Search results for: larynx cancer

Authors: Bharti Arora, Michael Chen, Steven Lun

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Plasmacytoid urothelial carcinoma (PUC) of the bladder is a rare and aggressive subtype of urothelial carcinoma that usually presents at an advanced clinical stage, has a predilection for early metastatic potential and is associated with poor prognosis. The first reported case of PUC was in 1991 and approximately 100 cases were reported in the literature worldwide. We present a case of a 43 year old female presenting with a 3-month history of urgency and frequency. Failing medical management of her urinary symptoms with anticholinergic medication, she underwent a diagnostic cystoscopy which revealed an erythematous and indurated bladder. Bladder biopsies of these regions revealed plasmacytoid urothelial carcinoma. Pre-operative staging scans were clear of any metastatic disease and the patient subsequently underwent a radical cystectomy and pelvic clearance with the formation of ileal conduit for urinary diversion. Histology confirmed plasmacytoid urothelial carcinoma with involvement of right upper vagina and focally positive margins in soft tissue at right and left sides of bladder. She received adjuvant chemotherapy but passed away within a year from disease progression. PUC can present atypically and our case highlights the role of cystoscopy in patients with persistent urinary symptoms. By reviewing the literature on PUC, we aim to raise awareness and improve understanding of this rare bladder cancer subtype amongst urologists.

Keywords: urology, bladder cancer, plasmacytoid urothelial cancer, literature review

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Authors: Huang Wei-Yi

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Objective: This article explores the intensive care nursing experience of a lung cancer patient with pulmonary embolism who was placed on ECMO. Following a sudden change in the patient’s condition and a consensus reached during a family meeting, the decision was made to withdraw life-sustaining equipment and collaborate with the palliative care team. Methods: The nursing period was from October 20 to October 27, 2023. The author monitored physiological data, observed, provided direct care, conducted interviews, performed physical assessments, and reviewed medical records. Together with the critical care team and bypass personnel, a comprehensive assessment was conducted using Gordon's Eleven Functional Health Patterns to identify the patient’s health issues, which included pain related to lung cancer and invasive devices, fear of death due to sudden deterioration, and altered tissue perfusion related to hemodynamic instability. Results: The patient was admitted with fever, back pain, and painful urination. During hospitalization, the patient experienced sudden discomfort followed by cardiac arrest, requiring multiple CPR attempts and ECMO placement. A subsequent CT angiogram revealed a pulmonary embolism. The patient's condition was further complicated by severe pain due to compression fractures, and a diagnosis of terminal lung cancer was unexpectedly confirmed, leading to emotional distress and uncertainty about future treatment. Throughout the critical care process, ECMO was removed on October 24, stabilizing the patient’s body temperature between 36.5-37°C and maintaining a mean arterial pressure of 60-80 mmHg. Pain management, including Morphine 8mg in 0.9% N/S 100ml IV drip q6h PRN and Ultracet 37.5 mg/325 mg 1# PO q6h, kept the pain level below 3. The patient was transferred to the ward on October 27 and discharged home on October 30. Conclusion: During the care period, collaboration with the medical team and palliative care professionals was crucial. Adjustments to pain medication, symptom management, and lung cancer-targeted therapy improved the patient’s physical discomfort and pain levels. By applying the unique functions of nursing and the four principles of palliative care, positive encouragement was provided. Family members, along with social workers, clergy, psychologists, and nutritionists, participated in cross-disciplinary care, alleviating anxiety and fear. The consensus to withdraw ECMO and life-sustaining equipment enabled the patient and family to receive high-quality care and maintain autonomy in decision-making. A follow-up call on November 1 confirmed that the patient was emotionally stable, pain-free, and continuing with targeted lung cancer therapy.

Keywords: intensive care, lung cancer, pulmonary embolism, ECMO

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Authors: Ms Azam Najafkouchak, David Todem, Dorothy Pathak, Pramod Pathak, Joseph Gardiner

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Propensity score (PS) methods have recently become the standard analysis as a tool for the causal inference in the observational studies where exposure is not randomly assigned, thus, confounding can impact the estimation of treatment effect on the outcome. For the binary outcome, the effect of treatment on the outcome can be estimated by odds ratios, relative risks, and risk differences. However, using the different PS methods may give you a different estimation of the treatment effect on the outcome. Several methods of PS analyses have been used mainly, include matching, inverse probability of weighting, stratification, and covariate adjusted on PS. Due to the dangers of discretizing continuous variables (exposure, covariates), the focus of this paper will be on how the variation in cut-points or boundaries will affect the average treatment effect (ATE) utilizing the stratification of PS method. Therefore, we are trying to avoid choosing arbitrary cut-points, instead, we continuously discretize the PS and accumulate information across all cut-points for inferences. We will use Monte Carlo simulation to evaluate ATE, focusing on two PS methods, stratification and covariate adjusted on PS. We will then show how this can be observed based on the analyses of the data from a case-control study of breast cancer, the Polish Women’s Health Study.

Keywords: average treatment effect, propensity score, stratification, covariate adjusted, monte Calro estimation, breast cancer, case_control study

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Authors: Brigitta Bodnár, Lajos Kovács, Zoltán Kupihár

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The cancer cells require higher amount of nucleoside building blocks for their proliferation, therefore they have significantly higher uptake of nucleosides by the different nucleoside transporters. Therefore, the conjugation with nucleosides may significantly increase the efficiency and selectivity of potential active pharmaceutical ingredients. On the other hand, the advantage of using a nucleoside could be either the higher activity on targeted enzymes overrepresented in cancer cells or an enhanced cellular uptake of the bioconjugates in these cells compared to the healthy ones. This fact can be used to make the nucleosides, as targeting moieties covalently bound to anti-cancer drug molecules which can selectively accumulate in cancer cells. However, in order to form the nucleoside-drug conjugates, such nucleoside building blocks are needed, which can selectively be coupled to the drug molecules containing even a high number of diverse functional groups. One of the most selective conjugation techniques is the copper-catalyzed azide-alkyne click reaction that requires the presence of an alkyl group on one of the conjugated molecules and an azide group on the other. In case of nucleosides, the development of azide group is simpler for which the replacement of the 5'-hydroxy group is the most suitable. This transformation generally involves many side reactions and result in very low yields. In addition, during our experiments, the transformation of the 2'-deoxyguanosine to the corresponding 5'-deoxy-5’-azido-2’-deoxyguanosine could not be performed with any of the methods described in the literature. Therefore, we have tried to overcome these difficulties with not only using the traditional process based on the 2 step exchange of tosyl to azide, but also using the Mitsunobu reaction which requires only one step. However, this path proved to be unsuccessful in spite of the optimizing the reaction conditions. Finally, a method has been developed whereby the azide groups were incorporated into the 5’-position resulting in significantly better yields compared to all other previous methods, and we were able to produce all the four nucleoside derivatives.

Keywords: 5'-azidonucleosides, bioconjugate, click reaction, proliferation

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Authors: Chao Hsing Yeh, Wei Chun Lin

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Background: Current management of aromatase inhibitor-induced arthralgia (AIA) in postmenopausal breast cancer survivors (PBCS) has limited effect. Method: In this prospective randomized clinical trial (RCT), a 4-week APA treatment was used to manage AIA. Twenty PBCS participated. After baseline data was collected, participants were waited for a month before they receive APA at a convenient time once a week for 4 weeks. Blood samples from participants in both groups were collected at baseline and after 4 weeks of treatment. The primary outcomes included: pain intensity, pain interference, stiffness, and physical function. Results: After the 4-week APA treatment, the pro-inflammatory cytokines and chemokines display a trend of mean percentage reduction (i.e., -22% in IL-1α, -4% in IL-1β, -1% in IL-2, -3% in IL-6, -19% in IL-12, -9% in Eotaxin, and -2% in MCP-1). The anti-inflammatory cytokine IL-10 and IL-13 (i.e., 5% in IL-10 and 29% in IL-13) increased from pre- to post-APA treatment. Significant positive correlation of percentage mean change was observed between symptom severity and eotaxin (ρ = 0.56; p < 0.01) & MCP-1 (ρ = 0.65; p < 0.01). Interference and chemokines (eotaxin & MIP-1) also shows positive correlation (ρ = 0.48; p < 0.01 & ρ = 0.39; p < 0.05). Another positive correlation was found between worst pain and chemokines (eotaxin, ρ = 0.48; p < 0.01 & MIP-1, ρ = 0.39; p < 0.05). Additionally, interference also shows positive correlation among IL-1α (ρ = 0.36; p < 0.05) and IL-β (ρ = 0.33; p < 0.05). Conclusion: These findings suggest that APA intervention may inhibit inflammation of AIA patients and chemokine could be one of the key factors of AIA symptom improvement.

Keywords: acupressure, cytokine, pain management, breast cancer survivors

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Authors: Akimitsu Kugimiya, Kouhei Iwato, Toru Saito, Jiro Kohda, Yasuhisa Nakano, Yu Takano

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The measurement of amino acid content is reported to be useful for the diagnosis of several types of diseases, including lung cancer, gastric cancer, colorectal cancer, breast cancer, prostate cancer, and diabetes. The conventional detection methods for amino acid are high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS), but they have several drawbacks as the equipment is cumbersome and the techniques are costly in terms of time and costs. In contrast, biosensors and biosensing methods provide more rapid and facile detection strategies that use simple equipment. The authors have reported a novel approach for the detection of each amino acid that involved the use of aminoacyl-tRNA synthetase (aaRS) as a molecular recognition element because aaRS is expected to a selective binding ability for corresponding amino acid. The consecutive enzymatic reactions used in this study are as follows: aaRS binds to its cognate amino acid and releases inorganic pyrophosphate. Hydrogen peroxide (H₂O₂) was produced by the enzyme reactions of inorganic pyrophosphatase and pyruvate oxidase. The Trinder’s reagent was added into the reaction mixture, and the absorbance change at 556 nm was measured using a microplate reader. In this study, an amino acid-sensing method using histidyl-tRNA synthetase (HisRS; histidine-specific aaRS) as molecular recognition element in combination with the Trinder’s reagent spectrophotometric method was developed. The quantitative performance and selectivity of the method were evaluated, and the optimal enzyme reaction and detection conditions were determined. The authors developed a simple and rapid method for detecting histidine with a combination of enzymatic reaction and spectrophotometric detection. In this study, HisRS was used to detect histidine, and the reaction and detection conditions were optimized for quantitation of these amino acids in the ranges of 1–100 µM histidine. The detection limits are sufficient to analyze these amino acids in biological fluids. This work was partly supported by Hiroshima City University Grant for Special Academic Research (General Studies).

Keywords: amino acid, aminoacyl-tRNA synthetase, biosensing, enzyme reaction

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Authors: M. L. Yeung

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With the surge of divorce rate and male cancer onset/death rates, the phenomenon of divorced wives in the facing cancer death of their ex-husbands is not uncommon in Hong Kong. Yet, there is a dearth of study on the experiences of bereaved-divorced wives in the Hong Kong cultural context. This project fills the knowledge gap by conducting a qualitative study for having interviewed four bereaved ex-wives, who returned to ex-husbands’ end-of-life caregiving and eventually grieved for the ex-spousal’s death. From the perspectives of attachment theory and disenfranchised grief in the Hong Kong cultural context, a ‘double-loss’ experience is found in which interviewees suffer from the first loss of divorce and the second loss of ex-husbands’ death. Traumatic childhood experiences, attachment needs, role ambiguity, unresolved emotions and unrecognized grief are found significant in their lived experiences which alert the ‘double-loss’ is worthy of attention. Extending a family-centered end-of-life and bereavement care services to divorced couples is called for, in which validation on the attachment needs, ex-couple reconciliation, and acknowledgement on the disenfranchised grief are essential for social work practice on this group of clienteles specifically in Hong Kong cultural context.

Keywords: changing family, disenfranchised grief, divorce, ex-spousal death, marriage

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Authors: Jalil ur Rehman, Ramesh C, Tailor, Isa Khan, Jahanzeeb Ashraf, Muhammad Afzal, Geofferry S. Ibbott

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The purpose of this analysis is to estimate secondary cancer risks after VMAT compared to other modalities of head and neck radiotherapy (IMRT, 3DCRT). Computer tomography (CT) scans of Radiological Physics Center (RPC) head and neck phantom were acquired with CT scanner and exported via DICOM to the treatment planning system (TPS). Treatment planning was done using four arc (182-178 and 180-184, clockwise and anticlockwise) for volumetric modulated arc therapy (VMAT) , Nine fields (200, 240, 280, 320,0,40,80,120 and 160), which has been commonly used at MD Anderson Cancer Center Houston for intensity modulated radiation therapy (IMRT) and four fields for three dimensional radiation therapy (3DCRT) were used. True beam linear accelerator of 6MV photon energy was used for dose delivery, and dose calculation was done with CC convolution algorithm with prescription dose of 6.6 Gy. Primary Target Volume (PTV) coverage, mean and maximal doses, DVHs and volumes receiving more than 2 Gy and 3.8 Gy of OARs were calculated and compared. Absolute point dose and planar dose were measured with thermoluminescent dosimeters (TLDs) and GafChromic EBT2 film, respectively. Quality Assurance of VMAT and IMRT were performed by using ArcCHECK method with gamma index criteria of 3%/3mm dose difference to distance to agreement (DD/DTA). PTV coverage was found 90.80 %, 95.80 % and 95.82 % for 3DCRT, IMRT and VMAT respectively. VMAT delivered the lowest maximal doses to esophagus (2.3 Gy), brain (4.0 Gy) and thyroid (2.3 Gy) compared to all other studied techniques. In comparison, maximal doses for 3DCRT were found higher than VMAT for all studied OARs. Whereas, IMRT delivered maximal higher doses 26%, 5% and 26% for esophagus, normal brain and thyroid, respectively, compared to VMAT. It was noted that esophagus volume receiving more than 2 Gy was 3.6 % for VMAT, 23.6 % for IMRT and up to 100 % for 3DCRT. Good agreement was observed between measured doses and those calculated with TPS. The averages relative standard errors (RSE) of three deliveries within eight TLD capsule locations were, 0.9%, 0.8% and 0.6% for 3DCRT, IMRT and VMAT, respectively. The gamma analysis for all plans met the ±5%/3 mm criteria (over 90% passed) and results of QA were greater than 98%. The calculations for maximal doses and volumes of OARs suggest that the estimated risk of secondary cancer induction after VMAT is considerably lower than IMRT and 3DCRT.

Keywords: RPC, 3DCRT, IMRT, VMAT, EBT2 film, TLD

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Authors: Ali Hamza

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Accurate segmentation of breast ultrasound images is of paramount importance in enhancing the diagnostic capabilities of breast cancer detection. This study presents an approach utilizing the U-Net architecture for segmenting breast ultrasound images aimed at improving the accuracy and reliability of mass identification within the breast tissue. The proposed method encompasses a multi-stage process. Initially, preprocessing techniques are employed to refine image quality and diminish noise interference. Subsequently, the U-Net architecture, a deep learning convolutional neural network (CNN), is employed for pixel-wise segmentation of regions of interest corresponding to potential breast masses. The U-Net's distinctive architecture, characterized by a contracting and expansive pathway, enables accurate boundary delineation and detailed feature extraction. To evaluate the effectiveness of the proposed approach, an extensive dataset of breast ultrasound images is employed, encompassing diverse cases. Quantitative performance metrics such as the Dice coefficient, Jaccard index, sensitivity, specificity, and Hausdorff distance are employed to comprehensively assess the segmentation accuracy. Comparative analyses against traditional segmentation methods showcase the superiority of the U-Net architecture in capturing intricate details and accurately segmenting breast masses. The outcomes of this study emphasize the potential of the U-Net-based segmentation approach in bolstering breast ultrasound image analysis. The method's ability to reliably pinpoint mass boundaries holds promise for aiding radiologists in precise diagnosis and treatment planning. However, further validation and integration within clinical workflows are necessary to ascertain their practical clinical utility and facilitate seamless adoption by healthcare professionals. In conclusion, leveraging the U-Net architecture for breast ultrasound image segmentation showcases a robust framework that can significantly enhance diagnostic accuracy and advance the field of breast cancer detection. This approach represents a pivotal step towards empowering medical professionals with a more potent tool for early and accurate breast cancer diagnosis.

Keywords: mage segmentation, U-Net, deep learning, breast cancer detection, diagnostic accuracy, mass identification, convolutional neural network

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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: Li-Ting Chen, Chih-Tao Cheng, I-Ping Huang, Jen-Ho Chang, Nien-Tzu Chang, Fei-Hsiu Hsiao

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Background: Insecurity adult attachment style may be triggered by cancer threat, which in turn influences depression symptoms. Dispositional mindfulness may have benefits of insecure attachment on depression for colorectal patient transfer to survivor. Objective: This study examined the mediating and moderating effects of quality of life (QOL) and dispositional mindfulness on the relationship between insecure attachment style and depression symptoms. Methods: A cross-sectional study design was used. Data were collected using the QOL functional and symptoms (EORTC-C30 and EORTC CR29), dispositional mindfulness (FFMQ), Short form of Experience in Close Relationships Revised Questionnaire (SF-ECRRQ), and depressive symptoms (BDI-II scale). Results: Of the 90 CRC survivors who participated, the indirect effect of both ECR anxiety (β=0.23, CI=0.05-0.44) and ECR avoidance (β=0.12, CI=0.02-0.24) on depression were significantly mediated through EORTC-C29 colorectal symptoms. Three components of dispositional mindfulness (i.e., acting of awareness, non-judging, non-reactivity) as the moderator in the relationship between ECR anxiety and depressive symptoms. Acting of awareness was a moderator in the relationship between ECR avoidance and depressive symptoms. Conclusions: There are two pathways from insecure attachment to depression: through the mediator of colorectal symptoms and the moderator of dispositional mindfulness. Cancer symptom management and mindfulness practices could improve the impact of insecure attachment on depression among CRC patients in a post-treatment transition period.

Keywords: acting of awareness, attachment style, colorectal cancer, disposisitonal mindfulness, depression

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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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