Search results for: cancer colorectal

Authors: Esther Friedlander, Philip Friedlander

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The use of immunotherapy that inhibits programmed death-1 (PD-1) or its ligand PD-L1 confers survival benefits in patients with non-small cell lung cancer (NSCLC). However, approximately 45% of patients experience primary treatment resistance, necessitating the development of strategies to improve efficacy. While the renin-angiotensin system (RAS) has systemic hemodynamic effects, tissue-specific regulation exists along with modulation of immune activity in part through regulation of myeloid cell activity, leading to the hypothesis that RAS inhibition may improve anti-PD-1/L-1 efficacy. A retrospective analysis was conducted that included 173 advanced solid tumor cancer patients treated at Valley Hospital, a community Hospital in New Jersey, USA, who were treated with a PD-1/L-1 inhibitor in a defined time period showing a statistically significant relationship between RAS pathway inhibition (RASi through concomitant treatment with an ACE inhibitor or angiotensin receptor blocker) and positive efficacy to the immunotherapy that was independent of age, gender and cancer type. Subset analysis revealed strong numerical benefit for efficacy in both patients with squamous and nonsquamous NSCLC as determined by documented clinician assessment of efficacy and by duration of therapy. A PUBMED literature search was now conducted to identify studies assessing the effect of RAS pathway inhibition on anti-PD-1/L1 efficacy in advanced solid tumor patients and compare these findings to those seen in the Valley Hospital retrospective study with a focus on NSCLC specifically. A total of 11 articles were identified assessing the effects of RAS pathway inhibition on the efficacy of checkpoint inhibitor immunotherapy in advanced cancer patients. Of the 11 studies, 10 assessed the effect on survival of RASi in the context of treatment with anti-PD-1/PD-L1, while one assessed the effect on CTLA-4 inhibition. Eight of the studies included patients with NSCLC, while the remaining 2 were specific to genitourinary malignancies. Of the 8 studies, two were specific to NSCLC patients, with the remaining 6 studies including a range of cancer types, of which NSCLC was one. Of these 6 studies, only 2 reported specific survival data for the NSCLC subpopulation. Patient characteristics, multivariate analysis data and efficacy data seen in the 2 NSLCLC specific studies and in the 2 basket studies, which provided data on the NSCLC subpopulation, were compared to that seen in the Valley Hospital retrospective study supporting a broader effect of RASi on anti-PD-1/L1 efficacy in advanced NSLCLC with the majority of studies showing statistically significant benefit or strong statistical trends but with one study demonstrating worsened outcomes. This comparison of studies extends published findings to the community hospital setting and supports prospective assessment through randomized clinical trials of efficacy in NSCLC patients with pharmacodynamic components to determine the effect on immune cell activity in tumors and on the composition of the tumor microenvironment.

Keywords: immunotherapy, cancer, angiotensin, efficacy, PD-1, lung cancer, NSCLC

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Authors: Shaira L. Kee, Michael Aaron G. Sy, Myles Joshua T. Tan, Hezerul Abdul Karim, Nouar AlDahoul

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Skin diseases are considered the fourth most common disease, with melanoma and non-melanoma skin cancer as the most common type of cancer in Caucasians. The alarming increase in Skin Cancer cases shows an urgent need for further research to improve diagnostic methods, as early diagnosis can significantly improve the 5-year survival rate. Machine Learning algorithms for image pattern analysis in diagnosing skin lesions can dramatically increase the accuracy rate of detection and decrease possible human errors. Several studies have shown the diagnostic performance of computer algorithms outperformed dermatologists. However, existing methods still need improvements to reduce diagnostic errors and generate efficient and accurate results. Our paper proposes an ensemble method to classify dermoscopic images into benign and malignant skin lesions. The experiments were conducted using the International Skin Imaging Collaboration (ISIC) image samples. The dataset contains 3,297 dermoscopic images with benign and malignant categories. The results show improvement in performance with an accuracy of 88% and an F1 score of 87%, outperforming other existing models such as support vector machine (SVM), Residual network (ResNet50), EfficientNetB0, EfficientNetB4, and VGG16.

Keywords: deep learning - VGG16 - efficientNet - CNN – ensemble – dermoscopic images - melanoma

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Authors: Chia-Yen Lee, Hao-Jen Wang, Jhih-Hao Lai

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In recent years, infrared (IR) imaging has been considered as a potential tool to assess the efficacy of chemotherapy and early detection of breast cancer. Regions of tumor growth with high metabolic rate and angiogenesis phenomenon lead to the high temperatures. Observation of differences between the heat maps in long term is useful to help assess the growth of breast cancer cells and detect breast cancer earlier, wherein the multi-time infrared image alignment technology is a necessary step. Representative feature points detection and matching are essential steps toward the good performance of image registration and quantitative analysis. However, there is no clear boundary on the infrared images and the subject's posture are different for each shot. It cannot adhesive markers on a body surface for a very long period, and it is hard to find anatomic fiducial markers on a body surface. In other words, it’s difficult to detect and match features in an IR sequence images. In this study, automated feature detection and matching algorithms with two type of automatic feature points (i.e., vascular branch points and modified Harris corner) are developed respectively. The preliminary results show that the proposed method could identify the representative feature points on the IR breast images successfully of 98% accuracy and the matching results of 93% accuracy.

Keywords: Harris corner, infrared image, feature detection, registration, matching

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Authors: Aleksandra Twarda, Dobrosława Krzemień, Grzegorz Dubin, Tad A. Holak

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Stabilin-2 belongs to the group of scavenger receptors and plays a crucial role in clearance of more than 10 ligands from the bloodstream, including hyaluronic acid, products of degradation of extracellular matrix and metabolic products. The Link domain, a defining feature of stabilin-2, has a sequence similar to Link domains in other hyaluronic acid receptors, such as CD44 or TSG-6, and is responsible for most of ligands binding. Present knowledge of signal transduction by stabilin-2, as well as ligands’ recognition and binding mechanism, is limited. Until now, no experimental structures have been solved for any segments of stabilin-2. It has recently been demonstrated that the stabilin-2 knock-out or blocking of the receptor by an antibody effectively opposes cancer metastasis by elevating the level of circulating hyaluronic acid. Moreover, loss of expression of stabilin-2 in a peri-tumourous liver correlates with increased survival. Solving of the crystal structure of stabilin-2 and elucidation of the binding mechanism of hyaluronic acid could enable the precise characterization of the interactions in the binding site. These results may allow for designing specific small-molecule inhibitors of stabilin-2 that could be used in cancer therapy. To carry out screening for crystallization of stabilin-2, we cloned constructs of the Link domain of various lengths with or without surrounding domains. The folding properties of the constructs were checked by nuclear magnetic resonance (NMR). It is planned to show the binding of hyaluronic acid to the Link domain using several biochemical methods, i.a. NMR, isothermal titration calorimetry and fluorescence polarization assay.

Keywords: stabilin-2, Link domain, X-ray crystallography, NMR, hyaluronic acid, cancer

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Authors: Hayrettin Eroglu, Adem Kara

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Recently there has been significant attention given to imaging of the biological tissues via microwave imaging techniques. In this study, a phantom for the test and calibration of Microwave imaging used in detecting unhealthy breast structure or tumors was produced by using sol gel method. The liquid and gel phantoms being used nowadays are not durable due to evaporation and their organic ingredients, hence a new design was proposed. This phantom was fabricated from materials that were widely available (water, salt, gelatin, and glycerol) and was easy to make. This phantom was aimed to be better from the ones already proposed in the literature in terms of its durability and stability. S Parameters of phantom was measured with 1-18 GHz Probe Kit and permittivity was calculated via Debye method in “85070” commercial software. One, three, and five-week measurements were taken for this phantom. Finally, it was verified that measurement results were very close to the real biological tissue measurement results.

Keywords: phantom, breast tissue, cancer, microwave imaging

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Authors: Agnė Mikalauskaitė, Renata Karpicz, Vitalijus Karabanovas, Arūnas Jagminas

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The use of biocompatible precursors for the synthesis and stabilization of fluorescent gold nanoclusters (NCs) with strong red photoluminescence creates an important link between natural sciences and nanotechnology. Herein, we report the cost-effective synthesis of Au nanoclusters by templating and reduction of chloroauric acid with the cheap amino acid food supplements. This synthesis under the optimized conditions leads to the formation of biocompatible Au NCs having good stability and intense red photoluminescence, peaked at 680 to 705 nm, with a quantum yield (QY) of ≈7% and the average lifetime of up to several µs. The composition and luminescent properties of the obtained NCs were compared with ones formed via well-known bovine serum albumin reduction approach. Our findings implied that synthesized Au NCs tend to accumulate in more tumorigenic breast cancer cells (line MDA-MB-213) and after dialysis can be prospective for bio imagining.

Keywords: gold nanoclusters, proteins, materials chemistry, red-photoluminescence, bioimaging

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Authors: Ming Ze Kao

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Static magnetic fields (SMF) are widely used in several medical applications, especially in diagnosis of tumors. However, biological effects of the SMFs on modulating cell physiology through the Lorentz force, which is highly frequency and magnitude dependent, remain to be elucidated. Specific patterns from SMFs of static MF, delivered by means of Halbach array magnets with a gradient increment of 6.857mT/mm from center to border, were found to have profound inhibitory effect on the growth rate of human cell line derived from Nasopharyngeal carcinoma patients. The SMFs, which were shown to be noncontact, selectively impact rapid dividing cells while quiescent cells stay intact. The phenomenon acts in two modes: the arrest of cell proliferation in the G2/M phase and destruction of cell mitosis in cell division. First mode is manifested by impacting the proper formation of mitotic spindle, whereas the second results in disintegration of the cancer cell. Both modes are demonstrated when SMF was applied for 24 hours to cancer cells, the results revealed that metaphase arrest during mitosis due to activation of DNA damage response (DDR), resulting in high expression of ATM-NBS1-CHEK signaling pathways and higher G2/M phase ratio compared with control group. Here, experimental data suggest that the SMFs cause activation of cell cycle checkpoints, which implies the MFs as a potential therapeutic modality as a sensitizer for radiotherapy or chemotherapy.

Keywords: static magnetic field, DNA damage response, Halbach array, magnetic therapy

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Authors: Vincent Murray

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The chromatin structure at the transcription start sites (TSSs) of genes is very important in the control of gene expression. In order for gene expression to occur, the chromatin structure at the TSS has to be altered so that the transcriptional machinery can be assembled and RNA transcripts can be produced. In particular, the nucleosome structure and positioning around the TSS has to be changed. Bleomycin is utilized as an anti-tumor agent to treat Hodgkin's lymphoma, squamous cell carcinoma, and testicular cancer. Bleomycin produces DNA damage in human cells and DNA strand breaks, especially double-strand breaks, are thought to be responsible for the cancer chemotherapeutic activity of bleomycin. Bleomycin is a large glycopeptide with molecular weight of approximately 1500 Daltons and hence its DNA strand cleavage activity can be utilized as a probe of chromatin structure. In this project, Illumina next-generation DNA sequencing technology was used to determine the position of DNA double-strand breaks at the TSSs of genes in intact cells. In this genome-wide study, it was found that bleomycin cleavage preferentially occurred at the TSSs of actively transcribed human genes in comparison with non-transcribed genes. There was a correlation between the level of enhanced bleomycin cleavage at TSSs and the degree of transcriptional activity. In addition, bleomycin was able to determine the position of nucleosomes at the TSSs of human genes. Bleomycin analogues were also utilized as probes of chromatin structure at the TSSs of human genes. In a similar manner to bleomycin, the bleomycin analogues 6′-deoxy-BLM Z and zorbamycin preferentially cleaved at the TSSs of human genes. Interestingly this degree of enhanced TSS cleavage inversely correlated with the cytotoxicity (IC50 values) of BLM analogues. This indicated that the degree of cleavage by bleomycin analogues at the TSSs of human genes was very important in the cytotoxicity of bleomycin and analogues. It also provided a deeper insight into the mechanism of action of this cancer chemotherapeutic agent since actively transcribed genes were preferentially targeted.

Keywords: anti-cancer activity, chromatin structure, cytotoxicity, gene expression, next-generation DNA sequencing

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Authors: Adebisi Adunola Demehin, Wanlaya Thamnarak, Jaruwan Chatwichien, Chatchakorn Eurtivong, Kiattawee Choowongkomon, Somsak Ruchirawat, Nopporn Thasana

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The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein involved in cellular signalling processes and, its aberrant activity is crucial in the development of many cancers such as lung cancer. Selaginellaceae are fern allies that have long been used in Chinese traditional medicine to treat various cancer types, especially lung cancer. Biflavonoids, the major secondary metabolites in Selaginellaceae, have numerous pharmacological activities, including anti-cancer and anti-inflammatory. For instance, amentoflavone induces a cytotoxic effect in the human NSCLC cell line via the inhibition of PARP-1. However, to the best of our knowledge, there are no studies on biflavonoids as EGFR inhibitors. Thus, this study aims to investigate the EGFR inhibitory activities of biflavonoids isolated from Selaginella siamensis and Selaginella bryopteris. Amentoflavone, tetrahydroamentoflavone, sciadopitysin, robustaflavone, robustaflavone-4-methylether, delicaflavone, and chrysocauloflavone were isolated from the ethyl-acetate extract of the whole plants. The structures were determined using NMR spectroscopy and mass spectrometry. In vitro study was conducted to evaluate their cytotoxicity against A549, HEPG2, and T47D human cancer cell lines using the MTT assay. In addition, a target-based assay was performed to investigate their EGFR inhibitory activity using the kinase inhibition assay. Finally, a molecular docking study was conducted to predict the binding modes of the compounds. Robustaflavone-4-methylether and delicaflavone showed the best cytotoxic activity on all the cell lines with IC50 (µM) values of 18.9 ± 2.1 and 22.7 ± 3.3 on A549, respectively. Of these biflavonoids, delicaflavone showed the most potent EGFR inhibitory activity with an 84% relative inhibition at 0.02 nM using erlotinib as a positive control. Robustaflavone-4-methylether showed a 78% inhibition at 0.15 nM. The docking scores obtained from the molecular docking study correlated with the kinase inhibition assay. Robustaflavone-4-methylether and delicaflavone had a docking score of 72.0 and 86.5, respectively. The inhibitory activity of delicaflavone seemed to be linked with the C2”=C3” and 3-O-4”’ linkage pattern. Thus, this study suggests that the structural features of these compounds could serve as a basis for developing new EGFR-TK inhibitors.

Keywords: anticancer, biflavonoids, EGFR, molecular docking, Selaginellaceae

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Authors: G. Meccariello, L. Della Ragione

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The exposure to outdoor air pollution causes lung cancer and increases the risk of bladder cancer. Because air pollution in urban areas is mainly caused by transportation, it is necessary to evaluate pollutant exhaust emissions from vehicles during their real-world use. Nevertheless their evaluation and reduction is a key problem, especially in the cities, that account for more than 50% of world population. A particular attention was given to the slope variability along the streets during each journey performed by the instrumented vehicle. In this paper we dealt with the problem of describing a quantitatively approach for the reconstruction of GPS coordinates and altitude, in the context of correlation study between driving cycles / emission / geographical location, during an experimental campaign realized with some instrumented cars. Finally the slope analysis can be correlated to the emission and consumption values in a specific road position, and it could be evaluated its influence on their behaviour.

Keywords: air pollution, driving cycles, GPS signal, slope, emission factor, fuel consumption

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Authors: Janet Wing-Chong Wai, Alex Chiu-Wing Lee, Hailey Hoi-Ching Tsang, Jeffrey Chiu, Kwok-Wing Tang

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Background: Mammography has limited sensitivity and specificity though it is the primary imaging technique for detection of early breast cancer. Ultrasound imaging and contrast-enhanced MRI are useful adjunct tools to mammography. The advantage of breast MRI is high sensitivity for invasive breast cancer. Therefore, indications for and use of breast magnetic resonance imaging have increased over the past decade. Objectives: 1. Cases demonstration on different indications for breast MR imaging. 2. To review of the common artifacts and pitfalls in breast MR imaging. Materials and Methods: This is a retrospective study including all patients underwent dynamic contrast-enhanced breast MRI examination in our centre, performed from Jan 2011 to Dec 2017. The clinical data and radiological images were retrieved from the EPR (electronic patient record), RIS (Radiology Information System) and PACS (Picture Archiving and Communication System). Results and Discussion: Cases including (1) Screening of the contralateral breast in patient with a new breast malignancy (2) Breast augmentation with free injection of unknown foreign materials (3) Finding of axillary adenopathy with an unknown site of primary malignancy (4) Neo-adjuvant chemotherapy: before, during, and after chemotherapy to evaluate treatment response and extent of residual disease prior to operation. Relevant images will be included and illustrated in the presentation. As with other types of MR imaging, there are different artifacts and pitfalls that can potentially limit interpretation of the images. Because of the coils and software specific to breast MR imaging, there are some other technical considerations that are unique to MR imaging of breast regions. Case demonstration images will be available in presentation. Conclusion: Breast MR imaging is a highly sensitive and reasonably specific method for the detection of breast cancer. Adherent to appropriate clinical indications and technical optimization are crucial for achieving satisfactory images for interpretation.

Keywords: MRI, breast, clinical, cancer

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Authors: Anna Rudzińska, Katarzyna Szklener, Pola Juchaniuk, Anna Rodzajweska, Katarzyna Machulska-Ciuraj, Monika Rychlik- Grabowska, Michał łOziński, Agnieszka Kolak-Bruks, SłAwomir Mańdziuk

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Introduction: Immune checkpoint inhibition (ICI) belongs to the modern forms of anti-cancer treatment. Due to the constant development and continuous research in the field of ICI, many aspects of the treatment are yet to be discovered. One of the less researched aspects of ICI treatment is the influence of the adverse effects on the treatment success rate. It is suspected that adverse events in the course of the ICI treatment indicate a better response rate and correlate with longer progression-free- survival. Methodology: The research was conducted with the usage of the documentation of the Department of Clinical Oncology and Chemotherapy. Data of the patients with a lung cancer diagnosis who were treated between 2019-2022 and received ICI treatment were analyzed. Results: Out of over 133 patients whose data was analyzed, the vast majority were diagnosed with non-small cell lung cancer. The majority of the patients did not experience adverse effects. Most adverse effects reported were classified as grade 1 or grade 2 according to CTCAE classification. Most adverse effects involved skin, thyroid and liver toxicity. Statistical significance was found for the adverse effect incidence and overall survival (OS) and progression-free survival (PFS) (p=0,0263) and for the time of toxicity onset and OS and PFS (p<0,001). The number of toxicity sites was statistically significant for prolonged PFS (p=0.0315). The highest OS was noted in the group presenting grade 1 and grade 2 adverse effects. Conclusions: Obtained results confirm the existence of the prolonged OS and PFS in the adverse-effects-charged patients, mostly in the group presenting mild to intermediate (Grade 1 and Grade 2) adverse effects and late toxicity onset. Simultaneously our results suggest a correlation between treatment response rate and the toxicity grade of the adverse effects and the time of the toxicity onset. Similar results were obtained in several similar research conducted - with the proven tendency of better survival in mild and moderate toxicity; meanwhile, other studies in the area suggested an advantage in patients with any toxicity regardless of the grade. The contradictory results strongly suggest the need for further research on this topic, with a focus on additional factors influencing the course of the treatment.

Keywords: adverse effects, immunotherapy, lung cancer, PD-1/PD-L1 inhibitors

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Authors: Vivek Bhat, Rohini Kelkar, Sanjay Biswas

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Introduction: Cancer patients are at increased risk of bacterial infections. This may due to the disease process itself, the effect of chemotherapeutic drugs or invasive procedures such as catheterization. A wide variety of bacteria including some emerging pathogens are increasingly being reported from these patients. The incidence of multidrug-resistant organisms particularly in the Gram negative group is also increasing, with higher resistance rates seen to cephalosporins, β-lactam/β-lactam inhibitor combinations, and the carbapenems. This study documents the bacteriological spectrum of infections and their resistance patterns in cancer patients. Methods: This study includes all bacterial isolates recovered from infections cancer patients over a period of 18 months. Samples included Blood cultures, Pus/wound swabs, urine, tissue biopsies, body fluids, catheter tips and respiratory specimens such as sputum and bronchoalveolar lavage (BAL). All samples were processed in the microbiology laboratory as per standard laboratory protocols. Organisms were identified to species level and antimicrobial susceptibility testing was performed manually by the disc diffusion technique or in the Vitek-2 (Biomereux, France) instrument. Interpretations were as per Clinical laboratory Standards Institute (CLSI) guidelines. Results: A total of 1150 bacterial isolates were cultured from 884 test samples during the study period. Of these 227 were Gram-positive and 923 were Gram-negative organisms. Staphylococcus aureus (99 isolates) was the commonest Gram-positive isolate followed by Enterococcus (79) and Gr A Streptococcus (30). Among the Gram negatives, E. coli (304), Pseudomonas aeruginosa (201) and Klebsiella pneumoniae (190) were the most common. Of the Staphylococcus aureus isolates 27.2% were methicillin resistant. Only 5.06% enterococci were vancomycin resistant. High rates of resistance to cefotaxime and ciprofloxacin were seen amongst E. coli (84.8% & 83.55%) and Klebsiella pneumoniae (71 & 62.1%) respectively. Resistance to carbapenems (meropenem) was high at 70% in Acinetobacter spp.; however all isolates were sensitive to colistin. Among the aminoglycosides, amikacin retained good efficacy against Escherichia coli (82.9%) and Pseudomonas aeruginosa (78.1%). Occasional isolates of emerging pathogens such as Chryseobacterium indologens, Roseomonas, and Achromobacter xyloxidans were also recovered. Conclusion: The common infections in cancer patients include respiratory, wound, tract infections and sepsis. The commonest isolates include Staphylococcus aureus, Enterococci, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. There is a high level of resistance to the commonly used antibiotics among Gram-negative organisms.

Keywords: bacteria, resistance, infection, cancer

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Authors: Ruqayya Naheed Khan, Romaisa Shamim, Awais Amjad Malik, Awais Naeem, Amina Iqbal Khan, Asad Parvaiz

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Objective: Patients undergoing axillary lymph node dissection (ALND) for metastatic lymph nodes in our hospital usually have drains placed in their axilla for a period of 6-10 days. We evaluated the post-op course of patients who underwent breast conservation surgery (BCS) along with ALND. Methods: A prospective cohort study was conducted at Shaukat Khanam Memorial Cancer Hospital from April 2017 to August 2017 including all lymph node positive breast cancer patients undergoing BCS with ALND. Patients were divided into two groups. Group A had no axillary drain while in Group B a drain was placed in axilla. Results: A total of 76 patients were included. 41 patients were included in group A and 35 patients in Group B. Median number of LNs dissected in group A was 17 and in group B was 15 (p value 0.443). Median operative time in group A was 84 min and in group B was 79 min (p value 0.223). Median hospital stay in both groups was 1 day (p value 0.78). At 2 weeks all patients in group A developed seroma as compared to none in group B (p value < 0.001). 3 of these patients in group A required aspiration of seroma due to pressure effects. Rest were managed conservatively. At 6 weeks only 50% patients had a seroma radiologically in Group A as compared to 33% in group B (p value 0.023). No intervention was required in any patients at week 6. QOL at 2 weeks was much better in Group A (7/41 patients had unsatisfactory response) as compared to group B (10/31 had unsatisfactory response). Results were statistically significant (p value 0.045). However, there wasn’t much difference in QOL at 6 weeks. Only 1 patient in group A had an unsatisfactory response. Average pain score at 2 weeks was similar in both groups (4.2 v/s 4.1 p value 0.73). Infection was seen in 1 patient in each group at 2 weeks (p value 0.668) and in only 1 patient in group A at 6 weeks (p value 0.067). Conclusion: We conclude from our study that there isn’t much difference in drain and no drain group in terms of wound infection and pain scores. No drain group is however associated with a better QOL in early post-op period.

Keywords: axillary drainage, axillary lymph node dissection, breast cancer, no drain in axilla

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Authors: Maryam Zahedifard, Fadhil Lafta Faraj, Maryam Hajrezaie, Nazia Abdul Majid, Mahmood Ameen Abdulla, Hapipah Mohd Ali

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In the current study, we prepared two new quinazoline schiff bases through condensation reaction of 2-aminobenzhydrazide with 5-bromosalicylaldehyde and 3-methoxy-5-bromosalicylaldehyde. The chemical structures of both newly synthesized compounds (1 and 2) were confirmed by FT-IR and X-ray crystallography studies. The cytotoxic effect of compounds was investigated against MCF-7 human breast cancer cells. MTT results showed that (1) and (2) decreased the viability of MCF-7 cells in a time-dependent manner, exhibiting an IC50 value of 3.23 ± 0.28 µg/mL and 3.41 ± 0.34 µg/mL, respectively, after a 72-hours treatment period. In contrast, they did not show significant anti-proliferative effect towards MCF-10A normal breast cells and WRL-68 normal liver cells. We found a perturbation in mitochondrial membrane potential and increased cytochrome c release from the mitochondria to the cytosol, suggesting an activation of apoptosis by compounds, which was confirmed by activation of the initiator caspase-9 and the executioner caspases-3/7. (1) was also able to trigger extrinsic pathway via activation of caspase-8 and inhibition of NF-κB translocation. The acute toxicity test showed no toxicity effect of the compounds in rats. Our results showed that the selected synthesized compounds are highly potent to induce apoptosis in MCF-7 cells via either intrinsic or extrinsic mitochondrial pathway.

Keywords: Quinazoline Schiff base, apoptosis, MCF-7 human breast cancer cell line, caspase, NF-κB translocation

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Authors: Akemi Nasu, Keiko Matsumoto

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Rehabilitation for cancer requires setting up individual goals for each patient and an approach that properly fits the stage of cancer when putting into practice. In order to cope with the daily changes in the patients' condition, the establishment of a good cooperative relationship between the nurses and the physiotherapists, occupational therapists, and speech-language-hearing therapists (therapists) becomes essential. This study will focus on the present situation of the cooperation between nurses and therapists, especially the speech-language-hearing therapists, and aim to elucidate what develops there. A semi-structured interview was conducted targeted at a physical therapist having practical experience in working in collaboration with nurses. The contents of the interview were transcribed and converted to data, and the data was encoded and categorized with sequentially increasing degrees of abstraction to conduct a qualitative explorative factor analysis of the data. When providing ethical explanations, particular care was taken to ensure that participants would not be subjected to any disadvantages as a result of participating in the study. In addition, they were also informed that their privacy would be ensured and that they have the right to decline to participate in the study. In addition, they were also informed that the results of the study would be announced publicly at an applicable nursing academic conference. This study has been approved following application to the ethical committee of the university with which the researchers are affiliated. The survey participant is a female speech-language-hearing therapist in her forties. As a result of the analysis, 6 categories were extracted consisting of 'measures to address appetite and aspiration pneumonia prevention', 'limitation of the care a therapist alone could provide', 'the all-inclusive patient- supportive care provided by nurses', 'expand the beneficial cooperation with nurses', 'providing education for nurses on the swallowing function utilizing videofluoroscopic examination of swallowing', 'enhancement of communication including conferences'. In order to improve the team performance, and for the teamwork competency necessary for the provision of safer care, mutual support is essential. As for the cooperation between nurses and therapists, this survey indicates that the maturing of the cooperation between professionals in order to improve nursing professionals' knowledge and enhance communication will lead to an improvement in the quality of the rehabilitation for cancer.

Keywords: cancer rehabilitation, nurses, speech-language-hearing therapists, interprofessional work

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Authors: Viacheslav Sushko, Viktor Sushko

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Pre-cancerous breast diseases are pathological changes that precede the appearance of adenocarcinoma. The most common benign breast disease is mastopathy. We examined the life and disease history of 114 women aged 58-69 who were diagnosed with adenocarcinoma of the breast at different stages of development. They filled out the Reeder Scale to determine the level of stress. The results of the study revealed that 62 of them had mastopathy at the age of 30-45 years old. These women refused surgical treatment for mastopathy. Five to six years before their diagnosis of adenocarcinoma of the mammary gland, 84 women had experienced severe stress (death of a beloved close relative, torture accompanied by rape, prolonged stay in extreme conditions (under bombardment and bombardment). In the assessment of data from completed Reeder scales, 114 women had a high level of mental stress, with a score from 1-1.72. The 84 women who suffered from severe stress showed overeating or a significant decrease in food intake, insomnia, apathy, increased irritability and restlessness, loss of interest in sexual relationships, forgetfulness, difficulty in performing routine work, prolonged uncontrollable headaches, unexplained fatigue, heart pain, reduced capacity for work. In conclusion, it is important to provide psychotherapy for breast cancer patients as the diagnosis, and the different stages of treatment are very stressful. It is also advisable to see a psychiatrist at an early stage and prevent distress and treat precancerous breast disease.

Keywords: breast cancer, distress, mastopathy, severe stress

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Authors: Helen Zhang

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Accurate segmentation of the airways from CT scans is crucial for early diagnosis of lung cancer. However, the existing airway segmentation algorithms often rely on thin-slice CT scans, which can be inconvenient and costly. This paper presents a set of machine learning-based 3D super-resolution algorithms along heterogeneous dimensions to improve the resolution of thicker CT scans to reduce the reliance on thin-slice scans. To evaluate the efficacy of the super-resolution algorithms, quantitative assessments using PSNR (Peak Signal to Noise Ratio) and SSIM (Structural SIMilarity index) were performed. The impact of super-resolution on airway segmentation accuracy is also studied. The proposed approach has the potential to make airway segmentation more accessible and affordable, thereby facilitating early diagnosis and treatment of lung cancer.

Keywords: 3D super-resolution, airway segmentation, thin-slice CT scans, machine learning

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Authors: M. A. I Perera, C. R. Wijesinghe, A. R. Weerasinghe

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his study was conducted to review and identify the unsupervised techniques that can be employed to analyze gene expression data in order to identify better subtypes of tumors. Identifying subtypes of cancer help in improving the efficacy and reducing the toxicity of the treatments by identifying clues to find target therapeutics. Process of gene expression data analysis described under three steps as preprocessing, clustering, and cluster validation. Feature selection is important since the genomic data are high dimensional with a large number of features compared to samples. Hierarchical clustering and K Means are often used in the analysis of gene expression data. There are several cluster validation techniques used in validating the clusters. Heatmaps are an effective external validation method that allows comparing the identified classes with clinical variables and visual analysis of the classes.

Keywords: cancer subtypes, gene expression data analysis, clustering, cluster validation

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Authors: Sarah Crawford, Gerry Lesley

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This research is a pre-clinical assessment of anti-cancer effects of novel non-steroidal diethyl stilbestrol-like estrogen analogs in estrogen-receptor positive/ progesterone-receptor positive human breast cancer microtumors of MCF 7 cell line. Tamoxifen analog formulation (Tam A1) was used as a single agent or in combination with therapeutic concentrations of 4-hydroxytamoxifen, currently used as a long-term treatment for the prevention of breast cancer recurrence in women with estrogen receptor positive/ progesterone receptor positive malignancies. At concentrations ranging from 30-50 microM, Tam A1 induced microtumor disaggregation and cell death. Incremental cytotoxic effects correlated with increasing concentrations of Tam A1. Live tumor microscopy showed that microtumos displayed diffuse borders and substrate-attached cells were rounded-up and poorly adherent. A complete cytotoxic effect was observed using 40-50 microM Tam A1 with time course kinetics similar to 4-hydroxytamoxifen. Combined treatment with TamA1 (30-50 microM) and 4-hydroxytamoxifen (10-15 microM) induced a highly cytotoxic, synergistic combined treatment response that was more rapid and complete than using 4-hydroxytamoxifen as a single agent therapeutic. Microtumors completely dispersed or formed necrotic foci indicating a highly cytotoxic combined treatment response. Moreover, breast cancer microtumors treated with both 4-hydroxytamoxifen and Tam A1 displayed lower levels of long-term post-treatment regrowth, a critical parameter of primary drug resistance, than observed for 4-hydroxytamoxifen when used as a single agent therapeutic. Tumor regrowth at 6 weeks post-treatment with either single agent 4-hydroxy tamoxifen, Tam A1 or a combined treatment was assessed for the development of drug resistance. Breast cancer cells treated with both 4-hydroxytamoxifen and Tam A1 displayed significantly lower levels of post-treatment regrowth, indicative of decreased drug resistance, than observed for either single treatment modality. The preclinical data suggest that combined treatment involving the use of tamoxifen analogs may be a novel clinical approach for long-term maintenance therapy in patients with estrogen-receptor positive/progesterone-receptor positive breast cancer receiving hormonal therapy to prevent disease recurrence. Detailed data on time-course, IC50 and tumor regrowth assays post- treatment as well as a proposed mechanism of action to account for observed synergistic drug effects will be presented.

Keywords: 4-hydroxytamoxifen, tamoxifen analog, drug-resistance, microtumors

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Authors: Nayab Kanwal, Noor Us Saher

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The management and utilization of food resources is becoming a big issue due to rapid urbanization, wastage and non-sustainable use of food, especially in developing countries. Therefore, the use of seafood as alternative sources is strongly promoted worldwide. Marine pollution strongly affects marine organisms, which ultimately decreases their export quality. The monitoring of contamination in marine organisms is a good indicator of the environmental quality as well as seafood quality. Monitoring the accumulation of chemical elements within various tissues of organisms has become a useful tool to survey current or chronic levels of heavy metal exposure within an environment. In this perspective, this study was carried out to compare the previous and current levels (Year 2012 and 2014) of heavy metals (Cd, Pb, Cr, Cu and Zn) in crabs marketed in Karachi and to estimate the toxicological risk associated with their intake. The accumulation of metals in marine organisms, both essential (Cu and Zn) and toxic (Pb, Cd and Cr), natural and anthropogenic, is an actual food safety issue. Significant (p>0.05) variations in metal concentrations were found in all crab species between the two years, with most of the metals showing high accumulation in 2012. For toxicological risk assessment, EWI (Estimated weekly intake), Target Hazard quotient (THQ) and cancer risk (CR) were also assessed and high EWI, Non- cancer risk (THQ < 1) showed that there is no serious threat associated with the consumption of shellfish species on Karachi coast. The Cancer risk showed the highest risk from Cd and Pb pollution if consumed in excess. We summarize key environmental health research on health effects associated with exposure to contaminated seafood. It could be concluded that considering the Pakistan coast, these edible species may be sensitive and vulnerable to the adverse effects of environmental contaminants; more attention should be paid to the Pb and Cd metal bioaccumulation and to toxicological risks to seafood and consumers.

Keywords: cancer risk, edible crabs, heavy metals pollution, risk assessment

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Authors: Agajie Likie Bogale, Tilahun Teklehaymanot, Getnet Mitike Kassie, Girmay Medhin, Jemal Haidar Ali, Nega Berhe Belay

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Objectives: The aim of this study is to evaluate the performance of visual inspection using acetic acid compared with HPV DNA testing among women living with HIV in Ethiopia. Methods: Acomparative cross-sectional study was conducted to address the aforementioned objective. Data were collected from January to October 2021 to compare the performance of these two screening modalities. Trained clinicians collected cervical specimens and immediately applied acetic acid for visual inspection. The HPV DNA testing was done using Abbott m2000rt/SP by trained laboratory professionals in accredited laboratories. A total of 578 HIV positive women with age 25-49 years were included. Results: Test positivity was 8.9% using VIA and 23.3% using HPV DNA test. The sensitivity and specificity of the VIA test were 19.2% and 95.1%, respectively, while the positive and negative predictive values of the VIA test were 54.4% and 79.4%, respectively. The strength of agreement between the two screening methods was poor (k=0.184), and the area under the curve was 0.572. The burden of genetic distribution of high risk HPV16 was 3.8%, and mixed HPV16& other HR HPV was 1.9%. Other high risk HPV types were predominant in this study (15.7%). Conclusion: The high positivity result using HPV DNA testing compared with VIA, and low sensitivity of VIA are indicating that the implementation of HPV DNA testing as the primary screening strategy is likely to reduce cervical cancer cases and deaths of women in the country.

Keywords: cervical cancer screening, HPV DNA, VIA, Ethiopia

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Authors: Aditya Manna

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Introduction: As in any developing countries state of West Bengal in India has a huge burden of cancer patients in advanced stage coming from rural area where awareness regarding the usefulness of palliative care in rather poor. Objective: Our goal is to give a pain free good quality of life in these advanced stage cancer patients. Objective of this study is to identify the main difficulties in achieving the above goal in a rural village setting in India. Method: Advanced cancer patients in need of palliative care in various villages in of rural India were selected for this study. Their symptoms and managements in that rural surroundings were evaluated by an NGO (under the guidance of a senior palliative care specialist) working in that area. An attempt was made to identify the main obstacles in getting proper palliative care in a rural setting. Results: Pain, fatigue are the main symptoms effecting these patients. In most patients pain and other symptoms control were grossly inadequate due to lack of properly trained manpower in the rural India. However regular homecare visits by a group of social workers were of immense help in the last few months of life. NGO team was well guided by a palliative care specialist. Conclusion: There is a wide gap of trained manpower in this filled in rural areas of India. Dedicated groups from rural area itself need encouragement and proper training, so that difficult symptoms can be managed locally along with necessary social and psychological support to these patients.

Keywords: palliative care, NGO, rural India, home care

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Authors: S. M. P Manjula, Ishara Amarathunga, Aryan Nath Koura, Jaideepraj Rao

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Background: Laparoscopic D2 Gastrectomy for non metastatic advanced Gastric cancer (AGC) has become a controversial topic as there are confronting ideas from experts in the field. Lack of consensus are mainly due to non feasibility of the dissection and safety and efficacy. Method: Data from all D2 Gastrectomies performed (both Subtotal and Total Gastrectomies) in our unit from 2009 December to 2013 December were retrospectively analysed. Computor database was prospectively maintained. Pathological stage two A (iiA) and above considered advanced Gastric cancers, who underwent curative intent D2 Gastrectomy were included for analysis(n=46). Four patients excluded from the study as peritoneal fluid cytology came positive for cancer cells and one patient exempted as microscopic resection margin positive(R1) after curative resection. Thirty day morbidity and mortality, operative time, lymph nodes harvest and survival (disease free and overall) analyzed. Results: Complete curative resection achieved in 40 patients. Mean age of the study population was 62.2 (32-88) and male to female ratio was 23: 17. Thirty day mortality (1/40) and morbidity (6/40). Average operative time 203.7 minutes (185- 400) and average lymphnodes harvest was 40.5 (18-91). Disease free survival of the AGC in this study population was 16.75 months (1-49). Average hospital stay was 6.8 days (3-31). Conclusion: Laparoscopic dissection is effective feasible and safe in AGC.

Keywords: laparoscopy, advanced gastric cancer, safety, efficacy

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Authors: Taleb Lotfi, Benarbia Maheidine, Allam Hamza, Boutira Fatima, Boukerche Abdelbaki

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Introduction and purpose of the study: This is a retrospective single-center study with an analytical aim to determine the prognostic factors for relapse in patients treated with radiotherapy after total laryngectomy with lymph node dissection for laryngeal cancer at the Emir Abdelkader cancer center in Oran (Algeria). Material and methods: During the study period from January 2014 to December 2018, eighty-nine patients (n=89) with squamous cell carcinoma of the larynx were treated with postoperative radiotherapy. Relapse-free survival was studied in the univariate analysis according to pre-treatment criteria using Kaplan-Meier survival curves. We performed a univariate analysis to identify relapse factors. Statistically significant factors have been studied in the multifactorial analysis according to the Cox model. Results and statistical analysis: The average age was 62.7 years (40-86 years). It was a squamous cell carcinoma in all cases. Postoperatively, the tumor was classified as pT3 and pT4 in 93.3% of patients. Histological lymph node involvement was found in 36 cases (40.4%), with capsule rupture in 39% of cases, while the limits of surgical excision were microscopically infiltrated in 11 patients (12.3%). Chemotherapy concomitant with radiotherapy was used in 67.4% of patients. With a median follow-up of 57 months (23 to 104 months), the probabilities of relapse-free survival and five-year overall survival are 71.2% and 72.4%, respectively. The factors correlated with a high risk of relapse were locally advanced tumor stage pT4 (p=0.001), tumor site in case of subglottic extension (p=0.0003), infiltrated surgical limits R1 (p=0.001), l lymph node involvement (p=0.002), particularly in the event of lymph node capsular rupture (p=0.0003) as well as the time between surgery and adjuvant radiotherapy (p=0.001). However, in the subgroup analysis, the major prognostic factors for disease-free survival were subglottic tumor extension (p=0.001) and time from surgery to adjuvant radiotherapy (p=0.005). Conclusion: Combined surgery and postoperative radiation therapy are effective treatment modalities in the management of laryngeal cancer. Close cooperation of the entire cervicofacial oncology team is essential, expressed during a multidisciplinary consultation meeting, with the need to respect the time between surgery and radiotherapy.

Keywords: laryngeal cancer, laryngectomy, postoperative radiotherapy, survival

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Authors: Mohammed A. Abutalib

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Papillary thyroid carcinoma (PTC) accounts for the most common type of thyroid cancer, a well-differentiated type. PTC is featured by biologically low-grade and less aggressive tumors with a survival rate of 10 years in most of the diagnosed cases. PTC can be presented with the involvement of cervical lymph nodes in about 50% of the patients, yet the distant spread is very uncommon. Herein, we discussed an early 50-year-old male patient with a history of PTC that presented to the emergency department complaining of shortness of breath and a radiological finding of hydrothorax. Cytologic examination, together with immune-histochemical staining and molecular studies of pleural effusion aspiration, concluded the definitive diagnosis of metastatic papillary thyroid carcinoma in the pleural space. PTC seldom causes metastatic niches in the pleural space, and this is a rare clinical presentation; nevertheless, a differential diagnosis of thyroid metastasis needs to be excluded.

Keywords: thyroid cancer, malignant pleural effusion, cytology aspiration, papillary thyroid carcinoma

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Authors: Nehir Nebioglu

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Chemotherapy is widely used for the treatment of cancer. Doxorubicin is an anti-cancer chemotherapy drug that is classified as an anthracycline antibiotic. Antitumor antibiotics consist of natural products produced by species of the soil fungus Streptomyces. These drugs act in multiple phases of the cell cycle and are known cell-cycle specific. Although DOX is a precious clinical antineoplastic agent, resistance is also a problem that limits its utility besides cardiotoxicity problem. The drug resistance of cancer cells results from multiple factors including individual variation, genetic heterogeneity within a tumor, and cellular evolution. The mechanism of resistance is thought to involve, in particular, ABCB1 (MDR1, Pgp) and ABCC1 (MRP1) as well as other transporters. Several studies on DOX-resistant cell lines have shown that resistance can be overcome by an inhibition of ABCB1, ABCC1, and ABCC2. This study attempts to understand the effects of different concentration levels of glucose treatment and starvation on the proliferation of Doxorubicin resistant cancer cells lines. To understand the effect of starvation, K562/Dox and K562 cell lines were treated with 0, 5 nM, 50 nM, 500 nM, 5 uM and 50 uM Dox concentrations in both starvation and normal medium conditions. In addition to this, to interpret the effect of glucose treatment, different concentrations (0, 1 mM, 5 mM, 25 mM) of glucose were applied to Dox-treated (with 0, 5 nM, 50 nM, 500 nM, 5 uM and 50 uM) K562/Dox and K652 cell lines. All results show significant decreasing in the cell count of K562/Dox, when cells were starved. However, while proliferation of K562/Dox lines decrease is associated with the increasingly applied Dox concentration, K562/Dox starved ones remain at the same proliferation level. Thus, the results imply that an amount of K562/Dox lines gain starvation resistance and remain resistant. Furthermore, for K562/Dox, there is no clear effect of glucose treatment in terms of cell proliferation. In the presence of a moderate level of glucose (5 mM), proliferation increases compared to other concentration of glucose for each different Dox application. On the other hand, a significant increase in cell proliferation in moderate level of glucose is only observed in 5 uM Dox concentration. The moderate concentration level of Dox can be examined in further studies. For the high amount of glucose (25 mM), cell proliferation levels are lower than moderate glucose application. The reason could be high amount of glucose may not be absorbable by cells. Also, in the presence of low amount of glucose, proliferation is decreasing in an orderly manner of increase in Dox concentration. This situation can be explained by the glucose depletion -Warburg effect- in the literature.

Keywords: drug resistance, cancer cells, chemotherapy, doxorubicin

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Authors: Maarja Karbus, Elsbet Lippmaa, Kadri Kööp, Mare Tupits

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Aim: The aim is to describe the experiences and needs of mothers of children with cancer in coping with the child's illness. Background: Cancer affects different life areas. Especially if it is a child, in this case the whole family is involved. Loved ones are mentally affected, there are limitations, and life changes need to be made to make the whole treatment regimen and recovery as comfortable as possible. Also, the whole process is expensive and time consuming. The research is part of a larger project that covers the experiences and needs of parents of children with chronic illness and coping strategies related to the child's illness. Design: Qualitative, empirical, descriptive research. Method: Semi-structured interviews were used to collect data and inductive content analysis was used to analyze the data. The interviews were conducted in the autumn of 2020, 5 respondents participated in the research. Results and Conclusions: The research revealed that the mothers' experiences of coping with a child's disease included health-related experiences, material aspects, changes in lifestyle, support systems and contact with professionals. Regarding the organizational and material aspects of life, the subjects presented experiences with economic problems, adaptation of changes in lifestyle, access to information and changes in the treatment process. With regard to health, the respondents identified experiences with the mother's physical and mental health and experiences with the health of an ill child. The experience of different support systems was related to the support of family, friends, acquaintances, various organizations and specialists. Experiences with specialist support included experiences with family relationships and positive and negatiive experiences with staff. The mothers' needs in dealing with the child's disease included the mother's emotional needs, the support of other family members, and the need for various support systems and services. The needs of coping with the child were the need for understanding, support, confidence, the need to be strong and courageous, the need to ignore one's own needs, and the need for personal time and rest. The needs of other family members included the needs of an ill child and the need to pay attention to other children in the family. The needs of different supporters and services were related to different helpers and different services.

Keywords: cancer, mother, coping, child, need, experience, illness

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Authors: Salwa Hagag Abdelaziz, Naglaa Fathy Youssef, Nadia Abdellatif Hassan, Rasha Wesam Abdelrahman

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Breast cancer is considered as a substantial health concern and practicing mammography screening [MS] is important in minimizing its related morbidity. So it is essential to have a better understanding of breast cancer screening behaviors of women and factors that influence utilization of them. The aim of this study is to identify the factors that are linked to MS behaviors among the Egyptian women. A cross-sectional descriptive design was carried out to provide a snapshot of the factors that are linked to MS behaviors. A convenience sample of 311 women was utilized and all eligible participants admitted to the Women Imaging Unit who are 40 years of age or above, coming for mammography assessment, not pregnant or breast feeding and who accepted to participate in the study were included. A structured questionnaire was developed by the researchers and contains three parts; Socio-demographic data; Motivating factors associated with MS; and association between MS and model of behavior change. The analyzed data indicated that most of the participated women (66.6 %) belonged to the age group of 40-49.A high proportion of participants (58.1%) of group having previous MS influenced by their neighbors to practice MS, whereas 32.7 % in group not having previous MS were influenced by family members which indicated significant differences (P <0.05). Doctors and media are shown to be the least influence of others to practice MS. Women with intention to have a future mammogram had higher OR (1.404) for practicing MS compared with women with no intention. Further studies are needed to examine the relation between Trans-theoretical Model [TTM] and practicing MS.

Keywords: breast cancer, mammography, screening behaviors, morbidity

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Authors: Amit Kamra, V. K. Jain, Pragya

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Mammography is widely used technique for breast cancer screening. There are various other techniques for breast cancer screening but mammography is the most reliable and effective technique. The images obtained through mammography are of low contrast which causes problem for the radiologists to interpret. Hence, a high quality image is mandatory for the processing of the image for extracting any kind of information from it. Many contrast enhancement algorithms have been developed over the years. In the present work, an efficient morphology based technique is proposed for contrast enhancement of masses in mammographic images. The proposed method is based on Multiscale Morphology and it takes into consideration the scale of the structuring element. The proposed method is compared with other state-of-the-art techniques. The experimental results show that the proposed method is better both qualitatively and quantitatively than the other standard contrast enhancement techniques.

Keywords: enhancement, mammography, multi-scale, mathematical morphology

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