Search results for: advanced cancer
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4251

Search results for: advanced cancer

3081 Stage-Gate Framework Application for Innovation Assessment among Small and Medium-Sized Enterprises

Authors: Indre Brazauskaite, Vilte Auruskeviciene

Abstract:

The paper explores the Stage-Gate framework application for innovation maturity among small and medium-sized enterprises (SMEs). Innovation management becomes an essential business survival process for all sizes of organizations that can be evaluated and audited systemically. This research systemically defines and assesses the innovation process from the perspective of the company’s top management. Empirical research explores attitudes and existing practices of innovation management in SMEs in Baltic countries. It structurally investigates the current innovation management practices, level of standardization, and potential challenges in the area. Findings allow to structure of existing practices based on an institutionalized model and contribute to a more advanced understanding of the innovation process among SMEs. Practically, findings contribute to advanced decision-making and business planning in the process.

Keywords: innovation measure, innovation process, SMEs, stage-gate framework

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3080 Tumour Radionuclides Therapy: in vitro and in vivo Dose Distribution Study

Authors: Rekaya A. Shabbir, Marco Mingarelli, Glenn Flux, Ananya Choudhury, Tim A. D. Smith

Abstract:

Introduction: Heterogeneity of dose distributions across a tumour is problematic for targeted radiotherapy. Gold nanoparticles (AuNPs) enhance dose-distributions of targeted radionuclides. The aim of this study is to demonstrate if tumour dose-distribution of targeted AuNPs radiolabelled with either of two radioisotopes (¹⁷⁷Lu and ⁹⁰Y) in breast cancer cells produced homogeneous dose distributions. Moreover, in vitro and in vivo studies were conducted to study the importance of receptor level on cytotoxicity of EGFR-targeted AuNPs in breast and colorectal cancer cells. Methods: AuNPs were functionalised with DOTA and OPPS-PEG-SVA to optimise labelling with radionuclide tracers and targeting with Erbitux. Radionuclides were chelated with DOTA, and the uptake of the radiolabelled AuNPs and targeted activity in vitro in both cell lines measured using liquid scintillation counting. Cells with medium (HCT8) and high (MDA-MB-468) EGFR expression were incubated with targeted ¹⁷⁷Lu-AuNPs for 4h, then washed and allowed to form colonies. Nude mice bearing tumours were used to study the biodistribution by injecting ¹⁷⁷Lu-AuNPs or ⁹⁰Y-AuNPs via the tail vein. Heterogeneity of dose-distribution in tumours was determined using autoradiography. Results: Colony formation (% control) was 81 ± 4.7% (HCT8) and 32 ± 9% (MDA-MB-468). High uptake was observed in the liver and spleen, indicating hepatobiliary excretion. Imaging showed heterogeneity in dose-distributions for both radionuclides across the tumours. Conclusion: The cytotoxic effect of EGFR-targeted AuNPs is greater in cells with higher EGFR expression. Dose-distributions for individual radiolabelled nanoparticles were heterogeneous across tumours. Further strategies are required to improve the uniformity of dose distribution prior to clinical trials.

Keywords: cancer cells, dose distributions, radionuclide therapy, targeted gold nanoparticles

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3079 Alternating Electric fields-Induced Senescence in Glioblastoma

Authors: Eun Ho Kim

Abstract:

Innovations have conjured up a mode of treating GBM cancer cells in the newly diagnosed patients in a period of 4.9 months at an improved median OS, which brings along only a few minor side effects in the phase III of the clinical trial. This mode has been termed the Alternating Electric Fields (AEF). The study at hand is aimed at determining whether the AEF treatment is beneficial in sensitizing the GBM cancer cells through the process of increasing the AEF –induced senescence. The methodology to obtain the findings for this research ranged across various components, such as obtaining and testing SA-β-gal staining, flow cytometry, Western blotting, morphology, and Positron Emission Tomography (PET) / Computed Tomography (CT), immunohistochemical staining and microarray. The number of cells that displayed a senescence-specific morphology and positive SA-ß-Gal activity gradually increased up to 5 days. These results suggest that p16, p21 and p27 are essential regulators of AEF -induced senescence via NF-κB activation. The results showed that the AEF treatment is functional in enhancing the AEF –induced senescence in the GBM cells via an apoptosis- independent mechanism. This research concludes that this mode of treatment is a trustworthy protocol that can be effectively employed to overcome the limitations of the conventional mode of treatment on GBM.

Keywords: alternating electric fields, senescence, glioblastoma, cell death

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3078 Noncovalent Antibody-Nanomaterial Conjugates: A Simple Approach to Produce Targeted Nanomedicines

Authors: Nicholas Fletcher, Zachary Houston, Yongmei Zhao, Christopher Howard, Kristofer Thurecht

Abstract:

One promising approach to enhance nanomedicine therapeutic efficacy is to include a targeting agent, such as an antibody, to increase accumulation at the tumor site. However, the application of such targeted nanomedicines remains limited, in part due to difficulties involved with biomolecule conjugation to synthetic nanomaterials. One approach recently developed to overcome this has been to engineer bispecific antibodies (BsAbs) with dual specificity, whereby one portion binds to methoxy polyethyleneglycol (mPEG) epitopes present on synthetic nanomedicines, while the other binds to molecular disease markers of interest. In this way, noncovalent complexes of nanomedicine core, comprising a hyperbranched polymer (HBP) of primarily mPEG, decorated with targeting ligands are able to be produced by simple mixing. Further work in this area has now demonstrated such complexes targeting the breast cancer marker epidermal growth factor receptor (EGFR) to show enhanced binding to tumor cells both in vitro and in vivo. Indeed the enhanced accumulation at the tumor site resulted in improved therapeutic outcomes compared to untargeted nanomedicines and free chemotherapeutics. The current work on these BsAb-HBP conjugates focuses on further probing antibody-nanomaterial interactions and demonstrating broad applicability to a range of cancer types. Herein are reported BsAb-HBP materials targeted towards prostate-specific membrane antigen (PSMA) and study of their behavior in vivo using ⁸⁹Zr positron emission tomography (PET) in a dual-tumor prostate cancer xenograft model. In this model mice bearing both PSMA+ and PSMA- tumors allow for PET imaging to discriminate between nonspecific and targeted uptake in tumors, and better quantify the increased accumulation following BsAb conjugation. Also examined is the potential for formation of these targeted complexes in situ following injection of individual components? The aim of this approach being to avoid undesirable clearance of proteinaceous complexes upon injection limiting available therapeutic. Ultimately these results demonstrate BsAb functionalized nanomaterials as a powerful and versatile approach for producing targeted nanomedicines for a variety of cancers.

Keywords: bioengineering, cancer, nanomedicine, polymer chemistry

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3077 Immunomodulatory Activity of Polysaccharide-Protein Complex Isolated from the Sclerotia of Polyporus Rhinocerus in Murine Macrophages

Authors: Chaoran Liu

Abstract:

Bioactive polysaccharides and polysaccharide-protein complex derived from mushrooms and fungi have a wide range of immunomodulatory activity with low side-effects and have therefore the potential to be developed as an adjuvant in cancer therapies. Mushrooms sclerotium is rich in polysaccharides and the polysaccharides isolated from the sclerotium of Polyporus rhinocerus have shown potent in vivo and in vitro immunomodulatory effects. Macrophages are considered to be an important component of the innate immune response against bacterial infection and cancer. To better understanding the immunomodulatory effects and its underlying mechanisms of sclerotial water-soluble polysaccharides extracted from P. rhinocerus on macrophages, the objectives of this study are to purify the water-soluble novel sclerotial polysaccharides and to characterize the structure and properties as well as to study the detailed molecular mechanisms of the in vitro immunomodulating effects in murine macrophages. The hot water-soluble fraction PRW from the sclerotium of P. rhinocerus was obtained using solvent extraction. PRW was further fractionated by membrane ultrafiltration to a give a fraction (PRW1) with molecular mass less than 50 kDa. PRW1 was characterized to be a polysaccharide-protein complex composed of 45.7% polysaccharide and 44.2% protein. The chemical structure of the carbohydrate moiety of PRW1 was elucidated by GC and FTIR to be mainly beta-D-glucan with trace amount of galactose and mannose. The immunomodulatory effects of PRW1 on murine RAW 264.7 macrophages were demonstrated in terms of the increase in nitric oxide production and cytokine production. Mechanistically, PRW1 initiates ERK phosphorylation to activate macrophages within 15 min and significantly improves the expression level of inducible NOS (iNOS) from 6 h after treatment. In summary, this study indicates that PRW1 is a potent immunomodulatory agent for macrophages and suggests that mushroom sclerotia from Polyporus rhinocerus requires for further investigation in cancer research.

Keywords: Polyporus rhinocerus, mushroom sclerotia, Polysaccharide-Protein Complex, macrophage activation

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3076 Nanoscale Metal-Organic Framework Coated Carbon Nitride Nanosheet for Combination Cancer Therapy

Authors: Rui Chen, Jinfeng Zhang, Chun-Sing Lee

Abstract:

In the past couple of decades, nanoscale metal-organic frameworks (NMOFs) have been highlighted as promising delivery platforms for biomedical applications, which combine many potent features such as high loading capacity, progressive biodegradability and low cytotoxicity. While NMOF has been extensively used as carriers for drugs of different modalities, so far there is no report on exploiting the advantages of NMOF for combination therapy. Herein, we prepared core-shell nanoparticles, where each nanoparticle contains a single graphitic-phase carbon nitride (g-C3N4) nanosheet encapsulated by a zeolitic-imidazolate frameworks-8 (ZIF-8) shell. The g-C3N4 nanosheets are effective visible-light photosensitizer for photodynamic therapy (PDT). When hosting DOX (doxorubicin), the as-synthesized core-shell nanoparticles could realize combinational photo-chemo therapy and provide dual-color fluorescence imaging. Therefore, we expect NMOFs-based core-shell nanoparticles could provide a new way to achieve much-enhanced cancer therapy.

Keywords: carbon nitride, combination therapy, drug delivery, nanoscale metal-organic frameworks

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3075 Breast Cancer Therapy-Related Cardiac Dysfunction Identifying in Kazakhstan: Preliminary Findings of the Cohort Study

Authors: Saule Balmagambetova, Zhenisgul Tlegenova, Saule Madinova

Abstract:

Cardiotoxicity associated with anticancer treatment, now defined as cancer therapy-related cardiac dysfunction (CTRCD), accompanies cancer patients and negatively impacts their survivorship. Currently, a cardio-oncological service is being created in Kazakhstan based on the provisions of the European Society of Cardio-oncology (ESC) Guidelines. In the frames of a pilot project, a cohort study on CTRCD conditions was initiated at the Aktobe Cancer center. One hundred twenty-eight newly diagnosed breast cancer patients started on doxorubicin and/or trastuzumab were recruited. Echocardiography with global longitudinal strain (GLS) assessment, biomarkers panel (cardiac troponin (cTnI), brain natriuretic peptide (BNP), myeloperoxidase (MPO), galectin-3 (Gal-3), D-dimers, C-reactive protein (CRP)), and other tests were performed at baseline and every three months. Patients were stratified by the cardiovascular risks according to the ESC recommendations and allocated into the risk groups during the pre-treatment visit. Of them, 10 (7.8%) patients were assigned to the high-risk group, 48 (37.5%) to the medium-risk group, and 70 (54.7%) to the low-risk group, respectively. High-risk patients have been receiving their cardioprotective treatment from the outset. Patients were also divided by treatment - in the anthracycline-based 83 (64.8%), in trastuzumab- only 13 (10.2%), and in the mixed anthracycline/trastuzumab group 32 individuals (25%), respectively. Mild symptomatic CTRCD was revealed and treated in 2 (1.6%) participants, and a mild asymptomatic variant in 26 (20.5%). Mild asymptomatic conditions are defined as left ventricular ejection fraction (LVEF) ≥50% and further relative reduction in GLS by >15% from baseline and/or a further rise in cardiac biomarkers. The listed biomarkers were assessed longitudinally in repeated-measures linear regression models during 12 months of observation. The associations between changes in biomarkers and CTRCD and between changes in biomarkers and LVEF were evaluated. Analysis by risk groups revealed statistically significant differences in baseline LVEF scores (p 0.001), BNP (p 0.0075), and Gal-3 (p 0.0073). Treatment groups found no statistically significant differences at baseline. After 12 months of follow-up, only LVEF values showed a statistically significant difference by risk groups (p 0.0011). When assessing the temporal changes in the studied parameters for all treatment groups, there were statistically significant changes from visit to visit for LVEF (p 0.003); GLS (p 0.0001); BNP (p<0.00001); MPO (p<0.0001); and Gal-3 (p<0.0001). No moderate or strong correlations were found between the biomarkers values and LVEF, between biomarkers and GLS. Between the biomarkers themselves, a moderate, close to strong correlation was established between cTnI and D-dimer (r 0.65, p<0.05). The dose-dependent effect of anthracyclines has been confirmed: the summary dose has a moderate negative impact on GLS values: -r 0.31 for all treatment groups (p<0.05). The present study found myeloperoxidase as a promising biomarker of cardiac dysfunction in the mixed anthracycline/trastuzumab treatment group. The hazard of CTRCD increased by 24% (HR 1.21; 95% CI 1.01;1.73) per doubling in baseline MPO value (p 0.041). Increases in BNP were also associated with CTRCD (HR per doubling, 1.22; 95% CI 1.12;1.69). No cases of chemotherapy discontinuation due to cardiotoxic complications have been recorded. Further observations are needed to gain insight into the ability of biomarkers to predict CTRCD onset.

Keywords: breast cancer, chemotherapy, cardiotoxicity, Kazakhstan

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3074 Cytotoxic Activity against Hepatocarcinoma and Cholangiocarcinoma Cells of Four Cathartic Herbal Medicines

Authors: Pranporn Kuropakornpong, Srisopa Ruangnoo, Arunporn Itharat

Abstract:

Liver cancer has the highest prevalence rate in the North and Northeast of Thailand. Four Thai medicinal plants such as resin of Ferula asafoetida Regel, latex of Aloe barbadensis Miller leaves, roots of Baliospermum manotanum, and latex of Garcinia hanburyi Hook are used in Thai traditional medicine as cathartic drug and detoxification in liver cancer patients. Thus, this research aimed to evaluate the cytotoxic activity of these plants against hepatocarcinoma (HepG2) and cholangiocarcinoma (KKU-M156) cells by SRB assay. These plants were macerated in 95% ethanol. The results showed that roots of Baliospermum manotanum and latex of Garcinia hanburyi Hook showed the strongest cytotoxicity against HepG2 (IC50 = 3.03+0.91 and 0.62+0.01µg/ml, respectively) and KKU-M156 (IC50 = 0.978+0.663 and 0.006+0.005 µg/ml, respectively). Latex of Garcinia hanburyi Hook also showed high cytotoxicity against normal cell line (IC50=8.86+0.31 µg/ml), and even though its selective values are high, dose of this herb should be limited.

Keywords: cholangiocarcinoma, cytotoxic activity, Garcinia hanburyi Hook, hepatocarcinoma

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3073 Establishment of the Regression Uncertainty of the Critical Heat Flux Power Correlation for an Advanced Fuel Bundle

Authors: L. Q. Yuan, J. Yang, A. Siddiqui

Abstract:

A new regression uncertainty analysis methodology was applied to determine the uncertainties of the critical heat flux (CHF) power correlation for an advanced 43-element bundle design, which was developed by Canadian Nuclear Laboratories (CNL) to achieve improved economics, resource utilization and energy sustainability. The new methodology is considered more appropriate than the traditional methodology in the assessment of the experimental uncertainty associated with regressions. The methodology was first assessed using both the Monte Carlo Method (MCM) and the Taylor Series Method (TSM) for a simple linear regression model, and then extended successfully to a non-linear CHF power regression model (CHF power as a function of inlet temperature, outlet pressure and mass flow rate). The regression uncertainty assessed by MCM agrees well with that by TSM. An equation to evaluate the CHF power regression uncertainty was developed and expressed as a function of independent variables that determine the CHF power.

Keywords: CHF experiment, CHF correlation, regression uncertainty, Monte Carlo Method, Taylor Series Method

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3072 Progress Towards Optimizing and Standardizing Fiducial Placement Geometry in Prostate, Renal, and Pancreatic Cancer

Authors: Shiva Naidoo, Kristena Yossef, Grimm Jimm, Mirza Wasique, Eric Kemmerer, Joshua Obuch, Anand Mahadevan

Abstract:

Background: Fiducial markers effectively enhance tumor target visibility prior to Stereotactic Body Radiation Therapy or Proton therapy. To streamline clinical practice, fiducial placement guidelines from a robotic radiosurgery vendor were examined with the goals of optimizing and standardizing feasible geometries for each treatment indication. Clinical examples of prostate, renal, and pancreatic cases are presented. Methods: Vendor guidelines (Accuray, Sunnyvale, Ca) suggest implantation of 4–6 fiducials at least 20 mm apart, with at least a 15-degree angular difference between fiducials, within 50 mm or less from the target centroid, to ensure that any potential fiducial motion (e.g., from respiration or abdominal/pelvic pressures) will mimic target motion. Also recommended is that all fiducials can be seen in 45-degree oblique views with no overlap to coincide with the robotic radiosurgery imaging planes. For the prostate, a standardized geometry that meets all these objectives is a 2 cm-by-2 cm square in the coronal plane. The transperineal implant of two pairs of preloaded tandem fiducials makes the 2 cm-by-2 cm square geometry clinically feasible. This technique may be applied for renal cancer, except repositioned in a sagittal plane, with the retroperitoneal placement of the fiducials into the tumor. Pancreatic fiducial placement via endoscopic ultrasound (EUS) is technically more challenging, as fiducial placement is operator-dependent, and lesion access may be limited by adjacent vasculature, tumor location, or restricted mobility of the EUS probe in the duodenum. Fluoroscopically assisted fiducial placement during EUS can help ensure fiducial markers are deployed with optimal geometry and visualization. Results: Among the first 22 fiducial cases on a newly installed robotic radiosurgery system, live x-ray images for all nine prostatic cases had excellent fiducial visualization at the treatment console. Renal and pancreatic fiducials were not as clearly visible due to difficult target access and smaller caliber insertion needle/fiducial usage. The geometry of the first prostate case was used to ensure accurate geometric marker placement for the remaining 8 cases. Initially, some of the renal and pancreatic fiducials were closer than the 20 mm recommendation, and interactive feedback with the proceduralists led to subsequent fiducials being too far to the edge of the tumor. Further feedback and discussion of all cases are being used to help guide standardized geometries and achieve ideal fiducial placement. Conclusion: The ideal tradeoffs of fiducial visibility versus the thinnest possible gauge needle to avoid complications needs to be systematically optimized among all patients, particularly in regards to body habitus. Multidisciplinary collaboration among proceduralists and radiation oncologists can lead to improved outcomes.

Keywords: fiducial, prostate cancer, renal cancer, pancreatic cancer, radiotherapy

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3071 Integrated Braking and Traction Torque Vectoring Control Based on Vehicle Yaw Rate for Stability improvement of All-Wheel-Drive Electric Vehicles

Authors: Mahmoud Said Jneid, Péter Harth

Abstract:

EVs with independent wheel driving greatly improve vehicle stability in poor road conditions. Wheel torques can be precisely controlled through electric motors driven using advanced technologies. As a result, various types of advanced chassis assistance systems (ACAS) can be implemented. This paper proposes an integrated torque vectoring control based on wheel slip regulation in both braking and traction modes. For generating the corrective yaw moment, the vehicle yaw rate and sideslip angle are monitored. The corrective yaw moment is distributed into traction and braking torques based on an equal-opposite components approach. The proposed torque vectoring control scheme is validated in simulation and the results show its superiority when compared to conventional schemes.

Keywords: all-wheel-drive, electric vehicle, torque vectoring, regenerative braking, stability control, traction control, yaw rate control

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3070 Hybrid-Nanoengineering™: A New Platform for Nanomedicine

Authors: Mewa Singh

Abstract:

Nanomedicine, a fusion of nanotechnology and medicine, is an emerging technology ideally suited to the targeted therapies. Nanoparticles overcome the low selectivity of anti-cancer drugs toward the tumor as compared to normal tissue and hence result-in less severe side-effects. Our new technology, HYBRID-NANOENGINEERING™, uses a new molecule (MR007) in the creation of nanoparticles that not only helps in nanonizing the medicine but also provides synergy to the medicine. The simplified manufacturing process will result in reduced manufacturing costs. Treatment is made more convenient because hybrid nanomedicines can be produced in oral, injectable or transdermal formulations. The manufacturing process uses no protein, oil or detergents. The particle size is below 180 nm with a narrow distribution of size. Importantly, these properties confer great stability of the structure. The formulation does not aggregate in plasma and is stable over a wide range of pH. The final hybrid formulation is stable for at least 18 months as a powder. More than 97 drugs, including paclitaxel, docetaxel, tamoxifen, doxorubicinm prednisone, and artemisinin have been nanonized in water soluble formulations. Preclinical studies on cell cultures of tumors show promising results. Our HYBRID-NANOENGINEERING™ platform enables the design and development of hybrid nano-pharmaceuticals that combine efficacy with tolerability, giving patients hope for both extended overall survival and improved quality of life. This study would discuss or present this new discovery of HYBRID-NANOENGINEERING™ which targets drug delivery, synergistic, and potentiating effects, and barriers of drug delivery and advanced drug delivery systems.

Keywords: nano-medicine, nano-particles, drug delivery system, pharmaceuticals

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3069 Decisional Regret in Men with Localized Prostate Cancer among Various Treatment Options and the Association with Erectile Functioning and Depressive Symptoms: A Moderation Analysis

Authors: Caren Hilger, Silke Burkert, Friederike Kendel

Abstract:

Men with localized prostate cancer (PCa) have to choose among different treatment options, such as active surveillance (AS) and radical prostatectomy (RP). All available treatment options may be accompanied by specific psychological or physiological side effects. Depending on the nature and extent of these side effects, patients are more or less likely to be satisfied or to struggle with their treatment decision in the long term. Therefore, the aim of this study was to assess and explain decisional regret in men with localized PCa. The role of erectile functioning as one of the main physiological side effects of invasive PCa treatment, depressive symptoms as a common psychological side effect, and the association of erectile functioning and depressive symptoms with decisional regret were investigated. Men with localized PCa initially managed with AS or RP (N=292) were matched according to length of therapy (mean 47.9±15.4 months). Subjects completed mailed questionnaires assessing decisional regret, changes in erectile functioning, depressive symptoms, and sociodemographic variables. Clinical data were obtained from case report forms. Differences among the two treatment groups (AS and RP) were calculated using t-tests and χ²-tests, relationships of decisional regret with erectile functioning and depressive symptoms were computed using multiple regression. Men were on average 70±7.2 years old. The two treatment groups differed markedly regarding decisional regret (p<.001, d=.50), changes in erectile functioning (p<.001, d=1.2), and depressive symptoms (p=.01, d=.30), with men after RP reporting higher values, respectively. Regression analyses showed that after adjustment for age, tumor risk category, and changes in erectile functioning, depressive symptoms were still significantly associated with decisional regret (B=0.52, p<.001). Additionally, when predicting decisional regret, the interaction of changes in erectile functioning and depressive symptoms reached significance for men after RP (B=0.52, p<.001), but not for men under AS (B=-0.16, p=.14). With increased changes in erectile functioning, the association of depressive symptoms with decisional regret became stronger in men after RP. Decisional regret is a phenomenon more prominent in men after RP than in men under AS. Erectile functioning and depressive symptoms interact in their prediction of decisional regret. Screening and treating depressive symptoms might constitute a starting point for interventions aiming to reduce decisional regret in this target group.

Keywords: active surveillance, decisional regret, depressive symptoms, erectile functioning, prostate cancer, radical prostatectomy

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3068 A Novel NRIS Index to Evaluate Brain Activity in Prefrontal Regions While Listening to First and Second Languages for Long Time Periods

Authors: Kensho Takahashi, Ko Watanabe, Takashi Kaburagi, Hiroshi Tanaka, Kajiro Watanabe, Yosuke Kurihara

Abstract:

Near-infrared spectroscopy (NIRS) has been widely used as a non-invasive method to measure brain activity, but it is corrupted by baseline drift noise. Here we present a method to measure regional cerebral blood flow as a derivative of NIRS output. We investigate whether, when listening to languages, blood flow can reasonably localize and represent regional brain activity or not. The prefrontal blood flow distribution pattern when advanced second-language listeners listened to a second language (L2) was most similar to that when listening to their first language (L1) among the patterns of mean and standard deviation. In experiments with 25 healthy subjects, the maximum blood flow was localized to the left BA46 of advanced listeners. The blood flow presented is robust to baseline drift and stably localizes regional brain activity.

Keywords: NIRS, oxy-hemoglobin, baseline drift, blood flow, working memory, BA46, first language, second language

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3067 Integrating Natural Language Processing (NLP) and Machine Learning in Lung Cancer Diagnosis

Authors: Mehrnaz Mostafavi

Abstract:

The assessment and categorization of incidental lung nodules present a considerable challenge in healthcare, often necessitating resource-intensive multiple computed tomography (CT) scans for growth confirmation. This research addresses this issue by introducing a distinct computational approach leveraging radiomics and deep-learning methods. However, understanding local services is essential before implementing these advancements. With diverse tracking methods in place, there is a need for efficient and accurate identification approaches, especially in the context of managing lung nodules alongside pre-existing cancer scenarios. This study explores the integration of text-based algorithms in medical data curation, indicating their efficacy in conjunction with machine learning and deep-learning models for identifying lung nodules. Combining medical images with text data has demonstrated superior data retrieval compared to using each modality independently. While deep learning and text analysis show potential in detecting previously missed nodules, challenges persist, such as increased false positives. The presented research introduces a Structured-Query-Language (SQL) algorithm designed for identifying pulmonary nodules in a tertiary cancer center, externally validated at another hospital. Leveraging natural language processing (NLP) and machine learning, the algorithm categorizes lung nodule reports based on sentence features, aiming to facilitate research and assess clinical pathways. The hypothesis posits that the algorithm can accurately identify lung nodule CT scans and predict concerning nodule features using machine-learning classifiers. Through a retrospective observational study spanning a decade, CT scan reports were collected, and an algorithm was developed to extract and classify data. Results underscore the complexity of lung nodule cohorts in cancer centers, emphasizing the importance of careful evaluation before assuming a metastatic origin. The SQL and NLP algorithms demonstrated high accuracy in identifying lung nodule sentences, indicating potential for local service evaluation and research dataset creation. Machine-learning models exhibited strong accuracy in predicting concerning changes in lung nodule scan reports. While limitations include variability in disease group attribution, the potential for correlation rather than causality in clinical findings, and the need for further external validation, the algorithm's accuracy and potential to support clinical decision-making and healthcare automation represent a significant stride in lung nodule management and research.

Keywords: lung cancer diagnosis, structured-query-language (SQL), natural language processing (NLP), machine learning, CT scans

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3066 Architectural Strategies for Designing Durable Steel Structural Systems

Authors: Alireza Taghdiri, Sara Ghanbarzade Ghomi

Abstract:

Nowadays, steel structures are used for not only common buildings but also high-rise construction and wide span covering. The advanced methods of construction as well as the advanced structural connections have a great effect on architecture. However a better use of steel structural systems will be achieved with the deep understanding of steel structures specifications and their substantial advantages. On the other hand, the steel structures face to the different environmental factors such as air flow which cause erosion and corrosion. With the time passing, the amount of these steel mass damages and also the imposed stress will be increased. In other words, the position of erosion in steel structures related to existing stresses indicates that effective environmental conditions will gradually decrease the structural resistance of steel components and result in decreasing the durability of steel components. In this paper, the durability of different steel structural components is evaluated and on the basis of these stress, architectural strategies for designing the system and the components of steel structures is recognized in order to achieve an optimum life cycle.

Keywords: durability, bending stress, erosion in steel structure, life cycle

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3065 Changing Patterns of Colorectal Cancer in Hail Region

Authors: Laila Salah Seada, Ashraf Ibrahim, Fawaz Al Rashid, Ihab Abdo, Hassan Kasim, Waleed Al Mansi, Saud Al Shabli

Abstract:

Background and Objectives: Colorectal carcinoma is increasing among both men and women worldwide. It has a multifactorial etiology including genetic factors, environmental factors and inflammatory conditions of the digestive tract. A clinicopathologic assessment of colorectal carcinoma in Hail region is done, considering any changing patterns in two 5-year periods from 2005-2009 (A) and from 2012 to 2017 (B). All data had been retrieved from histopathology files of King Khalid Hospital, Hail. Results: During period (A), 75 cases were diagnosed as colorectal carcinoma. Male patients comprised 56/75 (74.7%) of the study, with a mean age of 58.4 (36-97), while females were 19/75 (25.3%) with a mean age of 50.3(30-85) and the difference was significant (p = 0.05). M:F ratio was 2.9:1. Most common histological type was adenocarcioma in 68/75 (90.7%) patients mostly well differentiated in 44/68 (64.7%). Mucinous neoplasms comprised only 7/75 (9.3%) of cases and tended to have a higher stage (p = 0.04). During period (B), 115 cases were diagnosed with an increase of 53.3% in number of cases than period (A). Male to female ratio also decreased to 1.35:1, females being 44.83% more affected. Adenocarcinoma remained the prevalent type (93.9%), while mucinous type was still rare (5.2%). No distal metastases found at time of presentation. Localization of tumors was rectosigmoid in group (A) in 41.4%, which increased to 56.6% in group (B), with an increase of 15.2%. Iliocecal location also decreased from 8% to 3.5%, being 56.25% less. Other proximal areas of the colon were decreased by 25.75%, from 53.9% in group (A) to 40% in group (B). Conclusion: Colorectal carcinoma in Hail region has increased by 53.3% in the past 5 years, with more females being diagnosed. Localization has also shifted distally by 15.2%. These findings are different from Western world patterns which experienced a decrease in incidence and proximal shift of the colon cancer localization. This might be due to better diagnostic tools, population awareness of the disease, as well as changing of life style and/or food habits in the region.

Keywords: colorectal cancer, Hail Region, changing pattern, distal shift

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3064 Use of Natural Fibers in Landfill Leachate Treatment

Authors: Araujo J. F. Marina, Araujo F. Marcus Vinicius, Mulinari R. Daniella

Abstract:

Due to the resultant leachate from waste decomposition in landfills has polluter potential hundred times greater than domestic sewage, this is considered a problem related to the depreciation of environment requiring pre-disposal treatment. In seeking to improve this situation, this project proposes the treatment of landfill leachate using natural fibers intercropped with advanced oxidation processes. The selected natural fibers were palm, coconut and banana fiber. These materials give sustainability to the project because, besides having adsorbent capacity, are often part of waste discarded. The study was conducted in laboratory scale. In trials, the effluents were characterized as Chemical Oxygen Demand (COD), Turbidity and Color. The results indicate that is technically promising since that there were extremely oxidative conditions, the use of certain natural fibers in the reduction of pollutants in leachate have been obtained results of COD removals between 67.9% and 90.9%, Turbidity between 88.0% and 99.7% and Color between 67.4% and 90.4%. The expectation generated is to continue evaluating the association of efficiency of other natural fibers with other landfill leachate treatment processes.

Keywords: lndfill leachate, chemical treatment, natural fibers, advanced oxidation processes

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3063 Lymphatic Microvessel Density as a Prognostic Factor in Endometrial Carcinoma

Authors: Noha E. Hassan

Abstract:

Little is known regarding the influence of lymphatic microvessel density (LMVD) on prognosis in endometrial cancer. Prospective study was done in tertiary education and research hospital (Shatby Alexandria university hospital) on sixty patients presented with endometrial carcinoma underwent complete surgical staging. Our aim was to assess the intratumoral and peritumoral Lymphatic microvessel density (LMVD) of endometrial carcinomas identified by immunohistochemical staining using an antibody against podoplanin and to investigate their association with classical clinicopathological factors and prognosis. The result shows that high LMVD was associated with endometroid type of tumors, lesser myometrial, adnexal, cervical and peritoneal infiltration, lower tumor grade and stage and lesser recurrent cases. There is lower lymph node involvement among cases with high intratumoral LMVD and cases of high peritumoral LMVD; that reach statistical significance only among cases of high intratumoral LMVD. No association was seen between LMVD and lymphovascular space invasion. On the other hand, low LMVD was associated with poor outcome. Finally, we can conclude that increased LMVD is associated with favorable prognosis in endometrial cancer patients.

Keywords: endometrial carcinoma, lymphatic microvessel, microvessel density, prognosis

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3062 Histological Grade Concordance between Core Needle Biopsy and Corresponding Surgical Specimen in Breast Carcinoma

Authors: J. Szpor, K. Witczak, M. Storman, A. Orchel, D. Hodorowicz-Zaniewska, K. Okoń, A. Klimkowska

Abstract:

Core needle biopsy (CNB) is well established as an important diagnostic tool in diagnosing breast cancer and it is now considered the initial method of choice for diagnosing breast disease. In comparison to fine needle aspiration (FNA), CNB provides more architectural information allowing for the evaluation of prognostic and predictive factors for breast cancer, including histological grade—one of three prognostic factors used to calculate the Nottingham Prognostic Index. Several studies have previously described the concordance rate between CNB and surgical excision specimen in determination of histological grade (HG). The concordance rate previously ascribed to overall grade varies widely across literature, ranging from 59-91%. The aim of this study is to see how the data looks like in material at authors’ institution and are the results as compared to those described in previous literature. The study population included 157 women with a breast tumor who underwent a core needle biopsy for breast carcinoma and a subsequent surgical excision of the tumor. Both materials were evaluated for the determination of histological grade (scale from 1 to 3). HG was assessed only in core needle biopsies containing at least 10 well preserved HPF with invasive tumor. The degree of concordance between CNB and surgical excision specimen for the determination of tumor grade was assessed by Cohen’s kappa coefficient. The level of agreement between core needle biopsy and surgical resection specimen for overall histologic grading was 73% (113 of 155 cases). CNB correctly predicted the grade of the surgical excision specimen in 21 cases for grade 1 tumors (Kappa coefficient κ = 0.525 95% CI (0.3634; 0.6818), 52 cases for grade 2 (Kappa coefficient κ = 0.5652 95% CI (0.458; 0.667) and 40 cases for stage 3 tumors (Kappa coefficient κ = 0.6154 95% CI (0.4862; 0.7309). The highest level of agreement was observed in grade 3 malignancies. In 9 of 42 (21%) discordant cases, the grade was higher in the CNB than in the surgical excision. This composed 6% of the overall discordance. These results correspond to the noted in the literature, showing that underestimation occurs more frequently than overestimation. This study shows that authors’ institution’s histologic grading of CNBs and surgical excisions shows a fairly good correlation and is consistent with findings in previous reports. Despite the inevitable limitations of CNB, CNB is an effective method for diagnosing breast cancer and managing treatment options. Assessment of tumour grade by CNB is useful for the planning of treatment, so in authors’ opinion it is worthy to implement it in daily practice.

Keywords: breast cancer, concordance, core needle biopsy, histological grade

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3061 Experimental and Analytical Dose Assessment of Patient's Family Members Treated with I-131

Authors: Marzieh Ebrahimi, Vahid Changizi, Mohammad Reza Kardan, Seyed Mahdi Hosseini Pooya, Parham Geramifar

Abstract:

Radiation exposure to the patient's family members is one of the major concerns during thyroid cancer radionuclide therapy. The aim of this study was to measure the total effective dose of the family members by means of thermoluminescence personal dosimeter, and compare with those calculated by analytical methods. Eighty-five adult family members of fifty-one patients volunteered to participate in this research study. Considering the minimum and maximum range of dose rate from 15 µsv/h to 120 µsv/h at patients' release time, the calculated mean and median dose values of family members were 0.45 mSv and 0.28 mSv, respectively. Moreover, almost all family members’ doses were measured to be less than the dose constraint of 5 mSv recommended by Basic Safety Standards. Considering the influence parameters such as patient dose rate and administrated activity, the total effective doses of family members were calculated by TEDE and NRC formulas and compared with those of experimental results. The results indicated that, it is fruitful to use the quantitative calculations for releasing patients treated with I-131 and correct estimation of patients' family doses.

Keywords: effective dose, thermoluminescence, I-131, thyroid cancer

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3060 U11 Functionalised Luminescent Gold Nanoclusters for Pancreatic Tumor Cells Labelling

Authors: Regina M. Chiechio, Rémi Leguevél, Helene Solhi, Marie Madeleine Gueguen, Stephanie Dutertre, Xavier, Jean-Pierre Bazureau, Olivier Mignen, Pascale Even-Hernandez, Paolo Musumeci, Maria Jose Lo Faro, Valerie Marchi

Abstract:

Thanks to their ultra-small size, high electron density, and low toxicity, gold nanoclusters (Au NCs) have unique photoelectrochemical and luminescence properties that make them very interesting for diagnosis bio-imaging and theranostics. These applications require control of their delivery and interaction with cells; for this reason, the surface chemistry of Au NCs is essential to determine their interaction with the targeted biological objects. Here we demonstrate their ability as markers of pancreatic tumor cells. By functionalizing the surface of the NCs with a recognition peptite (U11), the nanostructures are able to preferentially bind to pancreatic cancer cells via a receptor (uPAR) overexpressed by these cells. Furthermore, the NCs can mark even the nucleus without the need of fixing the cells. These nanostructures can therefore be used as a non-toxic, multivalent luminescent platform, capable of selectively recognizing tumor cells for bioimaging, drug delivery, and radiosensitization.

Keywords: gold nanoclusters, luminescence, biomarkers, pancreatic cancer, biomedical applications, bioimaging, fluorescent probes, drug delivery

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3059 The Role of Il-6-Mediated NS5ATP9 Expression in Autophagy of Liver Cancer Cells

Authors: Hongping Lu, Kelbinur Tursun, Yaru Li, Yu Zhang, Shunai Liu, Ming Han

Abstract:

Objective: To investigate whether NS5ATP9 is involved in IL-6 mediated autophagy and the relationship between IL-6 and NS5ATP9 in liver cancer cells. Methods: 1. Detect the mRNA and protein levels of Beclin 1 after HepG2 cells were treated with or without recombinant human IL-6 protein. 2. Measure and compare of the changes of autophagy-related genes with their respective control, after IL-6 was silenced or neutralized with monoclonal antibody against human IL-6. 3. HepG2 cells were incubated with 50 ng/ml of IL-6 in the presence or absence of PDTC. The expression of NS5ATP9 was analyzed by Western blot after 48 h. 4. After NS5ATP9-silenced HepG2 cells had been treated with 50 ng/ml recombinant IL-6 protein, we detected the Beclin 1 and LC3B (LC3Ⅱ/Ⅰ) expression. 5. HepG2 cells were transfected with pNS5ATP9, si-NS5ATP9, and their respective control. Total RNA was isolated from cells and analyzed for IL-6. 6. Silence or neutralization of IL-6 in HepG2 cells which has been transfected with NS5ATP9. Beclin 1 and LC3 protein levels were analyzed by Western blot. Result: 1. After HepG2 were treated with recombinant human IL-6 protein, the expression of endogenous Beclin 1 was up-regulated at mRNA and protein level, and the conversion of endogenous LC3-I to LC3-II was also increased. These results indicated that IL-6 could induce autophagy. 2. When HepG2 cells were treated with IL-6 siRNA or monoclonal antibody against human IL-6, the expression of autophagy-related genes were decreased. 3. Exogenous human IL-6 recombinant protein up-regulated NS5ATP9 via NF-κB activation. 4. The expression of Beclin 1 and LC3B was down-regulated after IL-6 treated NS5ATP9-silenced HepG2 cells. 5. NS5ATP9 could reverse regulates IL-6 expression in HepG2 cells. 6. Silence or neutralization of IL-6 attenuates NS5ATP9-induced autophagy slightly. Conclusion: Our results implied that in HCC patients, maybe the higher level of IL-6 in the serum promoted the expression of NS5ATP9 and induced autophagy in cancer cells. And the over-expression of NS5ATP9 which induced by IL-6, in turn, increased IL-6 expression, further, promotes the IL-6/NS5ATP9-mediated autophagy and affects the progression of tumor. Therefore, NS5ATP9 silence might be a potential target for HCC therapy.

Keywords: autophagy, Hepatocellular carcinoma, IL-6, microenvironment, NS5ATP9

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3058 Molecular Docking and Synthesis of Nitrogen-Containing Bisphosphonates

Authors: S. Ghalem, M. Mesmoudi, I. Daoudand, H. Allali

Abstract:

The nitrogen-containing bisphosphonates (N-BPs) are well established as the treatments of choice for disorders of excessive bone resorption, myeloma and bone metastases, and osteoporosis. They inhibit farnesyl pyrophosphate synthase (FFPS), a key enzyme in the mevalonate pathway, resulting in inhibition of the prenylation of small GTP-binding proteins in osteoclasts and disruption of their cytoskeleton, adhesion/spreading, and invasion of cancer cells. A very few examples for synthesis of α-amino bisphosphonates based on several amino acids are known from the literature. In the present work, esters of aminoacid react with ketophsophonate (or their analog acid or acyl) to afford the desired products, α-iminophosphonates. The reaction of imine with dimethyl phosphate in the presence of catalytic amount of I2 give ester of α-aminobisphosphonate as sole product in good yield. Finally, we used computational docking methods to predict how several α-aminobisphosphonates bind to FPPS and how R and X influence. Pamidronate, β-aminobisphosphonate already marketed, was used as reference. These results are of interest since they represent a new and simple way to sythesize α-aminobisphosphonates with a free COOH group increased by R2 functionalisable and opening up the possibility of using the molecular docking to facilitate the design of other, novel FFPS inhibitors.

Keywords: drug research, cancer, α-amino bisphosphonates, molecular docking

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3057 99mTc Scintimammography in an Equivocal Breast Lesion

Authors: Malak Shawky Matter Elyas

Abstract:

Introduction: Early detection of breast cancer is the main tool to decrease morbidity and mortality rates. Many diagnostic tools are used, such as mammograms, ultrasound and magnetic resonance imaging, but none of them is conclusive, especially in very small sizes, less than 1 cm. So, there is a need for more accurate tools. Patients and methods: This study involved 13 patients with different breast lesions. 6 Patients had breast cancer, and one of them had metastatic axillary lymph nodes without clinically nor mammographically detected breast mass proved by biopsy and histopathology. Of the other 7 Patients, 4 of them had benign breast lesions proved by biopsy and histopathology, and 3 Patients showed Equivocal breast lesions on a mammogram. A volume of 370-444Mbq of (99m) Tc/ bombesin was injected. Dynamic 1-min images by Gamma Camera were taken for 20 minutes immediately after injection in the anterior view. Thereafter, two static images in anterior and prone lateral views by Gamma Camera were taken for 5 minutes. Finally, single-photon emission computed tomography images were taken for each patient. The definitive diagnosis was based on biopsy and histopathology. Results: 6 Patients with breast cancer proved by biopsy and histopathology showed Positive findings on Sestamibi (Scintimammography). 1 out of 4 Patients with benign breast lesions proved by biopsy and histopathology showed Positive findings on Sestamibi (Scintimammography) while the other 3 Patients showed Negative findings on Sestamibi. 3 Patients out of 3 Patients with equivocal breast findings on mammogram showed Positive Findings on Sestamibi (Scintimammography) and proved by biopsy and histopathology. Conclusions: While we agree that Scintimammography will not replace mammograms as a mass screening tool, we believe that many patients will benefit from Scintimammography, especially women with dense breast tissues and in the presence of breast implants that are difficult to diagnose by mammogram, wherein its sensitivity is low and in women with metastatic axillary lymph nodes without clinically nor mammographically findings. We can use Scintimammography in sentinel lymph node mapping as a more accurate tool, especially since it is non-invasive.

Keywords: breast., radiodiagnosis, lifestyle, surgery

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3056 Τhe Importance of Previous Examination Results, in Futural Differential Diagnostic Procedures and Especially in the Era of Covid-19

Authors: Angelis P. Barlampas

Abstract:

Purpose or Learning Objective It is well known that previous examinations play a major role in futural diagnosis, thus avoiding unnecessary new exams that cost in time and money both for the patient and the health system. A case is presented in which past patient’s results, in combination with the least needed new tests, give an easy final diagnosis. Methods or Background A middle aged man visited the emergency department complaining of hard controlled, persisting fever for the last few days. Laboratory tests showed an elevated number of white blood cells with neutrophil shift and abnormal CRP. The patient was admitted to hospital a month ago for continuing lungs symptomatology after a recent covid-19 infection. Results or Findings Computed tomography scanning showed a solid mass with spiculating margins in right lower lobe. After intravenous iodine contrast administration, there was mildly peripheral enhancement and eccentric non enhancing area. A pneumonic cancer was suspected. Comparison with the patient’s latest computed tomography revealed no mass in the area of interest but only signs of recent post covid-19 lung parenchyma abnormalities. Any new mass that appears in a month’s time span can not be a cancer but a benign lesion. It was obvious that an abscess was the most suitable explanation. The patient was admitted to hospital, and antibiotic therapy was given, with very good results. After a few days, the patient was afebrile and in good condition. Conclusion In this case , a PET scan or a biopsy was avoided, thanks to the patient’s medical history and the availability of previous examinations. It is worthy encouraging the patients to keep their medical records and organizing more efficiently the health system with the current technology of archiving the medical examinations, too.

Keywords: covid-19, chest ct, cancer, abscess, fever

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3055 Pathological Disparities in Patients Diagnosed with Prostate Imaging Reporting and Data System 3 Lesions: A Retrospective Study in a High-Volume Academic Center

Authors: M. Reza Roshandel, Tannaz Aghaei Badr, Batoul Khoundabi, Sara C. Lewis, Soroush Rais-Bahrami, John Sfakianos, Reza Mehrazin, Ash K. Tewari

Abstract:

Introduction: Prostate biopsy is the most reliable diagnostic method for choosing the appropriate management of prostate cancer. However, discrepancies between Gleason grade groups (GG) of different biopsies remain a significant concern. This study aims to assess the association of the radiological factors with GG discrepancies in patients with index Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions, using radical prostatectomy (RP) specimens as the most accurate and informative pathology. Methods: This single-institutional retrospective study was performed on a total of 2289 consecutive prostate cancer patients with combined targeted and systematic prostate biopsy followed by radical prostatectomy (RP). The database was explored for patients with the index PI-RADS 3 lesions version 2 and 2.1. Cancers with PI-RADS 4 or 5 scoring were excluded from the study. Patient characteristics and radiologic features were analyzed by multivariable logistic regression. Number-density of lesions was defined as the number of lesions per prostatic volume. Results: Of the 151 prostate cancer cases with PI-RADS 3 index lesions, 27% and 17% had upgrades and downgrades at RP, respectively. Analysis of grade changes showed no significant associations between discrepancies and the number or the number density of PI-RADS 3 lesions. Moreover, the study showed no significant association of the GG changes with race, age, location of the lesions, or prostate volume. Conclusions: This study demonstrated that in PI-RADS 3 cancerous nodules, the chance of the pathology changes in the final pathology of RP specimens was low. Furthermore, having multiple PI-RADS 3 nodules did not change the conclusion, as the possibility of grade changes in patients with multiple nodules was similar to those with solitary lesions.

Keywords: prostate, adenocarcinoma, multiparametric MRI, Gleason score, robot-assisted surgery

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3054 Role of Natural Products in Drug Discovery of Anti-Biotic and Anti-Cancer Agents

Authors: Sunil Kumar

Abstract:

For many years, small organic molecules derived naturally from microbes and plants have delivered a number of expedient therapeutic drug agents. The search for naturally occurring lead compounds has continued in recent years as well, with the constituents of marine flora and fauna along with those of telluric microorganisms and plants being investigated for their anti-bacterial and anti-cancer activities. It has been observed that such promising lead molecules incline to promptly generate substantial attention among scientists like synthetic organic chemists and biologists. Subsequently, the availability of a given precious natural product sample may be enriched, and it may be possible to determine a preliminary idea of structure-activity relationships to develop synthetic analogues. For instance, anti-tumor drug topotecan is a synthetic chemical compound similar in chemical structure to camptothecin which is found in extracts of Camptotheca acuminate. Similarly, researchers at AstraZeneca discovered anti-biotic pyrrolamide through a fragment-based lead generation approach from kibdelomycin, which is isolated from Staphylococcus aureuss.

Keywords: anticancer, antibiotic, lead molecule, natural product, synthetic analogues

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3053 Factor Associated with Uncertainty Undergoing Hematopoietic Stem Cell Transplantation

Authors: Sandra Adarve, Jhon Osorio

Abstract:

Uncertainty has been studied in patients with different types of cancer, except in patients with hematologic cancer and undergoing transplantation. The purpose of this study was to identify factors associated with uncertainty in adults patients with malignant hemato-oncology diseases who are scheduled to undergo hematopoietic stem cell transplantation based on Merle Mishel´s Uncertainty theory. This was a cross-sectional study with an analytical purpose. The study sample included 50 patients with leukemia, myeloma, and lymphoma selected by non-probability sampling by convenience and intention. Sociodemographic and clinical variables were measured. Mishel´s Scale of Uncertainty in Illness was used for the measurement of uncertainty. A bivariate and multivariate analyses were performed to explore the relationships and associations between the different variables and uncertainty level. For this analysis, the distribution of the uncertainty scale values was evaluated through the Shapiro-Wilk normality test to identify statistical tests to be used. A multivariate analysis was conducted through a logistic regression using step-by-step technique. Patients were 18-74 years old, with a mean age of 44.8. Over time, the disease course had a median of 9.5 months, an opportunity was found in the performance of the transplantation of < 20 days for 50% of the patients. Regarding the uncertainty scale, a mean score of 95.46 was identified. When the dimensions of the scale were analyzed, the mean score of the framework of stimuli was 25.6, of cognitive ability was 47.4 and structure providers was 22.8. Age was identified to correlate with the total uncertainty score (p=0.012). Additionally, a statistically significant difference was evidenced between different religious creeds and uncertainty score (p=0.023), education level (p=0.012), family history of cancer (p=0.001), the presence of comorbidities (p=0.023) and previous radiotherapy treatment (p=0.022). After performing logistic regression, previous radiotherapy treatment (OR=0.04 IC95% (0.004-0.48)) and family history of cancer (OR=30.7 IC95% (2.7-349)) were found to be factors associated with the high level of uncertainty. Uncertainty is present in high levels in patients who are going to be subjected to bone marrow transplantation, and it is the responsibility of the nurse to assess the levels of uncertainty and the presence of factors that may contribute to their presence. Once it has been valued, the uncertainty must be intervened from the identified associated factors, especially all those that have to do with the cognitive capacity. This implies the implementation and design of intervention strategies to improve the knowledge related to the disease and the therapeutic procedures to which the patients will be subjected. All interventions should favor the adaptation of these patients to their current experience and contribute to seeing uncertainty as an opportunity for growth and transcendence.

Keywords: hematopoietic stem cell transplantation, hematologic diseases, nursing, uncertainty

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3052 Development of a Core Set of Clinical Indicators to Measure Quality of Care for Thyroid Cancer: A Modified-Delphi Approach

Authors: Liane J. Ioannou, Jonathan Serpell, Cino Bendinelli, David Walters, Jenny Gough, Dean Lisewski, Win Meyer-Rochow, Julie Miller, Duncan Topliss, Bill Fleming, Stephen Farrell, Andrew Kiu, James Kollias, Mark Sywak, Adam Aniss, Linda Fenton, Danielle Ghusn, Simon Harper, Aleksandra Popadich, Kate Stringer, David Watters, Susannah Ahern

Abstract:

BACKGROUND: There are significant variations in the management, treatment and outcomes of thyroid cancer, particularly in the role of: diagnostic investigation and pre-treatment scanning; optimal extent of surgery (total or hemi-thyroidectomy); use of active surveillance for small low-risk cancers; central lymph node dissections (therapeutic or prophylactic); outcomes following surgery (e.g. recurrent laryngeal nerve palsy, hypocalcaemia, hypoparathyroidism); post-surgical hormone, calcium and vitamin D therapy; and provision and dosage of radioactive iodine treatment. A proven strategy to reduce variations in the outcome and to improve survival is to measure and compare it using high-quality clinical registry data. Clinical registries provide the most effective means of collecting high-quality data and are a tool for quality improvement. Where they have been introduced at a state or national level, registries have become one of the most clinically valued tools for quality improvement. To benchmark clinical care, clinical quality registries require systematic measurement at predefined intervals and the capacity to report back information to participating clinical units. OBJECTIVE: The aim of this study was to develop a core set clinical indicators that enable measurement and reporting of quality of care for patients with thyroid cancer. We hypothesise that measuring clinical quality indicators, developed to identify differences in quality of care across sites, will reduce variation and improve patient outcomes and survival, thereby lessening costs and healthcare burden to the Australian community. METHOD: Preparatory work and scoping was conducted to identify existing high quality, clinical guidelines and best practice for thyroid cancer both nationally and internationally, as well as relevant literature. A bi-national panel was invited to participate in a modified Delphi process. Panelists were asked to rate each proposed indicator on a Likert scale of 1–9 in a three-round iterative process. RESULTS: A total of 236 potential quality indicators were identified. One hundred and ninety-two indicators were removed to reflect the data capture by the Australian and New Zealand Thyroid Cancer Registry (ANZTCR) (from diagnosis to 90-days post-surgery). The remaining 44 indicators were presented to the panelists for voting. A further 21 indicators were later added by the panelists bringing the total potential quality indicators to 65. Of these, 21 were considered the most important and feasible indicators to measure quality of care in thyroid cancer, of which 12 were recommended for inclusion in the final set. The consensus indicator set spans the spectrum of care, including: preoperative; surgery; surgical complications; staging and post-surgical treatment planning; and post-surgical treatment. CONCLUSIONS: This study provides a core set of quality indicators to measure quality of care in thyroid cancer. This indicator set can be applied as a tool for internal quality improvement, comparative quality reporting, public reporting and research. Inclusion of these quality indicators into monitoring databases such as clinical quality registries will enable opportunities for benchmarking and feedback on best practice care to clinicians involved in the management of thyroid cancer.

Keywords: clinical registry, Delphi survey, quality indicators, quality of care

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