Search results for: portal vein tumor thrombosis

Authors: Hadi S. Hosseini, Larry A. Taber

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In the embryo, heart is initially a simple tubular structure that undergoes complex morphological changes as it transforms into a four-chambered pump. This work focuses on mechanisms that create heart tube (HT). The early embryo is composed of three relatively flat primary germ layers called endoderm, mesoderm, and ectoderm. Precardiac cells located within bilateral regions of the mesoderm called heart fields (HFs) fold and fuse along the embryonic midline to create the HT. The right and left halves of this plate fold symmetrically to bring their upper edges into contact along the midline, where they fuse. In a region near the fusion line, these layers then separate to generate the primitive HT and foregut, which then extend vertically. The anterior intestinal portal (AIP) is the opening at the caudal end of the foregut, which descends as the HT lengthens. The biomechanical mechanisms that drive this folding are poorly understood. Our central hypothesis is that folding is caused by differences in growth between the endoderm and mesoderm while subsequent extension is driven by contraction along the AIP. The feasibility of this hypothesis is examined using experiments with chick embryos and finite-element modeling (FEM). Fertilized white Leghorn chicken eggs were incubated for approximately 22-33 hours until appropriate Hamburger and Hamilton stage (HH5 to HH9) was reached. To inhibit contraction, embryos were cultured in media containing blebbistatin (myosin II inhibitor) for 18h. Three-dimensional models were created using ABAQUS (D. S. Simulia). The initial geometry consists of a flat plate including two layers representing the mesoderm and endoderm. Tissue was considered as a nonlinear elastic material with growth and contraction (negative growth) simulated using a theory, in which the total deformation gradient is given by F=F^*.G, where G is growth tensor and F* is the elastic deformation gradient tensor. In embryos exposed to blebbistatin, initial folding and AIP descension occurred normally. However, after HFs partially fused to create the upper part of the HT, fusion, and AIP descension stopped, and the HT failed to grow longer. These results suggest that cytoskeletal contraction is required only for the later stages of HT formation. In the model, a larger biaxial growth rate in the mesoderm compared to the endoderm causes the bilayered plate to bend ventrally, as the upper edge moves toward the midline, where it 'fuses' with the other half . This folding creates the upper section of the HT, as well as the foregut pocket bordered by the AIP. After this phase completes by stage HH7, contraction along the arch-shaped AIP pulls the lower edge of the plate downward, stretching the two layers. Results given by model are in reasonable agreement with experimental data for the shape of HT, as well as patterns of stress and strain. In conclusion, results of our study support our hypothesis for the creation of the heart tube.

Keywords: heart tube formation, FEM, chick embryo, biomechanics

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Authors: Masoumeh Haghbin Nazarpak, Hamidreza Tolabi, Aryan Ekhlasi

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Bone defects are mentioned as one of the most challenging clinical conditions, affecting millions of people each year. A fracture, osteoporosis, tumor, or infection usually causes these defects. At present, autologous and allogeneic grafts are used to correct bone defects, but these grafts have some difficulties, such as limited access, infection, disease transmission, and immune rejection. Bone tissue engineering is considered a new strategy for repairing bone defects. However, problems with scaffolds’ design with unique structures limit their clinical applications. In addition, numerous in-vitro studies have been performed on the behavior of bone cells in two-dimensional environments. Still, cells grow in physiological situations in the human body in a three-dimensional environment. As a result, the controlled design of porous structures with high structural complexity and providing the necessary flexibility to meet specific needs in bone tissue repair is beneficial. For this purpose, a three-dimensional composite scaffold based on gelatin and sodium alginate hydrogels is used in this research. In addition, the antibacterial drug-loaded halloysite nanotubes were introduced into the hydrogel scaffold structure to provide a suitable substrate for controlled drug release. The presence of halloysite nanotubes improved hydrogel’s properties, while the drug eliminated infection and disease transmission. Finally, it can be acknowledged that the composite scaffold prepared in this study for bone tissue engineering seems promising.

Keywords: halloysite nanotubes, bone tissue engineering, composite scaffold, controlled drug release

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Authors: Efe Mary Isike

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The variety of relationships between migrants and host communities is an enduring theme of migration studies. On one extreme, there are numerous examples of hostility towards ‘strangers’ who are either ejected from society or denied access to jobs, housing, education, healthcare and other aspects of normal life. More moderate treatments of those identified as different include expectations of assimilation in which host communities expect socially marginalized groups to conform to norms that they define. Both exclusion and assimilation attempt to manage the problem of difference by removing it. South Africa experienced great influx of African immigrants who worked in mines and farms under harsh and exploitative conditions before and after the institutionalization of apartheid. Although these labour migrants contributed a great deal to the economic development of South Africa, they were not given citizenship status. The formal democratization in 1994 came with dreams and expectations of a more inclusive South Africa, where black South Africans hoped to maximize their potential in a more free, fair and equal society. In the same vein, it also opened spaces for an influx of especially African immigrants into the country which set the stage for a new form of contest for belonging between South African citizens and African migrant settlers. One major manifestation of this contest was the violent xenophobic attacks against African immigrants which predate that of May 2008 and has continued with lower intensity across the country since then. While it is doubtless possible to find abundant evidence of antagonism in the relations between South Africans and African immigrants, the purpose of this study is to investigate the everyday realities of migrants in ordinary places who interact with a variety of people through their livelihood activities, marriages and social relationships, moving around towns and cities, in their residential areas, in faith-based organizations and other elements of everyday life. Rather than assuming all relations are hostile, this study intends to look at the breadth of everyday relationships within a specific context. Based on the foregoing, the main task of this study is to holistically examine and explain the nature of interactions between African migrants and South African citizens by analysing the social network ties that connect them in the specific case of Umhlathuze municipality. It will also investigate the variety of networks that exists between African migrants and South Africans and examine the nature of the linkages in the various networks identified between these two groups in Umhlathuze Municipality. Apart from a review of relevant literature, policies and other official documents, this paper will employ a purposive sample survey and in-depth interview of African immigrants and South Africans within their networks in selected suburbs in KwaZulu-Natal.

Keywords: migration, networks, development, host communities

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Authors: Ryan A. Black, Stacey A. McCaffrey

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Over the past few decades, great strides have been made towards improving the science in the measurement of psychological constructs. Item Response Theory (IRT) has been the foundation upon which statistical models have been derived to increase both precision and accuracy in psychological measurement. These models are now being used widely to develop and refine tests intended to measure an individual's level of academic achievement, aptitude, and intelligence. Recently, the field of clinical psychology has adopted IRT models to measure psychopathological phenomena such as depression, anxiety, and addiction. Because advances in IRT measurement models are being made so rapidly across various fields, it has become quite challenging for psychologists and other behavioral scientists to keep abreast of the most recent developments, much less learn how to employ and decide which models are the most appropriate to use in their line of work. In the same vein, IRT measurement models vary greatly in complexity in several interrelated ways including but not limited to the number of item-specific parameters estimated in a given model, the function which links the expected response and the predictor, response option formats, as well as dimensionality. As a result, inferior methods (a.k.a. Classical Test Theory methods) continue to be employed in efforts to measure psychological constructs, despite evidence showing that IRT methods yield more precise and accurate measurement. To increase the use of IRT methods, this study endeavors to provide a comprehensive overview of binary IRT models; that is, measurement models employed on test data consisting of binary response options (e.g., correct/incorrect, true/false, agree/disagree). Specifically, this study will cover the most basic binary IRT model, known as the 1-parameter logistic (1-PL) model dating back to over 50 years ago, up until the most recent complex, 4-parameter logistic (4-PL) model. Binary IRT models will be defined mathematically and the interpretation of each parameter will be provided. Next, all four binary IRT models will be employed on two sets of data: 1. Simulated data of N=500,000 subjects who responded to four dichotomous items and 2. A pilot analysis of real-world data collected from a sample of approximately 770 subjects who responded to four self-report dichotomous items pertaining to emotional consequences to alcohol use. Real-world data were based on responses collected on items administered to subjects as part of a scale-development study (NIDA Grant No. R44 DA023322). IRT analyses conducted on both the simulated data and analyses of real-world pilot will provide a clear demonstration of how to construct, evaluate, and compare binary IRT measurement models. All analyses will be performed using the new IRT procedure in SAS 9.4. SAS code to generate simulated data and analyses will be available upon request to allow for replication of results.

Keywords: instrument development, item response theory, latent trait theory, psychometrics

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Authors: Soma Kanta Baral

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Background: Since 1981, when the first AIDS case was reported, worldwide, more than 34 million people have been infected with HIV. Almost 95 percent of the people infected with HIV live in developing countries. As HBV & HIV share similar routes of transmission by sexual intercourse or drug use by parenteral injection, co-infection is common. Because of the limited access to healthcare & HIV treatment in developing countries, HIV-infected individuals are present late for care. Enumeration of CD4+ T cell count at the time of diagnosis has been useful to initiate the therapy in HIV infected individuals. The baseline CD4+ T cell count shows high immunological variability among patients. Methods: This prospective study was done in the serology section of the Department of Microbiology over a period of one year from august 2012 to July 2013. A total of 13037 individuals subjected for HIV test were included in the study comprising of 4982 males & 8055 females. Blood sample was collected by vein puncture aseptically with standard operational procedure in clean & dry test-tube. All blood samples were screened for HIV as described by WHO algorithm by Immuno-chromatography rapid kits. Further confirmation was done by biokit ELISA method as per the manufacturer’s guidelines. After informed consent, HIV positive individuals were screened for HBsAg by Immuno-chromatography rapid kits (Hepacard). Further confirmation was done by biokit ELISA method as per the manufacturer’s guidelines. EDTA blood samples were collected from the HIV sero-positive individuals for baseline CD4+ T count. Then, CD4+ T cells count was determined by using FACS Calibur Flow Cytometer (BD). Results: Among 13037 individuals screened for HIV, 104 (0.8%) were found to be infected comprising of 69(66.34%) males & 35 (33.65%) females. The study showed that the high infection was noted in housewives (28.7%), active age group (30.76%), rural area (56.7%) & in heterosexual route (80.9%) of transmission. Out of total HIV infected individuals, distribution of HBV co-infection was found to be 6(5.7%). All co- infected individuals were married, male, above the age of 25 years & heterosexual route of transmission. Baseline CD4+ T cell count of HIV infected patient was found higher (mean CD4+ T cell count; 283cells/cu.mm) than HBV co-infected patients (mean CD4+ T cell count; 91 cells/cu.mm). Majority (77.2%) of HIV infected & all co-infected individuals were presented in our center late (CD4+ T cell count;< 350/cu. mm) for diagnosis and care. Majority of co- infected 4 (80%) were late presented with advanced AIDS stage (CD4+ count; <200/cu.mm). Conclusions: The study showed a high percentage of HIV sero-positive & co- infected individuals. Baseline CD4+ T cell count of majority of HIV infected individuals was found to be low. Hence, more sustained and vigorous awareness campaigns & counseling still need to be done in order to promote early diagnosis and management.

Keywords: HIV/AIDS, HBsAg, co-infection, CD4+

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Authors: Laila Seada, Ashraf Ibrahim, Amjad Al Shammari

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Background and Objectives: Breast carcinoma is the most common cancer of females in Hail region, accounting for 31% of all diagnosed cancer cases followed by thyroid carcinoma (25%) and colorectal carcinoma (13%). Methods: In the present retrospective study, all cases of breast lesions received at the histopathology department in King Khalid Hospital, Hail, during the period from May 2011 to April 2016 have been retrieved from department files. For all cases, a trucut biopsy, lumpectomy, or modified radical mastectomy was available for histopathologic diagnosis, while 105/140 (75%) had, as well, preoperative fine needle aspirates (FNA). Results: 49 cases out of 140 (35%) breast lesions were carcinomas: 44/49 (89.75%) was invasive ductal, 2/49(4.1%) invasive lobular carcinomas, 1/49(2.05%) intracystic low grade papillary carcinoma and 2/49 (4.1%) ductal carcinoma in situ (DCIS). Mean age for malignant cases was 45.06 (+/-10.58): 32.6% were below the age of 40 and 30.6 below 50 years, 18.3% below 60 and 16.3% below 70 years. For the benign group, mean age was 32.52 (+/10.5) years. Benign lesions were in order of frequency: 34 fibroadenomas, 14 fibrocystic disease, 12 chronic mastitis, five granulomatous mastitis, three intraductal papillomas, and three benign phyllodes tumor. Tubular adenoma, lipoma, skin nevus, pilomatrixoma, and breast reduction specimens constituted the remaining specimens. Conclusion: Breast lesions are common in our series and invasive carcinoma accounts for more than 1/3^rd of the lumps, with 63.2% incidence in pre-menopausal ladies, below the age of 50 years. FNA as a non-invasive procedure, proved to be an effective tool in diagnosing both benign and malignant/suspicious breast lumps and should continue to be used as a first assessment line of palpable breast masses.

Keywords: age incidence, breast carcinoma, fine needle aspiration, hail region

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Authors: Angelis P. Barlampas

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Purpose: A 29 years old woman presented in the emergency department with psychiatric symptoms. The psychiatrist ordered a computed tomography scan as part of a general examination. Material and methods: The CT showed bilateral enlarged choroid plexus structures mimicking papillomata and situated in the trigones of the lateral ventricles. The left choroid plexus was heavily calcified, but the right one has no any obvious calcifications. Results: It is well kown that any brain mass can present with behavioral changes and even psychiatric symptomatology. Papillomata of the ventricular system have been described to cause psychotic episodes. According to literature, choroid plexus papillomas are seldom neuroepithelial intraventricular tumors, which are benign and categorized as WHO grade 1 tumors. They are more common in the pediatric population, but they can occur in the adults, too1. In addition, the distinction between choroid plexus papilloma and carcinoma is very difficult and impossible by imagine alone. It can only be implied with more advanced imaging, such as arterial spin labeling and MRI. The final diagnosis is, of course, after surgical excision. The usual location in adults is the fourth ventricle, but in children, it is the lateral ventricles. Their imaging appearance is that of a solid vascular tumor, which enhances intensely after the intravenous administration of contrast material. One out of fourth tumors presents speckled calcifications1. In our case, there are symmetrically sized masses at the trigones, and there are no calcifications in one of them, whereas the other one is grossly calcified. Also, there is no obvious hydrocephalus or any other evidence of increased intracranial pressure. General conclusions: When there is a new psychiatric patient, someone must undergo any possible examination, and of course, a brain CT study should be done to exclude any rare organic causes that may be responsible for the disease.

Keywords: phycosis, intraventricular masses, CT, brain calcifications

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Authors: Doaa Hashad, Amany Elyamany, Perihan Salem

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Introduction: Hepatitis C virus infection (HCV) constitutes a serious dilemma that has an impact on the health of millions of Egyptians. Hepatitis C virus related hepatocellular carcinoma (HCV-HCC) is a crucial consequence of HCV that represents the third cause of cancer-related deaths worldwide. Aim of the study: assess the use of mitochondrial DNA (mtDNA) content as a non-invasive molecular biomarker in hepatitis c virus related hepatocellular carcinoma (HCV-HCC). Methods: A total of 135 participants were enrolled in the study. Volunteers were assigned to one of three groups equally; a group of HCV related cirrhosis (HCV-cirrhosis), a group of HCV-HCC and a control group of age- and sex- matched healthy volunteers with no evidence of liver disease. mtDNA was determined using a quantitative real-time PCR technique. Results: mtDNA content was lowest in HCV-HCC cases. No statistically significant difference was observed between the group of HCV-cirrhosis and the control group as regards mtDNA level. HCC patients with multi-centric hepatic lesions had significantly lower mtDNA content. On using receiver operating characteristic curve analysis, a cutoff of 34 was assigned for mtDNA content to distinguish between HCV-HCC and HCV-cirrhosis patients who are not yet complicated by malignancy. Lower mtDNA was associated with greater HCC risk on using healthy controls, HCV-cirrhosis, or combining both groups as a reference group. Conclusions: mtDNA content might constitute a non-invasive molecular biomarker that reflects tumor burden in HCV-HCC cases and could be used as a predictor of HCC risk in patients of HCV-cirrhosis. In addition, the non significant difference of mtDNA level between HCV-cirrhosis patients and healthy controls could eliminate the grey zone created by the use of AFP in some cirrhotic patients.

Keywords: DNA copy number, HCC, HCV, mitochondrial

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Authors: Naim Izet Kajtazi

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Context: Frequently, the cause of raised intracranial pressure remains unresolved and rarely is related to spinal tumors, moreover less to spinal medulloblastoma without primary brain focus. Process: An 18-year-old woman had a 3-month history of headaches and impaired vision. Neurological examination revealed bilateral sixth cranial nerve palsies with bilateral papilloedema of grade III. No focal brain or spine lesion was found on imaging. Consecutive lumbar punctures showed high opening pressure and subsequent increasing protein level. The meningeal biopsy was negative. At one point, she developed an increasing headache, vomiting and back pain. Spine MRI showed diffuse nodular leptomeningeal enhancement with the largest nodule at T6–T7. Malignant cells were detected in cerebrospinal fluid. She underwent laminectomy with excisional biopsy, and pathology showed medulloblastoma WHO grade IV. Outcome: She was treated with chemotherapy and craniospinal irradiation and made a good recovery. Relevance: Primary spinal leptomeningeal medulloblastoma is extremely rare, especially without primary brain focus, but may cause increased intracranial pressure, even in the early microscopic phases, and it should be considered in the differential diagnosis if conventional and aggressive treatment of idiopathic intracranial hypertension fails. We assume that arachnoiditis from tumor seeding caused increased intracranial pressure. Appropriate neurosurgical intervention and surgical biopsy are mandated if a suspicious lesion is detected. Consider proper rescreening of the whole neuroaxis in refractory cases of intracranial hypertension.

Keywords: CNS infection, IIH, headache, primary spinal leptomeningeal medulloblastoma

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Authors: Muhammad Muzamil Khan, Asadullah Madni, Nina Filipczek, Jiayi Pan, Nayab Tahir, Hassan Shah, Vladimir Torchilin

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Lipid-polymer hybrid nanoparticles (LPHNP) are delivery systems for controlled drug delivery at tumor sites. The superior biocompatible properties of lipid and structural advantages of polymer can be obtained via this system for controlled drug delivery. In the present study, cisplatin-loaded lipid-chitosan hybrid nanoparticles were formulated by the single step ionic gelation method based on ionic interaction of positively charged chitosan and negatively charged lipid. Formulations with various chitosan to lipid ratio were investigated to obtain the optimal particle size, encapsulation efficiency, and controlled release pattern. Transmission electron microscope and dynamic light scattering analysis demonstrated a size range of 181-245 nm and a zeta potential range of 20-30 mV. Compatibility among the components and the stability of formulation were demonstrated with FTIR analysis and thermal studies, respectively. The therapeutic efficacy and cellular interaction of cisplatin-loaded LPHNP were investigated using in vitro cell-based assays in A2780/ADR ovarian carcinoma cell line. Additionally, the cisplatin loaded LPHNP exhibited a low toxicity profile in rats. The in-vivo pharmacokinetics study also proved a controlled delivery of cisplatin with enhanced mean residual time and half-life. Our studies suggested that the cisplatin-loaded LPHNP being a promising platform for controlled delivery of cisplatin in cancer therapy.

Keywords: cisplatin, lipid-polymer hybrid nanoparticle, chitosan, in vitro cell line study

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Authors: Stefan Gruden, Charlott Brunmark, Bo Holmqvist, Erwin D. Brenndorfer, Martin Johansson, Jian Liu, Ying Zhao, Niklas Axen, Moustapha Hassan

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Aim: The study was designed to evaluate the ability of the calcium sulfate-based NanoZolid® drug delivery technology to locally release the epidermal growth factor (EGF) protein while maintaining its biological activity. Methods: NanoZolid-formulated EGF protein labelled with a near-infrared dye (EGF-NIR) depots or EGF-NIR dissolved in PBS were injected subcutaneously into mice bearing EGF receptor (EGFR) positive human A549 lung cancer tumors inoculated subcutaneously. The release and biodistribution of the EGF-NIR were investigated in vivo longitudinally up to 96 hours post-administration, utilizing whole-body fluorescence imaging. In order to confirm the in vivo findings, histological analysis of tumor cryosections was performed to investigate EGF-NIR fluorescent signal and EGFR expression level by immunofluorescence labelling. Results: The in vivo fluorescence imaging showed a controlled release profile of the EGF-NIR loaded in the NanoZolid depots compared to free EGF-NIR. Histological analysis of the tumors further demonstrated a prevailing distribution of EGF-NIR in regions with high levels of EGFR expression. Conclusion: Calcium sulfate based depots can be used to formulate EGF while maintaining its biological activity, e.g., receptor binding capability. This may have good clinical potential for local delivery of biomolecules to enhance treatment efficacy and minimize systemic adverse effects.

Keywords: bioresorbable, calcium sulfate, controlled release, NanoZolid

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Authors: Ian Omung'a

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Breast cancer remains to be one of the deadliest cancers for women worldwide, with the risk of developing tumors being as high as 50 percent in Sub-Saharan African countries like Kenya. With as many as 42 percent of these cases set to be diagnosed late when cancer has metastasized and or the prognosis has become terminal, Full Field Digital [FFD] Mammography remains an effective screening technique that leads to early detection where in most cases, successful interventions can be made to control or eliminate the tumors altogether. FFD Mammograms have been proven to multiply more effective when used together with Computer-Aided Detection and Diagnosis [CADe] systems, relying on algorithmic implementations of Deep Learning techniques in Computer Vision to carry out deep pattern recognition that is comparable to the level of a human radiologist and decipher whether specific areas of interest in the mammogram scan image portray abnormalities if any and whether these abnormalities are indicative of a benign or malignant tumor. Within this paper, we review emergent Deep Learning techniques that will prove relevant to the development of State-of-The-Art FFD Mammogram CADe systems. These techniques will span self-supervised learning for context-encoded occlusion, self-supervised learning for pre-processing and labeling automation, as well as the creation of a standardized large-scale mammography dataset as a benchmark for CADe systems' evaluation. Finally, comparisons are drawn between existing practices that pre-date these techniques and how the development of CADe systems that incorporate them will be different.

Keywords: breast cancer diagnosis, computer aided detection and diagnosis, deep learning, whole mammogram classfication, ultrasound classification, computer vision

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Authors: Sonal Sethi, Mukesh Yadav, Abhimanyu Gupta

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The upcoming field of radiogenomics has the potential to upgrade the role of imaging in lung cancer management by noninvasive characterization of tumor histology and genetic microenvironment. Receptor positivity like epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) genotyping are critical in lung adenocarcinoma for treatment. As conventional identification of receptor positivity is an invasive procedure, we analyzed the features on non-invasive computed tomography (CT), which predicts the receptor positivity in lung adenocarcinoma. Retrospectively, we did a comprehensive study from 77 proven lung adenocarcinoma patients with CT images, EGFR and ALK receptor genotyping, and clinical information. Total 22/77 patients were receptor-positive (15 had only EGFR mutation, 6 had ALK mutation, and 1 had both EGFR and ALK mutation). Various morphological characteristics and metastatic distribution on CT were analyzed along with the clinical information. Univariate and multivariable logistic regression analyses were used. On multivariable logistic regression analysis, we found spiculated margin, lymphangitic spread, air bronchogram, pleural effusion, and distant metastasis had a significant predictive value for receptor mutation status. On univariate analysis, air bronchogram and pleural effusion had significant individual predictive value. Conclusions: Receptor positive lung cancer has characteristic imaging features compared with nonreceptor positive lung adenocarcinoma. Since CT is routinely used in lung cancer diagnosis, we can predict the receptor positivity by a noninvasive technique and would follow a more aggressive algorithm for evaluation of distant metastases as well as for the treatment.

Keywords: lung cancer, multidisciplinary cancer care, oncologic imaging, radiobiology

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Authors: Olatokunbo Yakeem

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Human trafficking is a crime against gross violations of human rights. Trafficking in persons is a severe socio-economic dilemma that affects the national and international dimensions. Human trafficking or modern-day-slavery emanated from slavery, and it has been in existence before the 6ᵗʰ century. Today, no country is exempted from dehumanizing human beings, and as a result, it has been an international issue. The United Nations (UN) presented the International Protocol to fight human trafficking worldwide, which brought about the international definition of human trafficking. The protocol is to prevent, suppress, and punish trafficking in persons, especially women and children. The trafficking protocol has a link with transnational organised crime rather than migration. Over a hundred and fifty countries nationwide have enacted their criminal and panel code trafficking legislation from the UN trafficking protocol. Sex trafficking is the most common type of exploitation of women and children. Other forms of this crime involve exploiting vulnerable victims through forced labour, child involvement in warfare, domestic servitude, debt bondage, and organ removal for transplantation. Trafficking of women and children into sexual exploitation represents the highest form of human trafficking than other types of exploitation. Trafficking of women and children can either happen internally or across the border. It affects all kinds of people, regardless of their race, social class, culture, religion, and education levels. However, it is more of a gender-based issue against females. Furthermore, human trafficking can lead to life-threatening infections, mental disorders, lifetime trauma, and even the victim's death. The study's significance is to explore why the root causes of women and children trafficking in Nigeria are based around poverty, entrusting children in the hands of relatives and friends, corruption, globalization, weak legislation, and ignorance. The importance of this study is to establish how the national, regional, and international organisations are using the 3P’s Protection, Prevention, and Prosecution) to tackle human trafficking. The methodology approach for this study will be a qualitative paradigm. The rationale behind this selection is that the qualitative method will identify the phenomenon and interpret the findings comprehensively. The data collection will take the form of semi-structured in-depth interviews through telephone and email. The researcher will use a descriptive thematic analysis to analyse the data by using complete coding. In summary, this study aims to recommend to the Nigerian federal government to include human trafficking as a subject in their educational curriculum for early intervention to prevent children from been coerced by criminal gangs. And the research aims to find the root causes of women and children trafficking. Also, to look into the effectiveness of the strategies in place to eradicate human trafficking globally. In the same vein, the research objective is to investigate how the anti-trafficking bodies such as law enforcement and NGOs collaborate to tackle the upsurge in human trafficking.

Keywords: children, Nigeria, trafficking, women

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Authors: Yuexin Liu, Gordon B. Mills, Russell R. Broaddus, John N. Weinstein

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The lethality of endometrioid endometrial cancer (EEC) is primarily attributable to the high-stage diseases. However, there are no available biomarkers that predict EEC patient staging at the time of diagnosis. We aim to develop a predictive scheme to help in this regards. Using reverse-phase protein array expression profiles for 210 EEC cases from The Cancer Genome Atlas (TCGA), we constructed a Protein Scoring of EEC Staging (PSES) scheme for surgical stage prediction. We validated and evaluated its diagnostic potential in an independent cohort of 184 EEC cases obtained at MD Anderson Cancer Center (MDACC) using receiver operating characteristic curve analyses. Kaplan-Meier survival analysis was used to examine the association of PSES score with patient outcome, and Ingenuity pathway analysis was used to identify relevant signaling pathways. Two-sided statistical tests were used. PSES robustly distinguished high- from low-stage tumors in the TCGA cohort (area under the ROC curve [AUC]=0.74; 95% confidence interval [CI], 0.68 to 0.82) and in the validation cohort (AUC=0.67; 95% CI, 0.58 to 0.76). Even among grade 1 or 2 tumors, PSES was significantly higher in high- than in low-stage tumors in both the TCGA (P = 0.005) and MDACC (P = 0.006) cohorts. Patients with positive PSES score had significantly shorter progression-free survival than those with negative PSES in the TCGA (hazard ratio [HR], 2.033; 95% CI, 1.031 to 3.809; P = 0.04) and validation (HR, 3.306; 95% CI, 1.836 to 9.436; P = 0.0007) cohorts. The ErbB signaling pathway was most significantly enriched in the PSES proteins and downregulated in high-stage tumors. PSES may provide clinically useful prediction of high-risk tumors and offer new insights into tumor biology in EEC.

Keywords: endometrial carcinoma, protein, protein scoring of EEC staging (PSES), stage

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Authors: Sylwia K. Naliwajko, Renata Markiewicz-Zukowska, Justyna Moskwa, Krystyna Gromkowska-Kepka, Konrad Mielcarek, Patryk Nowakowski, Katarzyna Socha, Anna Puscion-Jakubik, Maria H. Borawska

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Glioblastoma (grade IV WHO) is a rapidly progressive brain tumor with very high morbidity and mortality. The vast malignant gliomas are not curable despite the therapy (surgical, radiotherapy, chemotherapy) and patients seek alternative or complementary treatments. Patients often use cannabidiol (CBD) oil as an alternative therapy of glioblastoma. CBD is one of the cannabinoids, an active component of Cannabis sativa. THC (Δ9-tetrahydrocannabinol) can be addictive, and in many countries CBD oil without THC ( < 0,2%) is available. Propolis produced by bees from the resin collected from trees has antiglioma properties in vitro and can be used as a supplement in complementary therapy of gliomas. The aim of this study was to examine the influence of extract from CBD oil in combination with propolis extract on two glioblastoma cell lines. The MTT (Thiazolyl Blue Tetrazolium Bromide) test was used to determine the influence of CBD oil extract and polish propolis extract (PPE) on the viability of glioblastoma cell lines – U87MG and LN18. The cells were incubated (24, 48 and 72 h) with CBD oil extract and PPE. CBD extract was used in concentration 1, 1.5 and 3 µM and PPE in 30 µg/mL. The data were presented compared to the control. The statistical analysis was performed using Statistica v. 13.0 software. CBD oil extract in concentrations 1, 1.5 and 3 µM did not inhibit the viability of U87MG and LN18 cells (viability more than 90% cells compared to the control). There was no dose-response viability, and IC50 value was not recognized. PPE in the concentration of 30 µg/mL time-dependently inhibited the viability of U87MG and LN18 cell line (after 48 h the viability as a percent of the control was 59,7±6% and 57,8±7%, respectively). In a combination of CBD with PPE, the viability of the treated cells was similar to PPE used alone (58,2±7% and 56,5±9%, respectively). CBD oil extract did not show anti-glioma activity and in combination with PPE did not change the activity of PPE.

Keywords: anticancer, cannabidiol, cell line, glioblastoma

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Authors: Awais Naeem, Osama Shakeel, Aamir Ali Syed, Shahid Khattak

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Introduction: Laparoscopic right hemicolectomy is an advanced cancer surgery in today's era. The aim of this study was to evaluate the surgical and initial oncological outcomes after curative, laparoscopic resection of right sided colonic tumors. Also to compare our results with those of previous randomized trials. Methods And Procedures: We retrospectively analyzed the medical record files of all the patients who presented to our hospital with the diagnosis of right sided colon carcinoma from January 2012 to December 2017 and underwent laparoscopic right hemicolectomy. Demographics, operative findings and histopathological reports were all recorded on a preformed data sheet. All the analysis was performed on SPSS 20. Results: Total of 48 patients were included. There were 37 male and 11 female patients with mean age of 49.7 (range from 25 – 82). Mean hospital stay was 8.25 ± 3.17 days. Blood loss was 80mls and operative mean time was 240 minutes. Eighteen patients had extended right hemicolectomy. Median length of the specimen retrieved was 31cm (range, 14-59cm). Mean size of tumor was 6.44cm + 2.53. Total number of lymph nodes removed was 20.5 + 8.3. All had R0 resection. Post-operatively 2 patients had pelvic collection and there was no 30 day mortality. In 33 patients there was T3 disease, 5 had T2 and 10 had T4 disease. There was distant recurrence in 4 patients with peritoneal metastasis in 3 and liver metastasis in 1 patient. Forty-six patients are still alive and 44 are disease free. The mean follow-up period was 25.31 (12 to 60) months. Conclusion: Our early experience with Laparascopic Right hemicolectomy as a safe and oncologically feasible surgical option. We attained comparable surgical results with curative intent.

Keywords: right hemicolectomy, right sided colonic tumors, laparoscopic, curative intent

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Authors: Nathalie Baeza-Kallee, Raphaël Bergès, Victoria Hein, Stéphanie Cabaret, Jeremy Garcia, Abigaëlle Gros, Emeline Tabouret, Aurélie Tchoghandjian, Carole Colin, Dominique Figarella-Branger

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Glioblastoma (GBM) contains cancer stem cells that are resistant to treatment. GBM cancer stem cell expresses glycolipids recognized by the A2B5 antibody. A2B5, induced by the enzyme ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyl transferase 3 (ST8Sia3), plays a crucial role in the proliferation, migration, clonogenicity, and tumorigenesis of GBM cancer stem cells. Our aim was to characterize the resulting effects of neuraminidase that remove A2B5 in order to target GBM cancer stem cells. To this end, we set up a GBM organotypic slice model; quantified A2B5 expression by flow cytometry in U87-MG, U87-ST8Sia3, and GBM cancer stem cell lines, treated or not by neuraminidase; performed RNAseq and DNA methylation profiling; and analyzed the ganglioside expression by liquid chromatography-mass spectrometry in these cell lines, treated or not with neuraminidase. Results demonstrated that neuraminidase decreased A2B5 expression, tumor size, and regrowth after surgical removal in the organotypic slice model but did not induce a distinct transcriptomic or epigenetic signature in GBM CSC lines. RNAseq analysis revealed that OLIG2, CHI3L1, TIMP3, TNFAIP2, and TNFAIP6 transcripts were significantly overexpressed in U87-ST8Sia3 compared to U87-MG. RT-qPCR confirmed these results and demonstrated that neuraminidase decreased gene expression in GBM cancer stem cell lines. Moreover, neuraminidase drastically reduced ganglioside expression in GBM cancer stem cell lines. Neuraminidase, by its pleiotropic action, is an attractive local treatment against GBM.

Keywords: cancer stem cell, ganglioside, glioblastoma, targeted treatment

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Authors: Ahmed M. Kabel, Maaly A. Abd Elmaaboud

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Scleroderma is one of the connective tissue disorders characterized by skin and systemic fibrosis. Its pathogenesis involves multiple interrelated processes of autoimmunity, vasculopathy, inflammation, and oxidative stress. This study was a trial to explore the possible ameliorative effects of sodium valproate on an experimental model of skin fibrosis induced by bleomycin. Forty male BALB/c mice were divided into four equal groups as follows: control group; bleomycin group; bleomycin + sodium valproate group, and sodium valproate group. Mice were assessed for their body weight every four days throughout the whole study. Skin tissues were used to evaluate the oxidative stress parameters, transforming growth factor beta 1 (TGF-β1), tumor necrosis factor alpha (TNF-α), interleukin 15, and mammalian target of rapamycin (mTOR). Skin fibrosis was evaluated by measuring dermal thickness and staining the skin tissues with Masson trichrome stain. Also, the skin tissues were immunostained with alpha smooth muscle actin (α-SMA). Administration of sodium valproate to bleomycin-treated mice resulted in the restoration of the body weight with a significant decrease in the dermal thickness, amelioration of oxidative stress, suppression of TGF-β1 and mTOR expression, and significant reduction of the percentage of α-SMA immunostaining and the proinflammatory cytokine levels compared to mice treated with bleomycin alone. In conclusion, sodium valproate has an antifibrotic effect on skin fibrosis which may represent a beneficial therapeutic modality for the management of scleroderma.

Keywords: scleroderma, bleomycin, sodium valproate, skin fibrosis

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Authors: Meral Tuncbilek, Duygu Sac, Irem Durmaz, Rengul Cetin Atalay

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Nucleoside analogs are a pharmacologically diverse family that includes cytotoxic compounds, antiviral agents, and immunosuppressive molecules. Purine nucleoside derivatives such as fludarabine, cladribine, and pentostatin are significant drugs used in chemotherapy for the treatment of solid tumors and hematological malignancies. In this study, we synthesized novel purine ribonucleoside analogs containing a 4-(4-substituted phenylsulfonyl) piperazine in the substituent at N6- and O-substituted sulfonyl group at 5’-position as putative cytotoxic agents. The newly obtained compounds were then characterized for their cytotoxicity in human cancer cell lines. The 5’, 6-disubstituted 9-(β-D-ribofuranosyl)purine derivatives (44-67) were readily obtained from commercially available inosine in seven steps in very cost effective synthesis approach. The newly synthesized compounds were first evaluated for their anti-tumor activities against human liver (Huh7), colon (HCT116) and breast (MCF7) carcinoma cell lines. The IC50 values were in micromolar concentrations with 5’, 6-disubstituted purine nucleoside derivatives. Time-dependent IC50 values for each molecule were also calculated in comparison with known cytotoxic agents Camptothecin (CPT), 5-Fluorouracil (5-FU), Cladribine, Pentostatine and Fludarabine. N6-(4-trifluoromethyl phenyl) / N6-(4-bromophenyl) and 5’-O-(4-methoxybenzene sulfonyl) / 5’-O-(benzenesulfonyl) derivatives 54, 64 displayed the best cytotoxic activity with IC50 values of 8.8, 7 µM against MCF7 cell line. The N6-(4-methylphenyl) analog 50 was also very active (IC50= 10.7 μM) against HCT116 cell line. Furthermore, compound 64 had a better cytotoxic activity than the known cell growth inhibitors 5-FU and Fludarabine on Huh7 (1.5 vs 30.7, 29.9 μM for 5-FU and Fludarabine).

Keywords: cytotoxic activity, Huh7, HCT116, MCF7, nucleoside, synthesis

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Authors: Dong-Gyu Leem, Ji-Sun Shin, Sang Yoon Choi, Kyung-Tae Lee

Abstract:

In this study, we focused on the anti-proliferative effects of panaxydol, a C17 polyacetylenic compound derived from Panax ginseng roots, against various human cancer cells. We treated with panaxydol to various cancer cells and panaxydol treatment was found to significantly inhibit the proliferation of human lung cancer cells (A549) and human pancreatic cancer cells (AsPC-1 and MIA PaCa-2), of which AsPC-1 cells were most sensitive to its treatment. DNA flow cytometric analysis indicated that panaxydol blocked cell cycle progression at the G1 phase in A549 cells, which accompanied by a parallel reduction of protein expression of cyclin-dependent kinase (CDK) 2, CDK4, CDK6, cyclin D1 and cyclin E. CDK inhibitors (CDKIs), such as p21CIP1/WAF1 and p27KIP1, were gradually upregulated after panaxydol treatment at the protein levels. Furthermore, panaxydol induced the activation of p53 in A549 cells. In addition, panaxydol also induced apoptosis of AsPC-1 and MIA PaCa-2 cells, as shown by accumulation of subG1 and apoptotic cell populations. Panaxydol triggered the activation of caspase-3, -8, -9 and the cleavage of poly (ADP-ribose) polymerase (PARP). Reduction of mitochondrial transmembrane potential by panaxydol was determined by staining with dihexyloxacarbocyanine iodide. Furthermore, panaxydol suppressed the levels of anti-apoptotic proteins, XIAP and Bcl-2, and increased the levels of proapoptotic proteins, Bax and Bad. In addition, panaxydol inhibited the activation of Akt and extracellular signal-regulated kinase (ERK) and activated the p38 mitogen-activated protein kinase kinase (MAPK). Our results suggest that panaxydol is an anti-tumor compound that causes p53-mediated cell cycle arrest and apoptosis via mitochondrial apoptotic pathway in various cancer cells.

Keywords: apoptosis, cancer, G1 arrest, panaxydol

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Authors: Gehan ElAkabawy

Abstract:

Background: Diabetes mellitus causes severe deteriorations of almost all the organs and systems of the body, as well as significant damage to the oral cavity. The oral changes are mainly related to salivary glands dysfunction characterized by hyposalivation and xerostomia, which significantly reduce diabetic patients’ quality of life. Human dental pulp stem cells represent a promising source for cell-based therapies, owing to their easy, minimally invasive surgical access, and high proliferative capacity. It was reported that the trophic support mediated by dental pulp stem cells can rescue the functional and structural alterations of damaged salivary glands. However, potential differentiation and paracrine effects of human dental pulp stem cells in diabetic-induced parotid gland damage have not been previously investigated. Our study aimed to investigate the therapeutic effects of intravenous transplantation of human dental pulp stem cells (hDPSCs) on parotid gland injury in a rat model of streptozotocin (STZ)-induced type 1 diabetes. Methods: Thirty Sprague-Dawley male rats were randomly categorised into three groups: control, diabetic (STZ), and transplanted (STZ+hDPSCs). hDPSCs or vehicle was injected into the tail vein 7 days after STZ injection. The fasting blood glucose levels were monitored weekly. A glucose tolerance test was performed, and the parotid gland weight, salivary flow rate, oxidative stress indices, parotid gland histology, and caspase-3, vascular endothelial growth factor (VEGF), and proliferating cell nuclear antigen (PCNA) expression in parotid tissues were assessed 28 days post-transplantation. Results: Transplantation of hDPSCs downregulated blood glucose, improved the salivary flow rate, and reduced oxidative stress. The cells migrated to, survived, and differentiated into acinar, ductal, and myoepithelial cells in the STZ-injured parotid gland. Moreover, they downregulated the expression of caspase-3 and upregulated the expression of VEGF and PCNA, likely exerting pro-angiogenetic and antiapoptotic effects and promoting endogenous regeneration. In addition, the transplanted cells enhanced the parotid nitric oxide (NO) -tetrahydrobiopterin (BH4) pathway. Conclusions: Our results show that hDPSCs can migrate to and survive within the STZ-injured parotid gland, where they prevent its functional and morphological damage by restoring normal glucose levels, differentiating into parotid cell populations, and stimulating paracrine-mediated regeneration. Thus, hDPSCs may have therapeutic potential in the treatment of diabetes-induced parotid gland injury.

Keywords: dental pulp stem cells, diabetes, streptozotocin, parotid gland

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Authors: Abdelkrim Belhaoua, Jean-Pierre Radoux, Mariana Kuras, Vincent Récamier, Martial Piotto, Karim Elbayed, François Proust, Izzie Namer

Abstract:

This paper proposes an augmented reality system dedicated to neurosurgery in order to assist the surgeon during an operation. This work is part of the ExtempoRMN project (Funded by Bpifrance) which aims at analyzing during a surgical operation the metabolic content of tumoral brain biopsy specimens by HRMAS NMR. Patients affected with a brain tumor (gliomas) frequently need to undergo an operation in order to remove the tumoral mass. During the operation, the neurosurgeon removes biopsy specimens using image-guided surgery. The biopsy specimens removed are then sent for HRMAS NMR analysis in order to obtain a better diagnosis and prognosis. Image-guided refers to the use of MRI images and a computer to precisely locate and target a lesion (abnormal tissue) within the brain. This is performed using preoperative MRI images and the BrainLab neuro-navigation system. With the patient MRI images loaded on the Brainlab Cranial neuro-navigation system in the operating theater, surgeons can better identify their approach before making an incision. The Brainlab neuro-navigation tool tracks in real time the position of the instruments and displays their position on the patient MRI data. The results of the biopsy analysis by 1H HRMAS NMR are then sent back to the operating theater and superimposed on the 3D localization system directly on the MRI images. The method we have developed to communicate between the HRMAS NMR analysis software and Brainlab makes use of a combination of C++, VTK and the Insight Toolkit using OpenIGTLink protocol.

Keywords: neuro-navigation, augmented reality, biopsy, BrainLab, HR-MAS NMR

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Authors: Till Gramberg, Erwin Gross, Christoph Birenbaum

Abstract:

This paper presents the approach of the Easy2IoT research project. Easy2IoT aims to enable companies in the prefabrication sheet metal and sheet metal processing industry to enter the Industrial Internet of Things (IIoT) with a low-threshold and cost-effective approach. It focuses on the development of physical hardware and software to easily capture machine activities from on a sawing machine, benefiting various stakeholders in the SME value chain, including machine operators, tool manufacturers and service providers. The methodological approach of Easy2IoT includes an in-depth requirements analysis and customer interviews with stakeholders along the value chain. Based on these insights, actions, requirements and potential solutions for smart services are derived. The focus is on providing actionable recommendations, competencies and easy integration through no-/low-code applications to facilitate implementation and connectivity within production networks. At the core of the project is a novel, non-invasive measurement and analysis system that can be easily deployed and made IIoT-ready. This system collects machine data without interfering with the machines themselves. It does this by non-invasively measuring the tension on a sawing machine. The collected data is then connected and analyzed using artificial intelligence (AI) to provide smart services through a platform-based application. Three Smart Services are being developed within Easy2IoT to provide immediate benefits to users: Wear part and product material condition monitoring and predictive maintenance for sawing processes. The non-invasive measurement system enables the monitoring of tool wear, such as saw blades, and the quality of consumables and materials. Service providers and machine operators can use this data to optimize maintenance and reduce downtime and material waste. Optimize Overall Equipment Effectiveness (OEE) by monitoring machine activity. The non-invasive system tracks machining times, setup times and downtime to identify opportunities for OEE improvement and reduce unplanned machine downtime. Estimate CO2 emissions for connected machines. CO2 emissions are calculated for the entire life of the machine and for individual production steps based on captured power consumption data. This information supports energy management and product development decisions. The key to Easy2IoT is its modular and easy-to-use design. The non-invasive measurement system is universally applicable and does not require specialized knowledge to install. The platform application allows easy integration of various smart services and provides a self-service portal for activation and management. Innovative business models will also be developed to promote the sustainable use of the collected machine activity data. The project addresses the digitalization gap between large enterprises and SME. Easy2IoT provides SME with a concrete toolkit for IIoT adoption, facilitating the digital transformation of smaller companies, e.g. through retrofitting of existing machines.

Keywords: smart services, IIoT, IIoT-platform, industrie 4.0, big data

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Authors: D. Bhowmik, Y. Tian, Q. Yin, F. Zhu

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Cyclic GMP-AMP synthase (cGAS), recognises cytoplasmic double-stranded DNA (dsDNA), indicative of bacterial and viral infections, as well as the leakage of self DNA by cellular dysfunction and stresses, to elicit the host's immune responses. Viruses also have developed numerous strategies to antagonize the cGAS-STING pathway. Kaposi's sarcoma-associated herpesvirus (KSHV) is a human DNA tumor virus that is the causative agent of Kaposi’s sarcoma and several other malignancies. To persist in the host, consequently causing diseases, KSHV must overcome the host innate immune responses, including the cGAS-STING DNA sensing pathway. We already found that ORF52 or KicGAS (KSHV inhibitor of cGAS), an abundant and basic gamma herpesvirus-conserved tegument protein, directly inhibits cGAS enzymatic activity. To better understand the mechanism, we have performed the biochemical and structural characterization of full-length KicGAS and various mutants in regarding binding to DNA. We observed that KicGAS is capable of self-association and identified the critical residues involved in the oligomerization process. We also characterized the DNA-binding of KicGAS and found that KicGAS cooperatively oligomerizes along the length of the double stranded DNA, the highly conserved basic residues at the c-terminal disordered region are crucial for DNA recognition. Deficiency in oligomerization also affects DNA binding. Thus DNA binding by KicGAS sequesters DNA and prevents it from being detected by cGAS, consequently inhibiting cGAS activation. KicGAS homologues also inhibit cGAS efficiently, suggesting inhibition of cGAS is evolutionarily conserved mechanism among gamma herpesvirus. These results highlight the important viral strategy to evade this innate immune sensor.

Keywords: Kaposi's sarcoma-associated herpesvirus, KSHV, cGAS, DNA binding, inhibition

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Authors: A. Monika, Manu Sharma, Hong Boo Lee, Richa Dhingra, Neelima Dhingra

Abstract:

Nuclear factor-κappa B serve as a molecular lynchpin that links persistent infections and chronic inflammation to increased cancer risk. Inflammation has been recognized as a hallmark and cause of cancer. Natural products present a privileged source of inspiration for chemical probe and drug design. Herbal remedies were the first medicines used by humans due to the many pharmacologically active secondary metabolites produced by plants. Some of the metabolites like Lantadene (pentacyclic triterpenoids) from the weed Lantana camara has been known to inhibit cell division and showed anti-antitumor potential. The C-3 aromatic esters of lantadenes were synthesized, characterized and evaluated for cytotoxicity and inhibitory potential against Tumor necrosis factor alpha-induced activation of Nuclear factor-κappa B in lung cancer cell line A549. The 3-methoxybenzoyloxy substituted lead analogue inhibited kinase activity of the inhibitor of nuclear factor-kappa B kinase in a single-digit micromolar concentration. At the same time, the lead compound showed promising cytotoxicity against A549 lung cancer cells with IC50 ( half maximal inhibitory concentration) of 0.98l µM. Further, molecular docking of 3-methoxybenzoyloxy substituted analogue against Inhibitor of nuclear factor-kappa B kinase (Protein data bank ID: 3QA8) showed hydrogen bonding interaction involving oxygen atom of 3-methoxybenzoyloxy with the Arginine-31 and Glutamine-110. Encouraging results indicate the Lantadene’s potential to be developed as anticancer agents.

Keywords: anticancer, lantadenes, pentacyclic triterpenoids, weed

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Authors: Cigdem Karaaslan, Yalcin Duydu, Aylin Ustundag, Can Ozgur Yalcın, Hakan Goker

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Benzazole nucleus is found in the structure of many compounds as anticancer agents. Bendamustine (Alkylating agent), Nocodazole (Mitotic inhibitor), Veliparib (PARP inhibitor), Glasdegib (SMO inhibitor) are clinically used as anticancer therapeutics which bearing benzimidazole moiety. Based on the principle of bioisosterism in the present work, 23 compounds belonging to 2-(3,4-dimethoxy-phenyl) benzazoles and imidazopyridine series were synthesized and evaluated for their anticancer activities. N-(5-Chloro-2-hydroxyphenyl)-3,4-dimethoxybenzamide, was obtained by the amidation of 2-hydroxy-5-chloroaniline with 3,4-dimethoxybenzoic acid by using 1,1'-carbonyldiimidazole. Cyclization of benzamide derivative to benzoxazole, was achieved by p-toluenesulfonic acid. Other 1H-benz (or pyrido) azoles were prepared by the reaction between 2-aminothiophenol, o-phenylenediamine, o-pyridinediamine with sodium metabisulfite adduct of 3,4-dimethoxybenzaldehyde. The NMR assignments of the dimethoxy groups were established by the Nuclear Overhauser Effect Spectroscopy. A compound named, 5(4),7(6)-Dichloro-2-(3,4-dimethoxy) phenyl-1H-benzimidazole, bearing two chlorine atoms at the 5(4) and 7(6) positions of the benzene moiety of benzimidazole was found the most potent analogue, against A549 cells with the GI50 value of 1.5 µg/mL. In addition, 2-(3,4-Dimethoxyphenyl)-5,6-dimethyl-1H-benzimi-dazole showed remarkable cell growth inhibition against MCF-7 and HeLa cells with the GI₅₀ values of 7 and 5.5 µg/mL, respectively. It could be concluded that introduction of di-chloro atoms at the phenyl ring of 2-(3,4-dimethoxyphenyl)-1H-benzimidazoles increase significant cytotoxicity to selected human tumor cell lines in comparison to other all benzazoles synthesized in this study. Unsubstituted 2-(3,4-dimethoxyphenyl) imidazopyridines also gave the good inhibitory profile against A549 and HeLa cells.

Keywords: 3, 4-Dimethoxyphenyl, 1H-benzimidazole, benzazole, imidazopyridine

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Authors: Debasmita Mukhopadhyay, Manika Pal Bhadra

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MiRNAs contribute to oncogenesis either as tumor suppressors or oncogenes. Hence, discovery of miRNA-based therapeutics are imperative to ameliorate cancer. Modulation of miRNA maturation is accomplished via several therapeutic agents, including small molecules and oligonucleotides. Due to the attractive pharmacokinetic properties of small molecules over oligonucleotides, we set to identify small molecule inhibitors of a metastasis-inducing microRNA. Cytotoxicity profile of aza-flavanone C1 was analyzed in a panel of breast cancer cells employing the NCI-60 screen protocols. Flow cytometry, immunofluorescence and western blotting of apoptotic or EMT markers were performed to analyze the effect of C1. A dual luciferase assay unequivocally suggested that C1 repressed endogenous miR-10b in MDA-MB-231 cells. A derivative of aza-flavanone C1 is shown as a strong inhibitor miR-10b. Blockade of miR-10b by C1 resulted in decreased expression of miR-10b targets in an aggressive breast cancer cell line model, MDA-MB-231. Abrogation of TWIST1, an EMT-inducing transcription factor also contributed to C1 mediated apoptosis. Moreover C1 exhibited a specific and selective down-regulation of miR-10b and did not function as a general inhibitor of miRNA biogenesis or other oncomiRs of breast carcinoma. Aza-flavanone congener C1 functions as a potent inhibitor of the metastasis-inducing microRNA, miR-10b. Our present study provides evidence for targeting metastasis-inducing microRNA, miR-10b with a derivative of Aza-flavanone. Better pharmacokinetic properties of small molecules place them as attractive agents compared to nucleic acids based therapies to target miRNA. Further work, in generating analogues based on aza-flavanone moieties will significantly improve the affinity of the small molecules to bind miR-10b. Finally, it is imperative to develop small molecules as novel miRNA-therapeutics in the fight against cancer.

Keywords: breast cancer, microRNA, metastasis, EMT

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Authors: Alireza Barari, Ahmad Abdi

Abstract:

Introduction: Plyometric training (PT) is popular among individuals involved in dynamic sports, and is executed with a goal to improve muscular performance. Cytokines are considered as immunoregulatory molecules for regulation of immune function and other body responses. In addition, the pro-inflammatory cytokines, TNF-α andIL-1β, have been reported to be increased during and after exercises. If some of the cytokines which cause responses such as inflammation of cells in skeletal muscles, with manipulating of training program or optimizing nutrition, it can be avoided or limited from those injuries caused by cytokines release. Its shows that mistletoe extracts show immune-modulating effects. Materials and methods: present study was to investigate the effect of six weeks PT with or without mistletoe supplementation (MS)(10 mg/kg) on cytokine responses and performance in male basketball players. This study is semi-experimental. Statistic society of this study was basketball player’s male students of Mahmoud Abad city. Statistic samples are concluded of 32 basketball players with an age range of 14–17 years was selected from randomly. Selection of samples in four groups of 8 individuals Participants were randomly assigned to either an experimental group (E, n=16) that performed plyometric exercises with (n=8) or without (n=8) MS, or a control group that rested (C, n=16) with (n=8) or without (n=8) MS. Plants were collected in June from the Mazandaran forest in north of Iran. Then they dried in exposure to air without any exposition to sunlight, on a clean textile. For better drying the plants were high and down until they lost their water. Each subject consumed 10 mg/kg/day of extract for six weeks of intervention. Pre and post-testing was performed in the afternoon of the same day. Blood samples (10 ml) were collected from the intermediate cubital vein of the subjects. Serum concentration of IL-1β and TNF-α were measured by ELISA method. Data analysis was performed using pretest to posttest changes that assessed by t-test for paired samples. After the last plyometric training program, the second blood samples were in the next day. Group differences at baseline were evaluated using One-way ANOVA (post-hock Tukey) test is used for analysis and comparison of three group’s variables. Results: PT with or without MS improved the one repetition maximum leg and chest press, Sargeant test and power in RAST (P < 0.05). However there were no statistically significant differences between groups in Vo2max measures (P > 0.05). PT resulted in a significant increase in plasma IL-1β concentration from 1.08±0.4 mg/ml in pre-training to 1.68±0.18 mg/ml in post-training (P=0.006). While the MS significantly decreased the training-induced increment of IL-1β (P=0.007). In contrast, neither PT nor MS had any effect on TNF-α levels (P > 0.05). Discussion: The results of this investigation indicate that PT improved muscular performance and increases the IL-1β concentration. Increasing of IL-1β after exercise in damaged skeletal muscle has shown of the role of this cytokine in inflammation processes and damaged skeletal muscle repair. However mistletoe supplementation ameliorates the increment of IL-1β levels, indicating the beneficial effect of mistletoe on immune response following plyometric training.

Keywords: mistletoe supplementation, training, IL-1β, TNF-α

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Authors: Kantha Siddhanth Gujjari, Shaani Singhal, Robert Andrew Danks, Adrian Praeger

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Background: Trigeminal neuralgia (TN) is a heterogenous pain syndrome characterised by short paroxysms of lancinating facial pain in the distribution of the trigeminal nerve, often triggered by usually innocuous stimuli. TN has a low prevalence of less than 0.1%, of which 80% to 90% is caused by compression of the trigeminal nerve from an adjacent artery or vein. The root entry zone of the trigeminal nerve is most sensitive to neurovascular conflict (NVC), causing dysmyelination. Whilst microvascular decompression (MVD) is an effective treatment for TN with NVC, all patients do not achieve long-term pain relief. Pre-operative scoring systems by Panczykowski and Hardaway have been proposed but have not been externally validated. These pre-operative scoring systems are composite scores calculated according to a subtype of TN, presence and degree of neurovascular conflict, and response to medical treatments. There is discordance in the assessment of NVC identified on pre-operative magnetic resonance imaging (MRI) between neurosurgeons and radiologists. To our best knowledge, the prognostic impact for MVD of this difference of interpretation has not previously been investigated in the form of a composite scoring system such as those suggested by Panczykowski and Hardaway. Aims: This study aims to identify prognostic factors and externally validate the proposed scoring systems by Panczykowski and Hardaway for TN. A secondary aim is to investigate the prognostic difference between a neurosurgeon's interpretation of NVC on MRI compared with a radiologist’s. Methods: This retrospective cohort study included 95 patients who underwent de novo MVD in a single neurosurgical unit in Melbourne. Data was recorded from patients’ hospital records and neurosurgeon’s correspondence from perioperative clinic reviews. Patient demographics, type of TN, distribution of TN, response to carbamazepine, neurosurgeon, and radiologist interpretation of NVC on MRI, were clearly described prospectively and preoperatively in the correspondence. Scoring systems published by Panczykowski et al. and Hardaway et al. were used to determine composite scores, which were compared with the recurrence of TN recorded during follow-up over 1-year. Categorical data analysed using Pearson chi-square testing. Independent numerical and nominal data analysed with logistical regression. Results: Logistical regression showed that a Panczykowski composite score of greater than 3 points was associated with a higher likelihood of pain-free outcome 1-year post-MVD with an OR 1.81 (95%CI 1.41-2.61, p=0.032). The composite score using neurosurgeon’s impression of NVC had an OR 2.96 (95%CI 2.28-3.31, p=0.048). A Hardaway composite score of greater than 2 points was associated with a higher likelihood of pain-free outcome 1 year post-MVD with an OR 3.41 (95%CI 2.58-4.37, p=0.028). The composite score using neurosurgeon’s impression of NVC had an OR 3.96 (95%CI 3.01-4.65, p=0.042). Conclusion: Composite scores developed by Panczykowski and Hardaway were validated for the prediction of response to MVD in TN. A composite score based on the neurosurgeon’s interpretation of NVC on MRI, when compared with the radiologist’s had a greater correlation with pain-free outcomes 1 year post-MVD.

Keywords: de novo microvascular decompression, neurovascular conflict, prognosis, trigeminal neuralgia

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