Search results for: breast cancer cell lines

Authors: Osama Elsarrar, Marjorie Darrah, Richard Devin

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This paper discusses the idea of capturing an expert’s knowledge in the form of human understandable rules and then inserting these rules into a dynamic cell structure (DCS) neural network. The DCS is a form of self-organizing map that can be used for many purposes, including classification and prediction. This particular neural network is considered to be a topology preserving network that starts with no pre-structure, but assumes a structure once trained. The DCS has been used in mission and safety-critical applications, including adaptive flight control and health-monitoring in aerial vehicles. The approach is to insert expert knowledge into the DCS before training. Rules are translated into a pre-structure and then training data are presented. This idea has been demonstrated using the well-known Iris data set and it has been shown that inserting the pre-structure results in better accuracy with the same training.

Keywords: neural network, self-organizing map, rule extraction, rule insertion

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Authors: Lucian Mocan

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We present method of Nanoparticle enhanced laser thermal ablation of HepG2 cells (Human hepatocellular liver carcinomacell line), using gold nanoparticles combuned with a specific growth factor and demonstrate its selective therapeutic efficacy usig ex vivo specimens. Ex vivo-perfused liver specimens were obtained from hepatocellular carcinoma patients similarly to the surgical technique of transplantation. Ab bound to GNPs was inoculated intra-arterially onto the resulting specimen and determined the specific delivery of the nano-bioconjugate into the malignant tissue by means of the capillary bed. The extent of necrosis was considerable following laser therapy and at the same time surrounding parenchyma was not seriously affected. The selective photothermal ablation of the malignant liver tissue was obtained after the selective accumulation of Ab bound to GNPs into tumor cells following ex-vivo intravascular perfusion. These unique results may represent a major step in liver cancer treatment using nanolocalized thermal ablation by laser heating.

Keywords: HepG2 cells, gold nanoparticles, nanoparticle functionalization, laser irradiation

Procedia PDF Downloads 357

Authors: Mahesh Pal, Tripti Mishra, Chandana Rao, Dalip Upreti

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Cancer has been considered to be a very dreadful disease. Holmskioldia sanguinea is a large climbing shrub found in the Himalayas at an altitude of 5,000 ft and preliminary investigation showed the excellent yield of andrographolide and subjected for the anticancer activity. Protective effect of Holmskioldia sanguinea leaf ethanolic extract has been investigated against Ehrlich ascites carcinoma (EAC) and Daltons ascites lymphoma (DAL) in Swiss albino mice to evaluate the possible mechanism of action. The enzymatic antioxidant status was studied on tumor bearing mice, which shows the potential of the compound to possess significant free radical scavenging property and revealed significant tumor regression and prolonged survival time. The isolated bioactive molecule andrographolide from Holmskioldia sanguinea yields (2.5%) in subject to HPTLC/HPLC analysis. The cellular defense system constituting the superoxide dismutase, catalyses was enhanced whereby the lipid peroxidation content was restricted to a larger extent. The Holmskioldia sanguinea is a new source of andrographolide and demonstrated the potency in treatment of cancer.

Keywords: Holmskioldia sanguinea, tumor, mice, andrographolide

Procedia PDF Downloads 245

Authors: V. A. Adzika, D. Ayim-Aboagye, T. Gordh

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Background and aims: Prevalence of Sickle Cell Disease (SCD) is high in Ghana but not much is known in terms of research into non-medical strategies for managing and coping with the pain associated with SCD. This study was carried out to examine effective non-medical related strategies patients use to cope and manage their SCD condition. Methods: SCD patients (387) consisting of 180 males and 204 females between 18-65 years old years participated in the study. A cross-sectional research design was used in which participants completed questionnaires on pain, non-medical coping and management strategies, anxiety, and depression. Results of multiple regression analysis showed that socio-demographic characteristics contributed to the variance in the pain associated with SCD. Results: Over 90% of participants reported that pains associated with SCD were the main reason for seeking treatment in SCD crisis. In terms of non-medical related coping strategies, attending a place of worship and praying were the main coping strategies used in SCD crises, suggesting that patients’ beliefs, particularly in a supernatural being, served as a mitigating factor in the process of coping with the pain associated with SCD crisis. Also, avoidance and withdrawal from people and social activities were reported to be strategies used to cope effectively with the pain associated with SCD crisis. Conclusion: This indicates that it is imperative to incorporate non-medical related coping and management strategies, especially religious beliefs and psychosocial factors, to coping and management of the pain associated with SCD.

Keywords: anxiety, depression, sickle cell disease, quality of life, socio-demographic characteristics, Ghana

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Authors: Khairi El Battawy, Monika Skalicki

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The present investigation has been done on pure Egyptian Arabian mares that reared in private horse studs. Fifty non-pregnant mares were selected and examined to classify them as either being reproductively healthy or subfertile mares including clinical endometritis, early embryonic death, granulosa cell tumor, repeat breeder (post-breeding endometritis), and anoestrus mares. The purpose of the study was to assess oxidative/antioxidant biochemical metabolites, lipogram, trace elements and reproductive hormones throughout reproductive conditions in mares during regular estrous, anestrum, early pregnancy, granulose cell tumor, ovulation failure, and endometritis. Results showed intensification of the free radical-dependent process in the blood of infertile mare, especially mares with endometritis. Ultrasonography as a diagnostic tool diagnosis of endometritis in mares was an important step as it revealed much information concerning infertility problem.

Keywords: endometritis, ovulation, oxidative, mare

Procedia PDF Downloads 168

Authors: Mohamed Moussaoui

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A series of thirty-one potential inhibitors targeting the epidermal growth factor receptor kinase (EGFR), derived from quinazoline, underwent 3D-QSAR analysis using CoMFA and CoMSIA methodologies. The training and test sets of quinazoline derivatives were utilized to construct and validate the QSAR models, respectively, with dataset alignment performed using the lowest energy conformer of the most active compound. The best-performing CoMFA and CoMSIA models demonstrated impressive determination coefficients, with R² values of 0.981 and 0.978, respectively, and Leave One Out cross-validation determination coefficients, Q², of 0.645 and 0.729, respectively. Furthermore, external validation using a test set of five compounds yielded predicted determination coefficients, R² test, of 0.929 and 0.909 for CoMFA and CoMSIA, respectively. Building upon these promising results, eighteen new compounds were designed and assessed for drug likeness and ADMET properties through in silico methods. Additionally, molecular docking studies were conducted to elucidate the binding interactions between the selected compounds and the enzyme. Detailed molecular dynamics simulations were performed to analyze the stability, conformational changes, and binding interactions of the quinazoline derivatives with the EGFR kinase. These simulations provided deeper insights into the dynamic behavior of the compounds within the active site. This comprehensive analysis enhances the understanding of quinazoline derivatives as potential anti-cancer agents and provides valuable insights for lead optimization in the early stages of drug discovery, particularly for developing highly potent anticancer therapeutics

Keywords: 3D-QSAR, CoMFA, CoMSIA, ADMET, molecular docking, quinazoline, molecular dynamic, egfr inhibitors, lung cancer, anticancer

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Authors: Lian Wu, Mervyn Merrilees

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Chronic Obstructive Pulmonary Disease (COPD) is a worldwide problem, characterized by irreversible and progressive airflow obstruction. In New Zealand, it is currently the 4th commonest cause of death and exacerbations of COPD are a frequent cause of admission to hospital. Serum levels of Clara cell secretory protein-16 (CC-16) are believed to represent Clara cell toxicity. More recently, CC-16 has been found to be associated with smoker COPD. It is produced almost exclusively by non-ciliated Clara cells in the airways, and its primary function is to protect the lungs against oxidative stress and carcinogenesis. After acute exposure to cigarette smoke, serum levels of CC-16 become elevated. CC16 is a potent natural immune-suppressor and anti-inflammatory agent. In vitro, CC16 inhibits both monocyte and polymorphonuclear neutrophils chemotaxis and phagocytosis. CC16 also inhibits fibroblast chemotaxis. However, the role of CC-16 in non-smoking related COPD is still not clear. In this study, we investigated serum CC-16 levels in non-smoking related COPD. Methods: We compared non-smoker patients with COPD (FEV1<60% of predicted, FEV1/FVC <0.7, n=100) and individuals with normal lung function FEV1≥ 80% of predicted and FEV1/FVC≥ 0.7, n=80). All subjects had no smoking history. CC-16 was measured by ELISA. Results and conclusion: Serum CC-16 levels are reduced in individuals with non-smoking related COPD, and there is a weak correlation with disease severity in non-smoking related COPD group compared to non-smoker controls.

Keywords: COPD, CC-16, ELISA, non-smoking-related COPD

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Authors: Mohammadjavad Sotoudeheian, Soroush Nematollahi

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Crohn’s disease (CD) is a chronic gastrointestinal segment inflammation encompassing immune dysregulation in a genetically susceptible individual in response to the environmental triggers and interaction between the microbiome and immune system. Uncontrolled inflammation leads to long-term complications, including fibrotic strictures and enteric fistulae. Increased production of Th1 and Th17-cell cytokines and defects in T-regulatory cells have been associated with CD. Th17-cells are essential for protection against extracellular pathogens, but their atypical activity can cause autoimmunity. Intrinsic defects in the control of programmed cell death in the mucosal T-cell compartment are strongly implicated in the pathogenesis of CD. The apoptosis defect in mucosal T-cells in CD has been endorsed as an imbalance of the Bcl-2 and the Bax. The immune system encounters foreign antigens through microbial colonization of mucosal surfaces or infections. In addition, FOSL downregulated IL-26 expression, a cytokine that marks inflammatory Th17-populations in patients suffering from CD. Furthermore, the expression of IL-23 is associated with the transcription factor primary leucine zipper transcription factor ATF-like (Batf). Batf-deficiency demonstrated the crucial role of Batf in colitis development. Batf and IL-23 mediate their effects by inducing IL-6 production. Strong association of IL-23R, Stat3, and Stat4 with IBD susceptibility point to a critical involvement of T-cells. IL-23R levels in transfer fistula were dependent on the AP-1 transcription factor JunB that additionally controlled levels of RORγt by facilitating DNA binding of Batf. T lymphocytes lacking JunB failed to induce IL-23- and Th17-mediated experimental colitis highlighting the relevance of JunB for the IL-23/ Th17 pathway. The absence of T-bet causes unrestrained Th17-cell differentiation. T-cells are central parts of immune-mediated colon fistula. Especially Th17-cells were highly prevalent in inflamed IBD tissues, as RORγt is effective in preventing colitis. Intraepithelial lymphocytes (IEL) contain unique T-cell subsets, including cells expressing RORγt. Increased activated Th17 and decreased T-regulatory cells in inflamed intestinal tissues had been seen. T-cells differentiate in response to many cytokines, including IL-1β, IL-6, IL-23, and TGF-β, into Th17-cells, a process which is critically dependent on the Batf. IL-23 promotes Th17-cell in the colon. Batf manages the generation of IL-23 induced IL-23R+ Th17-cells. Batf is necessary for TGF-β/IL-6-induced Th17-polarization. Batf-expressing T-cells are the core of T-cell-mediated colitis. The human-specific parts of three AP-1 transcription factors, FOSL1, FOSL2, and BATF, are essential during the early stages of Th17 differentiation. BATF supports the Th17 lineage. FOSL1, FOSL2, and BATF make possession of regulatory loci of genes in the Th17 lineage cascade. The AP1 transcription factor Batf is identified to control intestinal inflammation and seems to regulate pathways within lymphocytes, which could theoretically control the expression of several genes. It shows central regulatory properties over Th17-cell development and is intensely upregulated within IBD-affected tissues. Here, we demonstrated that targeting Batf in IBD appears as a therapeutic approach that reduces colitogenic T-cell activities during fistula formation while aiming to affect inflammation in the gut epithelial cells.

Keywords: immune system, Crohn’s Disease, BATF, T helper cells, Bcl, interleukin, FOSL

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Authors: Hanan Khojah, RuAngelie Edrada-Ebel

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Neurodegenerative disease including Alzheimer’s disease is a major cause of long-term disability. Oxidative stress is frequently implicated as one of the key contributing factors to neurodegenerative diseases. Protection against neuronal damage remains a great challenge for researchers. Ficus carica (commonly known as fig) is a species of great antioxidant nutritional value comprising a protective mechanism against innumerable health disorders related to oxidative stress as well as Alzheimer’s disease. The purpose of this work was to characterize the non-polar active metabolites in Ficus carica endocarp, mesocarp, and exocarp. Crude extracts were prepared using several extraction solvents, which included 1:1 water: ethylacetate, acetone and methanol. The dried extracts were then solvent partitioned between equivalent amounts of water and ethylacetate. Purification and fractionation were accomplished by high-throughput chromatography. The isolated metabolites were tested on their effect on human neuroblastoma cell line by cell viability test and cell cytotoxicity assay with acrolein. Molecular weights of the active metabolites were determined via LC–HRESIMS and GC-EIMS. Metabolomic profiling was performed to identify the active metabolites by using differential expression analysis software (Mzmine) and SIMCA for multivariate analysis. Structural elucidation and identification of the interested active metabolites were studied by 1-D and 2-D NMR. Significant differences in bioactivity against a concentration-dependent assay on acrolein radicals were observed between the three fruit parts. However, metabolites obtained from mesocarp and the endocarp demonstrated bioactivity to scavenge ROS radical. NMR profiling demonstrated that aliphatic compounds such as γ-sitosterol tend to induce neuronal bioactivity and exhibited bioactivity on the cell viability assay. γ-Sitosterol was found in higher concentrations in the mesocarp and was considered as one of the major phytosterol in Ficus carica.

Keywords: alzheimer, Ficus carica, γ-Sitosterol, metabolomics

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Authors: Aishik Deb, Rituparna Sinha

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We have developed an algorithm to detect the abnormal segment/"structural variation in the genome across a number of samples. We have worked on simulated as well as real data from the BAM Files and have designed a segmentation algorithm where abnormal segments are detected. This algorithm aims to improve the accuracy and performance of the existing CNV-CH algorithm. The next-generation sequencing (NGS) approach is very fast and can generate large sequences in a reasonable time. So the huge volume of sequence information gives rise to the need for Big Data and parallel approaches of segmentation. Therefore, we have designed a map-reduce approach for the existing CNV-CH algorithm where a large amount of sequence data can be segmented and structural variations in the human genome can be detected. We have compared the efficiency of the traditional and map-reduce algorithms with respect to precision, sensitivity, and F-Score. The advantages of using our algorithm are that it is fast and has better accuracy. This algorithm can be applied to detect structural variations within a genome, which in turn can be used to detect various genetic disorders such as cancer, etc. The defects may be caused by new mutations or changes to the DNA and generally result in abnormally high or low base coverage and quantification values.

Keywords: cancer detection, convex hull segmentation, map reduce, next generation sequencing

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Authors: Donghee Kang

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Background: Cancer pain is very difficult to control as the mechanism of pain is varied, and the patient has several co-morbidities. The use of Intravenous Patient-Controlled Analgesia (IV-PCA) can effectively control underlying pain and breakthrough pain. Ketamine is used in many pain patients due to its unique analgesic effect. In this study, it was checked whether there was a difference in the amount of analgesic usage, pain control degree, and side effects between patients who controlled pain with fentanyl-based IV-PCA and those who added Ketamine for pain control. Methods: Among the patients referred to this department for cancer pain, IV-PCA was applied to patients who were taking sufficient oral analgesics but could not control them or had blood clotting disorders that made the procedure difficult, and this patient group was targeted. In IV-PCA, 3000 mcg of Fentanyl, 160 mg of Nefopam, and 0.3 mg of Ramosetrone were mixed with normal saline to make a total volume of 100 ml. Group F used this IV-PCA as it is, and group K mixed 250 mg of Ketamine with normal saline to make a total volume of 100 ml. For IV-PCA, the basal rate was 0.5ml/h, the bolus was set to 1ml when pressed once, and the lockout time was set to 15 minutes. If pain was not controlled after IV-PCA application, 500 mcg of Fentanyl was added, and if excessive sedation or breathing difficulties occurred, the use was stopped for one hour. After that, the degree of daily pain control, analgesic usage, and side effects were investigated for seven days using this IV-PCA. Results: There was no difference between the two groups in the demographic data. Both groups had adequate pain control. Initial morphine milligram equivalents did not differ between the two groups, but the total amount of Fentanyl used for seven days was significantly different between the two groups [p=0.014], and group F used more Fentanyl through IV-PCA. In addition, the amount of sleeping pills used during the seven days was higher in Group F [p<0.01]. Overall, there was no difference in the frequency of side effects between the two groups, but the nausea was more frequent in Group F [p=0.031]. Discussion: When the two groups were compared, pain control was good in both groups. This seems to be because Fentanyl-based IV-PCA showed an adequate pain control effect. However, there was a significant difference in the total amount of opioid (Fentanyl) used, which is thought to be the opioid-sparing effect of Ketamine. Also, among the side effects, nausea was significantly less, which is thought to be possible because the amount of opioids used in the Ketamine group was small. The frequency of requesting sleeping pills was significantly less in the group using Ketamine, and it seems that Ketamine also helped improve sleep quality. In conclusion, using Ketamine with an opioid to control pain seems to have advantages. IV-PCA, which can be used effectively when other procedures are difficult, is more effective and safer when used together with Ketamine than opioids alone.

Keywords: cancer pain, intravenous patient-controlled analgesia, Ketamine, opioid

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Authors: Mehdi Salari

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This work introduces a new experimental method of martensite treatment contains accumulative roll-bonding used for producing the nano/ultrafine grained structure in low carbon steel. The ARB process up to 4 cycles was performed under unlubricated conditions, while the annealing process was carried out in the temperature range of 450–550°C for 30–100 min. The microstructures of the deformed and annealed specimens were investigated. The results showed that in the annealed specimen at 450°C for 30 or 60 min, recrystallization couldn’t be completed. Decrease in time and temperature intensified the volume fraction of the martensite cell blocks. Fully equiaxed nano/ultrafine grained ferrite was developed from the martensite cell blocks during the annealing at temperature around 500°C for 100 min.

Keywords: martensite process, accumulative roll bonding, recrystallization, nanostructure, plain carbon steel

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Authors: Arpit Gite

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Purpose: We have evaluated the role of Total Neoadjuvant Therapy in patients with Locally Advanced Rectal cancer by giving Chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT) and, after that, the strategy of wait and watch. Methods: In this prospective case series, we evaluated the results of three locally advanced Rectal cancers, two cases Stage II (cT3N0) and one case Stage III ( cT4aN2). All three patients' growth was 4-6 cm from the anal verge. We have treated with Chemoradiotherapy to dose of 45Gy/25 Fractions to elective nodal regions (Inguinal node in anal canal Involvement)and Primary and mesorectum (Phase I) followed by 14.4Gy/8 Fractions to Primary and Mesorectum(Phase II) to a total dose of 59.4Gy/33 Fractions with concurrent chemotherapy Tab Capecitabine 825mg/m2 PO BD with Radiation therapy. After 6 weeks of completion of Chemoradiotherapy, advised six cycles of consolidative chemotherapy, CAPEOX regimen, Oxaliplatin 130mg/m2 on day 1 and Capecitabine 1000mg/m2 PO BD on days 1-14 repeated on a 21-day cycle for a total of six cycles. The primary endpoint is Disease-free survival (DFS); the secondary endpoint is adverse events related to chemoradiotherapy. Radiation toxicity is assessed by RTOG criteria, and chemotherapy toxicity is assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Results: After 6 weeks of completion of Chemoradiotherapy, we did PET-CT of all three patients; all three patients had a clinically complete response and we advised 6 cycles of consolidative chemotherapy. After completion of consolidative chemotherapy, again PET-CT and sigmoidoscopy, all three patients had complete response on PET-CT and no lesions on sigmoidoscopy and kept all three patients on wait and watch.2 patients had Grade 2 skin toxicities,1 patient had Grade 1 skin toxicity, .2 patients had Grade 2 lower GI toxicities, and 1 patient had Grade lower GI toxicity, both according to RTOG criteria. 3 patients had Grade 2 diarrhea due to capecitabine, and 1 patient had Grade 1 thrombocytopenia due to oxaliplatin assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Conclusion: Sphincter Preservation is possible with this regimen in those who don’t want to opt for surgery or in case of low-lying rectal cancer.

Keywords: locally advanced rectal cancer, sphincter preservation, chemoradiotherapy, consolidative chemotherapy

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Authors: Małgorzata Tomczyńska, Joanna Saluk-Bijak

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Background: Graves’ disease is a frequent organ-specific autoimmune thyroid disease, which characterized by the presence of different kind autoantibodies, that, in most cases, act as agonists of the thyrotropin receptor, leading to hyperthyroidism. Role of platelets and lymphocytes can be modulated in the pathophysiology of thyroid autoimmune diseases. Interference in the physiology of platelets can lead to enhanced activity of these cells. Activated platelets can bind to circulating lymphocytes and to affect lymphocyte adhesion. Platelets and lymphocytes can regulate mutual functions. Therefore, the activation of T lymphocytes, as well as blood platelets, is associated with the development of inflammation and oxidative stress within the target tissue. The present study was performed to investigate a platelet-lymphocyte relation by assessing the degree of their mutual aggregation in whole blood of patients with Graves’ disease. Also, the purpose of this study was to examine the impact of platelet interaction on lymphocyte migration capacity. Methods: 30 patients with Graves’ disease were recruited in the study. The matched 30 healthy subjects were served as the control group. Immunophenotyping of lymphocytes was carried out by flow cytometry method. A CytoSelect™ Cell Migration Assay Kit was used to evaluate lymphocyte migration and adhesion to blood platelets. Visual assessment of lymphocyte-platelet aggregate morphology was done using confocal microscope after magnetic cell isolation by Miltenyi Biotec. Results: The migration and functional responses of lymphocytes to blood platelets were greater in the group of Graves’ disease patients compared with healthy controls. The group of Graves’ disease patients exhibited a reduced T lymphocyte and a higher B cell count compared with controls. Based on microscopic analysis, more platelet-lymphocyte aggregates were found in patients than in control. Conclusions: Studies have shown that in Graves' disease, lymphocytes show increased platelet affinity, more strongly migrating toward them, and forming mutual cellular conglomerates. This may be due to the increased activation of blood platelets in this disease.

Keywords: blood platelets, cell migration, Graves’ disease, lymphocytes, lymphocyte-platelet aggregates

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Authors: A. E. Yakshin, D. Ijpes, J. M. Sturm, I. A. Makhotkin, M. D. Ackermann

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Applications like synchrotron optics, soft X-ray microscopy, X-ray astronomy, and wavelength dispersive X-ray fluorescence (WD-XRF) rely heavily on short- and ultra-short-period multilayer (ML) structures. In WD-XRF, ML serves as an analyzer crystal to disperse emission lines of light elements. The key requirement for the ML is to be highly reflective while also providing sufficient angular dispersion to resolve specific XRF lines. For these reasons, MLs with periods ranging from 1.0 to 2.5 nm are of great interest in this field. Due to the short period, the reflectance of such MLs is extremely sensitive to interface imperfections such as roughness and interdiffusion. Moreover, the thickness of the individual layers is only a few angstroms, which is close to the limit of materials to grow a continuous film. MLs with a period between 2.5 nm and 1.0 nm, combining tungsten (W) reflector with B₄C, Si, and Al spacers, were created and examined. These combinations show high theoretical reflectance in the full range from C-Kα (4.48nm) down to S-Kα (0.54nm). However, the formation of optically unfavorable compounds, intermixing, and interface roughness result in limited reflectance. A variety of techniques, including diffusion barriers, seed layers, and ion polishing for sputter-deposited MLs, were used to address these issues. Diffuse scattering measurements, photo-electron spectroscopy analysis, and X-ray reflectivity measurements showed a noticeable reduction of compound formation, intermixing, and interface roughness. This also resulted in a substantial increase in soft X-ray reflectance for W/Si, W/B4C, and W/Al MLs. In particular, the reflectivity of 1 nm period W/Si multilayers at the wavelength of 0.84 nm increased more than 3-fold – propelling forward the applicability of such multilayers for shorter wavelengths.

Keywords: interface engineering, reflectance, short period multilayer structures, x-ray optics

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Authors: Andrew Thayer, Courtney Rondeau, Paraskevi Papadopoulou

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The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) gene-editing technologies have generated considerable discussion about the applications and ethics of their use. However, no consistent guidelines for using CRISPR technologies have been developed -nor common legislation passed related to gene editing, especially as it is connected to genetically modified organisms (GMOs) in the European Union. The recent announcement that the first babies with CRISPR-edited genes were born, along with new studies exploring CRISPR’s applications in treating thalassemia, sickle-cell anemia, cancer, and certain forms of blindness, have demonstrated that the technology is developing faster than the policies needed to control it. Therefore, it can be seen that a reasonable and coherent regulatory framework for the use of CRISPR in human somatic and germline cells is necessary to ensure the ethical use of the technology in future years. The European Union serves as a unique region of interconnected countries without a standard set of regulations or legislation for CRISPR gene-editing. We posit that the EU would serve as a suitable model in comparing the legislations of its affiliated countries in order to understand the practicality and effectiveness of adopting majority-approved practices. Additionally, we present a proposed set of guidelines which could serve as a basis in developing a consistent regulatory framework for the EU countries to implement but also act as a good example for other countries to adhere to. Finally, an additional, multidimensional framework of smart solutions is proposed with which all stakeholders are engaged to become better-informed citizens.

Keywords: CRISPR, ethics, regulatory framework, European legislation

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Authors: S. Reshma Reghu, Shiburaj Sugathan, T. G. Nandu, K. B. Ramesh Kumar, Mathew Dan

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Bacterial diseases are considered to be one of the most prevalent health hazards in the developing world and many bacteria are becoming resistant to existing antibiotics making the treatment ineffective. Thus, it is necessary to find novel targets and develop new antibacterial drugs with a novel mechanism of action. The process of bacterial cell division is a novel and attractive target for new antibacterial drug discovery. FtsZ, a homolog of eukaryotic tubulin, is the major protein of the bacterial cell division machinery and is considered as an important antibacterial drug target. Zingiberaceae, the Ginger family consists of aromatic herbs with creeping rhizomes. Many of these plants have antimicrobial properties.This study aimed to determine the anti-bacterial activity of selected Zingiberaceous plants by targeting bacterial cell division protein, FtsZ. Essential oils and methanol extracts of Amomum ghaticum, Alpinia galanga, Kaempferia galanga, K. rotunda, and Zingiber officinale were tested to find its antibacterial efficiency using disc diffusion method against authentic bacterial strains obtained from MTCC (India). Essential oil isolated from A.galanga and Z.officinale were further assayed for FtsZ inhibition assay following non-radioactive malachite green-phosphomolybdate assay using E. coli FtsZ protein obtained from Cytoskelton Inc., USA. Z.officinale essential oil possess FtsZ inhibitory property. A molecular docking study was conducted with the known bioactive compounds of Z. officinale as ligands with the E. coli FtsZ protein homology model. Some of the major constituents of this plant like catechin, epicatechin, and gingerol possess agreeable docking scores. The results of this study revealed that several chemical constituents in Ginger plants can be utilised as potential source of antibacterial activity and it can warrant further investigation through drug discovery studies.

Keywords: antibacterial, FtsZ, zingiberaceae, docking

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Authors: Chaoran Liu

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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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Authors: Huseyin Apdik, Aysegul Dogan, Selami Demirci, Ezgi Avsar Apdik, Fikrettin Sahin

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Mesenchymal stem cells (MSCs) are crucial cell types for bone maintenance and growth along with resident bone progenitor cells providing bone tissue integrity during osteogenesis and skeletal growth. Any deficiency in this regulation would result in vital bone diseases. Of those, osteoporosis, characterized by a reduction in bone mass and mineral density, is a critical skeletal disease for especially elderly people. The commonly used drugs for the osteoporosis treatment are bisphosphonates (BPs). The most prominent role of BPs is to prevent bone resorption arisen from high osteoclast activity. However, administrations of bisphosphonates may also cause bisphosphonate-induced osteonecrosis of the jaw (BIONJ). Up to the present, the researchers have proposed several circumstances for BIONJ. However, effects of long-term and/or high dose usage of BPs on stem cell’s proliferation, survival, differentiation or maintenance capacity have not been evaluated yet. The present study will be held to; figure out BPs’ effects on MSCs in vitro in the aspect of cell proliferation and toxicity, migration, angiogenic activity, lineage specific gene and protein expression levels, mesenchymal stem cell properties and potential signaling pathways affected by BP treatment. Firstly, mesenchymal stem cell characteristics of Dental Pulp Stem Cells (DPSCs) and Periodontal Ligament Stem Cells (PDLSCs) were proved using flow cytometry analysis. Cell viability analysis was completed to determine the cytotoxic effects of BPs (Zoledronate (Zol), Alendronate (Ale) and Risedronate (Ris)) on DPSCs and PDLSCs by the 3-(4,5-di-methyl-thiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfo-phenyl)-2H-tetrazolium (MTS) assay. Non-toxic concentrations of BPs were determined at 24 h under growth condition, and at 21 days under osteogenic differentiation condition for both cells. The scratch assay was performed to evaluate their migration capacity under the usage of determined of BPs concentrations at 24 h. The results revealed that while the scratch closure is 70% in the control group for DPSCs, it was 57%, 66% and 66% in Zol, Ale and Ris groups, respectively. For PDLSs, while wound closure is 71% in control group, it was 65%, 66% and 66% in Zol, Ale and Ris groups, respectively. As future experiments, tube formation assay and aortic ring assay will be done to determinate angiogenesis abilities of DPSCs and PDLSCs treated with BPs. Expression levels of osteogenic differentiation marker genes involved in bone development will be determined using real time-polymerase change reaction (RT-PCR) assay and expression profiles of important proteins involved in osteogenesis will be evaluated using western blotting assay for osteogenically differentiated MSCs treated with or without BPs. In addition to these, von Kossa staining will be performed to measure calcium mineralization status of MSCs.

Keywords: bisphosphonates, bisphosphonate-induced osteonecrosis of the jaw, mesenchymal stem cells, osteogenesis

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

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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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Authors: Deepak Kumar, Ravi Rajwanshi, Mohd. Aslam Yusuf, Nisha Kant Pandey, Preeti Singh, Mukesh Saxena, Neera Bhalla Sarin

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Global issues are leading to concerns over food security. These include climate change, urbanization, increase in population subsequently leading to greater energy and water demand. Futuristic approach for crop improvement involves gene pyramiding for agronomic traits that empower the plants to withstand multiple stresses. In an earlier study from the laboratory, the efficacy of overexpressing γ-tocopherol methyl transferase (γ-TMT) gene from the vitamin E biosynthetic pathway has been shown to result in six-fold increase of the most biologically active form, the α-tocopherol in Brassica juncea which resulted in alleviation of salt, heavy metal and osmoticum induced stress by the transgenic plants. The glyoxalase I (gly I) gene from the glyoxalase pathway has also been earlier shown by us to impart tolerance against multiple abioitc stresses by detoxification of the cytotoxic compound methylglyoxal in Brassica juncea. Recently, both the transgenes were pyramided in Brassica juncea lines through sexual crosses involving two stable Brassica juncea lines overexpressing γ-TMT and gly I genes respectively. The transgene integration was confirmed by PCR analysis and their mRNA expression was evident by RT-PCR analysis. Preliminary physiological investigations showed ~55% increased seed germination under 200 mM NaCl stress in the pyramided line and 81% higher seed germination under 200 mM mannitol stress as compared to the WT control plants. The pyramided lines also retained more chlorophyll content when the leaf discs were floated on NaCl (200, 400 and 600 mM) or mannitol (200, 400 and 600 mM) compared to the WT control plants. These plants had higher Relative Water Content and greater solute accumulation under stress compared to the parental plants having γ-TMT or the glyI gene respectively. The studies revealed the synergy of two components from different metabolic pathways in enhancing stress hardiness of the transgenic B. juncea plants. It was concluded that pyramiding of genes (γ-TMT and glyI) from diverse pathways can lead to enhanced tolerance to salt and mannitol stress (simulating drought conditions). This strategy can prove useful in enhancing the crop yields under various abiotic stresses.

Keywords: abiotic stress, brassica juncea, glyoxalase I, α-tocopherol

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Authors: Seonaid Hume, Gordon Dobie, Graeme West

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Detecting and localizing radioactive sources is a necessity for safe and secure decommissioning of nuclear facilities. An important aspect for the management of the sort-and-segregation process is establishing the spatial distributions and quantities of the waste radionuclides, their type, corresponding activity, and ultimately classification for disposal. The data received from surveys directly informs decommissioning plans, on-site incident management strategies, the approach needed for a new cell, as well as protecting the workforce and the public. Manual classification of nuclear waste from a nuclear cell is time-consuming, expensive, and requires significant expertise to make the classification judgment call. Also, in-cell decommissioning is still in its relative infancy, and few techniques are well-developed. As with any repetitive and routine tasks, there is the opportunity to improve the task of classifying nuclear waste using autonomous systems. Hence, this paper proposes a new framework for the automatic classification of nuclear waste. This framework consists of five main stages; 3D spatial mapping and object detection, object classification, radiological mapping, source localisation based on gathered evidence and finally, waste classification. The first stage of the framework, 3D visual mapping, involves object detection from point cloud data. A review of related applications in other industries is provided, and recommendations for approaches for waste classification are made. Object detection focusses initially on cylindrical objects since pipework is significant in nuclear cells and indeed any industrial site. The approach can be extended to other commonly occurring primitives such as spheres and cubes. This is in preparation of stage two, characterizing the point cloud data and estimating the dimensions, material, degradation, and mass of the objects detected in order to feature match them to an inventory of possible items found in that nuclear cell. Many items in nuclear cells are one-offs, have limited or poor drawings available, or have been modified since installation, and have complex interiors, which often and inadvertently pose difficulties when accessing certain zones and identifying waste remotely. Hence, this may require expert input to feature match objects. The third stage, radiological mapping, is similar in order to facilitate the characterization of the nuclear cell in terms of radiation fields, including the type of radiation, activity, and location within the nuclear cell. The fourth stage of the framework takes the visual map for stage 1, the object characterization from stage 2, and radiation map from stage 3 and fuses them together, providing a more detailed scene of the nuclear cell by identifying the location of radioactive materials in three dimensions. The last stage involves combining the evidence from the fused data sets to reveal the classification of the waste in Bq/kg, thus enabling better decision making and monitoring for in-cell decommissioning. The presentation of the framework is supported by representative case study data drawn from an application in decommissioning from a UK nuclear facility. This framework utilises recent advancements of the detection and mapping capabilities of complex radiation fields in three dimensions to make the process of classifying nuclear waste faster, more reliable, cost-effective and safer.

Keywords: nuclear decommissioning, radiation detection, object detection, waste classification

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Authors: Amenah Dhannoon, Ciaran Martin Hurley, Laura Wrafter, Podraic J. Regan

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Introduction: The COVID-19 pandemic continues to present unprecedented challenges for healthcare systems. This has resulted in the pragmatic shift in the practice of plastic surgery units worldwide. During this period, many units reported a significant fall in urgent melanoma referrals, leading to patients presenting with advanced disease requiring more extensive surgery and inferior outcomes. Our objective was to evaluate our unit's experience with both non-invasive and invasive melanoma during the COVID-19 pandemic and characterize our experience and contrast it to that experienced by our neighbors in the UK, mainland Europe and North America. Methods: a retrospective chart review was performed on all patients diagnosed with invasive and non-invasive cutaneous melanoma between March to December of 2019 (control) compared to 2020 (COVID-19 pandemic) in a single plastic surgery unit in Ireland. Patient demographics, referral source, surgical procedures, tumour characteristics, radiological findings, oncological therapies and follow-up were recorded. All data were anonymized and stored in Microsoft Excel. Results: A total of 589 patients were included in the study. Of these, 314 (53%) with invasive melanoma, compared to 275 (47%) with the non-invasive disease. Overall, more patients were diagnosed with both invasive and non-invasive melanoma in 2020 than in 2019 (p<0.05). However, significantly longer waiting times in 2020 (64 days) compared to 2019 (28 days) (p<0.05), with the majority of the referral being from GP in 2019 (83%) compared to 61% in 2020. Positive sentinel lymph node were higher in 2019 at 56% (n=28) compared to 24% (n=22) in 2020. There was no statistically significant difference in the tutor characteristics or metastasis status. Discussion: While other countries have noticed a fall in the melanoma diagnosis. Our units experienced a higher number of disease diagnoses. This can be due to multiple reasons. In Ireland, the government reached an early agreement with the private sector to continue elective surgery on an urgent basis in private hospitals. This allowed access to local anesthetic procedures and local skin cancer cases were triaged to non-COVID-19 provider centers. Our unit also adapted a fast, effective and minimal patient contact strategy for triaging skin cancer based on telemedicine. Thirdly, a skin cancer nurse specialist maintained patient follow-ups and triaging a dedicated email service. Finally, our plastic surgery service continued to maintain a virtual complex skin cancer multidisciplinary team meeting during the pandemic, ensuring local clinical governance has adhered to each clinical case. Conclusion: Our study highlights that with the prompt efficient restructuring of services, we could reserve successful management of skin cancer even in the most devastating times. It is important to reflect on the success during the pandemic and emphasize the importance of preparation for a potentially difficult future

Keywords: malignant melanoma, skin cancer, COVID-19, triage

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Authors: Rohin Sharma, Sumantu Chaulagain

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This paper presents calculations of total energy of InGaN alloy carried out in a disordered quasirandom structure for a triclinic super cell. This structure replicates the disorder and composition effect in the alloy. First principle calculations within the density functional theory with the local density approximation approach is employed to accurately determine total energy of the system. Lattice constants and band gaps associated with the ground states are then estimated for different concentration ratios of the alloy. We provide precise results of quasirandom structures of the alloy and their lattice constants with the total energy and band gap energy of the system for the range of seven different composition ratios and their respective lattice parameters.

Keywords: DFT, ground state, LDA, quasicrystal, triclinic super cell

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Authors: N. Hasbullah, K. A. Sekak

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The sulfonated poly (ether ether ketone) SPEEK nanofiber membrane were successfully electrospun for Polymer Electrolyte Membrane (PEM) in Proton Exchange Membrane Fuel Cell (PEMFC) and their nanosized properties were investigated. The poly (ether ether ketone) PEEK victrex® grade 90p was sulfonated with concentrated sulfuric acid (95-98% w/w) at room temperature for 60 hours sulfonation times. The degree sulfonation of SPEEK are 70% was determined by H1 NMR and the functional groups of the SPEEK were characterize using FTIR. Then, the SPEEK nanofiber membrane were prepared via electrospinning method using DMAC as a solvent. The SPEEK sample were successfully electrospun using predetermine set up. FESEM show the electrospun fiber mat surface and confirmed the nanostructure membrane cell.

Keywords: polymer electrolyte membrane (PEM), sulfonated poly (ether ether ketone) (SPEEK), degree sulfonation, Electrospinning, Nanofibers

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Authors: Leila Rashki Ghaleno, Mohamad Amin Hajari, Leila Montazeri, Abdolhossein Shahverdi, Mojtaba Rezazadeh Valojerdi

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Background: Spermatogonia stem cells (SSCs) exhibit pluripotency, enabling them to undergo differentiation into many cell lineages, including neurons, glia, endothelial cells, and hepatocytes when cultured in vitro. Although the specific mechanisms are not yet fully understood, it has been observed that biopolymer agents, such as hyaluronic acid (HA) and alginate (Alg), have the potential to induce transdifferentiation of SSCs. The current work aimed to examine the process of in vitro spermatogenesis and the conversion of mouse testicular cells into hepatocytes and erythrocyte-like cells utilizing the HA-Alg hydrogel. Method: After being extracted from the testes of a 5-day postpartum mouse (5 DPP), the testicular cells were separated into two enzymatic stages and then put into a composite hydrogel containing 0.5% HA and 1% alginate. On days 14 and 28 of culture, the colonies' growth, the cells' viability, and their histology were assessed. Result: Despite observing significant cell proliferation on day 14 and the development of circular-shaped organoids on day 28, it was noted that the organoids generated in the HA-Alg medium tended to maintain their circular morphology on day 28. Notably, the testicular cells underwent transdifferentiation into cell types resembling erythrocytes and hepatocytes. The hepatocyte-like cells exhibited the presence of glycogen and lipid deposits, indicating their hepatocyte-like characteristics. Interestingly, immunostaining analysis revealed the secretion of albumin and the presence of VEGFR on day 14. However, on day 28, albumin expression was not detected, while the expression of Sox9 (a marker for hepatocytes), Vegf, CD34, and C-kit (markers for erythrocytes) showed increased levels in the gene expression evaluation. Conclusion: The present findings indicated that HA-Alg could be a potent and effective agent for the transdifferentiation of testis cells into erythrocyte and hepatocyte-like cells, as recent studies have confirmed the transformation of SSCs into hepatocyte cells during in vitro culture.

Keywords: 3D culture, mouse testicular cell, hyaluronic acid, liver organoids

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Authors: E. M. Hassan, A. L. Kalamkarov

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Two micromechanical models for 3D smart composite with embedded periodic or nearly periodic network of generally orthotropic reinforcements and actuators are developed and applied to cubic structures with unidirectional orientation of constituents. Analytical formulas for the effective piezothermoelastic coefficients are derived using the Asymptotic Homogenization Method (AHM). Finite Element Analysis (FEA) is subsequently developed and used to examine the aforementioned periodic 3D network reinforced smart structures. The deformation responses from the FE simulations are used to extract effective coefficients. The results from both techniques are compared. This work considers piezoelectric materials that respond linearly to changes in electric field, electric displacement, mechanical stress and strain and thermal effects. This combination of electric fields and thermo-mechanical response in smart composite structures is characterized by piezoelectric and thermal expansion coefficients. The problem is represented by unit-cell and the models are developed using the AHM and the FEA to determine the effective piezoelectric and thermal expansion coefficients. Each unit cell contains a number of orthotropic inclusions in the form of structural reinforcements and actuators. Using matrix representation of the coupled response of the unit cell, the effective piezoelectric and thermal expansion coefficients are calculated and compared with results of the asymptotic homogenization method. A very good agreement is shown between these two approaches.

Keywords: asymptotic homogenization method, finite element analysis, effective piezothermoelastic coefficients, 3D smart network composite structures

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Authors: Mosima M. Mabitsela

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Groundnut is preferably grown on light textured soils. Most of these light textured soils tend to be highly weathered and characterized by high soil acidity and low nutrient status. One major soil factor associated with infertility of acidic soils that can negatively depress groundnut yield is aluminium (Al) toxicity. In plants Al toxicity damages root cells, leading to inhibition of root growth as a result of the suppression of cell division, cell elongation and cell expansion in the apical meristem cells of the root. The end result is that roots become stunted and brittle, root hair development is poor, and the root apices become swollen. This study was conducted to determine the effects of aluminium (Al) toxicity on a range of groundnut varieties. Fifteen cultivars were tested in incremental aluminum (Al) supply in an ebb and flow solution culture laid out in a randomized complete block design. There were six aluminium (Al) treatments viz. 0 µM, 1 µM, 5.7 µM, 14.14 µM, 53.18 µM, and 200 µM. At 1 µM there was no inhibitory effect on the growth of groundnut. The inhibition of groundnut growth was noticeable from 5.7 µM to 200 µM, where the severe effect of aluminium (Al) stress was observed at 200 µM. The cultivars varied in their response to aluminium (Al) supply in solution culture. Groundnuts are one of the most important food crops in the world, and its supply is on a decline due to the light-textured soils that they thrive under as these soils are acidic and can easily solubilize aluminium (Al) to its toxic form. Consequently, there is a need to develop groundnut cultivars with high tolerance to soil acidity.

Keywords: aluminium toxicity, cultivars, reduction, root growth

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Authors: Warda Jabeen, Romaisa Shamim Khan, Osama Shakeel, Ahmed Faraz Bhatti, Raza Hussain

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Background: The worldwide incidence of cutaneous melanoma (CM) has been on the rise over the past few decades. Primary prevention and early treatment remain the focus of management to reduce the burden of disease. This entails identification of risk factors to prompt early diagnosis. In Pakistan, there is a scarcity of clinico-pathological data relating to cutaneous malignant melanoma. Objective: The purpose of this study was to analyze the epidemiological and clinical characteristics of patients presenting with cutaneous malignant melanoma in Pakistan, and to compare the results with other studies. Method: Shaukat Khanum Memorial Cancer Hospital and Research Centre is currently the only dedicated cancer hospital in the country, accepting patients from all over Pakistan. Majority of the patients, however, belong to the northern half of the country. From the recorded data of the hospital, all cutaneous melanoma cases were identified and evaluated. Results: Between 1997 and 2017, a total of 169 cutaneous melanoma patients were registered at Shaukat Khanum. Mean age was 47.5 years. The highest incidence of melanoma was seen in the age group 40-59 years (n=69, 40.8%). Most commonly reported clinical subtype was unspecified melanoma (n=154, 91%). Amongst those in which T stage was reported, the most frequently observed T-stage at presentation was T4 (n=23, 13.6%). With regards to body distribution, in our study CM was seen most commonly in the lower limb including the hip. The yearly incidence of melanoma has increased/remained stable from 2007 to 2017. Conclusion: cutaneous malignant melanoma is a fairly common disease in Pakistan. Patients tend to present at a more advanced stage as compared to patients in developed countries. Identification of risk factors and tumor characteristics is therefore of paramount importance to deal with these patients.

Keywords: epidemiology of cutaneous malignant melanoma, cutaneous malignant melanoma, Pakistan, skin cancer

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

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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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