Search results for: cancer caring
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2265

Search results for: cancer caring

1095 Germline Mutations of Mitogen-Activated Protein Kinases Pathway Signaling Pathway Genes in Children

Authors: Nouha Bouayed Abdelmoula, Rim Louati, Nawel Abdellaoui, Balkiss Abdelmoula, Oldez Kaabi, Walid Smaoui, Samir Aloulou

Abstract:

Background and Aims: Cardiofaciocutaneous syndrome (CFC) is an autosomal dominant disorder with the vast majority of cases arising by a new mutation of BRAF, MEK1, MEK2, or rarely, KRAS genes. Here, we report a rare Tunisian case of CFC syndrome for whom we identify SOS1 mutation. Methods: Genomic DNA was obtained from peripheral blood collected in an EDTA tube and extracted from leukocytes using the phenol/chloroform method according to standard protocols. High resolution melting (HRM) analysis for screening of mutations in the entire coding sequence of PTPN11 was conducted first. Then, HRM assays to look for hot spot mutations coding regions of the other genes of the RAS-MAPK pathway (RAt Sarcoma viral oncogene homolog Mitogen-Activated Protein Kinases Pathway): SOS1, SHOC2, KRAS, RAF1, KRAS, NRAS, CBL, BRAF, MEK1, MEK2, HRAS, and RIT1, were applied. Results: Heterozygous SOS1 point mutation clustered in exon 10, which encodes for the PH domain of SOS1, was identified: c.1655 G > A. The patient was a 9-year-old female born from a consanguineous couple. She exhibited pulmonic valvular stenosis as congenital heart disease. She had facial features and other malformations of Noonan syndrome, including macrocephaly, hypertelorism, ptosis, downslanting palpebral fissures, sparse eyebrows, a short and broad nose with upturned tip, low-set ears, high forehead commonly associated with bitemporal narrowing and prominent supraorbital ridges, short and/or webbed neck and short stature. However, the phenotype is also suggestive of CFC syndrome with the presence of more severe ectodermal abnormalities, including curly hair, keloid scars, hyperkeratotic skin, deep plantar creases, and delayed permanent dentition with agenesis of the right maxillary first molar. Moreover, the familial history of the patient revealed recurrent brain malignancies in the paternal family and epileptic disease in the maternal family. Conclusions: This case report of an overlapping RASopathy associated with SOS1 mutation and familial history of brain tumorigenesis is exceptional. The evidence suggests that RASopathies are truly cancer-prone syndromes, but the magnitude of the cancer risk and the types of cancer partially overlap.

Keywords: cardiofaciocutaneous syndrome, CFC, SOS1, brain cancer, germline mutation

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1094 Palliative Care: Optimizing the Quality of Life through Strengthening the Legal Regime of Bangladesh

Authors: Sonia Mannan, M. Jobair Alam

Abstract:

The concept of palliative care in Bangladesh largely remained limited to the sympathetic caring of patients with a life-limiting illness. Quality of Life (QoL) issues are rarely practiced in Bangladesh. Furthermore, palliative medicine, in the perspective of holistic palliative care service, does not have its proper recognition in Bangladesh. Apart from those socio-medical aspects, palliative care patients face legal issues that impact their quality of life, including access to health services and social benefits and dealing with other life-transactions of the patients and their families (such as disposing of property; planning for children). This paper is an attempt to articulate these legal dimensions of the right to palliative care in the context of Bangladesh. The major focus of this paper will be founded on the doctrinal analysis of the constitutional provisions and other relevant legislation on the right to health and their judicial interpretation, which is argued to offer a meaningful space for the right to palliative care. This paper will also investigate the gaps in the said legal framework to better secure such care. In conclusion, a few recommendations are made so that the palliative care practices in Bangladesh are better aligned with international standards, and it can respond more humanely to the patients who need palliative care.

Keywords: Bangladesh, constitution, legal regime, palliative care, quality of life

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1093 Teacher in Character Strengthening for Early Childhood

Authors: Siti Aisyah

Abstract:

This article discusses character education which is a very basic education for early childhood with the aim of instilling moral values to prevent unacceptable behaviours. Children can absorb good character when they are in a supportive environment, for that schools should understand and implement character education in the learning process. In the school environment, good character education and habituation can be developed. All parties in the school should be involved, especially the teachers. This research discusses how teachers apply characters on the values of responsibility, honesty, discipline, love and compassion, caring, courage, independence, hard work, mutual cooperation, courtesy, justice, self-control and tolerance. The respondents of this study were teachers involving 200 children from all over Indonesia. The methodology used was a survey method with the result that more than 80% of teachers have been able to exhibit the expected behaviours. The survey was conducted based on observations, types of tasks and assessed performance. The character values can be optimally taught in the school environment based on the teacher's ability to implement them. Through the character education in schools, children can also instil a positive outlook on life.

Keywords: teachers, character strengthening, early childhood, behavior

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1092 A Study of The Factors Predicting Radiation Exposure to Contacts of Saudi Patients Treated With Low-Dose Radioactive Iodine (I-131)

Authors: Khalid A. Salman, Shereen Wagih, Tariq Munshi, Musaed Almalki, Safwan Zatari, Zahid Khan

Abstract:

Aim: To measure exposure levels to family members and caregivers of Saudi patients treated with low dose I131 therapy, and household radiation exposure rate to predict different factors that can affect radiation exposure. Patients and methods: All adult self dependent patients with hyperthyroidism or cancer thyroid referred for low dose radioactive I131 therapy on outpatient basis are included. Radiation protection procedures are given to the participant and family members in details. TLD’s were dispensed to each participant in sufficient quantity for his/her family members living in the household. TLD’s are collected at fifth days post-dispense from patients who agreed to have a home visit during which the household is inspected and level of radiation contamination of surfaces was measured. Results: Thirty-two patients were enrolled in the current study, with a mean age of 43.1± 17.1 years Out of them 25 patients (78%) are females. I131 therapy was given in twenty patients (63%) for cancer thyroid of and for toxic goiter in the remaining twelve patients (37%), with an overall mean I131 dose of 24.1 ± 7.5mCi that is relatively higher in the former. The overall number of household family members and helpers of patients are 139, out of them77 are females (55.4%) & 62 are males (44.6%) with a mean age of 29.8± 17.6. The mean period of contact with the patient is 7.6 ±5.6hours. The cumulative radiation exposure shows that radiation exposure to all family members is below the exposure constraint (1mSv), with a range of 109 to 503uSv, and a mean value of 220.9±91 uSv. Numerical data shows a little higher exposure rate for family members of those who receive higher dose of I131 (patients with thyroid cancer) and household members who spent longer time with the patient, yet, the difference is statistically insignificant (P>0.05). Besides, no significant correlation was found between the degree of cumulative exposure of the family members to their gender, age, socioeconomic standard, educational level and residential factors. In the 21 home visits all data from bedrooms, reception areas and kitchens are below hazardous limits (0.5uSv/h) apart from bathrooms that give a slightly higher reading of 0.57±0.39 uSv/h in those with cancer thyroid who receive a higher radiation dose. A statistically significant difference was found between radiation exposure rate in bathrooms used by the patient versus those used by family members only, with a mean value of exposure rate of 0.701±0.21 uSv/h and 0.17±0.82 uSv/h respectively, with a p-value of 0.018 (<0.05). Conclusion: Family members of patients treated with low dose I131 on outpatient basis have a good compliance to radiation protection instruction if given properly with a cumulative radiation exposure rate evidently beyond the radiation exposure constraints of 1 mSv. Given I131 dose, hours spent with the patient, age, gender, socioeconomic standard, educational level and residential factors have no significant correlation with the cumulative radiation exposure. The patient bathroom exhibits more radiation exposure rate, needing more strict instructions for patient bathroom use and health hygiene.

Keywords: family members, radiation exposure, radioactive iodine therapy, radiation safety

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1091 Noninvasive Disease Diagnosis through Breath Analysis Using DNA-functionalized SWNT Sensor Array

Authors: W. J. Zhang, Y. Q. Du, M. L. Wang

Abstract:

Noninvasive diagnostics of diseases via breath analysis has attracted considerable scientific and clinical interest for many years and become more and more promising with the rapid advancement in nanotechnology and biotechnology. The volatile organic compounds (VOCs) in exhaled breath, which are mainly blood borne, particularly provide highly valuable information about individuals’ physiological and pathophysiological conditions. Additionally, breath analysis is noninvasive, real-time, painless and agreeable to patients. We have developed a wireless sensor array based on single-stranded DNA (ssDNA)-decorated single-walled carbon nanotubes (SWNT) for the detection of a number of physiological indicators in breath. Eight DNA sequences were used to functionalize SWNT sensors to detect trace amount of methanol, benzene, dimethyl sulfide, hydrogen sulfide, acetone and ethanol, which are indicators of heavy smoking, excessive drinking, and diseases such as lung cancer, breast cancer, cirrhosis and diabetes. Our tests indicated that DNA functionalized SWNT sensors exhibit great selectivity, sensitivity, reproducibility, and repeatability. Furthermore, different molecules can be distinguished through pattern recognition enabled by this sensor array. Thus, the DNA-SWNT sensor array has great potential to be applied in chemical or bimolecular detection for the noninvasive diagnostics of diseases and health monitoring.

Keywords: breath analysis, diagnosis, DNA-SWNT sensor array, noninvasive

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1090 Study on the Work-Life Balance of Selected Working Single Mothers in the Coastal Community of La Huerta, Paranaque

Authors: Idette Sheirina Biyo, Rhodora Lynn C. Lintag

Abstract:

This paper explores how the work-life balance of selected working single mothers situated in a coastal community is affecting their well-being. Working single mothers carry the responsibility of earning for their family while simultaneously exercising their motherhood. This study utilized a purposeful qualitative research through semi-structured interviews among ten working single mothers living in the coastal community of La Huerta, Parañaque in order to identify the following: a) experiences of the working single mothers, b) problems usually encountered, and c) how these problems are affecting their well-being. Dorothy Smith’s Feminist Standpoint theory is used as a theoretical lens in order to explain their work-life balance. Results have shown that despite their dual roles as the main income earners and heads of the households, they are not neglecting to care for their well-being. They consider getting sufficient rest, eating well, and going to church as forms of caring for their well-being. Other factors that affect their work-life balance include living arrangements, work hours, type of work, and income.

Keywords: coastal community, well-being, work-life balance, Working single mother

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1089 Apoptosis Activity of Persea declinata (Bl.) Kosterm Bark Methanolic Crude Extract

Authors: P. Narrima, C. Y. Looi, M. A. Mohd, H. M. Ali

Abstract:

Persea declinata (Bl.) Kosterm is a member of the Lauraceae family, widely distributed in Southeast Asia. It is from the same genus with avocado (Persea americana Mill), which is widely consumed as food and for medicinal purposes. In the present study, we examined the anticancer properties of Persea declinata (Bl.) Kosterm bark methanolic crude extract (PDM). PDM exhibited a potent antiproliferative effect in MCF-7 human breast cancer cells, with an IC50 value of 16.68 µg/mL after 48h of treatment. We observed that PDM caused cell cycle arrest and subsequent apoptosis in MCF-7 cells, as exhibited by increased population at G0/G1 phase, higher lactate dehydrogenase (LDH) release, and DNA fragmentation. Mechanistic studies showed that PDM caused significant elevation in ROS production, leading to perturbation of mitochondrial membrane potential, cell permeability, and activation of caspases-3/7. On the other hand, real-time PCR and Western blot analysis showed that PDM treatment increased the expression of the proapoptotic molecule, Bax, but decreased the expression of prosurvival proteins, Bcl-2 and Bcl-xL, in a dose-dependent manner. These findings imply that PDM could inhibit proliferation in MCF-7 cells via cell cycle arrest and apoptosis induction, indicating its potential as a therapeutic agent worthy of further development.

Keywords: antiproliferative, apoptosis, MCF-7 human breast cancer, Persea declinata

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1088 Projected Impact of Population Aging on Noncommunicable Disease Burden and Costs in the Kingdom of Saudi Arabia, 2020–2030

Authors: David C. Boettiger, Tracy Kuo Lin, Maram Almansour, Mariam M. Hamza, Reem Alsukait, Christopher H. Herbst, Nada Altheyab, Ayman Afghani, Faisal Kattan

Abstract:

Background The number of people aged greater than 65 years per 100 people aged 20–64 years is expected to almost double in The Kingdom of Saudi Arabia (KSA) between 2020 and 2030. We therefore aimed to quantify the growing non-communicable disease (NCD) burden in KSA between 2020 and 2030, and the impact this will have on the national health budget. Methods Ten priority NCDs were selected: ischemic heart disease, stroke, type 2 diabetes, chronic obstructive pulmonary disease, chronic kidney disease, dementia, depression, osteoarthritis, colorectal cancer, and breast cancer. Age- and sex-specific prevalence was projected for each priority NCD between 2020 and 2030. Treatment coverage rates were applied to the projected prevalence estimates to calculate the number of patients incurring treatment costs for each condition. For each priority NCD, the average cost-of-illness was estimated based on published literature. The impact of changes to our base-case model in terms of assumed disease prevalence, treatment coverage, and costs of care, coming into effect from 2023 onwards, were explored. Results The prevalence estimates for colorectal cancer and stroke were estimated to almost double between 2020 and 2030 (97% and 88% increase, respectively). The only priority NCD prevalence projected to increase by less than 60% between 2020 and 2030 was for depression (22% increase). It is estimated that the total cost of managing priority NCDs in KSA will increase from USD 19.8 billion in 2020 to USD 32.4 billion in 2030 (an increase of USD 12.6 billion or 63%). The largest USD value increases were projected for osteoarthritis (USD 4.3 billion), diabetes (USD 2.4 billion), and dementia (USD 1.9 billion). In scenario analyses, our 2030 projection for the total cost of managing priority NCDs varied between USD 29.2 billion - USD 35.7 billion. Conclusions Managing the growing NCD burden in KSA’s aging population will require substantial healthcare spending increases over the coming years.

Keywords: aging, non communicable disease, costs, Saudi Arabia

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1087 Mining the Proteome of Fusobacterium nucleatum for Potential Therapeutics Discovery

Authors: Abdul Musaweer Habib, Habibul Hasan Mazumder, Saiful Islam, Sohel Sikder, Omar Faruk Sikder

Abstract:

The plethora of genome sequence information of bacteria in recent times has ushered in many novel strategies for antibacterial drug discovery and facilitated medical science to take up the challenge of the increasing resistance of pathogenic bacteria to current antibiotics. In this study, we adopted subtractive genomics approach to analyze the whole genome sequence of the Fusobacterium nucleatum, a human oral pathogen having association with colorectal cancer. Our study divulged 1499 proteins of Fusobacterium nucleatum, which has no homolog in human genome. These proteins were subjected to screening further by using the Database of Essential Genes (DEG) that resulted in the identification of 32 vitally important proteins for the bacterium. Subsequent analysis of the identified pivotal proteins, using the KEGG Automated Annotation Server (KAAS) resulted in sorting 3 key enzymes of F. nucleatum that may be good candidates as potential drug targets, since they are unique for the bacterium and absent in humans. In addition, we have demonstrated the 3-D structure of these three proteins. Finally, determination of ligand binding sites of the key proteins as well as screening for functional inhibitors that best fitted with the ligands sites were conducted to discover effective novel therapeutic compounds against Fusobacterium nucleatum.

Keywords: colorectal cancer, drug target, Fusobacterium nucleatum, homology modeling, ligands

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1086 Detection of Cytotoxicity of Green Synthesized Silver, Gold, and Silver/Gold Bimetallic on Baby Hamster Kidney-21 Cells Using MTT Assay

Authors: Naila Sher, Mushtaq Ahmed, Nadia Mushtaq, Rahmat Ali Khan

Abstract:

In cancer therapy, nanoparticles (NPs) shall be applied possibly by inoculation in the veins of humans. This action will connect them with white (WBCs) and red blood cells (RBCs) in the bloodstream before they reach their main targeted cancer cells. However, possible effects of silver, gold, and silver/gold bimetallic NPs (Ag, Au, and Ag/Au BNPs) on baby hamster kidney-21 (BHK-21) cells were studied by MTT assay. Here, Ag, Au, and their Ag/Au BNPs (bimetallic nanoparticles) were synthesized by using Hippeastrum hybridum (HH) extract. These NPs were characterized by UV-visible spectroscopy, FT-IR, XRD, and EDX, and SEM analysis. XRD analysis conferring the crystal structure with an average size of 13.3, 10.72, and 8.34nm of Ag, Au, and Ag/Au BNPs, respectively. SEM showed that Ag, Au, and Ag/Au BNPs had irregular morphologies, with nano measures calculated sizes of 40, 30, and 20 nm respectively. EDX spectrometers confirmed the presence of elemental Ag signal of the AgNPs with 22.75%, Au signal of the AuNPs with 48.08%, Ag signal with 12%, and Au signal with 38.26% of the Ag/Au BNPs. The BHK-21cells were incubated in the existence of doxorubicin, plant extract, Ag, Au, and Ag/Au BNPs. The cytotoxic effects could be observed in a dose-dependent mode; doxorubicin and Ag/Au BNPs were more toxic than plant extract, Ag, and Au NPs. It is demonstrated that NPs interact with BHK-21cells and significantly reduce cell viability in a concentration-dependent manner. However, to reduce the potential threats of NPs further studies are recommended.

Keywords: hippeastrum hybridum, nanoparticle, BHK-21cells

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1085 DEKA-1 a Dose-Finding Phase 1 Trial: Observing Safety and Biomarkers using DK210 (EGFR) for Inoperable Locally Advanced and/or Metastatic EGFR+ Tumors with Progressive Disease Failing Systemic Therapy

Authors: Spira A., Marabelle A., Kientop D., Moser E., Mumm J.

Abstract:

Background: Both interleukin-2 (IL-2) and interleukin-10 (IL-10) have been extensively studied for their stimulatory function on T cells and their potential to obtain sustainable tumor control in RCC, melanoma, lung, and pancreatic cancer as monotherapy, as well as combination with PD-1 blockers, radiation, and chemotherapy. While approved, IL-2 retains significant toxicity, preventing its widespread use. The significant efforts undertaken to uncouple IL-2 toxicity from its anti-tumor function have been unsuccessful, and early phase clinical safety observed with PEGylated IL-10 was not met in a blinded Phase 3 trial. Deka Biosciences has engineered a novel molecule coupling wild-type IL-2 to a high affinity variant of Epstein Barr Viral (EBV) IL-10 via a scaffold (scFv) that binds to epidermal growth factor receptors (EGFR). This patented molecule, termed DK210 (EGFR), is retained at high levels within the tumor microenvironment for days after dosing. In addition to overlapping and non-redundant anti-tumor function, IL-10 reduces IL-2 mediated cytokine release syndrome risks and inhibits IL-2 mediated T regulatory cell proliferation. Methods: DK210 (EGFR) is being evaluated in an open-label, dose-escalation (Phase 1) study with 5 (0.025-0.3 mg/kg) monotherapy dose levels and (expansion cohorts) in combination with PD-1 blockers, or radiation or chemotherapy in patients with advanced solid tumors overexpressing EGFR. Key eligibility criteria include 1) confirmed progressive disease on at least one line of systemic treatment, 2) EGFR overexpression or amplification documented in histology reports, 3) at least a 4 week or 5 half-lives window since last treatment, and 4) excluding subjects with long QT syndrome, multiple myeloma, multiple sclerosis, myasthenia gravis or uncontrolled infectious, psychiatric, neurologic, or cancer disease. Plasma and tissue samples will be investigated for pharmacodynamic and predictive biomarkers and genetic signatures associated with IFN-gamma secretion, aiming to select subjects for treatment in Phase 2. Conclusion: Through successful coupling of wild-type IL-2 with a high affinity IL-10 and targeting directly to the tumor microenvironment, DK210 (EGFR) has the potential to harness IL-2 and IL-10’s known anti-cancer promise while reducing immunogenicity and toxicity risks enabling safe concomitant cytokine treatment with other anti-cancer modalities.

Keywords: cytokine, EGFR over expression, interleukine-2, interleukine-10, clinical trial

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1084 Investigation of Heavy Metals and Nitrate Level in Drinking Water and the Side Effects on Public Health in the Capital City of Iran

Authors: Iman Nazari, Behrouz Shaabani, Ali Ramouz

Abstract:

Regarding to the dramatic rise of cancer prevalence of cancers in Iran and also base on the investigations around environmental factors which causes cancer, The air and water pollution is in high level in Iran’s capital city this issue motivated us to start an investigation on concentration of heavy metals and nitrate in Tehran’s Tap water, additionally we investigated the effects of this contaminations on public health, it is clear that heavy metals and also nitrate are causes cancers directly and indirectly, we divided the city to four districts: (1) North, (2) East, (3) West, (4) South and totally collected over 30 samples from noted districts, we obvious difference in concentrations, after a study we founded the reasons of this difference, the old distribution system, non-standard sewage disposal system, travel up from contaminated rains, releasing industrial wastes waters without any pretreatment, the most important one is the old distribution system, Tehran is an old city hence distribution system is old too we know that the old water pipes were built from alloys which containing several of this harmful heavy metals, releasing of this heavy metals from pipes to the tap water is one of the most Important reasons, as the result we presented the concentrations by districts and the alternatives to decreasing the level of this contaminations.

Keywords: water quality, heavy metals, drinking water, environmental toxinology

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1083 Computer-Aided Classification of Liver Lesions Using Contrasting Features Difference

Authors: Hussein Alahmer, Amr Ahmed

Abstract:

Liver cancer is one of the common diseases that cause the death. Early detection is important to diagnose and reduce the incidence of death. Improvements in medical imaging and image processing techniques have significantly enhanced interpretation of medical images. Computer-Aided Diagnosis (CAD) systems based on these techniques play a vital role in the early detection of liver disease and hence reduce liver cancer death rate.  This paper presents an automated CAD system consists of three stages; firstly, automatic liver segmentation and lesion’s detection. Secondly, extracting features. Finally, classifying liver lesions into benign and malignant by using the novel contrasting feature-difference approach. Several types of intensity, texture features are extracted from both; the lesion area and its surrounding normal liver tissue. The difference between the features of both areas is then used as the new lesion descriptors. Machine learning classifiers are then trained on the new descriptors to automatically classify liver lesions into benign or malignant. The experimental results show promising improvements. Moreover, the proposed approach can overcome the problems of varying ranges of intensity and textures between patients, demographics, and imaging devices and settings.

Keywords: CAD system, difference of feature, fuzzy c means, lesion detection, liver segmentation

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1082 Mediterranean Diet, Duration of Admission and Mortality in Elderly, Hospitalized Patients: A Cross-Sectional Study

Authors: Christos Lampropoulos, Maria Konsta, Ifigenia Apostolou, Vicky Dradaki, Tamta Sirbilatze, Irini Dri, Christina Kordali, Vaggelis Lambas, Kostas Argyros, Georgios Mavras

Abstract:

Objectives: Mediterranean diet has been associated with lower incidence of cardiovascular disease and cancer. The purpose of our study was to examine the hypothesis that Mediterranean diet may protect against mortality and reduce admission duration in elderly, hospitalized patients. Methods: Sample population included 150 patients (78 men, 72 women, mean age 80±8.2). The following data were taken into account in analysis: anthropometric and laboratory data, dietary habits (MedDiet score), patients’ nutritional status [Mini Nutritional Assessment (MNA) score], physical activity (International Physical Activity Questionnaires, IPAQ), smoking status, cause and duration of current admission, medical history (co-morbidities, previous admissions). Primary endpoints were mortality (from admission until 6 months afterwards) and duration of admission, compared to national guidelines for closed consolidated medical expenses. Logistic regression and linear regression analysis were performed in order to identify independent predictors for mortality and admission duration difference respectively. Results: According to MNA, nutrition was normal in 54/150 (36%) of patients, 46/150 (30.7%) of them were at risk of malnutrition and the rest 50/150 (33.3%) were malnourished. After performing multivariate logistic regression analysis we found that the odds of death decreased 30% per each unit increase of MedDiet score (OR=0.7, 95% CI:0.6-0.8, p < 0.0001). Patients with cancer-related admission were 37.7 times more likely to die, compared to those with infection (OR=37.7, 95% CI:4.4-325, p=0.001). According to multivariate linear regression analysis, admission duration was inversely related to Mediterranean diet, since it is decreased 0.18 days on average for each unit increase of MedDiet score (b:-0.18, 95% CI:-0.33 - -0.035, p=0.02). Additionally, the duration of current admission increased on average 0.83 days for each previous hospital admission (b:0.83, 95% CI:0.5-1.16, p<0.0001). The admission duration of patients with cancer was on average 4.5 days higher than the patients who admitted due to infection (b:4.5, 95% CI:0.9-8, p=0.015). Conclusion: Mediterranean diet adequately protects elderly, hospitalized patients against mortality and reduces the duration of hospitalization.

Keywords: Mediterranean diet, malnutrition, nutritional status, prognostic factors for mortality

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1081 The Preventive Effect of Metformin on Paclitaxel-Induced Peripheral Neuropathy

Authors: AliAkbar Hafezi, Jamshid Abedi, Jalal Taherian, Behnam Kadkhodaei, Mahsa Elahi

Abstract:

Background. Peripheral neuropathy is a common side effect of the administration of neurotoxic chemotherapy agents. This adverse effect is a major dose-limiting factor of many commonly used chemotherapy drugs. Currently, there are no Food and Drug Administration (FDA) approved medications for the prevention or treatment of chemotherapy-induced peripheral neuropathy. Therefore, this study was performed to investigate the efficacy and safety of metformin on paclitaxel-induced peripheral neuropathy (PIPN). Methods. In this randomized clinical trial, cancer patients who were candidates for chemotherapy with paclitaxel referred to the radiation oncology departments in Iran from 2022 to 2023 were studied. Patients were randomly divided into two groups; 1- Case group (n = 30) received metformin 500 mg orally twice a day after meals during chemotherapy with paclitaxel, and 2- Control group (30 people) received chemotherapy without metformin or any additional medication. Patients were visited in terms of numbness or other neurological symptoms two weeks before chemotherapy, 1-2 days before and weekly during chemotherapy, and at the end of the study. They were assessed by nerve conduction study (NCS) before intervention and one week after the end of chemotherapy. The primary outcome was the efficacy in reducing PIPN and the secondary outcome was adverse effects. Eventually, the outcomes were compared between the two groups of patients. Results. A total of 60 female cancer patients receiving chemotherapy with paclitaxel were evaluated in two groups. The groups were matched in terms of age, body mass index, fasting blood sugar, smoking, pathologic stage, and creatinine levels. The results showed that 18 patients (60.0 %) in the case group and 23 patients (76.6 %) in the control group had PIPN clinically (P = 0.267), and NCS showed 11 patients (36.6 %) in the case group and 15 patients (50.0 %) in the control group suffered from PIPN which no significant difference was observed between the two groups (P = 0.435). Diarrhea (n = 3; 10.0 %) and nausea (n = 3; 10.0 %) were the most common side effects of metformin in the case group and no serious side effects (lactic acidosis and anemia) were found in these patients. Conclusion. This study indicated that metformin did not significantly prevent PIPN in cancer patients receiving chemotherapy, although the frequency of peripheral neuropathy in the case group was lower than in the control group. The use of metformin in the patients had acceptable safety and no serious side effects were reported.

Keywords: peripheral neuropathy, chemotherapy, paclitaxel, metformin

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1080 Isolation and Identification of Cytotoxic Compounds from Fruticose Lichen Roccella montagnei, and It’s in Silico Docking Study against CDK-10

Authors: Tripti Mishra, Shipra Shukla, Sanjeev Meena, , Ruchi Singh, Mahesh Pal, D. K. Upreti, Dipak Datta

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Roccella montagnei belongs to lichen family Roccelleceae growing luxuriantly along the coastal regions of India. As Roccella has been shown to be bioactive, we prepared methanolic extract and assessed its anticancer potential. The methanolic extract showed significant in vitro cytotoxic activity against four human cancer cell lines such as Colon (DLD-1, SW-620), Breast (MCF-7), Head and Neck (FaDu). This prompted us to isolate bioactive compounds through column chromatography. Two compounds Roccellic acid and Everninic acid have been isolated, out of which Everninic acid is reported for the first time. Both the compounds have been tested for in vitro cytotoxic activity in which Roccellic acid showed strong anticancer activity as compared to the Everninic acid. CDK-10 (Cyclin-dependent kinase) contributes to proliferation of cancer cells, and aberrant activity of these kinases has been reported in a wide variety of human cancers. These kinases, therefore, constitute biomarkers of proliferation and attractive pharmacological targets for the development of anticancer therapeutics. Therefore both the isolated compounds were tested for in silico molecular docking study against CDK-10 isomer enzyme to support the cytotoxic activity.

Keywords: cytotoxic activity, everninic acid, roccellic acid, R. montagnei

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1079 Breast Cancer Sensing and Imaging Utilized Printed Ultra Wide Band Spherical Sensor Array

Authors: Elyas Palantei, Dewiani, Farid Armin, Ardiansyah

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High precision of printed microwave sensor utilized for sensing and monitoring the potential breast cancer existed in women breast tissue was optimally computed. The single element of UWB printed sensor that successfully modeled through several numerical optimizations was multiple fabricated and incorporated with woman bra to form the spherical sensors array. One sample of UWB microwave sensor obtained through the numerical computation and optimization was chosen to be fabricated. In overall, the spherical sensors array consists of twelve stair patch structures, and each element was individually measured to characterize its electrical properties, especially the return loss parameter. The comparison of S11 profiles of all UWB sensor elements is discussed. The constructed UWB sensor is well verified using HFSS programming, CST programming, and experimental measurement. Numerically, both HFSS and CST confirmed the potential operation bandwidth of UWB sensor is more or less 4.5 GHz. However, the measured bandwidth provided is about 1.2 GHz due to the technical difficulties existed during the manufacturing step. The configuration of UWB microwave sensing and monitoring system implemented consists of 12 element UWB printed sensors, vector network analyzer (VNA) to perform as the transceiver and signal processing part, the PC Desktop/Laptop acting as the image processing and displaying unit. In practice, all the reflected power collected from whole surface of artificial breast model are grouped into several numbers of pixel color classes positioned on the corresponding row and column (pixel number). The total number of power pixels applied in 2D-imaging process was specified to 100 pixels (or the power distribution pixels dimension 10x10). This was determined by considering the total area of breast phantom of average Asian women breast size and synchronizing with the single UWB sensor physical dimension. The interesting microwave imaging results were plotted and together with some technical problems arisen on developing the breast sensing and monitoring system are examined in the paper.

Keywords: UWB sensor, UWB microwave imaging, spherical array, breast cancer monitoring, 2D-medical imaging

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1078 Microencapsulation of Probiotic and Evaluation for Viability, Antimicrobial Property and Cytotoxic Activities of its Postbiotic Metabolites on MCF-7 Breast Cancer Cell Line

Authors: Nkechi V. Enwuru, Bullum Nkeki, Elizabeth A. Adekoya, Olumide A. Adebesin, Rebecca F. Peters, Victoria A. Aikhomu, Mendie E. U.

Abstract:

Background: Probiotics are live microbial feed supplement beneficial for host. Probiotics and their postbiotic products have been used to prevent or treat various health conditions. However, the products cell viability is often low due to harsh conditions subjected during processing, handling, storage, and gastrointestinal transit. These strongly influence probiotics’ benefits; thus, viability is essential for probiotics to produce health benefits for the host. Microencapsulation is a promising technique with considerable effects on probiotic survival. The study is aimed to formulate a microencapsulated probiotic and evaluate its viability, antimicrobial efficacy, and cytotoxic activity of its postbiotic on the MCF-7 breast cancer cell line. Method: Human and animal raw milk were sampled for lactic acid bacteria. The isolated bacteria were identified using conventional and VITEK 2 systems. The identified lactic acid bacterium was encapsulated using spray-dried and extrusion methods. The free, encapsulated, and chitosan-coated encapsulated probiotics were tested for viability in simulated-gastric intestinal (SGI) fluid and different storage conditions at refrigerated (4oC) and room (25oC) temperatures. The disintegration time and weight uniformity of the spray-dried hard gelatin capsules were tested. The antimicrobial property of free and encapsulated probiotics was tested against enteric pathogenic isolates from antiretroviral therapy (ART) treated HIV-positive patients. The postbiotic of the free cells was extracted, and its cytotoxic effect on the MCF-7 breast cancer cell line was tested through an MTT assay. Result: The Lactobacillus plantarum was isolated from animal raw milk. Zero-size hard gelatin L. plantarum capsules with granules within a size range of 0.71–1.00 mm diameter was formulated. The disintegration time ranges from 2.14±0.045 to 2.91±0.293 minutes, while the average weight is 502.1mg. Simulated gastric solution significantly affected viability of both free and microcapsules. However, the encapsulated cells were more protected and viable due to impermeability in the microcapsules. Furthermore, the viability of free cells stored at 4oC and 25oC were less than 4 log CFU/g and 6 log CFU/g respectively after 12 weeks. However, the microcapsules stored at 4oC achieved the highest viability among the free and microcapsules stored at 25oC and the free cells stored at 4oC. Encapsulated cells were released in the simulated gastric fluid, viable and effective against the enteric pathogens tested. However, chitosan-coated calcium alginate encapsulated probiotics significantly inhibited Shigella flexneri, Candida albicans, and Escherichia coli. The Postbiotic Metabolites (PM) of L. plantarum produced a cytotoxic effect on the MCF-7 breast cancer cell line. The postbiotic showed significant cytotoxic activity similar to 5FU, a standard antineoplastic agent. The inhibition concentration of 50% growth (IC50) of postbiotic metabolite K3 is low and consistent with the IC50 of the positive control (Cisplatin). Conclusions: Lactobacillus plantarum postbiotic exhibited a cytotoxic effect on the MCF-7 breast cancer cell line and could be used as combined adjuvant therapy in breast cancer management. The microencapsulation technique protects the probiotics, improving their viability and delivery to the gastrointestinal tract. Chitosan enhances antibacterial efficacy; thus, chitosan-coated microencapsulated L. plantarum probiotics could be more effective and used as a combined therapy in HIV management of opportunistic enteric infection.

Keywords: probiotics, encapsulation, gastrointestinal conditions, antimicrobial effect, postbiotic, cytotoxicity effect

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1077 Elderly Home Care the Need of an Hour In India

Authors: Varsha Reddy Jayar

Abstract:

Background: Our elderly family members deserve our best care. It's our responsibility to ensure they're healthy and safe. The population of India is increasing rapidly. People are literally being born in the streets, and there is a high growth on taxes and healthcare costs. Indian families are challenged with taking care of everyone. When you have elderly parents and a demanding job, it can be difficult to take care of them. You might not have enough time to care for them when you're already working or dealing with emotional difficulties. Living alone in old age can cause older individuals to face many health risks. Many seniors find living and caring for themselves challenging when they live by themselves. This study explored the factors that affect whether or not elderly people choose to live in old age homes. Methods: This study was carried out on 123 elderly people living in different old age homes in Karnataka, India. The reason for their residence at the home was explored using an interview. Results: It was found that the most common reason for living in an old age home is due to abuse from children and grandchildren; the majority reported were Daughter in law issues in the family specific to the adjustment and understanding amongst them. Conclusion: More and more elderly people in India are choosing to stay in old age homes as they get older. The government and voluntary agencies must have some sort of arrangements for institutional support.

Keywords: old age home, elderly, Aging, challenges of aging

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1076 Chemical Composition of Essential Oil and in vitro Antibacterial and Anticancer Activity of the Hydroalcolic Extract from Coronilla varia

Authors: A. A. Dehpour, B. Eslami, S. Rezaie, S. F. Hashemian, F. Shafie, M. Kiaie

Abstract:

The aims of study were investigation on chemical composition essential oil and the effect of extract of Coronilla varia on antimicrobial and cytotoxicity activity. The essential oils of Coronilla varia is obtained by hydrodistillation and analyzed by (GC/MS) for determining their chemical composition and identification of their components. Antibacterial activity of plant extract was determined by disc diffusion method. The effect of hydroalcolic extracts from Cornilla varia investigated on MCF7 cancer cell line by MTT assay. The major components were Caryophyllene Oxide (60.19%), Alphacadinol (4.13%) and Homoadantaneca Robexylic Acid (3.31%). The extracts from Coronilla varia had interesting activity against Proteus mirabilis in the concentration of 700 µg/disc and did not show any activity against Staphylococus aureus, Bacillus subtillis, Klebsiella pneumonia and Entrobacter cloacae. The positive control, Ampicillin, Chloramphenicol and Cenphalothin had shown zone of inhibition resistant all bacteria. Corohilla varia ethanol extract could inhibit the proliferation of MCF7 cell line in RPMI 1640 medium. IC50 5(mg/ml) was the optimum concentration of extract from Coronilla varia inhibition of cell line growth. The MCF7 cancer cell line and Proteus mirabilis were more sensitive to Coronilla varia ethanol extract.

Keywords: Coronilla varia, essential oil, antibacterial, anticancer, hela cell line

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1075 A Case-Control Study on Dietary Heme/Nonheme Iron and Colorectal Cancer Risk

Authors: Alvaro L. Ronco

Abstract:

Background and purpose: Although our country is a developing one, it has a typical Western meat-rich dietary style. Based on estimates of heme and nonheme iron contents in representative foods, we carried out the present epidemiologic study, with the aim of accurately analyzing dietary iron and its role on CRC risk. Subjects/methods: Patients (611 CRC incident cases and 2394 controls, all belonging to public hospitals of our capital city) were interviewed through a questionnaire including socio-demographic, reproductive and lifestyle variables, and a food frequency questionnaire of 64 items, which asked about food intake 5 years before the interview. The sample included 1937 men and 1068 women. Controls were matched by sex and age (± 5 years) to cases. Food-derived nutrients were calculated from available databases. Total dietary iron was calculated and classified by heme or nonheme source, following data of specific Dutch and Canadian studies, and additionally adjusted by energy. Odds Ratios (OR) and 95% confidence intervals were calculated through unconditional logistic regression, adjusting for relevant potential confounders (education, body mass index, family history of cancer, energy, infusions, and others). A heme/nonheme (H/NH) ratio was created and the interest variables were categorized into tertiles, for analysis purposes. Results: The following risk estimations correspond to the highest tertiles. Total iron intake showed no association with CRC risk neither among men (OR=0.83, ptrend =.18) nor among women (OR=1.48, ptrend =.09). Heme iron was positively associated among men (OR=1.88, ptrend < .001) and for the overall sample (OR=1.44, ptrend =.002), however, it was not associated among women (OR=0.91, ptrend =.83). Nonheme iron showed an inverse association among men (OR=0.53, ptrend < .001) and the overall sample (OR=0.78, ptrend =.04), but was not associated among women (OR=1.46, ptrend =.14). Regarding H/NH ratio, risks increased only among men (OR=2.12, ptrend < .001) but lacked of association among women (OR=0.81, ptrend =.29). Conclusions. We have observed different types of associations between CRC risk and high dietary heme, nonheme and H/NH iron ratio. Therefore, the source of the available iron might be of importance as a link to colorectal carcinogenesis, perhaps pointing to reconsider the animal/plant proportions of this vital mineral within diet. Nevertheless, the different associations observed for each sex, demand further studies in order to clarify these points.

Keywords: chelation, colorectal cancer, heme, iron, nonheme

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1074 Anti-Inflammatory Effect of Omega-3 Fish-Oil Supplements: Eicosapentaenoic Acid and Docosahexaenoic Acid in Early-Stage Tumors

Authors: Corina Muscurel, Irina Stoian, Laura Gaman, Valeriu Atanasiu

Abstract:

Chronic inflammation predisposes cells to neoplastic transformation and is associated with angiogenesis. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) give rise to anti-inflammatory metabolites and decrease some inflammatory cytokines. The aim of the study was to analyze the effect of n-3 PUFAs intake on patients with tumors in early-stage (without regional or distant metastasis). There were two groups of patients: one group with colon tumors and one group with lung tumors. All patients took for 60 days daily supplements from fish-oil containing 600 mg eicosapentaenoic acid and 400 mg docosahexaenoic acid. The plasma markers were evaluated before and after PUFAs intake: ceruloplasmin (using p-phenylenediamine oxidase method), plasma total thiol groups (using dithiobis-nitrobenzoic acid method) and CEA (carcinoembryonic antigen using electrochemiluminescent immunoassay). The results reflect ceruloplasmin decrease (p < 0.05), plasma total thiol groups increase (not statistically significant) and CEA decrease (p < 0.05) after n-3 PUFAs intake. Conclusions: n-3 PUFAs intake is favorable in premalignant lesions or in early tumor stage and dietary fish-oil has anti-inflammatory effects and can contribute to reduce cancer progression.

Keywords: cancer, fish-oil, inflammation, n-3 polyunsaturated fatty acids

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1073 Development of Sustainable Composite Fabric from Orange Peel for Ladies’ Undergarments: A Different Approach Towards Eco-Friendly Textile Design

Authors: Abdul Hafeez, Samiya Shehzadi

Abstract:

This research paper presents a different approach towards eco-friendly textile design by developing a sustainable composite fabric from orange peel for ladies' undergarments. The research focuses on utilizing orange peel to develop a unique orange leather/composite (fabric) through a process involving heating, extracting, and subsequent sun-drying to obtain the composite. The sustainable composite fabric shows properties that are favorable to the development of environmentally friendly undergarments, which not only offer UV protection but also possess healing properties for the skin. Through comprehensive testing and analysis, it has been determined that the orange peel composite fabric has zero harmful effects on the skin, making it a safe and desirable material for intimate wear. Furthermore, the research suggests that the orange peel composite fabric has the potential to reduce the rate of cancer cell growth. While the exact mechanisms and factors contributing to this effect require further investigation, the initial findings indicate promising aspects of the fabric in terms of potential cancer-preventive properties. Research contribution to the field of sustainable textile design by introducing a usual and eco-friendly approach utilizing orange peel waste. This work opens up avenues for further exploration and development of innovative materials that are both sustainable and beneficial for human health.

Keywords: sustainability, composite textiles, extracting, undergarments, eco-friendly, orange peels

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1072 Targeting Glucocorticoid Receptor Eliminate Dormant Chemoresistant Cancer Stem Cells in Glioblastoma

Authors: Aoxue Yang, Weili Tian, Haikun Liu

Abstract:

Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Glucocorticoids (GCs) are used to treat GBM-associated edema. However, glucocorticoids participate in the physiological response to psychosocial stress, linked to poor cancer prognosis. This raises concern that glucocorticoids affect the tumor and BTSCs. Identifying markers specifically expressed by brain tumor stem cells (BTSCs) may enable specific therapies that spare their regular tissue-resident counterparts. By ribosome profiling analysis, we have identified that glycerol-3-phosphate dehydrogenase 1 (GPD1) is expressed by dormant BTSCs but not by NSCs. Through different stress-induced experiments in vitro, we found that only dexamethasone (DEXA) can significantly increase the expression of GPD1 in NSCs. Adversely, mifepristone (MIFE) which is classified as glucocorticoid receptors antagonists, could decrease GPD1 protein level and weaken the proliferation and stemness in BTSCs. Furthermore, DEXA can induce GPD1 expression in tumor-bearing mice brains and shorten animal survival, whereas MIFE has a distinct adverse effect that prolonged mice lifespan. Knocking out GR in NSC can block the upregulation of GPD1 inducing by DEXA, and we find the specific sequences on GPD1 promotor combined with GR, thus improving the efficiency of GPD1 transcription from CHIP-Seq. Moreover, GR and GPD1 are highly co-stained on GBM sections obtained from patients and mice. All these findings confirmed that GR could regulate GPD1 and loss of GPD1 Impairs Multiple Pathways Important for BTSCs Maintenance GPD1 is also a critical enzyme regulating glycolysis and lipid synthesis. We observed that DEXA and MIFE could change the metabolic profiles of BTSCs by regulating GPD1 to shift the transition of cell dormancy. Our transcriptome and lipidomics analysis demonstrated that cell cycle signaling and phosphoglycerides synthesis pathways contributed a lot to the inhibition of GPD1 caused by MIFE. In conclusion, our findings raise concern that treatment of GBM with GCs may compromise the efficacy of chemotherapy and contribute to BTSC dormancy. Inhibition of GR can dramatically reduce GPD1 and extend the survival duration of GBM-bearing mice. The molecular link between GPD1 and GR may give us an attractive therapeutic target for glioblastoma.

Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides

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1071 Deep Learning Approach for Colorectal Cancer’s Automatic Tumor Grading on Whole Slide Images

Authors: Shenlun Chen, Leonard Wee

Abstract:

Tumor grading is an essential reference for colorectal cancer (CRC) staging and survival prognostication. The widely used World Health Organization (WHO) grading system defines histological grade of CRC adenocarcinoma based on the density of glandular formation on whole slide images (WSI). Tumors are classified as well-, moderately-, poorly- or un-differentiated depending on the percentage of the tumor that is gland forming; >95%, 50-95%, 5-50% and <5%, respectively. However, manually grading WSIs is a time-consuming process and can cause observer error due to subjective judgment and unnoticed regions. Furthermore, pathologists’ grading is usually coarse while a finer and continuous differentiation grade may help to stratifying CRC patients better. In this study, a deep learning based automatic differentiation grading algorithm was developed and evaluated by survival analysis. Firstly, a gland segmentation model was developed for segmenting gland structures. Gland regions of WSIs were delineated and used for differentiation annotating. Tumor regions were annotated by experienced pathologists into high-, medium-, low-differentiation and normal tissue, which correspond to tumor with clear-, unclear-, no-gland structure and non-tumor, respectively. Then a differentiation prediction model was developed on these human annotations. Finally, all enrolled WSIs were processed by gland segmentation model and differentiation prediction model. The differentiation grade can be calculated by deep learning models’ prediction of tumor regions and tumor differentiation status according to WHO’s defines. If multiple WSIs were possessed by a patient, the highest differentiation grade was chosen. Additionally, the differentiation grade was normalized into scale between 0 to 1. The Cancer Genome Atlas, project COAD (TCGA-COAD) project was enrolled into this study. For the gland segmentation model, receiver operating characteristic (ROC) reached 0.981 and accuracy reached 0.932 in validation set. For the differentiation prediction model, ROC reached 0.983, 0.963, 0.963, 0.981 and accuracy reached 0.880, 0.923, 0.668, 0.881 for groups of low-, medium-, high-differentiation and normal tissue in validation set. Four hundred and one patients were selected after removing WSIs without gland regions and patients without follow up data. The concordance index reached to 0.609. Optimized cut off point of 51% was found by “Maxstat” method which was almost the same as WHO system’s cut off point of 50%. Both WHO system’s cut off point and optimized cut off point performed impressively in Kaplan-Meier curves and both p value of logrank test were below 0.005. In this study, gland structure of WSIs and differentiation status of tumor regions were proven to be predictable through deep leaning method. A finer and continuous differentiation grade can also be automatically calculated through above models. The differentiation grade was proven to stratify CAC patients well in survival analysis, whose optimized cut off point was almost the same as WHO tumor grading system. The tool of automatically calculating differentiation grade may show potential in field of therapy decision making and personalized treatment.

Keywords: colorectal cancer, differentiation, survival analysis, tumor grading

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1070 Elucidation of Dynamics of Murine Double Minute 2 Shed Light on the Anti-cancer Drug Development

Authors: Nigar Kantarci Carsibasi

Abstract:

Coarse-grained elastic network models, namely Gaussian network model (GNM) and Anisotropic network model (ANM), are utilized in order to investigate the fluctuation dynamics of Murine Double Minute 2 (MDM2), which is the native inhibitor of p53. Conformational dynamics of MDM2 are elucidated in unbound, p53 bound, and non-peptide small molecule inhibitor bound forms. With this, it is aimed to gain insights about the alterations brought to global dynamics of MDM2 by native peptide inhibitor p53, and two small molecule inhibitors (HDM201 and NVP-CGM097) that are undergoing clinical stages in cancer studies. MDM2 undergoes significant conformational changes upon inhibitor binding, carrying pieces of evidence of induced-fit mechanism. Small molecule inhibitors examined in this work exhibit similar fluctuation dynamics and characteristic mode shapes with p53 when complexed with MDM2, which would shed light on the design of novel small molecule inhibitors for cancer therapy. The results showed that residues Phe 19, Trp 23, Leu 26 reside in the minima of slowest modes of p53, pointing to the accepted three-finger binding model. Pro 27 displays the most significant hinge present in p53 and comes out to be another functionally important residue. Three distinct regions are identified in MDM2, for which significant conformational changes are observed upon binding. Regions I (residues 50-77) and III (residues 90-105) correspond to the binding interface of MDM2, including (α2, L2, and α4), which are stabilized during complex formation. Region II (residues 77-90) exhibits a large amplitude motion, being highly flexible, both in the absence and presence of p53 or other inhibitors. MDM2 exhibits a scattered profile in the fastest modes of motion, while binding of p53 and inhibitors puts restraints on MDM2 domains, clearly distinguishing the kinetically hot regions. Mode shape analysis revealed that the α4 domain controls the size of the cleft by keeping the cleft narrow in unbound MDM2; and open in the bound states for proper penetration and binding of p53 and inhibitors, which points to the induced-fit mechanism of p53 binding. P53 interacts with α2 and α4 in a synchronized manner. Collective modes are shifted upon inhibitor binding, i.e., second mode characteristic motion in MDM2-p53 complex is observed in the first mode of apo MDM2; however, apo and bound MDM2 exhibits similar features in the softest modes pointing to pre-existing modes facilitating the ligand binding. Although much higher amplitude motions are attained in the presence of non-peptide small molecule inhibitor molecules as compared to p53, they demonstrate close similarity. Hence, NVP-CGM097 and HDM201 succeed in mimicking the p53 behavior well. Elucidating how drug candidates alter the MDM2 global and conformational dynamics would shed light on the rational design of novel anticancer drugs.

Keywords: cancer, drug design, elastic network model, MDM2

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1069 Quantification and Preference of Facial Asymmetry of the Sub-Saharan Africans' 3D Facial Models

Authors: Anas Ibrahim Yahaya, Christophe Soligo

Abstract:

A substantial body of literature has reported on facial symmetry and asymmetry and their role in human mate choice. However, major gaps persist, with nearly all data originating from the WEIRD (Western, Educated, Industrialised, Rich and Developed) populations, and results remaining largely equivocal when compared across studies. This study is aimed at quantifying facial asymmetry from the 3D faces of the Hausa of northern Nigeria and also aimed at determining their (Hausa) perceptions and judgements of standardised facial images with different levels of asymmetry using questionnaires. Data were analysed using R-studio software and results indicated that individuals with lower levels of facial asymmetry (near facial symmetry) were perceived as more attractive, more suitable as marriage partners and more caring, whereas individuals with higher levels of facial asymmetry were perceived as more aggressive. The study conclusively asserts that all faces are asymmetric including the most beautiful ones, and the preference of less asymmetric faces was not just dependent on single facial trait, but rather on multiple facial traits; thus the study supports that physical attractiveness is not just an arbitrary social construct, but at least in part a cue to general health and possibly related to environmental context.

Keywords: face, asymmetry, symmetry, Hausa, preference

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1068 Nurses' and Patients’ Perception about Care: A Comparative Study

Authors: Evangelia Kotrotsiou, Mairy Gouva, Theodosios Paralikas, Maria Fiaka, Styliani Kotrotsiou, Maria Malliarou

Abstract:

The purpose of this research is to investigate the way nurses perceive the care provided in comparison to the way patients perceive it, taking into account existing literature. As far as the sample of research is concerned, it has come from the population of nurses working in the General Hospital of Thessaloniki, St. Paul and the patients of its surgical clinic. In the present study, the sample consists of 100 nurses and 88 patients. The questionnaire used was the Caring Nurse-Patient Interactions Scale: 23-Item Version, created by Cossette et al. (2006). In the case of both patients and nurses, a high score was observed in relational care in the case of the frequency of nursing care in daily practice, as well as the satisfaction of providing nursing care. Overall, patients rated higher clinical care in the case of the frequency of nursing care in daily practice, as well as the satisfaction of the clinical care they were given. On the other hand, nurses rated higher comfort care in the case of the frequency of nursing care in everyday practice, as well as relational care in the area of the importance of nursing care in everyday practice.

Keywords: nursing care, patient needs, patient satisfaction, care giving

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1067 Timing and Probability of Presurgical Teledermatology: Survival Analysis

Authors: Felipa de Mello-Sampayo

Abstract:

The aim of this study is to undertake, from patient’s perspective, the timing and probability of using teledermatology, comparing it with a conventional referral system. The dynamic stochastic model’s main value-added consists of the concrete application to patients waiting for dermatology surgical intervention. Patients with low health level uncertainty must use teledermatology treatment as soon as possible, which is precisely when the teledermatology is least valuable. The results of the model were then tested empirically with the teledermatology network covering the area served by the Hospital Garcia da Horta, Portugal, links the primary care centers of 24 health districts with the hospital’s dermatology department via the corporate intranet of the Portuguese healthcare system. Health level volatility can be understood as the hazard of developing skin cancer and the trend of health level as the bias of developing skin lesions. The results of the survival analysis suggest that the theoretical model can explain the use of teledermatology. It depends negatively on the volatility of patients' health, and positively on the trend of health, i.e., the lower the risk of developing skin cancer and the younger the patients, the more presurgical teledermatology one expects to occur. Presurgical teledermatology also depends positively on out-of-pocket expenses and negatively on the opportunity costs of teledermatology, i.e., the lower the benefit missed by using teledermatology, the more presurgical teledermatology one expects to occur.

Keywords: teledermatology, wait time, uncertainty, opportunity cost, survival analysis

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1066 Multicellular Cancer Spheroids as an in Vitro Model for Localized Hyperthermia Study

Authors: Kamila Dus-Szachniewicz, Artur Bednarkiewicz, Katarzyna Gdesz-Birula, Slawomir Drobczynski

Abstract:

In modern oncology hyperthermia (HT) is defined as a controlled tumor heating. HT treatment temperatures range between 40–48 °C and can selectively damage heat-sensitive cancer cells or limit their further growth, usually with minimal injury to healthy tissues. Despite many advantages, conventional whole-body and regional hyperthermia have clinically relevant side effects, including cardiac and vascular disorders. Additionally, the lack of accessibility of deep-seated tumor sites and impaired targeting micrometastases renders HT less effective. It is believed that above disadvantages can significantly overcome by the application of biofunctionalized microparticles, which can specifically target tumor sites and become activated by an external stimulus to provide a sufficient cellular response. In our research, the unique optical tweezers system have enabled capturing the silica microparticles, primary cells and tumor spheroids in highly controllable and reproducible environment to study the impact of localized heat stimulation on normal and pathological cell and within multicellular tumor spheroid. High throughput spheroid model was introduced to better mimic the response to HT treatment on tumors in vivo. Additionally, application of local heating of tumor spheroids was performed in strictly controlled conditions resembling tumor microenvironment (temperature, pH, hypoxia, etc.), in response to localized and nonhomogeneous hyperthermia in the extracellular matrix, which promotes tumor progression and metastatic spread. The lack of precise control over these well- defined parameters in basic research leads to discrepancies in the response of tumor cells to the new treatment strategy in preclinical animal testing. The developed approach enables also sorting out subclasses of cells, which exhibit partial or total resistance to therapy, in order to understand fundamental aspects of the resistance shown by given tumor cells in response to given therapy mode and conditions. This work was funded by the National Science Centre (NCN, Poland) under grant no. UMO-2017/27/B/ST7/01255.

Keywords: cancer spheroids, hyperthermia, microparticles, optical tweezers

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