Search results for: lung cancer diagnosis

Authors: A. Bouhaloufa, T. Kadri, S. Zouaoui, A. Belhacene

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To put more durable bridges, it is important to maintain existing structures, rather than investing in new structures. Instead of demolishing the old bridge and replace them with new, we must preserve and upgrade using better methods of diagnosis, auscultation and repair, the interest of this work is to increase the bearing capacity bridges damaged by additional prestressing, this type of reinforcement is growing continuously. In addition to excellent static strength, prestressing also has a very high resistance to fatigue, so it is suitable to solve the problem of failure of the bearing capacity of the bridges. This failure often comes to the development of overloads in quantity and quality, that is our daily traffic has increased and become very complicated, on the other hand its constituents are advanced in weight and speed and therefore almost all old bridges became unable to support the movement of the latter and remain disabled to all these problems. The main purpose of this work includes the following three aspects: - Determination of the main diseases and factors affecting the deterioration of bridges in Algeria, - Evaluation of the bearing capacity of bridges, - Proposal technical reinforcement to improve the bearing capacity of a degraded structure.

Keywords: bridges, repair, auscultation, diagnosis, pathology, additional prestressing

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Authors: Jixiang Lei, Alexander Fuchs, Franz Pernkopf, Katrin Ellermann

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Within the Space@Sea project, funded by the Horizon 2020 program, an island consisting of multiple platforms was designed. The platforms are connected by ropes and fenders. The connection is critical with respect to the safety of the whole system. Therefore, fault detection systems are investigated, which could detect early warning signs for a possible failure in the connection elements. Previously, a model-based method called Extended Kalman Filter was developed to detect the reduction of rope stiffness. This method detected several types of faults reliably, but some types of faults were much more difficult to detect. Furthermore, the model-based method is sensitive to environmental noise. When the wave height is low, a long time is needed to detect a fault and the accuracy is not always satisfactory. In this sense, it is necessary to develop a more accurate and robust technique that can detect all rope faults under a wide range of operational conditions. Inspired by this work on the Space at Sea design, we introduce a fault diagnosis method based on deep neural networks. Our method cannot only detect rope degradation by using the acceleration data from each platform but also estimate the contributions of the specific acceleration sensors using methods from explainable AI. In order to adapt to different operational conditions, the domain adaptation technique DANN is applied. The proposed model can accurately estimate rope degradation under a wide range of environmental conditions and help users understand the relationship between the output and the contributions of each acceleration sensor.

Keywords: fault diagnosis, deep learning, domain adaptation, explainable AI

Procedia PDF Downloads 180

Authors: Aoxue Yang, Weili Tian, Yonghe Wu, Haikun Liu

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Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Little progress has been made in therapeutic treatment of glioblastoma in the last decade despite rapid progress in molecular understanding of brain tumors1. Here we show that the stress hormone glucocorticoid is essential for the maintenance of brain tumor stem cells (BTSCs), which are resistant to conventional therapy. The glucocorticoid receptor (GR) regulates metabolic plasticity and chemoresistance of the dormant BTSC via controlling expression of GPD1 (glycerol-3-phosphate dehydrogenase 1), which is an essential regulator of lipid metabolism in BTSCs. Genomic, lipidomic and cellular analysis confirm that GR/GPD1 regulation is essential for BTSCs metabolic plasticity and survival. We further demonstrate that the GR agonist dexamethasone (DEXA), which is commonly used to control edema in glioblastoma, abolishes the effect of chemotherapy drug temozolomide (TMZ) by upregulating GPD1 and thus promoting tumor cell dormancy in vivo, this provides a mechanistic explanation and thus settle the long-standing debate of usage of steroid in brain tumor patient edema control. Pharmacological inhibition of GR/GPD1 pathway disrupts metabolic plasticity of BTSCs and prolong animal survival, which is superior to standard chemotherapy. Patient case study shows that GR antagonist mifepristone blocks tumor progression and leads to symptomatic improvement. This study identifies an important mechanism regulating cancer stem cell dormancy and provides a new opportunity for glioblastoma treatment.

Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides.

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Authors: Nurkhairul Bariyah Baharun, Afzan Adam, Reena Rahayu Md Zin

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Tumor microenvironment (TME) in breast cancer is mainly composed of cancer cells, immune cells, and stromal cells. The interaction between cancer cells and their microenvironment plays an important role in tumor development, progression, and treatment response. The TME in breast cancer includes tumor-infiltrating lymphocytes (TILs) that are implicated in killing tumor cells. TILs can be found in tumor stroma (sTILs) and within the tumor (iTILs). TILs in triple negative breast cancer (TNBC) have been demonstrated to have prognostic and potentially predictive value. The international Immune-Oncology Biomarker Working Group (TIL-WG) had developed a guideline focus on the assessment of sTILs using hematoxylin and eosin (H&E)-stained slides. According to the guideline, the pathologists use “eye balling” method on the H&E stained- slide for sTILs assessment. This method has low precision, poor interobserver reproducibility, and is time-consuming for a comprehensive evaluation, besides only counted sTILs in their assessment. The TIL-WG has therefore recommended that any algorithm for computational assessment of TILs utilizing the guidelines provided to overcome the limitations of manual assessment, thus providing highly accurate and reliable TILs detection and classification for reproducible and quantitative measurement. This study is carried out to develop a TNBC digital whole slide image (WSI) dataset from H&E-stained slides and IHC (CD4+ and CD8+) stained slides. TNBC cases were retrieved from the database of the Department of Pathology, Hospital Canselor Tuanku Muhriz (HCTM). TNBC cases diagnosed between the year 2010 and 2021 with no history of other cancer and available block tissue were included in the study (n=58). Tissue blocks were sectioned approximately 4 µm for H&E and IHC stain. The H&E staining was performed according to a well-established protocol. Indirect IHC stain was also performed on the tissue sections using protocol from Diagnostic BioSystems PolyVue™ Plus Kit, USA. The slides were stained with rabbit monoclonal, CD8 antibody (SP16) and Rabbit monoclonal, CD4 antibody (EP204). The selected and quality-checked slides were then scanned using a high-resolution whole slide scanner (Pannoramic DESK II DW- slide scanner) to digitalize the tissue image with a pixel resolution of 20x magnification. A manual TILs (sTILs and iTILs) assessment was then carried out by the appointed pathologist (2 pathologists) for manual TILs scoring from the digital WSIs following the guideline developed by TIL-WG 2014, and the result displayed as the percentage of sTILs and iTILs per mm² stromal and tumour area on the tissue. Following this, we aimed to develop an automated digital image scoring framework that incorporates key elements of manual guidelines (including both sTILs and iTILs) using manually annotated data for robust and objective quantification of TILs in TNBC. From the study, we have developed a digital dataset of TNBC H&E and IHC (CD4+ and CD8+) stained slides. We hope that an automated based scoring method can provide quantitative and interpretable TILs scoring, which correlates with the manual pathologist-derived sTILs and iTILs scoring and thus has potential prognostic implications.

Keywords: automated quantification, digital pathology, triple negative breast cancer, tumour infiltrating lymphocytes

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Authors: Anas Al-Ali, Mohammed Suleiman, Ayman Hussein

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Sulfur is an important element has many practical applications in present as nanoparticles. Nanosize sulfur particles also have many important applications like in pharmaceuticals, medicine, syn-thesis of nano-composites for lithium batteries, modification of carbon nano tubes. Different methods were used for nano-sized particle synthesis; among those, chemical precipitation, electrochemical method, micro emulsion technique, composing of oil, surfactant, co-surfactant, aqueous phases with the specific compositions and ultrasonic treatment of sulfur-cystine solution. In this work Sulfur nanoparticles (S NPs) were prepared by a quick precipitation method with and without using a surfactant to stabilize the formed S NPs. The synthesized S NPs were characterized by XRD, SEM and TEM in order to confirm their sizes and structures.Application of nanotechnology is suggested for diag-nosis and treatment of cancer. The anticancer activity of the prepared S NPs has been tested on various types of cancer cell clones including leukemia, kidney and colon cancers.

Keywords: sulfur nanoparticles (S-NPs), TEM, SEM, XRD

Procedia PDF Downloads 654

Authors: Rajiv Ratan Singh, Sachin Kumar Tripathi, Pradeep Kumar Yadav

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The timely evaluation, diagnosis, and treatment of people who have been exposed to toxic chemicals is a crucial component of emergency poison management in the medical field. The various substances that can poison include chemicals, medications, and naturally occurring poisons. The toxicology of the particular drug involved, as well as the symptoms and indicators of poisoning, must be thoroughly understood to handle poisoning emergencies effectively. One of the most important aspects of emergency poison management in medicine is the prompt examination, diagnosis, and treatment of persons who have been exposed to dangerous substances. To properly manage poisoning crises, one must have a good understanding of the toxicology of the particular medication concerned, as well as the signs and indicators of poisoning. Emergency management of poisoning includes not only prompt medical attention but also patient education, follow-up care, and monitoring for any long-term consequences. To achieve the greatest results for patients, the management of poisoning is a complicated and dynamic process that calls for collaboration between medical professionals, first responders, and toxicologists. All poisoned patients who present to the emergency room are assessed and diagnosed based on a collection of symptoms and a biochemical diagnosis, and they are then provided targeted, specialized treatment for the toxin identified. This article focuses on the loxodromic strategy as the primary method of treatment for poisoned patients. The authors of this article conclude that mortality and morbidity can be reduced if patients visit the emergency room promptly and receive targeted treatment.

Keywords: antidotes, blood poisoning, emergency medicine, gastric lavage, medico-legal aspects, patient care

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Authors: Moiseenko F. V., Volkov N. M., Zhabina A. S., Stepanova E. O., Kirillov A. V., Myslik A. V., Artemieva E. V., Agranov I. R., Oganesyan A. P., Egorenkov V. V., Abduloeva N. H., Aleksakhina S. Yu., Ivantsov A. O., Kuligina E. S., Imyanitov E. N., Moiseyenko V. M.

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Analysis of ctDNA in patients with NSCLC is an emerging biomarker. Multiple research efforts of quantitative or at least qualitative analysis before and during the first periods of treatment with TKI showed the prognostic value of ctDNA clearance. Still, these important results are not incorporated in clinical standards. We evaluated the role of ctDNA in EGFR-mutated NSCLC receiving first-line TKI. Firstly, we analyzed sequential plasma samples from 30 patients that were collected before intake of the first tablet (at baseline) and at 6, 12, 24, 36, and 48 hours after the “starting point.” EGFR-M+ allele was measured by ddPCR. Afterward, we included sequential qualitative analysis of ctDNA with cobas® EGFR Mutation Test v2 from 99 NSCLC patients before the first dose, after 2 and 4 months of treatment, and on progression. Early response analysis showed the decline of EGFR-M+ level in plasma within the first 48 hours of treatment in 11 subjects. All these patients showed objective tumor response. 10 patients showed either elevation of EGFR-M+ plasma concentration (n = 5) or stable content of circulating EGFR-M+ after the start of the therapy (n = 5); only 3 of these patients achieved an objective response (p = 0.026) when compared to the former group). The rapid decline of plasma EGFR-M+ DNA concentration also predicted for longer PFS (13.7 vs. 11.4 months, p = 0.030). Long-term ctDNA monitoring showed clinically significant heterogeneity of EGFR-mutated NSCLC treated with 1st line TKIs in terms of progression-free and overall survival. Patients without detectable ctDNA at baseline (N = 32) possess the best prognosis on the duration of treatment (PFS: 24.07 [16.8-31.3] and OS: 56.2 [21.8-90.7] months). Those who achieve clearance after two months of TKI (N = 42) have indistinguishably good PFS (19.0 [13.7 – 24.2]). Individuals who retain ctDNA after 2 months (N = 25) have the worst prognosis (PFS: 10.3 [7.0 – 13.5], p = 0.000). 9/25 patients did not develop ctDNA clearance at 4 months with no statistical difference in PFS from those without clearance at 2 months. Prognostic heterogeneity of EGFR-mutated NSCLC should be taken into consideration in planning further clinical trials and optimizing the outcomes of patients.

Keywords: NSCLC, EGFR, targeted therapy, ctDNA, prognosis

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Authors: Soumya Sajjan

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Liver cancer is the most common cancer disease worldwide in men and women, and is one of the few cancers still on the rise. Liver disease is the 4th leading cause of death. According to new NHS (National Health Service) figures, deaths from liver diseases have reached record levels, rising by 25% in less than a decade; heavy drinking, obesity, and hepatitis are believed to be behind the rise. In this study, we focus on Development of Diagnostic Classifier for Ultrasound liver lesion. Ultrasound (US) Sonography is an easy-to-use and widely popular imaging modality because of its ability to visualize many human soft tissues/organs without any harmful effect. This paper will provide an overview of underlying concepts, along with algorithms for processing of liver ultrasound images Naturaly, Ultrasound liver lesion images are having more spackle noise. Developing classifier for ultrasound liver lesion image is a challenging task. We approach fully automatic machine learning system for developing this classifier. First, we segment the liver image by calculating the textural features from co-occurrence matrix and run length method. For classification, Support Vector Machine is used based on the risk bounds of statistical learning theory. The textural features for different features methods are given as input to the SVM individually. Performance analysis train and test datasets carried out separately using SVM Model. Whenever an ultrasonic liver lesion image is given to the SVM classifier system, the features are calculated, classified, as normal and diseased liver lesion. We hope the result will be helpful to the physician to identify the liver cancer in non-invasive method.

Keywords: segmentation, Support Vector Machine, ultrasound liver lesion, co-occurance Matrix

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Authors: Vanitha Varadharaj, Vijalakshmi Krishnamurthy

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Annona squamosa Linn, commonly known as Sugar apple, belonging to the family Annonaceae, is said to show varied medicinal effects, including insecticide, antiovulatory and abortifacient. The alkaloid and flavonoids present in Annona squamosa leaf has proved to have antioxidant activity. The present work has been planned to investigate the effect of ethanolic leaf extract of Annona squamosa leaf on Den Induced wistar albino rats. The study was carried out to analyze the biochemical Parmeters like Total Proteins, Bilirubin, Enzymatic and Non –Enzymatic enzymes, Marker enzymes and Tumor markers in serum and also the histopathological studies in liver is carried out in control and DEN induced rats. Supplementation of ELAS (Ethanolic Leaf Extract Of Annona squamosa) reduced the liver weight and also reduced the tumour incidence. Chemoprevention group showed near normal values of bilirubin when compared with the control rats. Total protein was decreased in the cancer bearing group and on treatment with the extract the levels of protein were restored. Both in pre and post treatment group, the activities of enzymatic antioxidants such as superoxide dismutase, catalase, and Glutathione peroxidase were increased but in pre treated animals it was more effective than post treated animals. The non- enzymatic antioxidants such as vitamin C and vitamin E were brought back to normal level significantly in post and pre treated animals. Activities of marker enzymes such as SGOT, SGPT, ALP, γ GT were significantly elevated in the serum of cancer animals and the values returned to normal after treatment with the extract suggesting the hepato protective effect of the extract. Lipid peroxide was found to be elevated in the cancer induced group. This condition was brought back to the normal in the pre and post treated animals with ELAS. Histological examination also confirmed the anti- carcinogenic potential of ELAS, Cancer induced groups had a triple fold increase in their AFP values when compared to other groups. DEN treatment increased the level of AFP expression while ELAS partially counteracted the effect of it. So the scientific validation obtained from this study may pave way to many budding scientists to find new drugs from Annona squamosa for various ailments.

Keywords: annona squamosa, biochemical parmeters, cancer, leaf extract

Procedia PDF Downloads 331

Authors: Małgorzata Drzewiecka, Tomasz Śliwiński, Maciej Radek

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The inhibition of histone deacetyles (HDACs) holds promise as a potential anti-cancer therapy because histone and non-histone protein acetylation is frequently disrupted in cancer, leading to cancer initiation and progression. Additionally, histone deacetylase inhibitors (HDACi) such as class I HDAC inhibitor - valproic acid (VPA) have been shown to enhance the effectiveness of DNA-damaging factors, such as cisplatin or radiation. In this study, we found that, using of VPA in combination with talazoparib (BMN-637 – PARP1 inhibitor – PARPi) and/or Dacarabazine (DTIC - alkylating agent) resulted in increased DNA double strand break (DSB) and reduced survival (while not affecting primary melanocytes )and proliferation of melanoma cells. Furthermore, pharmacologic inhibition of class I HDACs sensitizes melanoma cells to apoptosis following exposure to DTIC and BMN-637. In addition, inhibition of HDAC caused sensitization of melanoma cells to dacarbazine and BMN-637 in melanoma xenografts in vivo. At the mRNA and protein level histone deacetylase inhibitor downregulated RAD51 and FANCD2. This study provides that combining HDACi, alkylating agent and PARPi could potentially enhance the treatment of melanoma, which is known for being one of the most aggressive malignant tumors. The findings presented here point to a scenario in which HDAC via enhancing the HR-dependent repair of DSBs created during the processing of DNA lesions, are essential nodes in the resistance of malignant melanoma cells to methylating agent-based therapies.

Keywords: melanoma, hdac, parp inhibitor, valproic acid

Procedia PDF Downloads 82

Authors: Godwin Dennison, C. E. Boulind, O. Gould, B. de Lacy Costello, J. Allison, P. White, P. Ewings, A. Wicaksono, N. J. Curtis, A. Pullyblank, D. Jayne, J. A. Covington, N. Ratcliffe, N. K. Francis

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Background: Colorectal symptoms are common but only infrequently represent serious pathology, including colorectal cancer (CRC). A large number of invasive tests are presently performed for reassurance. We investigated the feasibility of urinary volatile organic compound (VOC) testing as a potential triage tool in patients fast-tracked for assessment for possible CRC. Methods: A prospective, multi-centre, observational feasibility study was performed across three sites. Patients referred on NHS fast-track pathways for potential CRC provided a urine sample which underwent Gas Chromatography Mass Spectrometry (GC-MS), Field Asymmetric Ion Mobility Spectrometry (FAIMS) and Selected Ion Flow Tube Mass Spectrometry (SIFT-MS) analysis. Patients underwent colonoscopy and/or CT colonography and were grouped as either CRC, adenomatous polyp(s), or controls to explore the diagnostic accuracy of VOC output data supported by an artificial neural network (ANN) model. Results: 558 patients participated with 23 (4.1%) CRC diagnosed. 59% of colonoscopies and 86% of CT colonographies showed no abnormalities. Urinary VOC testing was feasible, acceptable to patients, and applicable within the clinical fast track pathway. GC-MS showed the highest clinical utility for CRC and polyp detection vs. controls (sensitivity=0.878, specificity=0.882, AUROC=0.884). Conclusion: Urinary VOC testing and analysis are feasible within NHS fast-track CRC pathways. Clinically meaningful differences between patients with cancer, polyps, or no pathology were identified therefore suggesting VOC analysis may have future utility as a triage tool. Acknowledgment: Funding: NIHR Research for Patient Benefit grant (ref: PB-PG-0416-20022).

Keywords: colorectal cancer, volatile organic compound, gas chromatography mass spectrometry, field asymmetric ion mobility spectrometry, selected ion flow tube mass spectrometry

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Authors: Md Shohidul Islam, Jongmyon Kim, Ui-pil Chong

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Medical image is an integral part of e-health care and e-diagnosis system. Medical image watermarking is widely used to protect patients’ information from malicious alteration and manipulation. The watermarked medical images are transmitted over the internet among patients, primary and referred physicians. The images are highly prone to corruption in the wireless transmission medium due to various noises, deflection, and refractions. Distortion in the received images leads to faulty watermark detection and inappropriate disease diagnosis. To address the issue, this paper utilizes error correction code (ECC) with (8, 4) Hamming code in an existing watermarking system. In addition, we implement the high complex ECC on a graphics processing units (GPU) to accelerate and support real-time requirement. Experimental results show that GPU achieves considerable speedup over the sequential CPU implementation, while maintaining 100% ECC efficiency.

Keywords: medical image watermarking, e-health system, error correction, Hamming code, GPU

Procedia PDF Downloads 290

Authors: S. Guruprasad, M. Z. Kurian, H. N. Suma

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Medical imaging modalities are becoming life saving components. These modalities are very much essential to doctors for proper diagnosis, treatment planning and follow up. Some modalities provide anatomical information such as Computed Tomography (CT), Magnetic Resonance Imaging (MRI), X-rays and some provides only functional information such as Positron Emission Tomography (PET). Therefore, single modality image does not give complete information. This paper presents the fusion of structural information in CT and functional information present in PET image. This fused image is very much essential in detecting the stages and location of abnormalities and in particular very much needed in oncology for improved diagnosis and treatment. We have implemented and compared image fusion techniques like pyramid, wavelet, and principal components fusion methods along with hybrid method of DWT and PCA. The performances of the algorithms are evaluated quantitatively and qualitatively. The system is implemented and tested by using MATLAB software. Based on the MSE, PSNR and ENTROPY analysis, PCA and DWT-PCA methods showed best results over all experiments.

Keywords: image fusion, pyramid, wavelets, principal component analysis

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Authors: Mohamed Hamada Abdelkader Fayed

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Background: To evaluate the diagnostic accuracy of (ADD-RS) with D-dimer as a screening test to exclude AAS. Methods: We conducted research for the studies examining the diagnostic accuracy of (ADD- RS)+ D-dimer to exclude the diagnosis of AAS, We searched MEDLINE, Embase, and Cochrane of Trials up to 31 December 2020. Results: We identified 3 studies using (ADD-RS) with D-dimer as a diagnostic tool for AAS, involving 3261 patients were AAS was diagnosed in 559(17.14%) patients. Overall results showed that the pooled sensitivities were 97.6 (95% CI 0.95.6, 99.6) at (ADD-RS)≤1(low risk group) with D-dimer and 97.4(95% CI 0.95.4,, 99.4) at (ADD-RS)>1(High risk group) with D-dimer., the failure rate was 0.48% at low risk group and 4.3% at high risk group respectively. Conclusions: (ADD-RS) with D-dimer was a useful screening test with high sensitivity to exclude Acute Aortic Syndrome.

Keywords: aortic dissection detection risk score, D-dimer, acute aortic syndrome, diagnostic accuracy

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Authors: John Rothrock

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Background: The role of transthoracic echocardiography (TTE) in the diagnosis and management of patients with acute ischemic stroke remains controversial. While many stroke subspecialist reserve TTE for selected patients, others consider the procedure obligatory for most or all acute stroke patients. This study was undertaken to assess the cost vs. benefit of 'routine' TTE. Methods: We examined a consecutive series of patients who were admitted to a single institution in 2019 for acute ischemic stroke and underwent TTE. We sought to determine the frequency with which the results of TTE led to a new diagnosis of cardioembolism, redirected therapeutic cerebrovascular management, and at least potentially influenced the short or long-term clinical outcome. We recorded the direct cost associated with TTE. Results: There were 1076 patients in the study group, all of whom underwent TTE. TTE identified an unsuspected source of possible/probable cardioembolism in 62 patients (6%), confirmed an initially suspected source (primarily endocarditis) in an additional 13 (1%) and produced findings that stimulated subsequent testing diagnostic of possible/probable cardioembolism in 7 patients ( < 1%). TTE results potentially influenced the clinical outcome in a total of 48 patients (4%). With a total direct cost of $1.51 million, the mean cost per case wherein TTE results potentially influenced the clinical outcome in a positive manner was $31,375. Diagnostically and therapeutically, TTE was most beneficial in 67 patients under the age of 55 who presented with 'cryptogenic' stroke, identifying patent foramen ovale in 21 (31%); closure was performed in 19. Conclusions: The utility of TTE in the setting of acute ischemic stroke is modest, with its yield greatest in younger patients with cryptogenic stroke. Given the greater sensitivity of transesophageal echocardiography in detecting PFO and evaluating the aortic arch, TTE’s role in stroke diagnosis would appear to be limited.

Keywords: cardioembolic, cost-benefit, stroke, TTE

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Authors: Frederick Anlimah, Vinod Gopaldasani, Catherine MacPhail, Brian Davies

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Aim: This study aims to identify the barriers and challenges hindering the implementation of effective controls and the adoption of safe work practices to protect workers from respirable crystalline silica (RCS) exposure. Problem or Situation: Tunnelling is one of many occupations that expose workers to the harmful effects of respirable crystalline silica. Despite various control measures, such as engineering controls and personal protective equipment, exposures remain inadequately controlled, leading to incurable silicosis and other severe illnesses, such as lung cancer. Methods: The research involved surveying tunnel construction workers, conducting interviews, and facilitating focus group discussions. Additionally, site observations and content analysis of work procedures and instructions were performed. Results: Preliminary data analysis reveals notable findings. While there is a commendable level of knowledge and commitment among management and workers concerning RCS exposure in tunnelling, there is a striking lack of prioritization regarding dust control. Moreover, the risks associated with dust exposure are not sufficiently acknowledged. Additionally, the data suggests that engineers and supervisors responsible for implementing dust controls often possess limited knowledge regarding the factors influencing the effectiveness of these measures. These findings emphasise the need for a paradigm shift, including higher prioritisation of dust control, adoption of holistic dust reduction strategies, and enhanced knowledge about effective control measures. Conclusion: This research shed light on tunnel construction workers' barriers and challenges in protecting themselves from RCS exposure. This knowledge will be essential in developing interventions and strategies to enhance dust exposure and prevent the adverse health effects of respirable crystalline silica exposure in tunnelling and similar industries.

Keywords: respirable crystalline silica, dust control, worker practices, exposure prevention, silicosis

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Authors: Fadzil Ahmad, Noor Ashidi Mat Isa

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This study introduces an improved genetic algorithm procedure that focuses search around near optimal solution corresponded to a group of elite chromosome. This is achieved through a novel crossover technique known as Segmented Multi Chromosome Crossover. It preserves the highly important information contained in a gene segment of elite chromosome and allows an offspring to carry information from gene segment of multiple chromosomes. In this way the algorithm has better possibility to effectively explore the solution space. The improved GA is applied for the automatic and simultaneous parameter optimization and feature selection of artificial neural network in pattern recognition of medical problem, the cancer and diabetes disease. The experimental result shows that the average classification accuracy of the cancer and diabetes dataset has improved by 0.1% and 0.3% respectively using the new algorithm.

Keywords: genetic algorithm, artificial neural network, pattern clasification, classification accuracy

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Authors: Saimir Heta, Kastriot Haxhirexha, Virtut Velmishi, Nevila Alliu, Ilma Robo

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Background: Testicular rotation can occur at any age. The possibility to save the testicle is the fastest possible surgical intervention which is indicated by the presence of acute pain even at rest. The time element is more important to diagnose and proceed further with surgical intervention. Testicular damage is a consequence which mainly depends on the moment of onset of symptoms, at the time when the symptoms are diagnosed, the earliest action to be performed is surgical intervention. Sometimes medical tests are needed to confirm a diagnosis, or to help identify another cause for symptoms; for example, the urine test, that is used to check for infection, associated with the scrotal ultrasound test. Control of blood flow to the longitudinal supply vessels of the testicles is indicated. The sign that indicates testicular rotation is a reduction in blood flow. This is the element which is distinguished from ultrasound examination. Surgery may be needed to determine if the patient’s symptoms are caused by the rotation of the testis or any other condition. Discussion: As a surgical intervention of the emergency, the torsion of the test depends very much on the duration of the torsion, as the success in the life of the testicle depends on the fastest surgical intervention. From the previous clinic, it is noted that in any case presented to the pediatric patient diagnosed with testicular rotation, there is always a link with personal history that the patient refers to the presence of a previous episode of testicular trauma. Literature supports this fact very logically. Conclusions: Salvation without testicular atrophy depends closely on establishing the diagnosis of testicular rotation as soon as possible. Following the logic above, it can be said that the diagnosis for rotation should be performed as soon as possible, to avoid consequences that will not be favorable for the patient.

Keywords: acute scrotum, test torsion, newborns, clinical presentation

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Authors: Arati Inamdar, Siddharth Bhattacharyya, Kester Haye

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Collision tumors are rare entities characterized by neoplasms of two different cell populations with distinct separating boundaries. Such tumors could be benign, malignant, or a combination of both. The exact mechanism of origin for collision tumors is predicted to be tumor heterogeneity or concurrent occurrence of neoplasm in the same organ. We present two cases of plasmacytoma presenting as a collision tumor, one with a tumor of hematological origin and another with a non-hematological origin, namely Chronic Lymphocytic Leukemia and Adenocarcinoma of the colon, respectively. The immunohistochemical stains and flowcytometry analysis performed on the specimens aided incorrect diagnosis. Interestingly, neoplastic cells of plasmacytoma in the first case demonstrated strong cytokeratin along with weak Epithelial Specific Antigen/ Epithelial cell adhesion molecule Monoclonal Antibody (MOC31) positivity, indicating that the tumor may influence the microenvironment of the tumor in the vicinity. Furthermore, the next-generation sequencing studies performed on the specimen with plasmacytoma and chronic lymphocytic lymphoma demonstrated BReast CAncer gene (BRCA2) and Tumor Necrosis Factor Alpha Induced Protein 3 (TNFAIP3) as a disease associated variants suggestive of risk for multiple tumors including collision tumors. Our reports highlight the unique collision tumors involving plasmacytoma, which have never been reported previously, as well as provide necessary insights about the underline genetic aberrations and tumor heterogeneity through sequencing studies and allow clonality assessment for subsequent tumors.

Keywords: BRCA2, collision tumor, chronic lymphocytic leukemia, plasmacytoma

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Authors: Nusrat Masood, Vijaya Dubey, Suaib Luqman

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Caspase 3, a member of cysteine-aspartic acid protease family, is an imperative indicator for cell death particularly when substantiating apoptosis. Thus, caspase 3 is an interesting target for the discovery and development of anticancer agent. We adopted a four level assessment of both terpenoids and flavonoids and thus experimentally performed the enzymatic assay in cell free system as well as in cancer cell line which was validated through real time expression and molecular interaction studies. A significant difference was observed with both the class of natural products indicating terpenoids as better activators of caspase 3 compared to flavonoids both in the cell free system as well as in cell lines. The expression analysis, activation constant and binding energy also correlate well with the enzyme activity. Overall, terpenoids had an unswerving effect on caspase 3 in all the tested system while flavonoids indirectly affect enzyme activity.

Keywords: Caspase 3, terpenoids, flavonoids, activation constant, binding energy

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Authors: Anca Dinischiotu, Sorina Nicoleta Voicu

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Silica nanoparticles (SiO2-NPs) are widely used in consumer products such as paints, plastics, insulation materials, tires, concrete production, as well as in gene delivery systems and imaging procedures. Environmental human exposure to them occurs during utilization of these products, in a time-dependent manner, the uptake being by topic and inhalation route especially. SiO2-NPs enter cells and induce membrane damage, oxidative stress and inflammatory reactions in a concentration-dependent manner. In this study, MRC-5 cells (human fetal lung fibroblasts) were exposed to amorphous SiO2-NPs at a dose of 62.5 μg/ml for 24, 48 and 72 hours. The size distribution of NPs was a lognormal function, in the range 3-14 nm. A time-dependent decrease of total reduced glutathione concentration by 36%, 50%, and 78% and an increase of NO level by 62%, 32%, respectively 24% compared to control were noticed. An up-regulation of NF-kB expression by 20%, 50% respectively 10% and of Nrf-2 by 139%, 58%, and 16% compared to control after 24, 48 and 72 hours was noticed also. The expression of IL-1β, IL-6, IL-8, and COX-2 was up-regulated in a time-dependent manner. Also, the expression of MMP-2 and MMP-9 were down-regulated after 48 and 72 hours, whereas their activities raised in a time-dependent manner. Exposure of cells to NPs up-regulated the expression of inducible NO synthase, as previously was shown, and probably this is the reason for the increased level of NO, that can react with the thiol groups of reduced glutathione molecules, diminishing its concentration Nrf2 is a transcription factor translocated in nucleus, under oxidative stress, where downstream gene expression activates in order to modulate the adaptive intracellular response against oxidative stress. The cross-talk between Nrf2 and NF-kB activities regulates the inflammatory processes. The activation of NF-kB could activate up-regulation of IL-1β, IL-6, and IL-8. The increase of COX-2 expression could be correlated with IL-1β one. Also, probably in response to the pro-inflammatory cytokines, MMP-2 and MMP-9 were induced and activated. In conclusion, the exposure of MRC-5 cells to SiO2-NPs generated inflammation in a time-dependent manner.

Keywords: inflammation, MRC-5 cells, oxidative stress, silica nanoparticles

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Authors: Manisha Bal, Remya Chinnamma Jose, B.C. Meikap

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Dust particles suspended in air are a major source of air pollution. A self-priming submerged venturi scrubber proven very effective in cases of handling nuclear power plant accidents is an efficient device to remove dust particles from the air and thus aids in pollution control. Venturi scrubbers are compact, have a simple mode of operation, no moving parts, easy to install and maintain when compared to other pollution control devices and can handle high temperatures and corrosive and flammable gases and dust particles. In the present paper, fly ash particles recognized as a high air pollutant substance emitted mostly from thermal power plants is considered as the dust particle. Its exposure through skin contact, inhalation and indigestion can lead to health risks and in severe cases can even root to lung cancer. The main focus of this study is on the removal of fly ash particles from polluted air using a self-priming venturi scrubber in submerged conditions using water as the scrubbing liquid. The venturi scrubber comprising of three sections: converging section, throat and diverging section is submerged inside a water tank. The liquid enters the throat due to the pressure difference composed of the hydrostatic pressure of the liquid and static pressure of the gas. The high velocity dust particles atomize the liquid droplets at the throat and this interaction leads to its absorption into water and thus removal of fly ash from the air. Detailed investigation on the scrubbing of fly ash has been done in this literature. Experiments were conducted at different throat gas velocities, water levels and fly ash inlet concentrations to study the fly ash removal efficiency. From the experimental results, the highest fly ash removal efficiency of 99.78% is achieved at the throat gas velocity of 58 m/s, water level of height 0.77m with fly ash inlet concentration of 0.3 x10⁻³ kg/Nm³ in the submerged condition. The effect of throat gas velocity, water level and fly ash inlet concentration on the removal efficiency has also been evaluated. Furthermore, experimental results of removal efficiency are validated with the developed empirical model.

Keywords: dust particles, fly ash, pollution control, self-priming venturi scrubber

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Authors: Meltem Koray, Arda Ozgon, Duygu Ofluoglu, Mehmet Yaltirik

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Oral ulcerations can be seen as a side effect of different drugs. These ulcers usually appear within a few weeks following drug treatment. In most of cases, these ulcers resist to conventional treatments, such as anesthetics, antiseptics, anti-inflammatory agents, cauterization, topical tetracycline and corticosteroid treatment. The diagnosis is usually difficult, especially in patients receiving multiple drug therapies. Hyaluronan or hyaluronic acid (HA) is a biomaterial that has been introduced as an alternative approach to enhance wound healing and also used for oral ulcer treatment. The aim of this report is to present the treatment of drug-induced oral ulceration on maxillary mucosa with HA gel. 60-year-old male patient was referred to Department of Oral and Maxillofacial Surgery complaining of oral ulcerations during few weeks. He had received chemotherapy and radiotherapy in 2014 with the diagnosis of nasopharyngeal carcinoma, and he has accompanying systemic diseases such as; cardiological, neurological diseases and gout. He is medicated with Escitalopram (Cipralex® 20mg), Quetiapine (Seroquel® 100mg), Mirtazapine (Zestat® 15mg), Acetylsalicylic acid (Coraspin® 100mg), Ramipril-hydrochlorothiazide (Delix® 2.5mg), Theophylline anhydrous (Teokap Sr® 200mg), Colchicine (Colchicum Dispert® 0.5mg), Spironolactone (Aldactone® 100mg), Levothyroxine sodium (Levotiron® 50mg). He had painful oral ulceration on the right side of maxillary mucosa. The diagnosis was 'drug-induced oral ulceration' and HA oral gel (Aftamed® Oral gel) was prescribed 3 times a day for 2 weeks. Complete healing was achieved within 3 weeks without any side effect and discomfort. We suggest that HA oral gel is a potentially useful local drug which can be an alternative for management of drug-induced oral ulcerations.

Keywords: drug-induced, hyaluronic acid, oral ulceration, maxillary mucosa

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Authors: A. Maciejak, M. Kiliszek, G. Opolski, D. Tulacz, A. Segiet, K. Matlak, S. Dobrzycki, G. Sygitowicz, B. Burzynska, M. Gora

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Introduction and aims: Acute myocardial infarction (AMI) is one of the most severe cardiovascular diseases affecting millions of patients each year worldwide. An early and accurate diagnosis of AMI is essential for optimal treatment. Therefore, new approaches that can complement and improve current strategies for AMI diagnosis are urgently needed. Recent studies have revealed the presence of stable circulating myocardial-derived microRNAs (miRNAs) in human peripheral blood, suggesting that such miRNAs could serve as potential biomarkers of infarction. The present study aimed to identify differentially expressed circulating miRNAs in ST-segment elevation myocardial infarction (STEMI) patients. Materials and methods: miRNA expression profile analysis was performed using Exiqon Serum/Plasma Focus microRNA PCR panel in plasma samples of n=16 patients on the first day of AMI (admission) and in samples from the same patients collected six months after AMI. Selected miRNAs were validated by RT-qPCR using serum samples from an independent set of n=14 AMI patients. Results: The profiling study identified 46 species of plasma miRNAs that were differentially expressed (p < 0.05) on admission compared to six months after AMI. The validation in the independent group of patients confirmed that miR-133b and miR-22-5p were significantly up-regulated upon AMI. Conclusions: Our results suggest that miRNA expression profiling provides better understanding of the changes that occur in the acute phase of MI in the myocardium and could be useful in determination of the potential role of extracellular miRNAs as paracrine signaling molecules. miR-22-5p represents a novel promising biomarker for the diagnosis of acute myocardial infarction.

Keywords: acute myocardial infarction, circulating microRNAs, microRNA expression profiling, miR-22-5p

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Authors: Yosep Chong, Yejin Kim, Jingyun Choi, Hwanjo Yu, Eun Jung Lee, Chang Suk Kang

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For the past decades, immunohistochemistry (IHC) has been playing an important role in the diagnosis of human neoplasms, by helping pathologists to make a clearer decision on differential diagnosis, subtyping, personalized treatment plan, and finally prognosis prediction. However, the IHC performed in various tumors of daily practice often shows conflicting and very challenging results to interpret. Even comprehensive diagnosis synthesizing clinical, histologic and immunohistochemical findings can be helpless in some twisted cases. Another important issue is that the IHC data is increasing exponentially and more and more information have to be taken into account. For this reason, we reached an idea to develop an expert supporting system to help pathologists to make a better decision in diagnosing human neoplasms with IHC results. We gave probabilistic decision tree algorithm and tested the algorithm with real case data of lymphoid neoplasms, in which the IHC profile is more important to make a proper diagnosis than other human neoplasms. We designed probabilistic decision tree based on Bayesian theorem, program computational process using MATLAB (The MathWorks, Inc., USA) and prepared IHC profile database (about 104 disease category and 88 IHC antibodies) based on WHO classification by reviewing the literature. The initial probability of each neoplasm was set with the epidemiologic data of lymphoid neoplasm in Korea. With the IHC results of 131 patients sequentially selected, top three presumptive diagnoses for each case were made and compared with the original diagnoses. After the review of the data, 124 out of 131 were used for final analysis. As a result, the presumptive diagnoses were concordant with the original diagnoses in 118 cases (93.7%). The major reason of discordant cases was that the similarity of the IHC profile between two or three different neoplasms. The expert supporting system algorithm presented in this study is in its elementary stage and need more optimization using more advanced technology such as deep-learning with data of real cases, especially in differentiating T-cell lymphomas. Although it needs more refinement, it may be used to aid pathological decision making in future. A further application to determine IHC antibodies for a certain subset of differential diagnoses might be possible in near future.

Keywords: database, expert supporting system, immunohistochemistry, probabilistic decision tree

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Authors: Maria Zulema Morquecho Vega, Fabiola CarolinaMiranda Castro, Rafael Verdugo Miranda, Ignacio Yocupicio Villegas, Ana lidia Barron Raygoza, Martin enrique MArquez Cordova, Jose Alberto Duarte Moller

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Background: Anemopsis californica, also called (tame grass) belongs to the Saururaceae family small, green plant. The blade is long and wide. Gives a white flower. The plant population is only found in humid, swampy habitats, it grows where there is water, along the banks of streams and water holes. In the winter, it dries up. The leaves, rhizomes, or roots of this plant have been used to treat a range of diseases. Some of its healing properties are used to treat wounds, cold and flu symptoms, spasmodic cough, infection, pain and inflammation, burns, swollen feet, as well as lung ailments, asthma, circulatory problems (varicose veins), rheumatoid arthritis, purifies blood, helps in urinary and digestive tract diseases, sores and healing, for headache, sore throat, diarrhea, kidney pain. The tea made from the leaves and roots is used to treat uterine cancer, womb cancer, relieves menstrual pain and stops excessive bleeding after childbirth. It is also used as a gynecological treatment for infections, hemorrhoids, candidiasis and vaginitis. Objective: To study the cytotoxicity of gels prepared with silver nanoparticles in AC extract combined with chitosan, collagen and hyaluronic acid as an alternative therapy for skin conditions. Methods: The Ag NPs were synthesized according to the following method. A 0.3 mg/mL solution is prepared in 10 ml of deionized water, adjust to pH 12 with NaOH, stirring is maintained constant magnetic and a temperature of 80 °C. Subsequently, 100 ul of a 0.1 M AgNO3 solution and kept stirring constantly for 15 min. Once the reaction is complete, measurements are performed by UV-Vis. A gel was prepared in a 5% solution of acetic acid with the respective nanoparticles and AC extract of silver in the extract of AC. Chitosan is added until the process begins to occur gel. At that time, collagen will be added in a ratio of 3 to 5 drops, and later, hyaluronic acid in 2% of the total compound formed. Finally, after resting for 24 hours, the cytotoxic effect of the gels was studied. in the presence of highly positive bacteria Staphylococcus aureus and highly negative for Escherichia coli. Cultures will be incubated for 24 hours in the presence of the compound and compared with the reference. Results: Silver nanoparticles obtained had a spherical shape and sizes among 20 and 30 nm. UV-Vis spectra confirm the presence of silver nanoparticles showing a surface plasmon around 420 nm. Finally, the test in presence of bacteria yield a good antibacterial property of this nanocompound and tests in people were successful. Conclusion: Gel prepared by biogenic synthesis shown beneficious effects in severe acne, acne vulgaris and wound healing with diabetic patients.

Keywords: anemopsis californica, nanomedicina, biotechnology, biomedicine

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Authors: Shantanu Arya, Sachin Sakhuja, Gunjan Mehta, Sanjay Munjal

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Stuttering may be defined as a speech disorder affecting the fluency domain of speech and characterized by covert features like word substitution, omittance and circumlocution and overt features like prolongation of sound, syllables and blocks etc. Many etiologies have been postulated to explain stuttering based on various experiments and research. Moreover, Breathlessness has also been reported by many individuals with stuttering for which breathing exercises are generally advised. However, no studies reporting objective evaluation of the pulmonary capacity and further objective assessment of the efficacy of breathing exercises have been conducted. Pulmonary Function Test which evaluates parameters like Forced Vital Capacity, Peak Expiratory Flow Rate, Forced expiratory flow Rate can be used to study the pulmonary behavior of individuals with stuttering. The study aimed: a) To identify speech motor & physiologic behaviours associated with stuttering by administering PFT. b) To recognize possible reasons for an association between speech motor behaviour & stuttering severity. In this regard, PFT tests were administered on individuals who reported signs and symptoms of stuttering and showed abnormal scores on Stuttering Severity Index. Parameters like Forced Vital Capacity, Forced Expiratory Volume, Peak Expiratory Flow Rate (L/min), Forced Expiratory Flow Rate (L/min) were evaluated and correlated with scores of Stuttering Severity Index. Results showed significant decrease in the parameters (lower than normal scores) in individuals with established stuttering. Strong correlation was also found between degree of stuttering and the degree of decrease in the pulmonary volumes. Thus, it is evident that fluent speech requires strong support of lung pressure and requisite volumes. Further research in demonstrating the efficacy of abdominal breathing exercises in this regard is needed.

Keywords: forced expiratory flow rate, forced expiratory volume, forced vital capacity, peak expiratory flow rate, stuttering

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Authors: Dipranjan Laha, Parimal Karmakar

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Metal oxide nanoparticles are well known to generate oxidative stress and deregulate normal cellular activities. Among these, transition metals copper oxide nanoparticles (CuO NPs) are more compelling than others and able to modulate different cellular responses. In this work, we have synthesized and characterized CuO NPs by various biophysical methods. These CuO NPs (~30 nm) induce autophagy in human breast cancer cell line, MCF7 in a time and dose-dependent manner. Cellular autophagy was tested by MDC staining, induction of green fluorescent protein light chain 3 (GFP-LC3B) foci by confocal microscopy, transfection of pBABE-puro mCherry-EGFP-LC3B plasmid and western blotting of autophagy marker proteins LC3B, beclin1, and ATG5. Further, inhibition of autophagy by 3-Methyladenine (3-MA) decreased LD50 doses of CuO NPs. Such cell death was associated with the induction of apoptosis as revealed by FACS analysis, cleavage of PARP, dephosphorylation of Bad and increased cleavage product of caspase3. siRNA-mediated inhibition of autophagy-related gene beclin1 also demonstrated similar results. Finally, induction of apoptosis by 3-MA in CuO NPs treated cells were observed by TEM. This study indicates that CuO NPs are a potent inducer of autophagy which may be a cellular defense against the CuO NPs mediated toxicity and inhibition of autophagy switches the cellular response into apoptosis. A combination of CuO NPs with the autophagy inhibitor is essential to induce apoptosis in breast cancer cells. Acknowledgments: The authors would like to acknowledge for financial support for this research work to the Department of Biotechnology (No. BT/PR14661/NNT/28/494/2010), Government of India.

Keywords: nanoparticle, autophagy, apoptosis, siRNA-mediated inhibition

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Authors: John Joseph S. Martis, Rohanchandra R. Gatty, Aaron Jose Fernandes, Rahul P. Nambiar

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Introduction: Surgery for breast cancer is either mastectomy or breast conservation surgery. The most commonly used incision for modified radical mastectomy is the transverse Stewart incision. But this incision may have the disadvantage of causing disparity between the closure lines of superior and inferior skin flaps in mastectomy and can cause overhanging of soft tissue below and behind the axilla. The curvizigzag incision, on principle, may help in this regard and can prevent scar migration beyond the anterior axillary line. This study aims to compare the two incisions in this regard. Methods: 100 patients with cancer of breast were included in the study after satisfying inclusion and exclusion criteria. They underwent surgery at Father Muller Medical College, Mangalore, India, between November 2019 to September 2021. The patients were divided into two groups. Group A patients were subjected to modified radical mastectomy with curvizigzag incision and group B patients with transverse Stewart incision. Results: Seroma on postoperative day1, day 2 was 0% in both the groups. Seroma on postoperative day 30 was present in 14% of patients in group B. 60% of patients in group B had sag of soft tissue below and behind the axilla, and none of the patients in group A had this problem. In 64% of the patients in group B, the incision crossed the anterior axillary fold, 64% of the patients in group B had tension in the incision site while approximation of the skin flaps. Conclusion: Curvizigzag incision is statistically better with lesser complications when compared to the transverse Stewart incision for modified radical mastectomy for carcinoma breast.

Keywords: breast cancer, curvizigzag incision, transverse Stewart incision, seroma, modified radical mastectomy

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Authors: Michio Kurosu

Abstract:

Alterations in glycosylation not only directly impact cell growth and survival but also facilitate tumor-induced immunomodulation and eventual metastasis. Identification of cell type-specific glycoconjugates (tumor markers) has led to the discovery of new assay systems for certain cancers via immunodetection reagents. N- and O-linked glycans are the most abundant forms of glycoproteins. Recent studies of cancer immunotherapy are based on the immunogenicity of truncated O-glycan chains (e.g., Tn, sTn, T, and sLea/x). The prevalence of N-linked glycan changes in the development of tumor cells is known; however, therapeutic antibodies against N-glycans have not yet been developed. This is due to the lack of specificity of N-linked glycans between normal/healthy and cancer cells. Abnormal branching of N-linked glycans has been observed, particularly in solid cancer cells. While the discovery of drug-like glycosyltransferase inhibitors that block the biosynthesis of specific branching has a very low likelihood of success, altered glycosylation levels can be exploited by suppressing N-glycan biosynthesis through the inhibition of dolichyl-phosphate N-acetylglucosaminephosphotransferase1 (DPAGT1) activity. Inhibition of DPAGT1 function leads to changes of O-glycosylation on proteins associated with mitochondria and zinc finger binding proteins (indirect effects). On the basis of dynamic crosstalk between DPAGT1 and Snail/Slung/ZEB1 (a family of transcription factors that promote the repression of the adhesion molecules), we have developed pharmacologically acceptable selective DPAGT1 inhibitors. Tunicamycin kills a wide range of cancer and healthy cells in a non-selective manner. In sharp contrast, our DPAGT1 inhibitors display strong cytostatic effects against 16 solid cancers, which require the overexpression of DPAGT1 in their progression but do not affect the cell viability of healthy cells. The identified DPAGT1 inhibitors possess impressive anti-metastatic ability in various solid cancer cell lines and induce their mitochondrial structural changes, resulting in apoptosis. A prototype DPAGT1 inhibitor, APPB has already been proven to shrink solid tumors (e.g., pancreatic cancers, triple-negative breast cancers) in vivo while suppressing metastases and has strong synergistic effects when combined with current cytotoxic drugs (e.g., paclitaxel). At this conference, our discovery of selective DPAGT1 inhibitors with drug-like properties and proof-of-pharmaceutical concept studies of a novel DPAGT1 inhibitor are presented.

Keywords: DPAGT1 inhibitors, anti-metastatic drugs, natural product based drug designs, cytostatic effects

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