Search results for: breast carcinoma

Authors: Parisa Mansour

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Introduction: Early diagnosis of coronavirus disease (COVID-19) is extremely important to isolate and treat patients in time, thus preventing the spread of the disease, improving prognosis and reducing mortality. High-resolution computed tomography (HRCT) chest imaging and artificial intelligence (AI)-based analysis of HRCT chest images can play a central role in the treatment of patients with COVID-19. Objective: To investigate different chest HRCT findings in different stages of COVID-19 pneumonia and to evaluate the potential role of artificial intelligence in the quantitative assessment of lung parenchymal involvement in COVID-19 pneumonia. Materials and Methods: This retrospective observational study was conducted between May 1, 2020 and August 13, 2020. The study included 2169 patients with COVID-19 who underwent chest HRCT. HRCT images showed the presence and distribution of lesions such as: ground glass opacity (GGO), compaction, and any special patterns such as septal thickening, inverted halo, mark, etc. HRCT findings of the breast at different stages of the disease (early: andlt) 5 days, intermediate: 6-10 days and late stage: >10 days). A CT severity score (CTSS) was calculated based on the extent of lung involvement on HRCT, which was then correlated with clinical disease severity. Use of artificial intelligence; Analysis of CT pneumonia and quot; An algorithm was used to quantify the extent of pulmonary involvement by calculating the percentage of pulmonary opacity (PO) and gross opacity (PHO). Depending on the type of variables, statistically significant tests such as chi-square, analysis of variance (ANOVA) and post hoc tests were applied when appropriate. Results: Radiological findings were observed in HRCT chest in 1438 patients. A typical pattern of COVID-19 pneumonia, i.e., bilateral peripheral GGO with or without consolidation, was observed in 846 patients. About 294 asymptomatic patients were radiologically positive. Chest HRCT in the early stages of the disease mostly showed GGO. The late stage was indicated by such features as retinal enlargement, thickening and the presence of fibrous bands. Approximately 91.3% of cases with a CTSS = 7 were asymptomatic or clinically mild, while 81.2% of cases with a score = 15 were clinically severe. Mean PO and PHO (30.1 ± 28.0 and 8.4 ± 10.4, respectively) were significantly higher in the clinically severe categories. Conclusion: Because COVID-19 pneumonia progresses rapidly, radiologists and physicians should become familiar with typical TC chest findings to treat patients early, ultimately improving prognosis and reducing mortality. Artificial intelligence can be a valuable tool in treating patients with COVID-19.

Keywords: chest, HRCT, covid-19, artificial intelligence, chest HRCT

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Authors: Judith Partouche-Sebban, Saeedeh Rezaee Vessal

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Because of the rising number of new cases of cancer, especially among women, it is more than essential to better understand how women experience cancer in order to bring them adapted to support and care and enhance their well-being and patient experience. Cancer stands for a traumatic experience in which the diagnosis, its medical treatments, and the related side effects lead to deep physical and psychological changes that may arouse considerable stress and anxiety. In order to reduce these negative emotions, women tend to use various defense mechanisms, among which denial has been defined as the most frequent mechanism used by breast cancer patients. This study aims to better understand the consequences of the experience of cancer and their link with the adoption of a denial strategy. The empirical research was done among female cancer survivors in France. Since the topic of this study is relatively unexplored, a qualitative methodology and open-ended interviews were employed. In total, 25 semi-directive interviews were conducted with a female with different cancers, different stages of treatment, and different ages. A systematic inductive method was performed to analyze data. The content analysis enabled to highlight three different denial-related behaviors among women with cancer, which serve a self-protective function. First, women who expressed high levels of anxiety confessed they tended to completely deny the existence of their cancer immediately after the diagnosis of their illness. These women mainly exhibit many fears and a deep distrust toward the medical context and professionals. This coping mechanism is defined by the patient as being unconscious. Second, other women deliberately decided to deny partial information about their cancer, whether this information is related to the stages of the illness, the emotional consequences, or the behavioral consequences of the illness. These women use this strategy as a way to avoid the reality of the illness and its impact on the different aspects of their life as if cancer does not exist. Third, some women tend to reinterpret and give meaning to their cancer as a way to reduce its impact on their life. To this end, they may use magical thinking or positive reframing, or reinterpretation. Because denial may lead to delays in medical treatments, this topic deserves a deep investigation, especially in the context of oncology. As denial is defined as a specific defense mechanism, this study contributes to the existing literature in service marketing which focuses on emotions and emotional regulation in healthcare services which is a crucial issue. Moreover, this study has several managerial implications for healthcare professionals who interact with patients in order to implement better care and support for the patients.

Keywords: cancer, coping mechanisms, denial, healthcare services

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Authors: Luciano Tarantino

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Gas gangrene is a rare, severe infection with a very high mortality rate caused by Clostridium species. The infection causes a non-suppurative localized producing gas lesion from which harmful toxins that impair the inflammatory response cause vessel damage and multiple organ failure. Gas gangrene of the liver is very rare and develops suddenly, often as a complication of abdominal surgery and liver transplantation. The present paper deals with a case of gas gangrene of the liver that occurred after percutaneous MW ablation of hepatocellular carcinoma, resulting in progressive liver necrosis and multi-organ failure in spite of specific antibiotics administration. The patient was successfully treated with percutaneous Radiofrequency ablation. Case report: Female, 76 years old, Child A class cirrhosis, treated with synchronous insertion of 3 MW antennae for large HCC (5.5 cm) in the VIII segment. 24 hours after treatment, the patient was asymptomatic and left the hospital . 2 days later, she complained of fever, weakness, abdominal swelling, and pain. Abdominal US detected a 2.3 cm in size gas-containing area, eccentric within the large (7 cm) ablated area. The patient was promptly hospitalized with the diagnosis of anaerobic liver abscess and started antibiotic therapy with Imipenem/cilastatine+metronidazole+teicoplanine. On the fourth day, the patient was moved to the ICU because of dyspnea, congestive heart failure, atrial fibrillation, right pleural effusion, ascites, and renal failure. Blood tests demonstrated severe leukopenia and neutropenia, anemia, increased creatinine and blood nitrogen, high-level FDP, and high INR. Blood cultures were negative. At US, unenhanced CT, and CEUS, a progressive enlargement of the infected liver lesion was observed. Percutaneous drainage was attempted, but only drops of non-suppurative brownish material could be obtained. Pleural and peritoneal drainages gave serosanguineous muddy fluid. The Surgeon and the Anesthesiologist excluded any indication of surgical resection because of the high perioperative mortality risk. Therefore, we asked for the informed consent of the patient and her relatives to treat the gangrenous liver lesion by percutaneous Ablation. Under conscious sedation, percutaneous RFA of GG was performed by double insertion of 3 cool-tip needles (Covidien LDT, USA ) into the infected area. The procedure was well tolerated by the patient. A dramatic improvement in the patient's condition was observed in the subsequent 24 hours and thereafter. Fever and dyspnea disappeared. Normalization of blood tests, including creatinine, was observed within 4 days. Heart performance improved, 10 days after the RFA the patient left the hospital and was followed-up with weekly as an outpatient for 2 months and every two months thereafter. At 18 months follow-up, the patient is well compensated (Child-Pugh class B7), without any peritoneal or pleural effusion and without any HCC recurrence at imaging (US every 3 months, CT every 6 months). Percutaneous RFA could be a valuable therapy of focal GG of the liver in patients non-responder to antibiotics and when surgery and liver transplantation are not feasible. A fast and early indication is needed in case of rapid worsening of patient's conditions.

Keywords: liver tumor ablation, interventional ultrasound, liver infection, gas gangrene, radiofrequency ablation

Procedia PDF Downloads 49

Authors: M. Roberts

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We Are Undefeatable - is a mass marketing behaviour change campaign that aims to support the least active people living with long term health conditions to be more active. This is an important issue to address because people with long term conditions are an historically underserved community for the sport and physical activity sector and the least active of those with long term conditions have the most to gain in health and wellbeing benefits. The campaign has generated a significant change in the way physical activity is communicated and people with long term conditions are represented in the media and marketing. The goal is to create a social norm around being active. The campaign is led by a unique partnership of organisations: the Richmond Group of Charities (made up of Age UK, Alzheimer’s Society, Asthma + Lung UK, Breast Cancer Now, British Heart Foundation, British Red Cross, Diabetes UK, Macmillan Cancer Support, Rethink Mental Illness, Royal Voluntary Service, Stroke Association, Versus Arthritis) along with Mind, MS Society, Parkinson’s UK and Sport England, with National Lottery Funding. It is underpinned by the COM-B model of behaviour change. It draws on the lived experience of people with multiple long term conditions to shape the look and feel of the campaign and all the resources available. People with long term conditions are the campaign messengers, central to the ethos of the campaign by telling their individual stories of overcoming barriers to be active with their health conditions. The central messaging is about finding a way to be active that works for the individual. We Are Undefeatable is evaluated through a multi-modal approach, including regular qualitative focus groups and a quantitative evaluation tracker undertaken three times a year. The campaign has highlighted the significant barriers to physical activity for people with long term conditions. This has changed the way our partnership talks about physical activity but has also had an impact on the wider sport and physical activity sector, prompting an increasing departure from traditional messaging and marketing approaches for this audience of people with long term conditions. The campaign has reached millions of people since its launch in 2019, through multiple marketing and partnership channels including primetime TV advertising and promotion through health professionals and in health settings. Its diverse storytellers make it relatable to its target audience and the achievable activities highlighted and inclusive messaging inspire our audience to take action as a result of seeing the campaign. The We Are Undefeatable campaign is a blueprint for physical activity campaigns; it not only addresses individual behaviour change but plays a role in addressing systemic barriers to physical activity by sharing the lived experience insight to shape policy and professional practice.

Keywords: behaviour change, long term conditions, partnership, relatable

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Authors: Priyanka Mokashi, Aparna Khanna, Nancy Pandita

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Diabetes mellitus is a chronic metabolic disorder which will be the 7th leading cause of death by 2030. The current line of treatment for the diabetes mellitus is oral antidiabetic drugs (biguanides, sulfonylureas, meglitinides, thiazolidinediones and alpha-glycosidase inhibitors) and insulin therapy depending upon the type 1 or type 2 diabetes mellitus. But, these treatments have their disadvantages, ranging from the developing of resistance to the drugs and adverse effects caused by them. Alternative to these synthetic agents, natural products provides a new insight for the development of more efficient and safe drugs due to their therapeutic values. Enicostema littorale blume (A. Raynal) is a traditional Indian plant belongs to the Gentianaceae family. It is widely distributed in Asia, Africa, and South America. There are few reports on Swrtiamarin, major component of this plant for its antidiabetic activity. However, the antidiabetic activity of flavonoids from E. littorale and their mechanism of action have not yet been elucidated. Flavonoids have a positive relationship with disease prevention and can act on various molecular targets and regulate different signaling pathways in pancreatic β-cells, adipocytes, hepatocytes and skeletal myofibers. They may exert beneficial effects in diabetes by (i) improving hyperglycemia through regulation of glucose metabolism in hepatocytes; (ii) enhancing insulin secretion and reducing apoptosis and promoting proliferation of pancreatic β-cells; (iii) increasing glucose uptake in hepatocytes, skeletal muscle and white adipose tissue (iv) reducing insulin resistance, inflammation and oxidative stress. Therefore, we have isolated four flavonoid rich fractions, Fraction A (FA), Fraction B (FB), Fraction C (FC), Fraction D (FD) from crude alcoholic hot (AH) extract from E. littorale, identified by LC/MS. Total eight flavonoids were identified on the basis of fragmentation pattern. Flavonoid FA showed the presence of swertisin, isovitexin, and saponarin; FB showed genkwanin, quercetin, isovitexin, FC showed apigenin, swertisin, quercetin, 5-O-glucosylswertisin and 5-O-glucosylisoswertisin whereas FD showed the presence of swertisin. Further, these fractions were assessed for their antidiabetic activity on stimulating glucose uptake in insulin-resistant HepG2 cell line model (IR/HepG2). The results showed that FD containing C-glycoside Swertisin has significantly increased the glucose uptake rate of IR/HepG2 cells at the concentration of 10 µg/ml as compared to positive control Metformin (0.5mM) which was determined by glucose oxidase- peroxidase method. It has been reported that enhancement of glucose uptake of cells occurs due the translocation of Glut4 vesicles to cell membrane through IR/IRS1/AKT pathway. Therefore, we have studied expressions of three genes IRS1, AKT and Glut4 by real-time PCR to evaluate whether they follow the same pathway or not. It was seen that the glucose uptake rate has increased in FD treated IR/HepG2 cells due to the activation of insulin receptor substrate-1 (IRS1) followed by protein kinase B (AKT) through phosphoinositide 3-kinase (PI3K) leading to translocation of Glut 4 vesicles to cell membrane, thereby enhancing glucose uptake and insulin sensitivity of insulin resistant HepG2 cells. Hence, the up-regulation indicated the mechanism of action through which FD (Swertisin) acts as antidiabetic candidate in the treatment of type 2 diabetes mellitus.

Keywords: E. littorale, glucose transporter, glucose uptake rate, insulin resistance

Procedia PDF Downloads 287

Authors: Kavita Khoiwal, Vatsla Dadhwal, K. Aparna Sharma, Dipika Deka, Plabani Sarkar

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Introduction: About 2.4 million (1.93 - 3.04 million) people are living with HIV/AIDS in India. Of all HIV infections, 39% (9,30,000) are among women. 5.4% of infections are from mother to child transmission (MTCT), 25,000 infected children are born every year. Besides the risk of mother to child transmission of HIV, these women are at risk of the higher adverse pregnancy outcome. The objectives of the study were to compare the obstetric and neonatal outcome in women who are HIV positive with low-risk HIV negative women and effect of antiretroviral drugs on preterm birth and IUGR. Materials and Methods: This is a retrospective case record analysis of 212 HIV-positive women delivering between 2002 to 2015, in a tertiary health care centre which was compared with 238 HIV-negative controls. Women who underwent medical termination of pregnancy and abortion were excluded from the study. Obstetric outcome analyzed were pregnancy induced hypertension, HIV positive intrauterine growth restriction, preterm birth, anemia, gestational diabetes and intrahepatic cholestasis of pregnancy. Neonatal outcome analysed were birth weight, apgar score, NICU admission and perinatal transmission.HIV-positiveOut of 212 women, 204 received antiretroviral therapy (ART) to prevent MTCT, 27 women received single dose nevirapine (sdNVP) or sdNVP tailed with 7 days of zidovudine and lamivudine (ZDV + 3TC), 15 received ZDV, 82 women received duovir and 80 women received triple drug therapy depending upon the time period of presentation. Results: Mean age of 212 HIV positive women was 25.72+3.6 years, 101 women (47.6 %) were primigravida. HIV positive status was diagnosed during pregnancy in 200 women while 12 women were diagnosed prior to conception. Among 212 HIV positive women, 20 (9.4 %) women had preterm delivery (< 37 weeks), 194 women (91.5 %) delivered by cesarean section and 18 women (8.5 %) delivered vaginally. 178 neonates (83.9 %) received exclusive top feeding and 34 neonates (16.03 %) received exclusive breast feeding. When compared to low risk HIV negative women (n=238), HIV positive women were more likely to deliver preterm (OR 1.27), have anemia (OR 1.39) and intrauterine growth restriction (OR 2.07). Incidence of pregnancy induced hypertension, diabetes mellitus and ICP was not increased. Mean birth weight was significantly lower in HIV positive women (2593.60+499 gm) when compared to HIV negative women (2919+459 gm). Complete follow up is available for 148 neonates till date, rest are under evaluation. Out of these 7 neonates found to have HIV positive status. Risk of preterm birth (P value = 0.039) and IUGR (P value = 0.739) was higher in HIV positive women who did not receive any ART during pregnancy than women who received ART. Conclusion: HIV positive pregnant women are at increased risk of adverse pregnancy outcome. Multidisciplinary team approach and use of highly active antiretroviral therapy can optimize the maternal and perinatal outcome.

Keywords: antiretroviral therapy, HIV infection, IUGR, preterm birth

Procedia PDF Downloads 239

Authors: Sunidhi Sood, Drashti Narendrakumar Shah, Aakarsh Sharma, Nirali Harsh Panchal, Maria Karizhenskaia

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Cancer is a global health concern, causing a significant number of deaths, with chemotherapy being a standard treatment method. However, chemotherapy often induces side effects that profoundly impact the physical and emotional well-being of patients, lowering their overall quality of life (QoL). This research aims to investigate the potential of music and art therapy as holistic adjunctive therapy for cancer patients undergoing chemotherapy, offering non-pharmacological support. This is achieved through a comprehensive review of existing literature with a focus on the following themes, including stress and anxiety alleviation, emotional expression and coping skill development, transformative changes, and pain management with mood upliftment. A systematic search was conducted using Medline, Google Scholar, and St. Lawrence College Library, considering original, peer-reviewed research papers published from 2014 to 2023. The review solely incorporated studies focusing on the impact of music and art therapy on the health and overall well-being of cancer patients undergoing chemotherapy in North America. The findings from 16 studies involving pediatric oncology patients, females affected by breast cancer, and general oncology patients show that music and art therapies significantly reduce anxiety (standardized mean difference: -1.10) and improve perceived stress (median change: -4.0) and overall quality of life in cancer patients undergoing chemotherapy. Furthermore, music therapy has demonstrated the potential to decrease anxiety, depression, and pain during infusion treatments (average changes in resilience scale: 3.4 and 4.83 for instrumental and vocal music therapy, respectively). This data calls for consideration of the integration of music and art therapy into supportive care programs for cancer patients undergoing chemotherapy. Moreover, it provides guidance to healthcare professionals and policymakers, facilitating the development of patient-centered strategies for cancer care in Canada. Further research is needed in collaboration with qualified therapists to examine its applicability and explore and evaluate patients' perceptions and expectations in order to optimize the therapeutic benefits and overall patient experience. In conclusion, integrating music and art therapy in cancer care promises to substantially enhance the well-being and psychosocial state of patients undergoing chemotherapy. However, due to the small population size considered in existing studies, further research is needed to bridge the knowledge gap and ensure a comprehensive, patient-centered approach, ultimately enhancing the quality of life (QoL) for individuals facing the challenges of cancer treatment.

Keywords: anxiety, cancer, chemotherapy, depression, music and art therapy, pain management, quality of life

Procedia PDF Downloads 29

Authors: Nguyen J. M., Lucas G., Ruan S., Digonnet H., Antonioli D.

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Introduction: Deep Learning (DL) is a very powerful tool for analyzing image data. But for tabular data, it cannot compete with machine learning methods like XGBoost. The research question becomes: can tabular data be transformed into images that can be analyzed by simple CNNs (Convolutional Neuron Networks)? Will DL be the absolute tool for data classification? All current solutions consist in repositioning the variables in a 2x2 matrix using their correlation proximity. In doing so, it obtains an image whose pixels are the variables. We implement a technology, DeepNIC, that offers the possibility of obtaining an image for each variable, which can be analyzed by simple CNNs. Material and method: The 'ROP' (Regression OPtimized) model is a binary and atypical decision tree whose nodes are managed by a new artificial neuron, the Neurop. By positioning an artificial neuron in each node of the decision trees, it is possible to make an adjustment on a theoretically infinite number of variables at each node. From this new decision tree whose nodes are artificial neurons, we created the concept of a 'Random Forest of Perfect Trees' (RFPT), which disobeys Breiman's concepts by assembling very large numbers of small trees with no classification errors. From the results of the RFPT, we developed a family of 10 statistical information criteria, Nguyen Information Criterion (NICs), which evaluates in 3 dimensions the predictive quality of a variable: Performance, Complexity and Multiplicity of solution. A NIC is a probability that can be transformed into a grey level. The value of a NIC depends essentially on 2 super parameters used in Neurops. By varying these 2 super parameters, we obtain a 2x2 matrix of probabilities for each NIC. We can combine these 10 NICs with the functions AND, OR, and XOR. The total number of combinations is greater than 100,000. In total, we obtain for each variable an image of at least 1166x1167 pixels. The intensity of the pixels is proportional to the probability of the associated NIC. The color depends on the associated NIC. This image actually contains considerable information about the ability of the variable to make the prediction of Y, depending on the presence or absence of other variables. A basic CNNs model was trained for supervised classification. Results: The first results are impressive. Using the GSE22513 public data (Omic data set of markers of Taxane Sensitivity in Breast Cancer), DEEPNic outperformed other statistical methods, including XGBoost. We still need to generalize the comparison on several databases. Conclusion: The ability to transform any tabular variable into an image offers the possibility of merging image and tabular information in the same format. This opens up great perspectives in the analysis of metadata.

Keywords: tabular data, CNNs, NICs, DeepNICs, random forest of perfect trees, classification

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Authors: Asghar Arif

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Lung cancer has been recognized as one of the greatest common cancers, causing the annual mortality rate of about 1.2 million people in the world. Lung cancer is the most prevalent cancer in men and the third-most common cancer among women (after breast and digestive cancers).Recent evidences have shown the inflammatory process as one of the potential factors of cancer. Tuberculosis (TB), pneumonia, and chronic bronchitis are among the most important inflammation-inducing factors in the lungs, among which TB has a more profound role in the emergence of cancer.TB is one of the important mortality factors throughout the world, and 205,000 death cases are reported annually due to this disease. Chronic inflammation and fibrosis due to TB can induce genetic mutation and alternations. Parenchyma tissue of lung is involved in both diseases of TB and lung cancer, and continuous cough in lung cancer, morphological vascular variations, lymphocytosis processes, and generation of immune system mediators such as interleukins, are all among the factors leading to the hypothesis regarding the role of TB in lung cancer Some reports have shown that the induction of necrosis and apoptosis or TB reactivation, especially in patients with immune-deficiency, may result in increasing IL-17 and TNF_α, which will either decrease P53 activity or increase the expression of Bcl-2, decrease Bax-T, and cause the inhibition of caspase-3 expression due to decreasing the expression of mitochondria cytochrome oxidase. It has been also indicated that following the injection of BCG vaccine, the host immune system will be reinforced, and in particular, the rates of gamma interferon, nitric oxide, and interleukin-2 are increased. Therefore, CD4 + lymphocyte function will be improved, and the person will be immune against cancer.Numerous prospective studies have so far been conducted on the role of TB in lung cancer, and it seems that this disease is effective in that particular cancer.One of the main challenges of lung cancer is its correct and timely diagnosis. Unfortunately, clinical symptoms (such as continuous cough, hemoptysis, weight loss, fever, chest pain, dyspnea, and loss of appetite) and radiological images are similar in TB and lung cancer. Therefore, anti-TB drugs are routinely prescribed for the patients in the countries with high prevalence of TB, like Pakistan. Regarding the similarity in clinical symptoms and radiological findings of lung cancer, proper diagnosis is necessary for TB and respiratory infections due to nontuberculousmycobacteria (NTM). Some of the drug resistive TB cases are, in fact, lung cancer or NTM lung infections. Acid-fast staining and histological study of phlegm and bronchial washing, culturing and polymerase chain reaction TB are among the most important solutions for differential diagnosis of these diseases. Briefly, it is assumed that TB is one of the risk factors for cancer. Numerous studies have been conducted in this regard throughout the world, and it has been observed that there is a significant relationship between previous TB infection and lung cancer. However, to prove this hypothesis, further and more extensive studies are required. In addition, as the clinical symptoms and radiological findings of TB, lung cancer, and non-TB mycobacteria lung infections are similar, they can be misdiagnosed as TB.

Keywords: TB and lung cancer, TB people, TB servivers, TB and HIV aids

Procedia PDF Downloads 47

Authors: Apurva Singh, S. P. Jaiswar, Apala Priyadarshini, Akancha Pandey

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Objective: The aim of this study is to find the association of PON1 gene polymorphism with pesticides In RPL subjects. Background: Recurrent pregnancy loss (RPL) is defined as three or more sequential abortions before the 20th week of gestation. Pesticides and its derivatives (organochlorine and organophosphate) are proposed to accommodate a ruler chemical for RPL in the sub-humid region of India. The paraoxonase-1 enzyme (PON1) plays an important role in the toxicity of some organophosphate pesticides, with low PON1 activity being associated with higher pesticide sensitivity Methodology: This is a case-control study done in Department of Obstetrics & Gynaecology & Department of Biochemistry, K.G.M.U, Lucknow, India. The subjects were enrolled after fulfilling the inclusion & exclusion criteria. Inclusion criteria: Cases- Subject having two or more spontaneous abortions & Control- Healthy female having one or more alive child was selected. Exclusion criteria: Cases & Control- Subject having the following disease will be excluded from the study Diabetes mellitus, Hypertension, Tuberculosis, Immunocompromised patients, any endocrine disorder and genital, colon or breast cancer any other malignancies. Blood samples were collected in EDTA tubes from cases & healthy control women & genomic DNA was extracted by phenol-chloroform method. The estimation of pesticides residue from blood was done by HPLC. Biochemical estimation was also performed. Genotyping of PON1 gene polymorphism was performed by RFLP. Statistical analysis of the data was performed using the SPSS16.3 software. Results: A sum of total 14 pesticides (12 organochlorine and 2 organophosphate) selected on the basis of their persistent nature and consumption rate. The significant level of pesticide (ppb) estimated by the Mann whiney test and it was found to be significant at higher level of β-HCH (p:0.04), γ-HCH (p:0.001), δ-HCH (p: 0.002), chloropyrifos (p:0.001), pp-DDD (p:0.001) and fenvalrate (p: 0.001) in case group compare to its control. The level of antioxidant enzymes were found to be significantly decreased among the cases. Wild homozygous TT was more frequent and prevalent among control groups. However, heterozygous group (Tt) was more in cases than control groups (CI-0.3-1.3) (p=0.06). Conclusion: Higher levels of pesticides with endocrine disrupting potential in cases indicate the possible role of these compounds as one of the causes of recurrent pregnancy loss. Possibly, increased pesticide level appears to indicate increased levels of oxidative damage that has been associated with the possible cause of Recurrent Miscarriage, it may reflect indirect evidence of toxicity rather than the direct cause. Since both factors are reported to increase risk, individuals with higher levels of these 'Toxic compounds' especially in 'high-risk genotypes' might be more susceptible to recurrent pregnancy loss.

Keywords: paraoxonase, pesticides, PON1, RPL

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Authors: Jaci Mastrandrea

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Background: The National Comprehensive Cancer Network (NCCN) recommends that healthcare institutions have established processes for integrating palliative care (PC) into cancer treatment and that all cancer patients be screened for PC needs upon initial diagnosis as well as throughout the entire continuum of care (National Comprehensive Cancer Network, 2021). Early PC screening is directly correlated with improved patient outcomes. The Sky Lakes Cancer Treatment Center (SLCTC) is an institution that has access to PC services yet does not have protocols in place for identifying patients with palliative needs or a standardized referral process. The aim of this quality improvement project is to improve early access to PC services by establishing a standardized screening and referral process for outpatient oncology patients. Method: The sample population included all adult patients with an oncology diagnosis who presented to the SLCTC for treatment during the project timeline from March 15th, 2022, to April 29th, 2022. The “Palliative and Supportive Needs Assessment'' (PSNA) screening tool was developed from validated and evidence-based PC referral criteria. The tool was initially implemented using paper forms and later was integrated into the Epic-Beacon EHR system. Patients were screened by registered nurses on the SLCTC treatment team. Nurses responsible for screening patients received an educational inservice prior to implementation. Patients with a PSNA score of three or higher were considered to be a positive screen. Scores of five or higher triggered a PC referral order in the patient’s EHR for the oncologist to review and approve. All patients with a positive screen received an educational handout on the topic of PC, and the EHR was flagged for follow-up. Results: Prior to implementation of the PSCNA screening tool, the SLCTC had zero referrals to PC in the past year, excluding referrals to hospice. Data was collected from the first 100 patient screenings completed within the eight-week data collection period. Seventy-three percent of patients met criteria for PC referral with a score greater than or equal to three. Of those patients who met referral criteria, 53.4% (39 patients) were referred for a palliative and supportive care consultation. Patients that were not referred to PC upon meeting the criteria were flagged in the EHR for re-screening within one to three months. Patients with lung cancer, chronic hematologic malignancies, breast cancer, and gastrointestinal malignancy most frequently met criteria for PC referral and scored highest overall on the scale of 0-12. Conclusion: The implementation of a standardized PC screening tool at the SLCTC significantly increased awareness of PC needs among cancer patients in the outpatient setting. Additionally, data derived from this quality improvement project supports the national recommendation for PC to be an integral component of cancer treatment across the entire continuum of care.

Keywords: oncology, palliative care, symptom management, symptom screening, ambulatory oncology, cancer, supportive care

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Authors: Rakesh Mishra

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India’s Demography has always amazed the world because of its unprecedented outcomes in the presence of multifaceted socioeconomic and geographical characteristics. Being the first one to implement family panning in 1952, it occupies 2nd largest population of the world, with some of its state like Uttar Pradesh contributing 5th largest population to the world population surpassing Brazil. Being the one with higher in number it is more prone to the demographic disparity persisting into its territories brought upon by the inequalities in availability, accessibility and attainability of socioeconomic and various other resources. Fifth goal of Millennium Development Goal emphasis to improve maternal and child health across the world as Children’s development is very important for the overall development of society and the best way to develop national human resources is to take care of children. The target is to reduce the infant deaths by three quarters between 1990 and 2015. Child health status depends on the care and delivery by trained personnel, particularly through institutional facilities which is further associated with the status of the mother. However, delivery in institutional facilities and delivery by skilled personnel are rising slowly in India. The main objective of the present study is to measure the child health status on based on the educational and occupational background of the women in India. Study indicates that women education plays a very crucial role in deciding the health of the new born care and access to family planning, but the women autonomy indicates to have mixed results in different states of India. It is observed that rural women are 1.61 times more likely to exclusive breastfed their children compared to urban women. With respect to Hindu category, women belonging to other religious community were 21 percent less likely to exclusive breastfed their child. Taking scheduled caste as reference category, the odds of exclusive breastfeeding is found to be decreasing in comparison to other castes, and it is found to be significant among general category. Women of high education status have higher odds of using family planning methods in most of the southern states of India. By and large, girls and boys are about equally undernourished. Under nutrition is generally lower for first births than for subsequent births and consistently increases with increasing birth order for all measures of nutritional status. It is to be noted that at age 12-23 months, when many children are being weaned from breast milk, 30 percent of children are severely stunted and around 21 percent are severely underweight. So, this paper presents the evidence on the patterns of prevailing child health status in India and its states with reference to the mother socioeconomics and biological characteristics and examines trends in these, and discusses plausible explanations.

Keywords: immunization, exclusive breastfeeding, under five mortality, binary logistic regression, ordinal regression and life table

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Authors: Raj Kishore Swain, Kamdev Sethy, Sumanta Kumar Mishra

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Selenium is an essential trace element for the chicken with a variety of biological functions like growth, fertility, immune system, hormone metabolism, and antioxidant defense systems. Selenium deficiency in chicken causes exudative diathesis, pancreatic dystrophy and nutritional muscle dystrophy of the gizzard, heart and skeletal muscle. Additionally, insufficient immunity, lowering of production ability, decreased feathering of chickens and increased embryo mortality may occur due to selenium deficiency. Nano elemental selenium, which is bright red, highly stable, soluble and of nano meter size in the redox state of zero, has high bioavailability and low toxicity due to the greater surface area, high surface activity, high catalytic efficiency and strong adsorbing ability. To assess the effect of dietary nano-Se on performance and expression of gene in Vencobb broiler birds in comparison to its inorganic form (sodium selenite), four hundred fifty day-old Vencobb broiler chicks were randomly distributed into 9 dietary treatment groups with two replicates with 25 chicks per replicate. The dietary treatments were: T1 (Control group): Basal diet; T2: Basal diet with 0.3 ppm of inorganic Se; T3: Basal diet with 0.01875 ppm of nano-Se; T4: Basal diet with 0.0375 ppm of nano-Se; T5: Basal diet with 0.075 ppm of nano-Se, T6: Basal diet with 0.15 ppm of nano-Se, T7: Basal diet with 0.3 ppm of nano-Se, T8: Basal diet with 0.60 ppm of nano-Se, T9: Basal diet with 1.20 ppm of nano-Se. Nano selenium was synthesized by mixing sodium selenite with reduced glutathione and bovine serum albumin. The experiment was carried out in two phases: starter phase (0-3 wks), finisher phase (4-5 wk) in deep litter system. The body weight at the 5th week was best observed in T4. The best feed conversion ratio at the end of 5th week was observed in T4. Erythrocytic catalase, glutathione peroxidase and superoxide dismutase activity were significantly (P < 0.05) higher in all the nano selenium treated groups at 5th week. The antibody titers (log2) against Ranikhet diseases vaccine immunization of 5th-week broiler birds were significantly higher (P < 0.05) in the treatments T4 to T7. The selenium levels in liver, breast, kidney, brain, and gizzard were significantly (P < 0.05) increased with increasing dietary nano-Se indicating higher bioavailability of nano-Se compared to inorganic Se. The real time polymer chain reaction analysis showed an increase in the expression of antioxidative gene in T4 and T7 group. Therefore, it is concluded that supplementation of nano-selenium at 0.0375 ppm over and above the basal level can improve the body weight, antioxidant enzyme activity, Se bioavailability and expression of the antioxidative gene in broiler birds.

Keywords: chicken, growth, immunity, nano selenium

Procedia PDF Downloads 142

Authors: Tuba Denkceken, Ayse Nur Sarı, Volkan Ihsan Tore, Mahmut Denkceken

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The aim of the presented study was to develop a newly motorized spectroscopy system. Our system is composed of probe and motor parts. The probe part consists of bioimpedance and fiber optic components that include two platinum wires (each 25 micrometer in diameter) and two fiber cables (each 50 micrometers in diameter) respectively. Probe was examined on tissue phantom (polystyrene microspheres with different diameters). In the bioimpedance part of the probe current was transferred to the phantom and conductivity information was obtained. Adjacent two fiber cables were used in the fiber optic part of the system. Light was transferred to the phantom by fiber that was connected to the light source and backscattered light was collected with the other adjacent fiber for analysis. It is known that the nucleus expands and the nucleus-cytoplasm ratio increases during the cancer progression in the cell and this situation is one of the most important criteria for evaluating the tissue for pathologists. The sensitivity of the probe to particle (nucleus) size in phantom was tested during the study. Spectroscopic data obtained from our system on phantom was evaluated by multivariate statistical analysis. Thus the information about the particle size in the phantom was obtained. Bioimpedance and fiber optic experiments results which were obtained from polystyrene microspheres showed that the impedance value and the oscillation amplitude were increasing while the size of particle was enlarging. These results were compatible with the previous studies. In order to motorize the system within the motor part, three driver electronic circuits were designed primarily. In this part, supply capacitors were placed symmetrically near to the supply inputs which were used for balancing the oscillation. Female capacitors were connected to the control pin. Optic and mechanic switches were made. Drivers were structurally designed as they could command highly calibrated motors. It was considered important to keep the drivers’ dimension as small as we could (4.4x4.4x1.4 cm). Then three miniature step motors were connected to each other along with three drivers. Since spectroscopic techniques are quantitative methods, they yield more objective results than traditional ones. In the future part of this study, it is planning to get spectroscopic data that have optic and impedance information from the cell culture which is normal, low metastatic and high metastatic breast cancer. In case of getting high sensitivity in differentiated cells, it might be possible to scan large surface tissue areas in a short time with small steps. By means of motorize feature of the system, any region of the tissue will not be missed, in this manner we are going to be able to diagnose cancerous parts of the tissue meticulously. This work is supported by The Scientific and Technological Research Council of Turkey (TÜBİTAK) through 3001 project (115E662).

Keywords: motorized spectroscopy, phantom, scanning system, tissue scanning

Procedia PDF Downloads 171

Authors: Aqeel Ahmed Shad, Tanveer Ahmad, Muhammad Farooq Iqbal, Muhammad Javaid Asad

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The supplemental effects of novel protease produced from Bacillus subtilis K-5 and beta-mannanase were evaluated on growth performance, carcass characteristics, nutrients digestibility, blood profile and intestinal morphometry of broilers fed guar meal (Cyamopsis tetragonoloba) based diets with reduced Crude Protein (CP), Essential Amino Acids (EAAs), and Metabolizable energy (ME) contents. One-day old Ross 308 broiler chicks (n=360) were randomly allotted to thirty six experimental units in a way that each of the nine dietary treatments received four replicates with ten birds per replicate. A control diet without guar meal (0GM) was formulated with standard nutrient specifications of Ross 308 for the starter and finisher phases. Two negative control diets, one with 5% (5GM) and second with 10% (10GM) guar meal, were formulated with reduction of 5% CP, 5% EAAs and 80 Kcal/kg ME. These three basal diets (no enzyme) were supplemented with novel protease enzyme (PROT) and commercial beta-mannanase (Beta-M) enzyme. The birds were reared up to 35d of age. The data on weekly body weight gain (BWG) and feed intake were recorded to compute feed:gain for the starter (0-21d) and finisher (22-35d) phases. At the end of 35d of experimental period, four birds per experimental unit were randomly selected for blood samples collection and later slaughtered for ileal digesta, intestinal tract and carcass trait sampling. The data on overall performance (1-35d) indicated improved (P<0.05) BWG and feed:gain in birds supplemented with PROT (1.41% and 1.67) and Beta-M (2.79% and 1.64) than non-supplemented groups. Improved (P<0.05) carcass yield, breast meat yield and thigh meat yield were noted with the supplementation of Beta-M. However, non-significant (P>0.05) effect on carcass traits was noted in broiler fed guar meal based PROT supplemented diets. Crude protein digestibility, nitrogen retention (Nret) and apparent digestibility coefficient for nitrogen (ADCN) were improved (P<0.05) only with PROT. The improvement in apparent metabolizable energy (AME) and apparent metabolizable energy corrected for nitrogen (AMEn) was noted (P<0.05) with both supplemented enzymes. However, no effect (P>0.05) of enzyme addition was noted on blood glucose, total protein and cholesterol. Improved villus height of duodenum, jejunum and ileum was noted (P<0.05) with the addition of both enzymes. The EAAs digestibility was improved (P<0.05) only with PROT. In conclusion, beta-mannanase and protease supplementation better improved the overall bird performance in low nutrient profile guar meal based diets than non-supplemented diets.

Keywords: novel protease, guar meal, broilers, low protein diets, low metabolizable energy diets, nutrients digestibility

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Authors: Esra Yuksel, Dilek Duman, Levent Yeniay, Sezgin Ulukaya

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Sentinel lymph node biopsy (SLNB) is a minimal invasive technique with lower morbidity in axillary staging of breast cancer. Isosulfan blue stain is frequently used in SLNB and regarded as safe. The present case report aimed to report severe decrement in SpO2 following isosulfan blue administration, as well as skin and urine signs and inconsistency with clinical picture in a 67-year-old ,77 kg, ASA II female case that underwent SLNB under general anesthesia. Ten minutes after subcutaneous administration of 10 ml 1% isosulfan blue by the surgeons into the patient, who were hemodynamically stable, SpO2 first reduced to 87% from 99%, and then to 75% in minutes despite 100% oxygen support. Meanwhile, blood pressure and EtCO2 monitoring was unremarkable. After specifying that anesthesia device worked normally, airway pressure did not increase and the endotracheal tube has been placed accurately, the blood sample was taken from the patient for arterial gas analysis. A severe increase was thought in MetHb concentration since SpO2 persisted to be 75% although the concentration of inspired oxygen was 100%, and solution of 2500 mg ascorbic acid in 500 ml 5% Dextrose was given to the patient via intravenous route until the results of arterial blood gas were obtained. However, arterial blood gas results were as follows: pH: 7.54, PaCO2: 23.3 mmHg, PaO2: 281 mmHg, SaO2: %99, and MetHb: %2.7. Biochemical analysis revealed a blood MetHb concentration of 2%.However, since arterial blood gas parameters were good, hemodynamics of the patient was stable and methemoglobin concentration was not so high, the patient was extubated after surgery when she was relaxed, cooperated and had adequate respiration. Despite the absence of respiratory or neurological distress, SpO2 value was increased only up to 85% within 2 hours with 5 L/min oxygen support via face mask in the surgery room as the patient was extubated. At that time, the skin of particularly the upper part of her body has turned into blue, more remarkable on the face. The color of plasma of the blood taken from the patient for biochemical analysis was blue. The color of urine coming throughout the urinary catheter placed in intensive care unit was also blue. Twelve hours after 5 L/min. oxygen inhalation via a mask, the SpO2 reached to 90%. During monitoring in intensive care unit on the postoperative 1st day, facial color and urine color of the patient was still blue, SpO2 was 92%, and arterial blood gas levels were as follows: pH: 7.44, PaO2: 76.1 mmHg, PaCO2: 38.2 mmHg, SaO2: 99%, and MetHb 1%. During monitoring in clinic on the postoperative 2nd day, SpO2 was 95% without oxygen support and her facial and urine color turned into normal. The patient was discharged on the 3rd day without any problem.In conclusion, SLNB is a less invasive alternative to axillary dissection. However, false pulse oximeter reading due to pigment interference is a rare complication of this procedure. Arterial blood gas analysis should be used to confirm any fall in SpO2 reading during monitoring.

Keywords: isosulfan blue, pulse oximetry, SLNB, methemoglobinemia

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Authors: Navid Kaboudi, Ali Shayanfar

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Introduction: Feeding infants with safe milk from the beginning of their life is an important issue. Drugs which are used by mothers can affect the composition of milk in a way that is not only unsuitable, but also toxic for infants. Consuming permeable drugs during that sensitive period by mother could lead to serious side effects to the infant. Due to the ethical restrictions of drug testing on humans, especially women, during their lactation period, computational approaches based on structural parameters could be useful. The aim of this study is to develop mechanistic models to predict the M/P ratio of drugs during breastfeeding period based on their structural descriptors. Methods: Two hundred and nine different chemicals with their M/P ratio were used in this study. All drugs were categorized into two groups based on their M/P value as Malone classification: 1: Drugs with M/P>1, which are considered as high risk 2: Drugs with M/P>1, which are considered as low risk Thirty eight chemical descriptors were calculated by ACD/labs 6.00 and Data warrior software in order to assess the penetration during breastfeeding period. Later on, four specific models based on the number of hydrogen bond acceptors, polar surface area, total surface area, and number of acidic oxygen were established for the prediction. The mentioned descriptors can predict the penetration with an acceptable accuracy. For the remaining compounds (N= 147, 158, 160, and 174 for models 1 to 4, respectively) of each model binary regression with SPSS 21 was done in order to give us a model to predict the penetration ratio of compounds. Only structural descriptors with p-value<0.1 remained in the final model. Results and discussion: Four different models based on the number of hydrogen bond acceptors, polar surface area, and total surface area were obtained in order to predict the penetration of drugs into human milk during breastfeeding period About 3-4% of milk consists of lipids, and the amount of lipid after parturition increases. Lipid soluble drugs diffuse alongside with fats from plasma to mammary glands. lipophilicity plays a vital role in predicting the penetration class of drugs during lactation period. It was shown in the logistic regression models that compounds with number of hydrogen bond acceptors, PSA and TSA above 5, 90 and 25 respectively, are less permeable to milk because they are less soluble in the amount of fats in milk. The pH of milk is acidic and due to that, basic compounds tend to be concentrated in milk than plasma while acidic compounds may consist lower concentrations in milk than plasma. Conclusion: In this study, we developed four regression-based models to predict the penetration class of drugs during the lactation period. The obtained models can lead to a higher speed in drug development process, saving energy, and costs. Milk/plasma ratio assessment of drugs requires multiple steps of animal testing, which has its own ethical issues. QSAR modeling could help scientist to reduce the amount of animal testing, and our models are also eligible to do that.

Keywords: logistic regression, breastfeeding, descriptors, penetration

Procedia PDF Downloads 39

Authors: Roni Ramon-Gonen, Amir Dori, Shahar Shelly

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Background and objectives: Healthcare professionals produce abundant textual information in their daily clinical practice. The extraction of insights from all the gathered information, mainly unstructured and lacking in normalization, is one of the major challenges in computational medicine. In this respect, text mining assembles different techniques to derive valuable insights from unstructured textual data, so it has led to being especially relevant in Medicine. Neurological patient’s history allows the clinician to define the patient’s symptoms and along with the result of the nerve conduction study (NCS) and electromyography (EMG) test, assists in formulating a differential diagnosis. Past medical history (PMH) helps to direct the latter. In this study, we aimed to identify relevant PMH, understand which PMHs are common among patients in the referral cohort and documented by the medical staff, and examine the differences by sex and age in a large cohort based on textual format notes. Methods: We retrospectively identified all patients with abnormal NCS between May 2016 to February 2022. Age, gender, and all NCS attributes reports were recorded, including the summary text. All patients’ histories were extracted from the text report by a query. Basic text cleansing and data preparation were performed, as well as lemmatization. Very popular words (like ‘left’ and ‘right’) were deleted. Several words were replaced with their abbreviations. A bag of words approach was used to perform the analyses. Different visualizations which are common in text analysis, were created to easily grasp the results. Results: We identified 5282 unique patients. Three thousand and five (57%) patients had documented PMH. Of which 60.4% (n=1817) were males. The total median age was 62 years (range 0.12 – 97.2 years), and the majority of patients (83%) presented after the age of forty years. The top two documented medical histories were diabetes mellitus (DM) and surgery. DM was observed in 16.3% of the patients, and surgery at 15.4%. Other frequent patient histories (among the top 20) were fracture, cancer (ca), motor vehicle accident (MVA), leg, lumbar, discopathy, back and carpal tunnel release (CTR). When separating the data by sex, we can see that DM and MVA are more frequent among males, while cancer and CTR are less frequent. On the other hand, the top medical history in females was surgery and, after that, DM. Other frequent histories among females are breast cancer, fractures, and CTR. In the younger population (ages 18 to 26), the frequent PMH were surgery, fractures, trauma, and MVA. Discussion: By applying text mining approaches to unstructured data, we were able to better understand which medical histories are more relevant in these circumstances and, in addition, gain additional insights regarding sex and age differences. These insights might help to collect epidemiological demographical data as well as raise new hypotheses. One limitation of this work is that each clinician might use different words or abbreviations to describe the same condition, and therefore using a coding system can be beneficial.

Keywords: abnormal studies, healthcare analytics, medical history, nerve conduction studies, text mining, textual analysis

Procedia PDF Downloads 63

Authors: Luci V. Hyett

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The criminal law of England and Wales currently deems that a person cannot consent to the infliction of injury upon their own body, where the level of harm is considered to be Actual or Grevious. This renders the defence of consent of the victim as being unavailable to those persons carrying out an Alternative Body Modification procedure. However, the criminalization of consensual injury is more appropriately deemed as being categorized as an offense against public morality and not one against the person, which renders the State’s involvement in the autonomous choices of a consenting adult, when determining what can be done to one’s own body, an arbitrary one. Furthermore, to recognise in law that a person is capable of giving a valid consent to socially acceptable cosmetic interventions that largely consist of procedures designed to aesthetically please men and, not those of people who want to modify their bodies for other reasons means that patriarchal attitudes are continuing to underpin public repulsion and inhibit social acceptance of such practices. Theoretical analysis will begin with a juridical examination of R v M(B) [2019] QB 1 where the High Court determined that Alternative Body Modification was not a special category exempting a person so performing from liability for Grevious Bodily Harm using the defence of consent. It will draw from its reasoning which considered that ‘the removal of body parts were medical procedures being carried out for no medical reason by someone not qualified to carry them out’ which will form the basis of this enquiry. It will consider the philosophical work of Georgio Agamben when analysing whether the biopolitical climate in the UK, which places the optimization of the perfect, healthy body at the centre of political concern can explain why those persons who wish to engage in Alternative Body Modification are treated as the ‘Exception’ to that which is normal using the ‘no medical reason’ canon to justify criminalisation, rather than legitimising the industry through regulation. It will consider, through a feminist lens, the current conflict in law between traditional cosmetic interventions which alter one’s physical appearance for socially accepted aesthetic purposes such as those to the breast, lip and buttock and, modifications described as more outlandish such as earlobe stretching, tooth filing and transdermal implants to create horns and spikes under the skin. It will assert that ethical principles relating to the psychological impact of body modification described as ‘alternative’ is used as a means to exclude person’s seeking such a procedure from receiving safe and competent treatment via a registered cosmetic surgeon which leads to these increasingly popular surgery’s being performed in Tattoo parlours throughout the UK as an extension to other socially acceptable forms of self-modification such as piercings. It will contend that only by ‘inclusive exclusion’ will those ‘othered’ through ostracisation be welcomed into the fold of normality and this can only be achieved through recognition of alternative body modification as a legitimate cosmetic intervention, subject to the same regulatory framework as existing practice. This would assist in refocusing the political landscape by erring on the side of liberty rather than that of biology.

Keywords: biopolitics, body modification, consent, criminal law

Procedia PDF Downloads 84

Authors: A. Delimitsou, C. Gouedard, E. Konstanta, A. Koletis, S. Patera, E. Manou, K. Spaho, S. Murray

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Background: There remains a lack of International Standard Control Reference materials for Next Generation Sequencing-based approaches or device calibration. We have designed and validated dsDNA biomimetic reference materials for targeted such approaches incorporating proprietary motifs (patent pending) for device/test calibration. They enable internal single-sample calibration, alleviating sample comparisons to pooled historical population-based data assembly or statistical modelling approaches. We have validated such an approach for BRCA Copy Number Variation analytics using iQRS™-CNVSUITE versus Mixed Ligation-dependent Probe Amplification. Methods: Standard BRCA Copy Number Variation analysis was compared between mixed ligation-dependent probe amplification and next generation sequencing using a cohort of 198 breast/ovarian cancer patients. Next generation sequencing based copy number variation analysis of samples spiked with iQRS™ dsDNA biomimetics were analysed using proprietary CNVSUITE software. Mixed ligation-dependent probe amplification analyses were performed on an ABI-3130 Sequencer and analysed with Coffalyser software. Results: Concordance of BRCA – copy number variation events for mixed ligation-dependent probe amplification and CNVSUITE indicated an overall sensitivity of 99.88% and specificity of 100% for iQRS™-CNVSUITE. The negative predictive value of iQRS-CNVSUITE™ for BRCA was 100%, allowing for accurate exclusion of any event. The positive predictive value was 99.88%, with no discrepancy between mixed ligation-dependent probe amplification and iQRS™-CNVSUITE. For device calibration purposes, precision was 100%, spiking of patient DNA demonstrated linearity to 1% (±2.5%) and range from 100 copies. Traditional training was supplemented by predefining the calibrator to sample cut-off (lock-down) for amplicon gain or loss based upon a relative ratio threshold, following training of iQRS™-CNVSUITE using spiked iQRS™ calibrator and control mocks. BRCA copy number variation analysis using iQRS™-CNVSUITE™ was successfully validated and ISO15189 accredited and now enters CE-IVD performance evaluation. Conclusions: The inclusion of a reference control competitor (iQRS™ dsDNA mimetic) to next generation sequencing-based sequencing offers a more robust sample-independent approach for the assessment of copy number variation events compared to mixed ligation-dependent probe amplification. The approach simplifies data analyses, improves independent sample data analyses, and allows for direct comparison to an internal reference control for sample-specific quantification. Our iQRS™ biomimetic reference materials allow for single sample copy number variation analytics and further decentralisation of diagnostics to single patient sample assessment.

Keywords: validation, diagnostics, oncology, copy number variation, reference material, calibration

Procedia PDF Downloads 45

Authors: Brayden Mi

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Reverse time migration has been widely used in the Petroleum exploration industry to reveal subsurface images and to detect rock and fluid properties since the early 1980s. The seismic technology involves the construction of a velocity model through interpretive model construction, seismic tomography, or full waveform inversion, and the application of the reverse-time propagation of acquired seismic data and the original wavelet used in the acquisition. The methodology has matured from 2D, simple media to present-day to handle full 3D imaging challenges in extremely complex geological conditions. Conventional Ultrasound computed tomography (USCT) utilize travel-time-inversion to reconstruct the velocity structure of an organ. With the velocity structure, USCT data can be migrated with the “bend-ray” method, also known as migration. Its seismic application counterpart is called Kirchhoff depth migration, in which the source of reflective energy is traced by ray-tracing and summed to produce a subsurface image. It is well known that ray-tracing-based migration has severe limitations in strongly heterogeneous media and irregular acquisition geometries. Reverse time migration (RTM), on the other hand, fully accounts for the wave phenomena, including multiple arrives and turning rays due to complex velocity structure. It has the capability to fully reconstruct the image detectable in its acquisition aperture. The RTM algorithms typically require a rather accurate velocity model and demand high computing powers, and may not be applicable to real-time imaging as normally required in day-to-day medical operations. However, with the improvement of computing technology, such a computational bottleneck may not present a challenge in the near future. The present-day (RTM) algorithms are typically implemented from a flat datum for the seismic industry. It can be modified to accommodate any acquisition geometry and aperture, as long as sufficient illumination is provided. Such flexibility of RTM can be conveniently implemented for the application in USCT imaging if the spatial coordinates of the transmitters and receivers are known and enough data is collected to provide full illumination. This paper proposes an implementation of a full 3D RTM algorithm for USCT imaging to produce an accurate 3D acoustic image based on the Phase-shift-plus-interpolation (PSPI) method for wavefield extrapolation. In this method, each acquired data set (shot) is propagated back in time, and a known ultrasound wavelet is propagated forward in time, with PSPI wavefield extrapolation and a piece-wise constant velocity model of the organ (breast). The imaging condition is then applied to produce a partial image. Although each image is subject to the limitation of its own illumination aperture, the stack of multiple partial images will produce a full image of the organ, with a much-reduced noise level if compared with individual partial images.

Keywords: illumination, reverse time migration (RTM), ultrasound computed tomography (USCT), wavefield extrapolation

Procedia PDF Downloads 47

Authors: Jaci Marie Mastrandrea, Rosario Haro

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Background: The National Comprehensive Cancer Network (NCCN) recommends that healthcare institutions have established processes for integrating palliative care (PC) into cancer treatment and that all cancer patients be screened for PC needs upon initial diagnosis as well as throughout the entire continuum of care (National Comprehensive Cancer Network, 2021). Early PC screening and intervention is directly associated with improved patient outcomes. The Sky Lakes Cancer Treatment Center (SLCTC) is an institution that has access to PC services yet does not have protocols in place for identifying patients with palliative needs or a standardized referral process. The aim of this quality improvement project was to improve early access to PC services by establishing a standardized screening and referral process for outpatient oncology patients. Method: The sample population included all adult patients with an oncology diagnosis who presented to the SLCTC for treatment during the project timeline. The “Palliative and Supportive Needs Assessment'' (PSNA) screening tool was developed from validated, evidence-based PC referral criteria. The tool was initially implemented using paper forms, and data was collected over a period of eight weeks. Patients were screened by nurses on the SLCTC oncology treatment team. Nurses responsible for screening patients received an educational inservice prior to implementation. Patients with a PSNA score of three or higher received an educational handout on the topic of PC and education about PC and symptom management. A score of five or higher indicates that PC referral is strongly recommended, and the patient’s EHR is flagged for the oncology provider to review orders for PC referral. The PSNA tool was approved by Sky Lakes administration for full integration into Epic-Beacon. The project lead collaborated with the Sky Lakes’ information systems team and representatives from Epic on the tool’s aesthetic and functionality within the Epic system. SLCTC nurses and physicians were educated on how to document the PSNA within Epic and where to view results. Results: Prior to the implementation of the PSNA screening tool, the SLCTC had zero referrals to PC in the past year, excluding referrals to hospice. Data was collected from the completed screening assessments of 100 patients under active treatment at the SLCTC. Seventy-three percent of patients met criteria for PC referral with a score greater than or equal to three. Of those patients who met referral criteria, 53.4% (39 patients) were referred for a palliative and supportive care consultation. Patients that were not referred to PC upon meeting criteria were flagged in EPIC for re-screening within one to three months. Patients with lung cancer, chronic hematologic malignancies, breast cancer, and gastrointestinal malignancy most frequently met the criteria for PC referral and scored highest overall on the scale of 0-12. Conclusion: The implementation of a standardized PC screening tool at the SLCTC significantly increased awareness of PC needs among cancer patients in the outpatient setting. Additionally, data derived from this quality improvement project supports the national recommendation for PC to be an integral component of cancer treatment across the entire continuum of care.

Keywords: oncology, palliative and supportive care, symptom management, outpatient oncology, palliative screening tool

Procedia PDF Downloads 82

Authors: M. Koksal, T. Ozyazici, E. Gurdal, M. Yarım, E. Demirpolat, M. B. Y. Aycan

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The discovery of new drugs in cancer chemotherapy is still a major topic because of severe side effects, selectivity problems and resistance development potential of existing drugs. In recent years, combined anticancer therapies or multi-acting drugs are clinically preferred over traditional cytotoxic treatment, with the aim of avoiding resistance and toxic side effects. Arrangement of multi-acting targets can be carried out either by combination of several drugs with different mechanisms or by usage of a single chemical compound capable of regulating several targets of a disease with multiple factors. In literature, several pyrimidine and piperazine derivatives have been involved in the structure of many compounds which have been used as chemotherapeutic agents along with wide clinical applications. The aim of this study is to combine pyrimidine and piperazine core structures to research and develop novel piperazinylpyrimidine derivatives with selective cytotoxicity over cancer cells. In this study, a group of novel 6-fluorophenyl-3-[2-(substitutedpiperazinyl)ethyl] hexahydropyrimidine-2,4-dione derivatives designed to observe the desired anticancer activity due to pyrimidine and piperazine based scaffolds. Target compounds were obtained by the reaction of appropriate piperazine derivatives and 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-dione. The synthetic pathway of 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-dione was started with Rodionov reaction using aldehyde, malonic acid and ammonium acetate in ethanol. Isolated β-fluorophenyl-β-amino acids were treated with 2-chloroethylisocyanate in the presence of an aqueous sodium hydroxide solution at room temperature to yield the sodium salts of the corresponding ureido acids. By addition of a mineral acid, ureido acids were precipitated. Later, these ureido acids were refluxed in thionyl chloride to give the 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-di-one which were furthermore treated with secondary amines. Structures of purified compounds were characterized with IR, 1H-NMR, 13C-NMR, mass spectroscopies and elemental analysis. All of the compounds gave satisfactory analytical and spectroscopic data, which were in full accordance with their depicted structures. In IR spectra of the compounds, N-H group was seen at 3230-3213 cm⁻¹. C-H was seen at 3100-2820 cm⁻¹ and C=O vibrational peaks were observed approximately at 1725 and 1665 cm⁻¹ in accordance with literature. In the NMR spectra of target compounds, the methylene protons of piperazine give two separate multiplet peaks around 3.5 and 4.5 ppm representing the successful N-alkylation of the structure. The cytotoxic activity of the synthesized compounds was investigated on human bronchial epithelial (BEAS 2B), lung (A549), colon adenocarcinoma (COLO205) and breast (MCF7) cell lines, by means of sulphorhodamine B (SRB) assays in triplicate. IC₅₀ values of the screened derivatives were found in range of 11.8-78 µM. This project was supported by The Scientific and Technological Research Council of Turkey (TUBITAK, Project no: 215S157).

Keywords: cytotoxicity, hexahydropyrimidine, piperazine, sulphorhodamine B assay

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Authors: Divya SY. Ang, Mark B. Tan, Nicholas EM. Yeo, Siti RB. Sudirman, Khong Yik Chew

Abstract:

Introduction: The importance of the amalgamation of technological and engineering advances with surgical principles of reconstruction cannot be overemphasized. With earlier detection of cancer, consequences of high-speed living and neglect, like traumatic injuries and infection, resulting in increasingly younger patients with bone defects. This may result in malformations and suboptimal function that is more noticeable and palpable in the younger, active demographic. Our team proposes a technique that encapsulates a mesh of multidisciplinary effort, tissue engineering and reconstructive principles. Methods/Materials: Our patient was a young competitive footballer in his early 30s who was diagnosed with submandibular adenoid cystic carcinoma with bony involvement. He was thus counselled for a right hemi mandibulectomy, the floor of mouth resection, right selective neck dissection, tracheostomy, and free fibular flap reconstruction of his mandible and required post-operative radiotherapy. Being young and in his prime sportsman years, he was unable to accept the morbidities associated with using his fibula to reconstruct his mandible despite it being the gold standard reconstructive option. The fibula is an ideal vascularized bone flap because it’s reliable and easily shaped with relatively minimal impact on functional outcomes. The fibula contributes to 30% of weightbearing and is the attachment for the lateral compartment muscles; it is stronger in footballers concerning lateral bending. When harvesting the fibula, the distal 6-8cm and up to 10% of the total length is preserved to maintain the ankle’s stability, thus, minimizing the impact on daily activities. There are studies that have noted gait variability post-operatively. Therefore, returning to a premorbid competitive level may be doubtful. To improve his functional outcomes, the decision was made to try and restore the fibula's form and function. Using the concept of Fused Deposition Modelling (FDM), our team comprising of Plastics, Otolaryngology, Orthopedics and Radiology, worked with Osteopore to design a 3D bioresorbable implant to regenerate the fibula defect (14.5cm). Bone marrow was harvested via reaming the contralateral hip prior to the wide resection. 30mls of his blood was obtained for extracting platelet rich plasma. These were packed into the Osteopore 3D-printed bone scaffold. This was then secured into the fibula defect with titanium plates and screws. The flexor hallucis longus and soleus were anchored along the construct and intraosseous membrane, done in a single setting. Results: He was reviewed closely as an outpatient over 10 months post operatively. He reported no discernable loss or difference in ankle function. He is satisfied and back in training and our team has video and photographs that substantiate his progress. Conclusion: FDM allows regeneration of long bone defects. However, we aimed to also restore his eversion and inversion that is imperative for footballers and hence reattached his previously dissected muscles along the length of the Osteopore implant. We believe that the reattachment of the muscle stabilizes not only the construct but allows optimum muscle tensioning when moving his ankle. This is a simple but effective technique in restoring complete function and form in a young patient whose minute muscle control is imperative to life.

Keywords: fused deposition modelling, functional reconstruction, lower limb bony defects, regenerative surgery, 3D printing, tissue engineering

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Authors: Aastha Arora, Vikas Bhuria, Saurabh Singh, Uma Pathak, Shweta Mathur, Puja P. Hazari, Rajat Sandhir, Ravi Soni, Anant N. Bhatt, Bilikere S. Dwarakanath

Abstract:

Radiotherapy is an effective curative and palliative option for patients with thoracic malignancies. However, lung injury, comprising of pneumonitis and fibrosis, remains a significant clin¬ical complication of thoracic radiation, thus making it a dose-limiting factor. Also, injury to the lung is often reported as part of multi-organ failure in victims of accidental radiation exposures. Radiation induced inflammatory response in the lung, characterized by leukocyte infiltration and vascular changes, is an important contributing factor for the injury. Therefore, countermeasure agents to attenuate radiation induced inflammatory response are considered as an important approach to prevent chronic lung damage. Although Amifostine, the widely used, FDA approved radio-protector, has been found to reduce the radiation induced pneumonitis during radiation therapy of non-small cell lung carcinoma, its application during mass and field exposure is limited due to associated toxicity and ineffectiveness with the oral administration. The amifostine analogue (DRDE-30) overcomes this limitation as it is orally effective in reducing the mortality of whole body irradiated mice. The current study was undertaken to investigate the potential of DRDE-30 to ameliorate radiation induced lung damage. DRDE-30 was administered intra-peritoneally, 30 minutes prior to 13.5 Gy thoracic (60Co-gamma) radiation in C57BL/6 mice. Broncheo- alveolar lavage fluid (BALF) and lung tissues were harvested at 12 and 24 weeks post irradiation for studying inflammatory and fibrotic markers. Lactate dehydrogenase (LDH) leakage, leukocyte count and protein content in BALF were used as parameters to evaluate lung vascular permeability. Inflammatory cell signaling (p38 phosphorylation) and anti-oxidant status (MnSOD and Catalase level) was assessed by Western blot, while X-ray CT scan, H & E staining and trichrome staining were done to study the lung architecture and collagen deposition. Irradiation of the lung increased the total protein content, LDH leakage and total leukocyte count in the BALF, reflecting endothelial barrier dysfunction. These disruptive effects were significantly abolished by DRDE-30, which appear to be linked to the DRDE-30 mediated abrogation of activation of the redox-sensitive pro- inflammatory signaling cascade, the MAPK pathway. Concurrent administration of DRDE-30 with radiation inhibited radiation-induced oxidative stress by strengthening the anti-oxidant defense system and abrogated p38 mitogen-activated protein kinase activation, which was associated with reduced vascular leak and macrophage recruitment to the lungs. Histopathological examination (by H & E staining) of the lung showed radiation-induced inflammation of the lungs, characterized by cellular infiltration, interstitial oedema, alveolar wall thickening, perivascular fibrosis and obstruction of alveolar spaces, which were all reduced by pre-administration of DRDE-30. Structural analysis with X-ray CT indicated lung architecture (linked to the degree of opacity) comparable to un-irradiated mice that correlated well with the lung morphology and reduced collagen deposition. Reduction in the radiation-induced inflammation and fibrosis brought about by DRDE-30 resulted in a profound increase in animal survival (72 % in the combination vs 24% with radiation) observed at the end of 24 weeks following irradiation. These findings establish the potential of the Amifostine analogue, DRDE-30, in reducing radiation induced pulmonary injury by attenuating the inflammatory and fibrotic responses.

Keywords: amifostine, fibrosis, inflammation, lung injury radiation

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Authors: Farrah Putri Salmanida, Mei-Li Wu, Rika Wahyuningtyas, Wen-Bin Chung, Hso-Chi Chaung, Ko-Tung Chang

Abstract:

Within the field of immunotherapy, oncolytic virotherapy (OVT) employs dual approaches that directly eliminate tumor cells while preserving healthy ones and indirectly reprogram the tumor microenvironment (TME) to elicit antitumor responses. Within the TME, tumor associated macrophages (TAMs) manifest characteristics akin to those of anti-inflammatory M2 macrophages, thus earning the designation of M2-like TAMs. In prior research, two antigens denoted as A1 (g6Ld10T) and A3 (ORF6L5), derived from a complete sequence of ORF5 with partial sequence of ORF6 in Porcine Reproductive and Respiratory Syndrome Virus Genotype 2 (PRRSV-2), demonstrated the capacity to repolarize M2-type porcine alveolar macrophages (PAMs) into M1 phenotypes. In this study, we sought for utilizing OVT strategies by introducing A1 or A3 on TAMs to endow them with the anti-tumor traits of M1 macrophages while retaining their capacity to target cancer cells. Upon exposing human THP-1-derived M2 macrophages to a cross-species test with 2 µg/ml of either A1 or A3 for 24 hours, real time PCR revealed that A3, but not A1, treated cells exhibited upregulated gene expressions of M1 markers (CCR7, IL-1ß, CCL2, Cox2, CD80). These cells reacted to virus-derived antigen, as evidenced by increased expression of pattern-recognition receptors TLR3, TLR7, and TLR9, subsequently providing feedback in the form of type I interferon responses like IFNAR1, IFN-ß, IRF3, IRF7, OAS1, Mx1, and ISG15. Through an MTT assay, only after 15 µg/ml of A3 treatment could the cell viability decrease, with a predicted IC50 of 16.96 µg/ml. Interestingly, A3 caused dose-dependent toxicity to a rat C6 glial cancer cell line even at doses as low as 2.5 µg/ml and reached its IC50 at 9.419 µg/ml. Using Annexin V/7AAD staining and PCR test, we deduced that a significant proportion of C6 cells were undergoing the early apoptosis phase predominantly through the intrinsic apoptosis cascade involving Bcl-2 family proteins. Following this stage, we conducted a test on A3’s repolarization ability, which revealed a significant rise in M1 gene expression markers, such as TNF, CD80, and IL-1ß, in M2-like TAMs generated in vitro from murine RAW264.7 macrophages grown with conditioned medium of 4T1 breast cancer cells. This was corroborated by the results of transcriptome analysis, which revealed that the primary subset among the top 10 to top 30 significantly upregulated differentially expressed genes (DEGs) dominantly consisted of M1 macrophages profiles, including Ccl3, Ccl4, Csf3, TNF, Bcl6b, Stc1, and Dusp2. Our findings unveiled the remarkable potential of the PRRSV-derived antigen A3 to repolarize macrophages while also being capable of selectively inducing apoptosis in cancerous cells. While further in vivo study is needed for A3, it holds promise as an adjuvant by its dual effects in cancer therapy modalities.

Keywords: cancer cell apoptosis, interferon responses, macrophage repolarization, recombinant protein

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Authors: Ashok Kumar, Parveen Parveen

Abstract:

India is bestowed with an extremely high population of plant species with medicinal value and even has two biodiversity hotspots. Indian systems of medicine including Ayurveda, Siddha and Unani have historically been serving humankind across the world since time immemorial. About 1500 plant species have well been documented in Ayurvedic Nighantus as official medicinal plants. Additionally, several hundred species of plants are being routinely used as medicines by local people especially tribes living in and around forests. The natural resources for medicinal plants have unscientifically been over-exploited forcing rapid depletion in their genetic diversity. Moreover, renewed global interest in herbal medicines may even lead to additional depletion of medicinal plant wealth of the country, as about 95% collection of medicinal plants for pharmaceutical preparation is being carried out from natural forests. On the other hand, huge export market of medicinal and aromatic plants needs to be seriously tapped for enhancing inflow of foreign currency. Asparagus racemosus Willd., a member of family Liliaceae, is one of thirty-two plant species that have been identified as priority species for cultivation and conservation by the National Medicinal Plant Board (NMPB), Government of India. Though attention is being focused on standardization of agro-techniques and extraction methods, little has been designed on genetic improvement and selection of desired types with higher root production and saponin content, a basic ingredient of medicinal value. The saponin not only improves defense mechanisms and controls diabetes but the roots of this species promote secretion of breast milk, improved lost body weight and considered as an aphrodisiac. There is ample scope for genetic improvement of this species for enhancing productivity substantially, qualitatively and quantitatively. It is emphasized to select desired genotypes with sufficient genetic diversity for important economic traits. Hybridization between two genetically divergent genotypes could result in the synthesis of new F1 hybrids consisting of useful traits of both the parents. The evaluation of twenty seed sources of Asparagus racemosus assembled different geographical locations of India revelled high degree of variability for traits of economic importance. The maximum genotypic and phenotypic variance was observed for shoot height among shoot related traits and for root length among root related traits. The shoot height, genotypic variance, phenotypic variance, genotypic coefficient of variance, the phenotypic coefficient of variance was recorded to be 231.80, 3924.80, 61.26 and 1037.32, respectively, where those of the root length were 9.55, 16.80, 23.46 and 41.27, respectively. The maximum genetic advance and genetic gain were obtained for shoot height among shoot-related traits and root length among root-related traits. Index values were developed for all seed sources based on the four most important traits, and Panthnagar (Uttrakhand), Jodhpur (Rajasthan), Dehradun (Uttarakhand), Chandigarh (Punjab), Jammu (Jammu & Kashmir) and Solan (Himachal Pradesh) were found to be promising seed sources.

Keywords: asparagus, genetic, genotypes, variance

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Authors: Farhana Karim, Abdullah N. S. Khan, Mohiuddin A. K. Chowdhury, Nabila Zaka, Alexander Manu, Shams El Arifeen, Sk Masum Billah

Abstract:

Breastfeeding, an integral part of newborn care, can reduce 55-87% of all-cause neonatal mortality and morbidity. Early initiation of breastfeeding within 1 hour of birth can avert 22% of newborn mortality. Only 45% of world’s newborns and 42% of newborns in South-Asia are put to the breast within one hour of birth. In Bangladesh, only a half of the mothers practice early initiation of breastfeeding which is less likely to be practiced if the baby is born in a health facility. This study aims to generate strong evidence for early initiation of breastfeeding practices in the government health facilities and to explore the associated factors influencing the practice. The study was conducted in selected health facilities in three neighbouring districts of Northern Bangladesh. Total 249 normal vaginal delivery cases were observed for 24 hours since the time of birth. The outcome variable was initiation of breastfeeding within 1 hour while the explanatory variables included type of health facility, privacy, presence of support person, stage of labour at admission, need for augmentation of labour, complications during delivery, need for episiotomy, spontaneous cry of the newborn, skin-to-skin contact with mother, post-natal contact with the service provider, receiving a post-natal examination and counselling on breastfeeding during postnatal contact. The simple descriptive statistics were employed to see the distribution of samples according to socio-demographic characteristics. Kruskal-Wallis test was carried out for testing the equality of medians among two or more categories of each variable and P-value is reported. A series of simple logistic regressions were conducted with all the potential explanatory variables to identify the determining factors for breastfeeding within 1 hour in a health facility. Finally, multiple logistic regression was conducted including the variables found significant at bi-variate analyses. Almost 90% participants initiated breastfeeding at the health facility and median time to initiate breastfeeding was 38 minutes. However, delivering in a sub-district hospital significantly delayed the breastfeeding initiation in comparison to delivering in a district hospital. Maintenance of adequate privacy and presence of separate staff for taking care of newborn significantly reduced the time in early breastfeeding initiation. Initiation time was found longer if the mother had an augmented labour, obstetric complications, and the newborn needed resuscitation. However, the initiation time was significantly early if the baby was put skin-to-skin on mother’s abdomen and received a postnatal examination by a provider. After controlling for the potential confounders, the odds of initiating breastfeeding within one hour of birth is higher if mother gives birth in a district hospital (AOR 3.0: 95% CI 1.5, 6.2), privacy is well-maintained (AOR 2.3: 95% CI 1.1, 4.5), babies cry spontaneously (AOR 7.7: 95% CI 3.3, 17.8), babies are put to skin-to-skin contact with mother (AOR 4.6: 95% CI 1.9, 11.2) and if the baby is examined by a provider in the facility (AOR 4.4: 95% CI 1.4, 14.2). The evidence generated by this study will hopefully direct the policymakers to identify and prioritize the scopes for creating and supporting early initiation of breastfeeding in the health facilities.

Keywords: Bangladesh, early initiation of breastfeeding, health facility, normal vaginal delivery, skin to skin contact

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Authors: Parag Katira, Frederika Rentzeperis, Zuzanna Nowicka, Giada Fiandaca, Thomas Veith, Jack Farinhas, Noemi Andor

Abstract:

Resource limitations shape the outcome of competitions between genetically heterogeneous pre-malignant cells. One example of such heterogeneity is in the ploidy (DNA content) of pre-malignant cells. A whole-genome duplication (WGD) transforms a diploid cell into a tetraploid one and has been detected in 28-56% of human cancers. If a tetraploid subclone expands, it consistently does so early in tumor evolution, when cell density is still low, and competition for nutrients is comparatively weak – an observation confirmed for several tumor types. WGD+ cells need more resources to synthesize increasing amounts of DNA, RNA, and proteins. To quantify resource limitations and how they relate to ploidy, we performed a PAN cancer analysis of WGD, PET/CT, and MRI scans. Segmentation of >20 different organs from >900 PET/CT scans were performed with MOOSE. We observed a strong correlation between organ-wide population-average estimates of Oxygen and the average ploidy of cancers growing in the respective organ (Pearson R = 0.66; P= 0.001). In-vitro experiments using near-diploid and near-tetraploid lineages derived from a breast cancer cell line supported the hypothesis that DNA content influences Glucose- and Oxygen-dependent proliferation-, death- and migration rates. To model how subpopulations with variable DNA content compete in the resource-limited environment of the human brain, we developed a stochastic state-space model of the brain (S3MB). The model discretizes the brain into voxels, whereby the state of each voxel is defined by 8+ variables that are updated over time: stiffness, Oxygen, phosphate, glucose, vasculature, dead cells, migrating cells and proliferating cells of various DNA content, and treat conditions such as radiotherapy and chemotherapy. Well-established Fokker-Planck partial differential equations govern the distribution of resources and cells across voxels. We applied S3MB on sequencing and imaging data obtained from a primary GBM patient. We performed whole genome sequencing (WGS) of four surgical specimens collected during the 1ˢᵗ and 2ⁿᵈ surgeries of the GBM and used HATCHET to quantify its clonal composition and how it changes between the two surgeries. HATCHET identified two aneuploid subpopulations of ploidy 1.98 and 2.29, respectively. The low-ploidy clone was dominant at the time of the first surgery and became even more dominant upon recurrence. MRI images were available before and after each surgery and registered to MNI space. The S3MB domain was initiated from 4mm³ voxels of the MNI space. T1 post and T2 flair scan acquired after the 1ˢᵗ surgery informed tumor cell densities per voxel. Magnetic Resonance Elastography scans and PET/CT scans informed stiffness and Glucose access per voxel. We performed a parameter search to recapitulate the GBM’s tumor cell density and ploidy composition before the 2ⁿᵈ surgery. Results suggest that the high-ploidy subpopulation had a higher Glucose-dependent proliferation rate (0.70 vs. 0.49), but a lower Glucose-dependent death rate (0.47 vs. 1.42). These differences resulted in spatial differences in the distribution of the two subpopulations. Our results contribute to a better understanding of how genomics and microenvironments interact to shape cell fate decisions and could help pave the way to therapeutic strategies that mimic prognostically favorable environments.

Keywords: tumor evolution, intra-tumor heterogeneity, whole-genome doubling, mathematical modeling

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Authors: Manuel I. Capel, Antonio Tomeu, Alberto Salguero

Abstract:

Tumor growth from a transformed cancer-cell up to a clinically apparent mass spans through a range of spatial and temporal magnitudes. Through computer simulations, Cellular Automata (CA) can accurately describe the complexity of the development of tumors. Tumor development prognosis can now be made -without making patients undergo through annoying medical examinations or painful invasive procedures- if we develop appropriate CA-based software tools. In silico testing mainly refers to Computational Biology research studies of application to clinical actions in Medicine. To establish sound computer-based models of cellular behavior, certainly reduces costs and saves precious time with respect to carrying out experiments in vitro at labs or in vivo with living cells and organisms. These aim to produce scientifically relevant results compared to traditional in vitro testing, which is slow, expensive, and does not generally have acceptable reproducibility under the same conditions. For speeding up computer simulations of cellular models, specific literature shows recent proposals based on the CA approach that include advanced techniques, such the clever use of supporting efficient data structures when modeling with deterministic stochastic cellular automata. Multiparadigm and multiscale simulation of tumor dynamics is just beginning to be developed by the concerned research community. The use of stochastic cellular automata (SCA), whose parallel programming implementations are open to yield a high computational performance, are of much interest to be explored up to their computational limits. There have been some approaches based on optimizations to advance in multiparadigm models of tumor growth, which mainly pursuit to improve performance of these models through efficient memory accesses guarantee, or considering the dynamic evolution of the memory space (grids, trees,…) that holds crucial data in simulations. In our opinion, the different optimizations mentioned above are not decisive enough to achieve the high performance computing power that cell-behavior simulation programs actually need. The possibility of using multicore and GPU parallelism as a promising multiplatform and framework to develop new programming techniques to speed-up the computation time of simulations is just starting to be explored in the few last years. This paper presents a model that incorporates parallel processing, identifying the synchronization necessary for speeding up tumor growth simulations implemented in Java and C++ programming environments. The speed up improvement that specific parallel syntactic constructs, such as executors (thread pools) in Java, are studied. The new tumor growth parallel model is proved using implementations with Java and C++ languages on two different platforms: chipset Intel core i-X and a HPC cluster of processors at our university. The parallelization of Polesczuk and Enderling model (normally used by researchers in mathematical oncology) proposed here is analyzed with respect to performance gain. We intend to apply the model and overall parallelization technique presented here to solid tumors of specific affiliation such as prostate, breast, or colon. Our final objective is to set up a multiparadigm model capable of modelling angiogenesis, or the growth inhibition induced by chemotaxis, as well as the effect of therapies based on the presence of cytotoxic/cytostatic drugs.

Keywords: cellular automaton, tumor growth model, simulation, multicore and manycore programming, parallel programming, high performance computing, speed up

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