase in NK, CD3 +, LT helper and Cytotoxic T cells. Thereafter, an increase in the expression of the cytokines IFNγ and TNFα were noticed while an inhibition in TGFβ, IL8 and IL10 accompanied this immune response activation. Therefore, our work has shown for the first time that a fractionized PDT protocol using a folate-targeted PDT is effective for treatment of ovarian cancer. The interest in using PDT in this case, goes beyond the local induction of tumor apoptosis only, but can promote subsequent anti-tumor response. Most of the therapies currently used to treat ovarian cancer, have an uncooperative outcomes on the host immune response. The readiness of a tumor adjuvant treatment like PDT adequate in eliminating the tumor and in concert stimulating anti-tumor immunity would be weighty.

Keywords: folate receptor, ovarian cancer, photodynamic therapy, humanized mice model

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4017 Differences in Patient Satisfaction Observed between Female Japanese Breast Cancer Patients Who Receive Breast-Conserving Surgery or Total Mastectomy

Authors: Keiko Yamauchi, Motoyuki Nakao, Yoko Ishihara

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The increase in the number of women with breast cancer in Japan has required hospitals to provide a higher quality of medicine so that patients are satisfied with the treatment they receive. However, patients’ satisfaction following breast cancer treatment has not been sufficiently studied. Hence, we investigated the factors influencing patient satisfaction following breast cancer treatment among Japanese women. These women underwent either breast-conserving surgery (BCS) (n = 380) or total mastectomy (TM) (n = 247). In March 2016, we conducted a cross-sectional internet survey of Japanese women with breast cancer in Japan. We assessed the following factors: socioeconomic status, cancer-related information, the role of medical decision-making, the degree of satisfaction regarding the treatments received, and the regret arising from the medical decision-making processes. We performed logistic regression analyses with the following dependent variables: extreme satisfaction with the treatments received, and regret regarding the medical decision-making process. For both types of surgery, the odds ratio (OR) of being extremely satisfied with the cancer treatment was significantly higher among patients who did not have any regrets compared to patients who had. Also, the OR tended to be higher among patients who chose to play a wanted role in the medical decision-making process, compared with patients who did not. In the BCS group, the OR of being extremely satisfied with the treatment was higher if, at diagnosis, the patient’s youngest child was older than 19 years, compared with patients with no children. The OR was also higher if patient considered the stage and characteristics of their cancer significant. The OR of being extremely satisfied with the treatments was lower among patients who were not employed on full-time basis, and among patients who considered the second medical opinions and medical expenses to be significant. These associations were not observed in the TM group. The OR of having regrets regarding the medical decision-making process was higher among patients who chose to play a role in the decision-making process as they preferred, and was also higher in patients who were employed on either a part-time or contractual basis. For both types of surgery, the OR was higher among patients who considered a second medical opinion to be significant. Regardless of surgical type, regret regarding the medical decision-making process decreases treatment satisfaction. Patients who received breast-conserving surgery were more likely to have regrets concerning the medical decision-making process if they could not play a role in the process as they preferred. In addition, factors associated with the satisfaction with treatment in BCS group but not TM group included the second medical opinion, medical expenses, employment status, and age of the youngest child at diagnosis.

Keywords: medical decision making, breast-conserving surgery, total mastectomy, Japanese

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4016 Clinical Nursing Experience in Managing a Uterine Cancer Patient with Psychogenic Shock During the Extracorporeal Membrane Oxygenation Weaning Process

Authors: Syue-Wen Lin

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Objective: This article discusses the nursing experience of caring for a uterine cancer patient who experienced cardiogenic shock and was weaned off ECMO. The patient was placed on ECMO due to cardiogenic shock and initially struggled with anxiety caused by the physical discomfort from the disease and multiple medical devices, as well as the isolation in the ICU and restrictions on physical activity. Over time, the patient was able to wean off ECMO and perform daily activities and rehabilitation independently. Methods: The nursing period was from January 6 to January 9. Through observation, direct care, interviews, physical assessments, and case reviews, the intensive care team and bypass personnel conducted a comprehensive assessment using Gordon's 11 functional health patterns. The assessment identified three main nursing health problems: pain, anxiety, and decreased cardiac tissue perfusion. Results: The author consulted a psychologist to employ open communication techniques and empathetic care to build a trusting nurse-patient relationship. A patient-centered intensive cancer care plan was developed. Pain was assessed using a pain scale, and pain medications were adjusted in consultation with a pharmacist. Lavender essential oil therapy, light music, and pillows were used to distract and alleviate pain. The patient was encouraged to express feelings and family members were invited to increase visits and provide companionship to reduce the uncertainty caused by cancer and illness. Vital signs were closely monitored, and nursing interventions were provided to maintain adequate myocardial perfusion. Post-ECMO, the patient was encouraged to engage in rehabilitation and cardiopulmonary training. Conclusion: A key takeaway from the care process is the importance of observing not only the patient's vital signs but also their psychological state, especially when dealing with cancer patients on ECMO. The patient's greatest source of comfort was the presence of family, which helped alleviate anxiety. Healthcare providers play multiple critical roles as advocates, coordinators, educators, and counselors, listening to and accepting the patient’s emotional responses. The report aims to provide clinical cancer nurses with a reference to improve the quality of care and alleviate cancer-related discomfort.

Keywords: ECMO, uterine cancer, palliative care, Gordon's 11 functional health patterns

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4015 Ventilator Associated Pneumonia in a Medical Intensive Care Unit, Incidence and Risk Factors: A Case Control Study

Authors: Ammar Asma, Bouafia Nabiha, Ben Cheikh Asma, Ezzi Olfa, Mahjoub Mohamed, Sma Nesrine, Chouchène Imed, Boussarsar Hamadi, Njah Mansour

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Background: Ventilator-associated pneumonia (VAP) is currently recognized as one of the most relevant causes of morbidity and mortality among intensive care unit (ICU) patients worldwide. Identifying modifiable risk factors for VAP could be helpful for future controlled interventional studies aiming at improving prevention of VAP. The purposes of this study were to determine the incidence and risk factors for VAP in in a Tunisian medical ICU. Materials / Methods: A retrospective case-control study design based on the prospective database collected over a 14-month period from September 15th, 2015 through November 15th, 2016 in an 8-bed medical ICU. Patients under ventilation for over 48 h were included. The number of cases was estimated by Epi-info Software with the power of statistical test equal to 90 %. Each case patient was successfully matched to two controls according to the length of mechanical ventilation (MV) before VAP for cases and the total length of MV in controls. VAP in the ICU was defined according to American Thoracic Society; Infectious Diseases Society of America guidelines. Early onset or late-onset VAP were defined whether the infectious process occurred within or after 96 h of ICU admission. Patients’ risk factors, causes of admission, comorbidities and respiratory specimens collected were reviewed. Univariate and multivariate analyses were performed to determine variables associated with VAP with a p-value < 0.05. Results: During the period study, a total of 169 patients under mechanical ventilation were considered, 34 patients (20.11%) developed at least one episode of VAP in the ICU. The incidence rate for VAP was 14.88/1000 ventilation days. Among these cases, 9 (26.5 %) were early-onset VAP and 25 (73.5 %) were late-onset VAP. It was a certain diagnosis in 66.7% of cases. Tracheal aspiration was positive in 80% of cases. Multi-drug resistant Acinerobacter baumanii was the most common species detected in cases; 67.64% (n=23). The rate of mortality out of cases was 88.23% (n= 30). In univariate analysis, the patients with VAP were statistically more likely to suffer from cardiovascular diseases (p=0.035) and prolonged duration of sedation (p=0.009) and tracheostomy (p=0.001), they also had a higher number of re-intubation (p=0.017) and a longer total time of intubation (p=0.012). Multivariate analysis showed that cardiovascular diseases (OR= 4.44; 95% IC= [1.3 - 14]; p=0.016), tracheostomy (OR= 4.2; 95% IC= [1.16 -15.12]; p= 0.028) and prolonged duration of sedation (OR=1.21; 95% IC= [1.07, 1.36]; p=0.002) were independent risk factors for the development of VAP. Conclusion: VAP constitutes a therapeutic challenge in an ICU setting, therefore; strategies that effectively prevent VAP are needed. An infection control-training program intended to all professional heath care in this unit insisting on bundles and elaboration of procedures are planned to reduce effectively incidence rate of VAP.

Keywords: case control study, intensive care unit, risk factors, ventilator associated pneumonia

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4014 Phenotype of Cutaneous Squamous Cell Carcinoma in a Brazilian City with a Tropical Climate

Authors: Julia V. F. Cortes, Maria E. V. Amarante, Carolina L. Cerdeira, Roberta B. V. Silva

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Nonmelanoma skin cancer is more commonly diagnosed than all other malignancies combined. In that group, cutaneous squamous cell carcinoma stands out for having the highest probability of metastasis and recurrence after treatment, in addition to being the second most prevalent form of skin cancer. Its main risk factors include exposure to carcinogens, such as ultraviolet radiation related to sunlight exposure, smoking, alcohol consumption, and human papillomavirus (HPV) infection. Considering the increased risk of skin cancer in the Brazilian population, caused by the high incidence of solar radiation, and the importance of identifying risk phenotypes for the accomplishment of public health actions, an epidemiological study was conducted in a city with a tropical climate located in southeastern Brazil, aiming to identify the target population and assist in primary and secondary prevention. This study describes the profile of patients with cutaneous squamous cell cancer, correlating the variables, sex, age, and differentiation. The study used as primary data source the results of anatomopathological exams delivered from January 2015 to December 2019 for patients registered at one pathology service, which analyzes the results of biopsies, Thus, 66 patients with cutaneous squamous cell carcinoma were analyzed. The most affected age group was 60 years or older (78.79%), emphasizing that moderately differentiated (79.49%) and well-differentiated forms (66.67%) are prevalent in this age group, resulting in a difference of 12.82 percentage points between them. In addition, the predominant sex was male (58%), and it was found that half of the women and 65.79% of men had a moderately differentiated type, whereas the well-differentiated type was slightly more frequent in women. It is worth noting that the moderately differentiated subtype has a 59.20% prevalence among all cases. Thus, it was concluded that the most affected age group was 60 years or older and that men were more affected. As for the subtype, the moderately differentiated one, which is recognized for presenting the second-highest risk for metastasis, was prevalent in this study, affecting 6.6% more men and predominating in the elderly.

Keywords: cutaneous squamous cell carcinoma, epidemiology, skin cancer, spinal cell cancer

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4013 Robotic Lingulectomy for Primary Lung Cancer: A Video Presentation

Authors: Abraham J. Rizkalla, Joanne F. Irons, Christopher Q. Cao

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Purpose: Lobectomy was considered the standard of care for early-stage non-small lung cancer (NSCLC) after the Lung Cancer Study Group trial demonstrated increased locoregional recurrence for sublobar resections. However, there has been heightened interest in segmentectomies for selected patients with peripheral lesions ≤2cm, as investigated by the JCOG0802 and CALGB140503 trials. Minimally invasive robotic surgery facilitates segmentectomies with improved maneuverability and visualization of intersegmental planes using indocyanine green. We hereby present a patient who underwent robotic lingulectomy for an undiagnosed ground-glass opacity. Methodology: This video demonstrates a robotic portal lingulectomy using three 8mm ports and a 12mm port. Stereoscopic direct vision facilitated the identification of the lingula artery and vein, and intra-operative bronchoscopy was performed to confirm the lingula bronchus. The intersegmental plane was identified by indocyanine green and a near-infrared camera. Thorough lymph node sampling was performed in accordance with international standards. Results: The 18mm lesion was successfully excised with clear margins to achieve R0 resection with no evidence of malignancy in the 8 lymph nodes sampled. Histopathological examination revealed lepidic predominant adenocarcinoma, pathological stage IA. Conclusion: This video presentation exemplifies the standard approach for robotic portal lingulectomy in appropriately selected patients.

Keywords: lung cancer, robotic segmentectomy, indocyanine green, lingulectomy

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4012 Tumor Detection of Cerebral MRI by Multifractal Analysis

Authors: S. Oudjemia, F. Alim, S. Seddiki

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This paper shows the application of multifractal analysis for additional help in cancer diagnosis. The medical image processing is a very important discipline in which many existing methods are in search of solutions to real problems of medicine. In this work, we present results of multifractal analysis of brain MRI images. The purpose of this analysis was to separate between healthy and cancerous tissue of the brain. A nonlinear method based on multifractal detrending moving average (MFDMA) which is a generalization of the detrending fluctuations analysis (DFA) is used for the detection of abnormalities in these images. The proposed method could make separation of the two types of brain tissue with success. It is very important to note that the choice of this non-linear method is due to the complexity and irregularity of tumor tissue that linear and classical nonlinear methods seem difficult to characterize completely. In order to show the performance of this method, we compared its results with those of the conventional method box-counting.

Keywords: irregularity, nonlinearity, MRI brain images, multifractal analysis, brain tumor

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4011 Topic-Specific Differences and Lexical Variations in the Use of Violence Metaphors: A Cognitive Linguistic Study of YouTube Breast Cancer Discourse in New Zealand and Pakistan

Authors: Sara Malik, Andreea. S. Calude, Joseph Ulatowski

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This paper explores how speakers from New Zealand and Pakistan with breast cancer use violence metaphors to communicate the intensity of their experiences during various stages of illness. With the theoretical foundation in Conceptual Metaphor Theory and the use of Metaphor Identification Procedure for metaphor analysis, this study investigates how speakers with breast cancer use violence metaphors in different cultural contexts. it collected a corpus of forty-six personal narratives from New Zealand and thirty-six from Pakistan, posted between 2011 and 2023 on YouTube by breast cancer organisations, such as ‘NZ Breast Cancer Foundation’ and ‘Pink Ribbon Pakistan’. The data was transcribed using the Whisper AI tool and then curated to include only patients’ discourse, further organised into eight narrative topics: testing phase, treatment phase, remission phase, family support, campaigns and awareness efforts, government support and funding, general information and religious discourse. In this talk, it discuss two aspects of the use of violence metaphors, a) differences in the use of violence metaphors across various narrative topics, and b) lexical variations in the choice of such metaphors. The findings suggest that violence metaphors were used differently across various stages of illness experience. For instance, during the ‘testing phase,’ violence metaphors were employed to convey a sense of punishment as reflected in statements like, ‘Feeling like it was a death sentence, an immediate death sentence’ (NZ Example) and ‘Jese hi aap ko na breast cancer ka pata chalta hai logon ko yeh hona shuru ho jata hai ke oh bas ab to moat ka parwana mil gaya hai’ (Because as soon as you find out you have breast cancer people start to feel that you have received a death warrant) (PK Example). On the other hand, violence metaphor during the ‘treatment phase’ highlighted negative experiences related to chemotherapy as seen in statements like ‘The first lot of chemo I had was disastrous’ (NZ Example) and ‘...chemotherapy ke to, it's the worst of all, it's like a healing poison’ (chemotherapy, it's the worst of all, it's like a healing poison) (PK Example). Second, lexical variations revealed how ‘sunburn’ (a common phenomenon in the NZ) was used as a metaphor to describe the effects of radiotherapy, whereas in the discourse from Pakistan, a more general term, 'burn,' was used instead. In this talk, we will explore the possible reasons behind the different word choices made by speakers from both countries to describe the same process. This study contributes to understanding the use of violence metaphors across various narrative topics of the illness experience and explains how and why speakers from two different countries use lexical variations to describe the same process.

Keywords: metaphors, breast cancer discourse, cognitive linguistics, lexical variations, New zealand english, pakistani urdu

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4010 Systematic Identification of Noncoding Cancer Driver Somatic Mutations

Authors: Zohar Manber, Ran Elkon

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Accumulation of somatic mutations (SMs) in the genome is a major driving force of cancer development. Most SMs in the tumor's genome are functionally neutral; however, some cause damage to critical processes and provide the tumor with a selective growth advantage (termed cancer driver mutations). Current research on functional significance of SMs is mainly focused on finding alterations in protein coding sequences. However, the exome comprises only 3% of the human genome, and thus, SMs in the noncoding genome significantly outnumber those that map to protein-coding regions. Although our understanding of noncoding driver SMs is very rudimentary, it is likely that disruption of regulatory elements in the genome is an important, yet largely underexplored mechanism by which somatic mutations contribute to cancer development. The expression of most human genes is controlled by multiple enhancers, and therefore, it is conceivable that regulatory SMs are distributed across different enhancers of the same target gene. Yet, to date, most statistical searches for regulatory SMs have considered each regulatory element individually, which may reduce statistical power. The first challenge in considering the cumulative activity of all the enhancers of a gene as a single unit is to map enhancers to their target promoters. Such mapping defines for each gene its set of regulating enhancers (termed "set of regulatory elements" (SRE)). Considering multiple enhancers of each gene as one unit holds great promise for enhancing the identification of driver regulatory SMs. However, the success of this approach is greatly dependent on the availability of comprehensive and accurate enhancer-promoter (E-P) maps. To date, the discovery of driver regulatory SMs has been hindered by insufficient sample sizes and statistical analyses that often considered each regulatory element separately. In this study, we analyzed more than 2,500 whole-genome sequence (WGS) samples provided by The Cancer Genome Atlas (TCGA) and The International Cancer Genome Consortium (ICGC) in order to identify such driver regulatory SMs. Our analyses took into account the combinatorial aspect of gene regulation by considering all the enhancers that control the same target gene as one unit, based on E-P maps from three genomics resources. The identification of candidate driver noncoding SMs is based on their recurrence. We searched for SREs of genes that are "hotspots" for SMs (that is, they accumulate SMs at a significantly elevated rate). To test the statistical significance of recurrence of SMs within a gene's SRE, we used both global and local background mutation rates. Using this approach, we detected - in seven different cancer types - numerous "hotspots" for SMs. To support the functional significance of these recurrent noncoding SMs, we further examined their association with the expression level of their target gene (using gene expression data provided by the ICGC and TCGA for samples that were also analyzed by WGS).

Keywords: cancer genomics, enhancers, noncoding genome, regulatory elements

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4009 The Association between Gene Polymorphisms of GPX, SEPP1, and SEP15, Plasma Selenium Levels, Urinary Total Arsenic Concentrations, and Prostate Cancer

Authors: Yu-Mei Hsueh, Wei-Jen Chen, Yung-Kai Huang, Cheng-Shiuan Tsai, Kuo-Cheng Yeh

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Prostate cancer occurs in men over the age of 50, and rank sixth of the top ten cancers in Taiwan, and the incidence increased gradually over the past decade in Taiwan. Arsenic is confirmed as a carcinogen by International Agency for Research on (IARC). Arsenic induces oxidative stress may be a risk factor for prostate cancer, but the mechanism is not clear. Selenium is an important antioxidant element. Whether the association between plasma selenium levels and risk of prostate cancer are modified by different genotype of selenoprotein is still unknown. Glutathione peroxidase, selenoprotein P (SEPP1) and 15 kDa selenoprotein (SEP 15) are selenoprotein and regulates selenium transport and the oxidation and reduction reaction. However, the association between gene polymorphisms of selenoprotein and prostate cancer is not yet clear. The aim of this study is to determine the relationship between plasma selenium, polymorphism of selenoprotein, urinary total arsenic concentration and prostate cancer. This study is a hospital-based case-control study. Three hundred twenty-two cases of prostate cancer and age (±5 years) 1:1 matched 322 control group were recruited from National Taiwan University Hospital, Taipei Medical University Hospital, and Wan Fang Hospital. Well-trained personnel carried out standardized personal interviews based on a structured questionnaire. Information collected included demographic and socioeconomic characteristics, lifestyle and disease history. Blood and urine samples were also collected at the same time. The Research Ethics Committee of National Taiwan University Hospital, Taipei, Taiwan, approved the study. All patients provided informed consent forms before sample and data collection. Buffy coat was to extract DNA, and the polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) was used to measure the genotypes of SEPP1 rs3797310, SEP15 rs5859, GPX1 rs1050450, GPX2 rs4902346, GPX3 rs4958872, and GPX4 rs2075710. Plasma concentrations of selenium were determined by inductively coupled plasma mass spectrometry (ICP-MS).Urinary arsenic species concentrations were measured by high-performance liquid chromatography links hydride generator and atomic absorption spectrometer (HPLC-HG-AAS). Subject with high education level compared to those with low educational level had a lower prostate cancer odds ratio (OR) Mainland Chinese and aboriginal people had a lower OR of prostate cancer compared to Fukien Taiwanese. After adjustment for age, educational level, subjects with GPX1 rs1050450 CT and TT genotype compared to the CC genotype have lower, OR of prostate cancer, the OR and 95% confidence interval (Cl) was 0.53 (0.31-0.90). SEPP1 rs3797310 CT+TT genotype compared to those with CC genotype had a marginally significantly lower OR of PC. The low levels of plasma selenium and the high urinary total arsenic concentrations had the high OR of prostate cancer in a significant dose-response manner, and SEPP1 rs3797310 genotype modified this joint association.

Keywords: prostate cancer, plasma selenium concentration, urinary total arsenic concentrations, glutathione peroxidase, selenoprotein P, selenoprotein 15, gene polymorphism

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4008 Minimal Invasive Esophagectomy for Esophageal Cancer: An Institutional Review From a Dedicated Centre of Pakistan

Authors: Nighat Bakhtiar, Ali Raza Khan, Shahid Khan Khattak, Aamir Ali Syed

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Introduction: Chemoradiation followed by resection has been the standard therapy for resectable (cT1-4aN0-3M0) esophageal carcinoma. The optimal surgical approach remains a matter of debate. Therefore, the purpose of this study was to share our experiences of minimal invasive esophagectomies concerning morbidity, mortality and oncological quality. This study aims to enlighten the world about the surgical outcomes after minimally invasive esophagectomy at Shaukat Khanum Hospital Lahore. Objective: The purpose of this study is to review an institutional experience of Surgical outcomes of Minimal Invasive esophagectomies for esophageal cancer. Methodology: This retrospective study was performed after ethical approval at Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC) Pakistan. Patients who underwent Minimal Invasive esophagectomies for esophageal cancer from March 2018 to March 2023 were selected. Data was collected through the human information system (HIS) electronic database of SKMCH&RC. Data was described using mean and median with minimum and maximum values for quantitative variables. For categorical variables, a number of observations and percentages were reported. Results: A total of 621 patients were included in the study, with the mean age of the patient was 39 years, ranging between 18-58 years. Mean Body Mass Index of patients was 21.2.1±4.1. Neo-adjuvant chemoradiotherapy was given to all patients. The mean operative time was 210.36 ± 64.51 minutes, and the mean blood loss was 121 milliliters. There was one mortality in 90 days, while the mean postoperative hospital stay was 6.58 days with a 4.64 standard deviation. The anastomotic leak rate was 4.2%. Chyle leak was observed in 12 patients. Conclusion: The minimal invasive technique is a safe approach for esophageal cancers, with minimal complications and fast recovery.

Keywords: minimal invasive, esophagectomy, laparscopic, cancer

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4007 Molecular and Phytochemical Fingerprinting of Anti-Cancer Drug Yielding Plants in South India

Authors: Alexis John de Britto

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Studies were performed to select the superior genotypes based on intra-specific variations, caused by phytogeographical, climatic and edaphic parameters of three anti cancer drug yielding mangrove plants such as Acanthus ilicifolius L., Calophyllum inophyllum L. and Excoecaria agallocha L. using ISSR (Inter Simple Sequence Repeats) markers and phytochemical analysis such as preliminary phytochemical tests, TLC, HPTLC, HPLC and antioxidant tests. The plants were collected from five different geographical locations of the East Coast of south India. Genetic heterozygosity, Nei’s gene diversity, Shannon’s information index and Percentage of polymorphism between the populations were calculated using POPGENE software. Cluster analysis was performed using UPGMA algorithm. AMOVA and correlations between genetic diversity and soil factors were analyzed. Combining the molecular and phytochemical variations superior genotypes were selected. Conservation constraints and methods of efficient exploitation of the species are discussed.

Keywords: anti-cancer drug yielding plants, DNA fingerprinting, phytochemical analysis, selection of superior genotypes

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4006 Prediction of Endotracheal Tube Size in Children by Predicting Subglottic Diameter Using Ultrasonographic Measurement versus Traditional Formulas

Authors: Parul Jindal, Shubhi Singh, Priya Ramakrishnan, Shailender Raghuvanshi

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Background: Knowledge of the influence of the age of the child on laryngeal dimensions is essential for all practitioners who are dealing with paediatric airway. Choosing the correct endotracheal tube (ETT) size is a crucial step in pediatric patients because a large-sized tube may cause complications like post-extubation stridor and subglottic stenosis. On the other hand with a smaller tube, there will be increased gas flow resistance, aspiration risk, poor ventilation, inaccurate monitoring of end-tidal gases and reintubation may also be required with a different size of the tracheal tube. Recent advancement in ultrasonography (USG) techniques should now allow for accurate and descriptive evaluation of pediatric airway. Aims and objectives: This study was planned to determine the accuracy of Ultrasonography (USG) to assess the appropriate ETT size and compare it with physical indices based formulae. Methods: After obtaining approval from Institute’s Ethical and Research committee, and parental written and informed consent, the study was conducted on 100 subjects of either sex between 12-60 months of age, undergoing various elective surgeries under general anesthesia requiring endotracheal intubation. The same experienced radiologist performed ultrasonography. The transverse diameter was measured at the level of cricoids cartilage by USG. After USG, general anesthesia was administered using standard techniques followed by the institute. An experienced anesthesiologist performed the endotracheal intubations with uncuffed endotracheal tube (Portex Tracheal Tube Smiths Medical India Pvt. Ltd.) with Murphy’s eye. He was unaware of the finding of the ultrasonography. The tracheal tube was considered best fit if air leak was satisfactory at 15-20 cm H₂O of airway pressure. The obtained values were compared with the values of endotracheal tube size calculated by ultrasonography, various age, height, weight-based formulas and diameter of right and left little finger. The correlation of the size of the endotracheal tube by different modalities was done and Pearson's correlation coefficient was obtained. The comparison of the mean size of the endotracheal tube by ultrasonography and by traditional formula was done by the Friedman’s test and Wilcoxon sign-rank test. Results: The predicted tube size was equal to best fit and best determined by ultrasonography (100%) followed by comparison to left little finger (98%) and right little finger (97%) and age-based formula (95%) followed by multivariate formula (83%) and body length (81%) formula. According to Pearson`s correlation, there was a moderate correlation of best fit endotracheal tube with endotracheal tube size by age-based formula (r=0.743), body length based formula (r=0.683), right little finger based formula (r=0.587), left little finger based formula (r=0.587) and multivariate formula (r=0.741). There was a strong correlation with ultrasonography (r=0.943). Ultrasonography was the most sensitive (100%) method of prediction followed by comparison to left (98%) and right (97%) little finger and age-based formula (95%), the multivariate formula had an even lesser sensitivity (83%) whereas body length based formula was least sensitive with a sensitivity of 78%. Conclusion: USG is a reliable method of estimation of subglottic diameter and for prediction of ETT size in children.

Keywords: endotracheal intubation, pediatric airway, subglottic diameter, traditional formulas, ultrasonography

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4005 Coping Techniques, Repertoire, and Flexibility in Parental Adjustment to Pediatric Cancer

Authors: Michael Dolgin, Oz Hamtzani, Talma Kushnir

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A literature review has shown that while parents of children with cancer experience increased levels of psychological distress associated with their child's medical condition, considerable variability in parental adjustment is evident. Of the factors that may account for this variability, little attention has been devoted to the simultaneous interaction of three coping constructs and their role in parental adjustment: (1) Coping techniques employed, (2) Repertoire of coping techniques, and (3) Flexibility in applying coping techniques. While these constructs have been studied individually in relation to adjustment in general, studies to date have not included them together within a single conceptual model and research design and evaluated them in a clinical population. The objective of the current study was to determine how these three coping technique constructs interact to impact parental adjustment to pediatric cancer. A cross-sectional sample of 145 parents of children in active cancer treatment completed standardized measures of coping techniques, repertoire, flexibility, and parental distress. A hierarchical multiple regression analysis demonstrated that 37% of the variance in parental distress was predicted by the use of avoidance-focused coping techniques [F(1,118)=69.843, p<.001], with an additional 3% predicted by coping repertoire [F(2,117)=7.63, p=.00] for a total of 40% variance explained. Coping flexibility was found to mediate the relationship between coping repertoire and parental distress. These findings suggest that coping techniques employed by parents (problem/emotion-focused vs. avoidance-focused), as well as coping repertoire, significantly impact parental adjustment. Flexibility in applying coping techniques within one’s coping repertoire further contributes to parental adjustment. Implications for further study and clinical intervention will be presented.

Keywords: coping techniques, repertoire, flexibility, adjustment

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4004 Patients’ Perspective on Early Discharge with Drain in situ after Breast Cancer Surgery

Authors: Laila Al-Balushi, Suad Al-Kharosui

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Due to the increasing number of breast cancer cases in Oman and the impact of the novel coronavirus disease 2019 (COVID-19 on bed situation in the hospital, a policy of early discharge (ED) with drain after breast cancer surgery was initiated at one of the tertiary hospitals in Oman. The uniqueness of this policy is no home visit follow-up, conducted after discharge and the main mode of communication was Instagram media. This policy then was evaluated by conducting a quasi-experimental study using a questionnaire with ten open and closed-ended questions, five questions to explore patient experience using a five-point Likert scale. A total of 41 female patients responded to the questionnaire. Almost 96% of the participants stated being well informed about drain care pre- and post-surgery at home. 9% of the participants developed early sign of infection and was managed at out-patient clinics. Participants with bilateral drains expressed more pain than those with single drain. 90% stated satisfied being discharged with breast drain whereas 10% preferred to stay in the hospital until the drains were removed. This study found that the policy of ED with a drain after BC surgery is practical and well-accepted by most patients. The role of breast nurse and presence of family and institutional support enhanced the success of the policy implementation. To optimize patient care, conducting a training program by breast nurse for nurses at local health centres about care management of patients with drain could improve care and enhance patient satisfaction.

Keywords: breast cancer, surgery, early discharge, surgical drain

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4003 Evaluation of Immune Checkpoint Inhibitors in Cancer Therapy

Authors: Mir Mohammad Reza Hosseini

Abstract:

In new years immune checkpoint inhibitors have gathered care as being one of the greatest talented kinds of immunotherapy on the prospect. There has been a specific emphasis on the immune checkpoint molecules, cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1). In 2011, ipilimumab, the primary antibody obstructive an immune checkpoint (CTLA4) was authorized. It is now documented that recognized tumors have many devices of overpowering the antitumor immune response, counting manufacture of repressive cytokines, staffing of immunosuppressive immune cells, and upregulation of coinhibitory receptors recognized as immune checkpoints. This was fast followed by the growth of monoclonal antibodies directing PD1 (pembrolizumab and nivolumab) and PDL1 (atezolizumab and durvalumab). Anti-PD1/PDL1 antibodies have developed some of the greatest extensively set anticancer therapies. We also compare and difference their present place in cancer therapy and designs of immune-related toxicities and deliberate the role of dual immune checkpoint inhibition and plans for the organization of immune-related opposing proceedings. In this review, the employed code and present growth of numerous immune checkpoint inhibitors are abridged, while the communicating device and new development of Immune checkpoint inhibitors in cancer therapy-based synergistic therapies with additional immunotherapy, chemotherapy, phototherapy, and radiotherapy in important and clinical educations in the historical 5 years are portrayed and tinted. Lastly, we disapprovingly measure these methods and effort to find their fortes and faintness based on pre-clinical and clinical information.

Keywords: checkpoint, cancer therapy, PD-1, PDL-1, CTLA4, immunosuppressive

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4002 The Beta-Fisher Snedecor Distribution with Applications to Cancer Remission Data

Authors: K. A. Adepoju, O. I. Shittu, A. U. Chukwu

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In this paper, a new four-parameter generalized version of the Fisher Snedecor distribution called Beta- F distribution is introduced. The comprehensive account of the statistical properties of the new distributions was considered. Formal expressions for the cumulative density function, moments, moment generating function and maximum likelihood estimation, as well as its Fisher information, were obtained. The flexibility of this distribution as well as its robustness using cancer remission time data was demonstrated. The new distribution can be used in most applications where the assumption underlying the use of other lifetime distributions is violated.

Keywords: fisher-snedecor distribution, beta-f distribution, outlier, maximum likelihood method

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4001 The Determination of Self-Esteem, Life Satisfaction, Anxiety and Depression Levels among Patients with Stoma

Authors: Tugba Cinarli, Tugba Kavalali Erdogan, Sevil Masat, Dilek Kiymaz, Nida Kiyici, Zeliha Koc

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This study was conducted in a descriptive and cross-sectional manner, in order to determine the self-esteem, life satisfaction and depression/anxiety levels of the patients with stoma. The study was conducted between June 15, 2016 and June 15, 2017 among 196 oncology patients that were hospitalized in the general surgery clinic of a public hospital in Turkey. The case group consisted of 98 cancer patients with stoma and the control group consisted of 98 cancer patients without stoma. The data were collected through the Coopersmith Self-Esteem Scale, Life Satisfaction Scale, the Hospital Anxiety and Depression Scale, and a 21-question survey that aimed to determine the sociodemographic and clinical properties of the patients. The data were analyzed with percentage analysis, Mann Whitney U-test, Chi-square test and Spearmen’s correlation test. It was determined that for the case group; 44.9% had colon cancer, 29.6% had rectal cancer; 50% underwent temporary colostomia, 15.3% underwent permanent colostomia, 34.7% underwent temporary ileostomy. The experimental group's findings for the Coopersmith Self-Esteem Scale, Life Satisfaction Scale, the Anxiety Subscale and the Depression subscale were 64 (20 - 84), 17 (5 - 38), 10 (1 - 18), and 9 (1 - 19), respectively. The control group's findings for the Coopersmith Self-Esteem Scale, Life Satisfaction Scale, the Anxiety Subscale and the Depression Subscale were 68 (32 - 92), 21 (7 - 31), 8.5 (1 - 18), and 8 (1 - 18), respectively. It was found that the Coopersmith Self-Esteem Scale, Life Satisfaction Scale, and the Anxiety Subscale findings were significantly different for the experimental and control groups (p<0.05). It was determined that the self-esteem levels were positively correlated with life satisfaction and negatively correlated with anxiety and depression; also, the life satisfaction levels were negatively correlated with anxiety and depression. It is suggested that the nursing interventions should be planned in order to improve life-satisfaction and self-esteem levels of the patients, and to decrease depression and anxiety.

Keywords: anxiety, cancer, life satisfaction, self-esteem

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4000 Factors Influencing Family Resilience and Quality of Life in Pediatric Cancer Patients and Their Caregivers: A Cluster Analysis

Authors: Li Wang, Dan Shu, Shiguang Pang, Lixiu Wang, Bing Xiang Yang, Qian Liu

Abstract:

Background: Cancer is one of the most severe diseases in childhood; long-term treatment and its side effects significantly impact the patient's physical, psychological, social functioning and quality of life while also placing substantial physical and psychological burdens on caregivers and families. Family resilience is crucial for children with cancer, helping them cope better with the disease and supporting the family in facing challenges together. As a family-level variable, family resilience requires information from multiple family members. However, to our best knowledge, there is currently no research investigating family resilience from both the perspectives of pediatric cancer patients and their caregivers. Therefore, this study aims to investigate the family resilience and quality of life of pediatric cancer patients from a patient–caregiver dyadic perspective. Methods: A total of 149 dyads of patients diagnosed with pediatric cancer patients and their principal caregivers were recruited from oncology departments of 4 tertiary hospitals in Wuhan and Taiyuan, China. All participants completed questionnaires that identified their demographic and clinical characteristics as well as assessed their family resilience and quality of life for both the patients and their caregivers. K-means cluster analysis was used to identify different clusters of family resilience based on the reports from patients and caregivers. Multivariate logistic regression and linear regression are used to analyze the factors influencing family resilience and quality of life, as well as the relationship between the two. Results: Three clusters of family resilience were identified: a cluster of high family resilience (HR), a cluster of low family resilience (LR), and a cluster of discrepant family resilience (DR). Most (67.1%) families fell into the cluster with low resilience. Characteristics such as the types of caregivers perceived social support of the patient were different among the three clusters. Compared to the LR group, families where the mother is the caregiver and where the patient has high social support are more likely to be assigned to the HR. The quality of life for caregivers was consistently highest in the HR cluster and lowest in the LR cluster. The patient's quality of life is not related to family resilience. In the linear regression analysis of the patient's quality of life, patients who are the first-born have higher quality of life, while those living with their parents have lower quality of life. The participants' characteristics were not associated with the quality of life for caregivers. Conclusions: In most families, family resilience was low. Families with maternal caregivers and patients receiving high levels of social support are more inclined to be higher levels of family resilience. Family resilience was linked to the quality of life of caregivers of pediatric cancer patients. The clinical implications of this findings suggest that healthcare and social support organizations should prioritize and support the participation of mothers in caregiving responsibilities. Furthermore, they should assist families in accessing social support to enhance family resilience. This study also emphasizes the importance of promoting family resilience for enhancing family health and happiness, as well as improving the quality of life for caregivers.

Keywords: pediatric cancer, cluster analysis, family resilience, quality of life

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3999 Real Time PCR Analysis of microRNA Expression in Oral Cancer

Authors: Karl Kingsley

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Many mechanisms are involved in the control of cellular differentiation and growth, which are often dysregulated in many cancers. Many distinct pathways are involved in these mechanisms of control, including deoxyribonuclease (DNA) methyltransferase and histone deacetylase (HDAC) activation that controls both genetic and epigenetic modifications and micro ribonucleic acid (RNA) expression. Less is known about the expression of DNA methyltransferase (DNMT) and HDAC in oral cancers and the effect on microRNA expression. The primary objective of this study was to evaluate the expression of DNMT and HDAC family members in oral cancer and the concomitant expression of cancer-associated microRNAs. Using commercially available oral cancers, including squamous cell carcinoma (SCC)-4, SCC-9, SCC-15, and SCC-25, RNA was extracted and screened for DNMT, HDAC, and microRNA expression using highly-specific primers and quantitative polymerase chain reaction (qPCR). These data revealed low or absent expression of DNMT-1, which is associated with cellular differentiation but increased expression of DNMT-3a and DNMT-3b in all SCC cell lines compared with normal non-cancerous cell controls. In addition, no expression of HDAC1 and HDAC2 expression was found among the normal, non-cancerous cells but was highly expressed in each of the SCC cell lines examined. Differential expression of oncogenic and cancer-associated microRNAs was also observed among the SCC cell lines, including miR-21, miR-133, miR-149, miR-155, miR-365, and miR-720. These findings also appeared to vary according to observed growth rates among these cells. These data may be the first to demonstrate the expression and association between HDAC and DNMT3 family members among oral cancers. In addition, the differential expression of these epigenetic modifiers may be associated with the expression of specific microRNAs in these cancers, which have not previously been observed to the best of the author's knowledge. In addition, some associations and relationships may exist between the expression of these biomarkers and the rates of growth and proliferation, which may suggest that these expression patterns might represent potentially useful biomarkers to determine tumor aggressiveness and other phenotypic behaviors among oral cancers.

Keywords: oral cancer, DNA methyltransferase, histone deacetylase, microRNA

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3998 The Current Level of Shared Decision-Making in Head-And-Neck Oncology: An Exploratory Study – Preliminary Results

Authors: Anne N. Heirman, Song Duimel, Rob van Son, Lisette van der Molen, Richard Dirven, Gyorgi B. Halmos, Julia van Weert, Michiel W.M. van den Brekel

Abstract:

Objectives: Treatments for head-neck cancer are drastic and often significantly impact the quality of life and appearance of patients. Shared decision-making (SDM) beholds a collaboration between patient and doctor in which the most suitable treatment can be chosen by integrating patient preferences, values, and medical information. SDM has a lot of advantages that would be useful in making difficult treatment choices. The objective of this study was to determine the current level of SDM among patients and head-and-neck surgeons. Methods: Consultations of patients with a non-cutaneous head-and-neck malignancy facing a treatment decision were selected and included. If given informed consent, the consultation was recorded with an audio recorder, and the patient and surgeon filled in a questionnaire immediately after the consultation. The SDM level of the consultation was scored objectively by independent observers who judged audio recordings of the consultation using the OPTION5-scale, ranging from 0% (no SDM) to 100% (optimum SDM), as well as subjectively by patients (using the SDM-Q-9 and Control preference scale) and clinicians (SDM-Q-Doc, modified control preference scale) percentages. Preliminary results: Five head-neck surgeons have each at least seven recorded conversations with different patients. One of them was trained in SDM. The other four had no experience with SDM. Most patients were male (74%), and oropharyngeal carcinoma was the most common diagnosis (41%), followed by oral cancer (33%). Five patients received palliative treatment of which two patients were not treated recording guidelines. At this moment, all recordings are scored by the two independent observers. Analysis of the results will follow soon. Conclusion: The current study will determine to what extent there is a discrepancy between the objective and subjective level of shared decision-making (SDM) during a doctor-patient consultation in Head-and-Neck surgery. The results of the analysis will follow shortly.

Keywords: head-and-neck oncology, patient involvement, physician-patient relations, shared decision making

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3997 Hypoxia Tolerance, Longevity and Cancer-Resistance in the Mole Rat Spalax – a Liver Transcriptomics Approach

Authors: Hanno Schmidt, Assaf Malik, Anne Bicker, Gesa Poetzsch, Aaron Avivi, Imad Shams, Thomas Hankeln

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The blind subterranean mole rat Spalax shows a remarkable tolerance to hypoxia, cancer-resistance and longevity. Unravelling the genomic basis of these adaptations will be important for biomedical applications. RNA-Seq gene expression data were obtained from normoxic and hypoxic Spalax and rat liver tissue. Hypoxic Spalax broadly downregulates genes from major liver function pathways. This energy-saving response is likely a crucial adaptation to low oxygen levels. In contrast, the hypoxiasensitive rat shows massive upregulation of energy metabolism genes. Candidate genes with plausible connections to the mole rat’s phenotype, such as important key genes related to hypoxia-tolerance, DNA damage repair, tumourigenesis and ageing, are substantially higher expressed in Spalax than in rat. Comparative liver transcriptomics highlights the importance of molecular adaptations at the gene regulatory level in Spalax and pinpoints a variety of starting points for subsequent functional studies.

Keywords: cancer, hypoxia, longevity, transcriptomics

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3996 Comparison of the Dose Reached to the Rectum and Bladder in Two Treatment Methods by Tandem and Ovoid and Tandem and Ring in the High Dose Rate Brachytherapy of Cervical Cancer

Authors: Akbar Haghzadeh Saraskanroud, Amir Hossein Yahyavi Zanjani, Niloofar Kargar, Hanieh Ahrabi

Abstract:

Cervical cancer refers to an unusual growth of cells in the cervix. The cervix is the lower part of the uterus, which connects to the vagina. Various risk factors such as human papillomavirus (HPV), having a weakened immune system, smoking or breathing in secondhand smoke, reproductive factors, and obesity play important roles in causing most cervical cancers. When cervical cancer happens, surgery is often the first treatment option to remove it. Other treatments might include chemotherapy and targeted therapy medicines. Radiation therapy with high-energy photon beams also may be used. Sometimes combined treatment, including radiation with low-dose chemotherapy, was applied. Intracavitary brachytherapy is an integral part of radiotherapy for locally advanced gynecologic malignancies such as cervical cancer. In the treatment of cervical cancer, there are different tools for doing brachytherapy. Two combinations of different applicators for this purpose are Tandem and Ovoid and Tandem and Ring. This study evaluated the dose differences between these two methods in the organs at risk of the rectum, sigmoid, and bladder. In this study, the treatment planswere simulated by the Oncentra treatment planning system and Tandem, Ovid, and Rings of different sizes. CT scan images of 23 patients were treated with HDR_BT Elekta Flexitron system were used for this study. Contouring of HR-CTV, rectum and bladder was performed for all patients. Then, the received dose of 0.1 and 0.2cc volumes of organs at risk were obtained and compared for these two methods: T-Ovoid and T-Ring. By doing investigations and dose measurements of points A and B and the volumes specified by ICRU, it seems that when comparing ring and ovoid to tandem and ovoid, the total dose to the rectum was lower by about 11%, and the bladder was 7%. In the case of HR CTV, this comparison showed that this ratio is about 7% better. Figure 1 shows the amount of decrease in rectum dose in the T-Ring method compared to T-Ovoid. Figure 2 indicates the amount of decrease in bladder dose in the T-Ring method compared to T-Ovoid. Finally, figure 3 illustrates the amount of HR-CTV coverage in the T-Ring method compared to the T-Ovoid.

Keywords: cervical cancer, brachytherapy, rectum, tandem and ovoid, tandem and ring.

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3995 Using Lysosomal Immunogenic Cell Death to Target Breast Cancer via Xanthine Oxidase/Micro-Antibody Fusion Protein

Authors: Iulianna Taritsa, Kuldeep Neote, Eric Fossel

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Lysosome-induced immunogenic cell death (LIICD) is a powerful mechanism of targeting cancer cells that kills circulating malignant cells and primes the host’s immune cells against future remission. Current immunotherapies for cancer are limited in preventing recurrence – a gap that can be bridged by training the immune system to recognize cancer neoantigens. Lysosomal leakage can be induced therapeutically to traffic antigens from dying cells to dendritic cells, which can later present those tumorigenic antigens to T cells. Previous research has shown that oxidative agents administered in the tumor microenvironment can initiate LIICD. We generated a fusion protein between an oxidative agent known as xanthine oxidase (XO) and a mini-antibody specific for EGFR/HER2-sensitive breast tumor cells. The anti-EGFR single domain antibody fragment is uniquely sourced from llama, which is functional without the presence of a light chain. These llama micro-antibodies have been shown to be better able to penetrate tissues and have improved physicochemical stability as compared to traditional monoclonal antibodies. We demonstrate that the fusion protein created is stable and can induce early markers of immunogenic cell death in an in vitro human breast cancer cell line (SkBr3). Specifically, we measured overall cell death, as well as surface-expressed calreticulin, extracellular ATP release, and HMGB1 production. These markers are consensus indicators of ICD. Flow cytometry, luminescence assays, and ELISA were used respectively to quantify biomarker levels between treated versus untreated cells. We also included a positive control group of SkBr3 cells dosed with doxorubicin (a known inducer of LIICD) and a negative control dosed with cisplatin (a known inducer of cell death, but not of the immunogenic variety). We looked at each marker at various time points after cancer cells were treated with the XO/antibody fusion protein, doxorubicin, and cisplatin. Upregulated biomarkers after treatment with the fusion protein indicate an immunogenic response. We thus show the potential for this fusion protein to induce an anticancer effect paired with an adaptive immune response against EGFR/HER2+ cells. Our research in human cell lines here provides evidence for the success of the same therapeutic method for patients and serves as the gateway to developing a new treatment approach against breast cancer.

Keywords: apoptosis, breast cancer, immunogenic cell death, lysosome

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