Search results for: primary tumor

Authors: Niklas Ravn-Boess, Nainita Bhowmick, Takamitsu Hattori, Shohei Koide, Christopher Park, Dimitris Placantonakis

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Background: Glioblastoma (GBM) is the most common and deadly primary brain malignancy in adults. Tumor propagation, brain invasion, and resistance to therapy critically depend on GBM stem-like cells (GSCs); however, the mechanisms that regulate GSC self-renewal are incompletely understood. Given the aggressiveness and poor prognosis of GBM, it is imperative to find biomarkers that could also translate into novel drug targets. Along these lines, we have identified a cell surface antigen, CD97 (ADGRE5), an adhesion G protein-coupled receptor (GPCR), that is expressed on GBM cells but is absent from non-neoplastic brain tissue. CD97 has been shown to promote invasiveness, angiogenesis, and migration in several human cancers, but its frequency of expression and functional role in regulating GBM growth and survival, and its potential as a therapeutic target has not been investigated. Design: We assessed CD97 mRNA and protein expression in patient derived GBM samples and cell lines using publicly available RNA-sequencing datasets and flow cytometry, respectively. To assess CD97 function, we generated shRNA lentiviral constructs that target a sequence in the CD97 extracellular domain (ECD). A scrambled shRNA (scr) with no predicted targets in the genome was used as a control. We evaluated CD97 shRNA lentivirally transduced GBM cells for Ki67, Annexin V, and DAPI. We also tested CD97 KD cells for their ability to self-renew using clonogenic tumorsphere formation assays. Further, we utilized synthetic Abs (sAbs) generated against the ECD of CD97 to test for potential antitumor effects using patient-derived GBM cell lines. Results: CD97 mRNA expression was expressed at high levels in all GBM samples available in the TCGA cohort. We found high levels of surface CD97 protein expression in 6/6 patient-derived GBM cell cultures, but not human neural stem cells. Flow cytometry confirmed downregulation of CD97 in CD97 shRNA lentivirally transduced cells. CD97 KD induced a significant reduction in cell growth in 3 independent GBM cell lines representing mesenchymal and proneural subtypes, which was accompanied by reduced (~20%) Ki67 staining and increased (~30%) apoptosis. Incubation of GBM cells with sAbs (20 ug/ ml) against the ECD of CD97 for 3 days induced GSC differentiation, as determined by the expression of GFAP and Tubulin. Using three unique GBM patient derived cultures, we found that CD97 KD attenuated the ability of GBM cells to initiate sphere formation by over 300 fold, consistent with an impairment in GSC self-renewal. Conclusion: Loss of CD97 expression in patient-derived GBM cells markedly decreases proliferation, induces cell death, and reduces tumorsphere formation. sAbs against the ECD of CD97 reduce tumorsphere formation, recapitulating the phenotype of CD97 KD, suggesting that sAbs that inhibit CD97 function exhibit anti-tumor activity. Collectively, these findings indicate that CD97 is necessary for the proliferation and survival of human GBM cells and identify CD97 as a promising therapeutically targetable vulnerability in GBM.

Keywords: adhesion GPCR, CD97, GBM stem cell, glioblastoma

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Authors: Robin L. Rohrer

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Introduction: Pre-natal or early childhood exposure to the medical radiation used in diagnosis or treatment is an identified risk for childhood cancers but can be difficult to document. The author developed a family questionnaire/interview form to identify possible exposures. Aims: This retrospective study examines pre-natal and early childhood medical radiation exposure in a cohort of children diagnosed with a solid tumor including brain tumors from 1985-2015 at the Children’s Hospital of Pittsburgh (CHP). The hospital is a tri-state regional referral center which treats about 150-180 new cases of cancer in children per year. About 70% are diagnosed with a solid tumor. Methods: Each consented family so far (approximately 50% of the cohort) has been interviewed in person or by the phone call. Medical staff and psycho- social staff referred patient families for the interview with the author. Results: Among the families interviewed to date at least one medical radiation exposure has been identified (pre-conception, pre-natal or early childhood) in over 70% of diagnosed children. These exposures have included pre-conception sinus or chest CT or X-ray in either parent, sinus CT or X-ray in the mother or diagnostic radiation of chest or abdomen in children. Conclusions: Exposures to medical radiation for a child later diagnosed with cancer may occur at several critical junctures. These exposures may well contribute to a ‘perfect storm’ in the still elusive causes of childhood cancer. The author plans to expand the study from 1975 to present to hopefully further document these junctures.

Keywords: pediatric, solid tumors, medical radiation, cancer

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Authors: Savita Dixit

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Rutin is the bioactive flavonoid isolated from the straw part of Triticum aestivum and possess various pharmacological applications. The aim of this study is to evaluate the chemopreventive potential of rutin in an experimental skin carcinogenesis mice model system. Skin tumor was induced by topical application of 7, 12-dimethyl benz(a) anthracene (DMBA) and promoted by croton oil in Swiss albino mice. To assess the chemopreventive potential of rutin, it was orally administered at a concentration of (200 mg/kg and 400 mg/kg body weight) continued three times weekly for 16th weeks. The development of skin carcinogenesis was assessed by histopathological analysis. Reductions in tumor size and cumulative number of papillomas were seen due to rutin treatment. Average latent period was significantly increased as compared to carcinogen-treated control. Rutin produced a significant decrease in the activity of serum enzyme serum glutamate oxalate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP) and bilirubin when compared with the control. They significantly increased the levels of enzyme involved in oxidative stress glutathione (GSH), superoxide dismutase (SOD) and catalase. The elevated level of lipid peroxidase in the control group was significantly inhibited by rutin administration. The results of the present study suggest the chemopreventive effect of rutin in DMBA and croton oil-induced skin carcinogenesis in swiss albino mice and one of the probable reasons would be its antioxidant potential.

Keywords: chemoprevention, papilloma, rutin, skin carcinogenesis

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Authors: Nilofar Mohammadi Ahvazi, Somayeh Ansari, Mohammad Hossein Haghighizadeh, Zahra Abbaspoor

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Introduction: Dysmenorrhea is one of the common causes of decreased efficiency at work, education and decreased quality of life of women. The aim of this study was to compare virtual and face-to-face training programs in reducing pain and improving the quality of life of female students with primary dysmenorrhea in Ahvaz. Methods: In this quasi-experimental study, 112 female students living in the dormitories of Ahvaz University of Medical Sciences with moderate to severe primary dysmenorrhea were divided into two face-to-face and virtual groups using blocks of size 4. The educational intervention was carried out in two groups at a specific hour before the start of the first menstrual cycle. Data were collected with the help of a quality-of-life questionnaire (Sf-36), visual analog scale (VAS), and McGill questionnaire and were analyzed using descriptive and analytical tests with the help of SPSS version 25 software. Findings: The average age of the research subjects was 25.93±2.00, and the average duration of dysmenorrhea in each period was 2.49 days. There was no statistically significant difference in the quality of life of the students before the intervention, but after the educational intervention, a statistically significant difference was found between the two groups in terms of the quality of life and its dimensions (p<0.001). They were the same before the intervention, But after the intervention, the difference became significant (p<0.001). Conclusion: The virtual training method, like face-to-face training, can improve the quality of life and reduce the severity of primary dysmenorrhea pain in students. Therefore, depending on the conditions, both educational methods can be used.

Keywords: primary dysmenorrhea, face-to-face training, virtual, training

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Authors: Azza H. El-Medany, Hanan H. Hagar, Jamila H. El-Medany

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Ulcerative colitis (UC) is one of chronic inflammatory diseases primarily affecting colon with unknown etiology. Some researches papers mentioned the possibility of the use of drugs that affect the angiotensin II in reducing the complication of ulcerative colitis. The aim of the present study is to evaluate the potential protective and therapeutic effects of captopril and valsartan on ulcerative colitis induced experimentally in rats using acetic acid. The results were assessed by histological assessment of colonic tissues and measurement of malondialdehyde (MDA), tumor necrosis factor (TNF-α), transforming growth factor (TGF-1B), angiotensin converting enzyme (ACE), reduced glutathione (GSH) and platelet activating factor (PAF) levels in colonic tissues. Oral pre-treatment with captopril or valsartan in a dose of 30 mgkg-1 body weight for 2 weeks before induction of colitis (prophylactic groups) and continuously for 2 weeks after induction (therapeutic groups) significantly reduce MDA, TNF-α, PAF, TGF-1B and ACE levels in colonic tissues as compared to acetic acid control group. Also, a significant increase in GSH level was observed in colonic tissues. Captopril and valsartan attenuated the macroscopic and microscopic colonic damage induced by acetic acid. These results suggest that either captopril or valsartan may be effective as prophylactic or treatment of UC through inhibition of ACE and scavenging effect on oxygen-derived free radicals.

Keywords: captopril, valsartan, angiotensin converting enzyme, reduced glutathione, tumor necrosis factor

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Authors: Anna Dabrowska

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Taking Daniel Goleman’s (1994) belief that success in life depends on IQ in 20% and in 80% on emotional intelligence, and that it is worth considering emotional intelligence as an important factor in human performance and development potential, the aim of the paper is to explore the range of emotions experienced by university students who represent Society 5.0. This quantitative and qualitative study is meant to explore not only the list of the most and least experienced emotions by the students, but also the main reasons behind these feelings. The database of the study consists of 115 respondents out of 129 students of the 1st and 5th year of Applied Linguistics at Maria Curie-Skłodowska University, which constitutes 89% of those being surveyed. The data is extracted from the anonymous questionnaire, which comprises young people’s answers and discourse concerning the causes of their most experienced emotions. Following Robert Plutchik’s theory of eight primary emotions, i.e. anger, fear, sadness, disgust, surprise, anticipation, trust, and joy, we adopt his argument for the primacy of these emotions by showing each to be the trigger of behaviour with high survival value. In fact, all other emotions are mixed or derivative states; that is, they occur as combinations, mixtures, or compounds of the primary emotions. Accordingly, the eight primary emotions, and their mixed states, are checked in the study on the students.

Keywords: emotions, intelligence, students, discourse study, emotional intelligence

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Authors: Michio Kurosu

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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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Authors: Reema Alghamdi, Rasees Aleisa, Layan Sukkar

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The primary objective of this research is to conduct an examination of the Flo menstrual cycle application. We do that by evaluating the user experience and their satisfaction with integrated AI features. The study seeks to gather data from primary resources, primarily through surveys, to gather different insights about the application, like its usability functionality in addition to the overall user satisfaction. The focus of our project will be particularly directed towards the impact and user perspectives regarding the integration of artificial intelligence features within the application, contributing to an understanding of the holistic user experience.

Keywords: period, women health, machine learning, AI features, menstrual cycle

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Authors: Seyyed Farzad Motevalli-Haghi, Javad Rafinejad, Mahboobeh Hosseni, Jamshid Yazdani-Charati, Behzad Parsi

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Background and purpose: Pediculosis is a worldwide public health concern. This descriptive study was performed on primary-school-aged children to determine the prevalence of pediculosis and its risk factors in Mazandaran Province, Iran, on basis of geographic information system (GIS). Materials and methods: A random sampling method was used to select 45237 school-aged children from Sari to Ramsar cities during September 2012 to June 2013. Data were collected from the selected schools by five trained nursing inspectors. A detailed questionnaire was filled for each child prior to hair examination following which examination was carried out to detect head lice as well as eggs/nits. Data were analyzed chi-square test. Finally, the GIS map was obtained in province informational chart. Results: 823 primary-school children (of 45237) were infected with lice in Mazandaran Province. The mean infection prevalence was 1.4% in cities 5.64% in rural area from Sari to Ramsar. There were significant relationships between pediculosis and some factors (P<0.05). GIS map revealed that the contamination was less in west than in east and central regions. Conclusion: Increasing awareness and training of teachers and parents, as well as improving standards of personal health can significantly reduce the prevalence of pediculosis.

Keywords: pediculosis capitis, primary school children, epidemiology, geographic information system (GIS), Mazandaran, Iran

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Authors: Tonguc Basaran

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History is a record of a people’s past based on a critical examination of documents and other facts. The essentials of this historical method are not beyond the grasp of even young children. Concrete examples, such as the story of the Rosetta stone, which enabled Champollion to establish the first principles of the deciphering of Egyptian hieroglyphics, vividly illustrate the fundamental processes involved. This search for the facts can be used to illustrate one side of the search for historic truth. The other side is the truth of historic interpretation. The facts cannot be changed, but the interpretation of them can and does change.

Keywords: history, primary education, teaching methods, social studies

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Authors: Rama Bhargava, Surabhi Nishad

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The infusion of nanofluids has dramatically enhanced the heat-carrying capacity of the fluids, applicable to many engineering and medical process where the temperature below freezing is required. Cryosurgery is an efficient therapy for the treatment of cancer, but sometimes the excessive cooling may harm the nearby healthy cells. Efforts are therefore done to develop a model which can cause to generate the low temperature as required. In the present study, a mathematical model is developed based on the bioheat transfer equation to simulate the heat transfer from the probe on a tumor (with irregular domain) using the hybrid technique consisting of element free Galerkin method with αα-family of approximation. The probe is loaded will nano-particles. The effects of different nanoparticles, namely Al₂O₃, Fe₃O₄, Au on the heat-producing rate, is obtained. It is observed that the temperature can be brought to (60°C)-(-30°C) at a faster freezing rate on the infusion of different nanoparticles. Besides increasing the freezing rate, the volume of the nanoparticle can also control the size and growth of ice crystals formed during the freezing process. The study is also made to find the time required to achieve the desired temperature. The problem is further extended for multi tumors of different shapes and sizes. The irregular shape of the frozen domain and the direction of ice growth are very sensitive issues, posing a challenge for simulation. The Meshfree method has been one of the accurate methods in such problems as a domain is naturally irregular. The discretization is done using the nodes only. MLS approximation is taken in order to generate the shape functions. Sufficiently accurate results are obtained.

Keywords: cryosurgery, EFGM, hybrid, nanoparticles

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Authors: Kgomotso Matobole, Pascal Mwenge, Tumisang Seodigeng

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The global urbanisation and worldwide economic growth have caused a high rate of food waste generation, resulting in environmental pollution. Food waste disposed on landfills decomposes to produce methane (CH₄), a greenhouse gas. Inadequate waste management practices contribute to food waste polluting the environment. Thus effective organic fraction of municipal solid waste (OFMSW) management and treatment are attracting widespread attention in many countries. This problem can be minimised by the employment of anaerobic digestion process, since food waste is rich in organic matter and highly biodegradable, resulting in energy generation and waste volume reduction. The current study investigated the Biomethane Potential (BMP) of the Vaal University of Technology canteen food waste using anaerobic digestion. Tests were performed on canteen food waste, as a substrate, with total solids (TS) of 22%, volatile solids (VS) of 21% and moisture content of 78%. The tests were performed in batch reactors, at a mesophilic temperature of 37 °C, with two different types of inoculum, primary and digested sludge. The resulting CH₄ yields for both food waste with digested sludge and primary sludge were equal, being 357 Nml/g VS. This indicated that food waste form this canteen is rich in organic and highly biodegradable. Hence it can be used as a substrate for the anaerobic digestion process. The food waste with digested sludge and primary sludge both fitted the first order kinetic model with k for primary sludge inoculated food waste being 0.278 day^-1 with R² of 0.98, whereas k for digested sludge inoculated food waste being 0.034 day^-1, with R² of 0.847.

Keywords: anaerobic digestion, biogas, bio-methane potential, food waste

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Authors: Ayşegül Bilge, Hacer Demirkol, Merve Uğuryol

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Therapeutic touch is one of the most important methods of complementary and alternative treatments. Therapeutic touch requires the sharing of universal energy. Therapeutic touch (TT) provides the interaction between the patient and the nurse. In addition, nurses can be aware of physical and mental symptoms of patients through therapeutic touch. Therapeutic touch (TT) is short-term provides the advantage for the nurse. For this reason, nurses have to be aware of the importance of therapeutic touch and they can use it from the primary care to tertiary care in nursing practices at in health field.

Keywords: health care services, complementary treatment, nursing, therapeutic touch

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Authors: Wenbo Yu, Zihao Yuan, Zhipeng Guo, Shoumei Xiong

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Under different slow shot speeds in vacuum assisted high pressure die casting (VHPDC) process, plate-shaped specimens of hypereutectic A390 aluminum alloy were produced. According to the results, the vacuum pressure inside the die cavity increased linearly with the increasing slow shot speed at the beginning of mold filling. Meanwhile, it was found that the tensile properties of vacuum die castings were deteriorated by the porosity content. In addition, the average primary Si size varies between 14µm to 23µm, which has a binary functional relationship with the slow shot speeds. Due to the vacuum effect, the castings were treated by T6 heat treatment. After heat treatment, microstructural morphologies revealed that needle-shaped and thin-flaked eutectic Si particles became rounded while Al2Cu dissolved into α-Al matrix. For the as-received sample in-situ tensile test, microcracks firstly initiate at the primary Si particles and propagated along Al matrix with a transgranular fracture mode. In contrast, for the treated sample, the crack initiated at the Al2Cu particles and propagated along Al grain boundaries with an intergranular fracture mode. In-situ three bending test, microcracks firstly formed in the primary Si particles for both samples. Subsequently, the cracks between primary Si linked along Al grain boundaries in as received sample. In contrast, the cracks in primary Si linked through the solid lines in Al matrix. Furthermore, the fractography revealed that the fracture mechanism has evolved from brittle transgranular fracture to a fracture mode with many dimples after heat treatment.

Keywords: A390 aluminum, vacuum assisted high pressure die casting, heat treatment, mechanical properties

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Authors: Azzah Alghamdi

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The Interactive White Boards (IWBs) as one of the innovative educational technologies have been extensively investigated in advanced countries such as the UK, US, and Australia. However, there is a significant lack of research studies, which mainly examine the use of IWBs in Saudi Arabia. Therefore, this study aims to investigate the attitudes of primary teachers towards using IWBs in both the teaching and learning processes. Moreover, it aims to investigate if there is any significant difference between male teachers and females regarding their attitudes towards using this technology. This study concentrated on teachers in primary schools, which participated in Tatweer project in the city of Jeddah, in Saudi Arabia. Mixed methods approach was employed in this study using a designed questionnaire, classroom observations, and a semi-structured interview. 587 teachers (286 men and 301 women) from Tatweer primary schools were completed the questionnaire as well as twenty teachers were interviewed including seven female teachers were observed in their classrooms. The findings of this study indicated that approximately 11% of the teachers within the sample (n=587) had negative attitudes towards the use of IWBs in the teaching and learning processes. However, the majority of them nearly 89% agreed about the benefits of using IWBs in their classrooms. Additionally, all the twenty teachers who were interviewed (including the seven observed female teachers) had positive attitudes towards the use of these technologies. Moreover, 87% of male teachers and 91% of female teachers who completed the questionnaire accepted the usefulness of using IWBs in improving their teaching and students' learning. Thus, this indicates that there was no significant difference between male and female teachers in Tatweer primary schools in terms of their views about using these innovative technologies in their lessons. The findings of the current study will help the Ministry of Education to improve the policies of using IWBs in Saudi Arabia. Indeed, examining teachers’ attitudes towards IWBs is a very important issue because they are the main users in classrooms. Hence, their views should be considered to addressing the powers and boundaries of using IWBs. Moreover, students will feel comfortable to use IWBs if their teachers accept and use them well.

Keywords: IWBs, Saudi teachers’ views, Tatweer schools, teachers' gender

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Authors: Chintan Chandrachud

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When primary legislation is challenged for breaching fundamental rights, many courts around the world adopt interpretive techniques to avoid finding such legislation incompatible or invalid. In the UK, these techniques find sanction in section 3 of the Human Rights Act 1998, which directs courts to interpret legislation in a manner which is compatible with European Convention rights, ‘so far as it is possible to do so’. In India, courts begin with the interpretive presumption that Parliament intended to comply with fundamental rights under the Constitution of 1949. In comparing rights-compliant interpretation of primary legislation under the Human Rights Act and the Indian Constitution, this paper makes two arguments. First, that in the absence of a section 3-type mandate, Indian courts have a smaller range of interpretive tools at their disposal in interpreting primary legislation in a way which complies with fundamental rights. For example, whereas British courts frequently read words into statutes, Indian courts consider this an inapposite interpretive technique. The second argument flows naturally from the first. Given that Indian courts have a smaller interpretive toolbox, one would imagine that ceteris paribus, Indian courts’ power to strike down legislation would be triggered earlier than the declaration of incompatibility is in the UK. However, this is not borne out in practice. Faced with primary legislation which appears to violate fundamental rights, Indian courts often reluctantly uphold the constitutionality of statutes (rather than striking them down), as opposed to British courts, which make declarations of incompatibility. The explanation for this seeming asymmetry hinges on the difference between the ‘strike down’ power and the declaration of incompatibility. Whereas the former results in the disapplication of a statute, the latter throws the ball back into Parliament’s court, if only formally.

Keywords: constitutional law, judicial review, constitution of India, UK Human Rights Act

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Authors: Rafia S. Al-lamki, Jun Wang, Simon Pacey, Jordan Pober, John R. Bradley

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Tumor necrosis factor alpha (TNF), signaling through TNFR2, may act an autocrine growth factor for renal tubular epithelial cells. Clear cell renal carcinomas (ccRCC) contain cancer stem cells (CSCs) that give rise to progeny which form the bulk of the tumor. CSCs are rarely in cell cycle and, as non-proliferating cells, resist most chemotherapeutic agents. Thus, recurrence after chemotherapy may result from the survival of CSCs. Therapeutic targeting of both CSCs and the more differentiated bulk tumor populations may provide a more effective strategy for treatment of RCC. In this study, we hypothesized that TNFR2 signaling will induce CSCs in ccRCC to enter cell cycle so that treatment with ligands that engage TNFR2 will render CSCs susceptible to chemotherapy. To test this hypothesis, we have utilized wild-type TNF (wtTNF) or specific muteins selective for TNFR1 (R1TNF) or TNFR2 (R2TNF) to treat either short-term organ cultures of ccRCC and adjacent normal kidney (NK) tissue or cultures of CD133+ cells isolated from ccRCC and adjacent NK, hereafter referred to as stem cell-like cells (SCLCs). The effect of cyclophosphamide (CP), currently an effective anticancer agent, was tested on CD133+SCLCs from ccRCC and NK before and after R2TNF treatment. Responses to TNF were assessed by flow cytometry (FACS), immunofluorescence, and quantitative real-time PCR, TUNEL, and cell viability assays. Cytotoxic effect of CP was analyzed by Annexin V and propidium iodide staining with FACS. In addition, we assessed the effect of TNF on isolated SCLCs differentiation using a three-dimensional (3D) culture system. Clinical samples of ccRCC contain a greater number SCLCs compared to NK and the number of SCSC increases with higher tumor grade. Isolated SCLCs show expression of stemness markers (oct4, Nanog, Sox2, Lin28) but not differentiation markers (cytokeratin, CD31, CD45, and EpCAM). In ccRCC organ cultures, wtTNF and R2TNF increase CD133 and TNFR2 expression and promote cell cycle entry whereas wtTNF and R1TNF increase TNFR1 expression and promote cell death of SCLCs. Similar findings are observed in SCLCs isolated from NK but the effect was greater in SCLCs isolated from ccRCC. Application of CP distinctly triggered apoptotic and necrotic cell death in SLCSs pre-treatment with R2TNF as compared to CP treatment alone, with SCLCs from ccRCC more sensitive to CP compared to SLCS from NK. Furthermore, TNF promotes differentiation of SCLCs to an epithelial phenotype in 3D cultures, confirmed by cytokeratin expression and loss of stemness markers Nanog and Sox2. The differentiated cells show positive expression of TNF and TNFR2. These findings provide evidence that selective engagement of TNFR2 drive CSCs to cell proliferation/differentiation, and targeting of cycling cells with TNFR2 agonist in combination with anti-cancer agents may be a potential therapy for RCC.

Keywords: cancer stem cells, ccRCC, cell cycle, cell death, TNF, TNFR1, TNFR2, CD133

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Authors: Elizabeth Oyenike Abegunrin

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This study is borne out of the dire need to improve the academic achievement of pupils in social studies. The paper attempted to reconcile the lacuna in teacher’s gender and primary school pupils’ achievement. With specific reference to Social Studies classroom, the aim of this study was to detail how pupils’ achievement is a function of the teacher’s gender as well as to establish the link (if any) between teacher’s gender and pupils’ educational achievement. The significance of this was to create gender-template standard for teachers, school owners, administrators and policy makers to follow in the course of engendering pupils’ achievement in Social Studies. By adopting a quasi-experimental research design, a sample of two hundred pupils was selected across five primary schools in Education District I, Lagos State and assigned to experimental and control groups. A 40-item Gender and Social Studies Achievement Test (GSSAT) was used to obtain data from the pupils. Having analyzed the data collected using Pearson Product Moment Correlation (PPMC), a reliability of 0.78 was obtained. Result revealed that teacher’s gender (male/female) had no significant effect on pupils’ achievement in Social Studies and that there was significant interaction effect of teacher’s commitment devoid of gender on the general education output of pupils in Social Studies. Taken together, the results revealed that there is a high degree correlation between teacher’s commitment and pupils academic achievement in social studies, and not gender-based. The study recommended that social studies teachers should re-assess their classroom instructional strategies and use more innovative instructional methods and techniques that will give the pupils equal opportunities to excel in social studies, rather than their gender differences.

Keywords: gender, academic achievement, social studies, primary school

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Authors: James Jin, Weisi Xia, Runzhe Gao, Alain Vandal, Darren Svirkis, Andrew Hill

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Background: Post-haemorrhoidectomy pain is concerned by patients/clinicians. Minimizing the postoperation pain is highly interested clinically. Combinations of topical cream targeting three hypothesised post-haemorrhoidectomy pain mechanisms were developed and their effectiveness were evaluated. Specifically, a multi-centred double-blinded randomized clinical trial (RCT) was conducted in adults undergoing excisional haemorrhoidectomy. The primary analysis was conveyed on the data collected to evaluate the effectiveness of the combinations of topical cream targeting three hypothesized pain mechanisms after the operations. Methods: 192 patients were randomly allocated to 4 arms (each arm has 48 patients), and each arm was provided with pain cream 10% metronidazole (M), M and 2% diltiazem (MD), M with 4% lidocaine (ML), or MDL, respectively. Patients were instructed to apply topical treatments three times a day for 7 days, and record outcomes for 14 days after the operations. The primary outcome was VAS pain on day 4. Covariates and models were selected in the blind review stage. Multiple imputations were applied for the missingness. LMER, GLMER models together with natural splines were applied. Sandwich estimators and Wald statistics were used. P-values < 0.05 were considered as significant. Conclusions: The addition of topical lidocaine or diltiazem to metronidazole does not add any benefit. ML had significantly better pain and recovery scores than combination MDL. Multimodal topical analgesia with ML after haemorrhoidectomy could be considered for further evaluation. Further trials considering only 3 arms (M, ML, MD) might be worth exploring.

Keywords: RCT, primary analysis, multiple imputation, pain scores, haemorrhoidectomy, analgesia, lmer

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Authors: Margaret Nohilly, Fionnuala Tynan

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Wellbeing in not only a national priority in Ireland but in the international context. A review of the literature highlights the consistent efforts of researchers to define the concept of wellbeing. This study sought to explore the understating of Wellbeing in Irish primary schools. National Wellbeing Guidelines in the Irish context frame the concept of wellbeing through a mental health paradigm, which is but one aspect of wellbeing. This exploratory research sought the views of Irish primary school teachers on their understanding of the concept of wellbeing and the practical application of strategies to promote wellbeing both in the classroom and across the school. Teacher participants from four counties in the West of Ireland were invited to participate in focus group discussion and workshops through the Education Centre Network. The purpose of this process was twofold; firstly to explore teachers’ understanding of wellbeing in the primary school context and, secondly, for teachers to be co-creators in the development of practical strategies for classroom and whole school implementation. The voice of the teacher participants was central to the research design. The findings of this study indicate that the definition of wellbeing in the Irish context is too abstract a definition for teachers and the focus on mental health dominates the discourse in relation to wellbeing. Few teachers felt that they were addressing wellbeing adequately in their classrooms and across the school. The findings from the focus groups highlighted that while teachers are incorporating a range of wellbeing strategies including mindfulness and positive psychology, there is a clear disconnect between the national definition and the implementation of national curricula which causes them concern. The teacher participants requested further practical strategies to promote wellbeing at whole school and classroom level within the framework of the Irish Primary School Curriculum and enable them to become professionally confident in developing a culture of wellbeing. In conclusion, considering wellbeing is a national priority in Ireland, this research promoted the timely discussion the wellbeing guidelines and the development of a conceptual framework to define wellbeing in concrete terms for practitioners. The centrality of teacher voices ensured the strategies proposed by this research is both practical and effective. The findings of this research have prompted the development of a national resource which will support the implementation of wellbeing in the primary school at both national and international level.

Keywords: definition, wellbeing, strategies, curriculum

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Authors: Mrinal Kanti Bhowmik, Kakali Das Jr., Barin Kumar De, Debotosh Bhattacharjee

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Breast cancer is the most common cancer and a leading cause of death for women in the 35 to 55 age group. Early detection of breast cancer can decrease the mortality rate of breast cancer. Mammography is considered as a ‘Gold Standard’ for breast cancer detection and a very popular modality, presently used for breast cancer screening and detection. The screening of digital mammograms often leads to over diagnosis and a consequence to unnecessary traumatic & painful biopsies. For that reason recent studies involving the use of thermal imaging as a screening technique have generated a growing interest especially in cases where the mammography is limited, as in young patients who have dense breast tissue. Tumor is a significant sign of breast cancer in both mammography and thermography. The tumors are complex in structure and they also exhibit a different statistical and textural features compared to the breast background tissue. Fractal geometry is a geometry which is used to describe this type of complex structure as per their main characteristic, where traditional Euclidean geometry fails. Over the last few years, fractal geometrics have been applied mostly in many medical image (1D, 2D, or 3D) analysis applications. In breast cancer detection using digital mammogram images, also it plays a significant role. Fractal is also used in thermography for early detection of the masses using the thermal texture. This paper presents an overview of the recent aspects and initiatives of fractals in breast cancer detection in both mammography and thermography. The scope of fractal geometry in automatic breast cancer detection using digital mammogram and thermogram images are analysed, which forms a foundation for further study on application of fractal geometry in medical imaging for improving the efficiency of automatic detection.

Keywords: fractal, tumor, thermography, mammography

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Authors: Howard Gomwe, Eunice Seekoe, Philemon Lyoka, Chioneso Show Marange, Dennyford Mafa

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Background: This study was designed to assess PA levels and sedentary behavior among primary school learners in the Eastern Cape province of South Africa. Methods: A cross-sectional study was adopted to assess the patterns and levels of PA and sedentary behavior using the Physical Activity Questionnaire for Older Children (PAQ-C). Results: Using complete case analysis, 870 randomly selected participants (boys = 351 and girls = 519) aged 9 to 14 years were retained. The sample comprised of primary school learners, both boys and girls; aged 9-14 years old, who were randomly selected from rural, urban and peri-urban areas in the Eastern Cape Province of South Africa. Overly, the sample had a mean PAQ-C score of 2.33 ± 0.43. The mean of PA in boys was significantly higher (p = 0.003) in comparison with the girls. The 13 to 14 age group had a significantly higher PA level (p = 0.014). Learners from urban areas (n = 136; 77.3%) engaged more in sedentary behaviour as compared to those from rural areas (n = 252; 54.9%). Conclusion: The findings demonstrated low levels of PA and high engagement of sedentary behavior, which have negative implications on the health, growth and development of children. The study, therefore, recommends relevant stakeholders to implement interventions aimed to promote the increase in PA and reduction in sedentary behaviors for primary school learners in the Eastern Cape province in South Africa.

Keywords: learners, physical activity, sedentary behavior, south Africa

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Authors: Yasmin M. Attia, Hanan S. El-Abhar, Mahmoud M. Al Marzabani, Samia A. Shouman

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Background: Tamoxifen (TAM) is the most commonly used hormone therapy for the treatment of early and metastatic breast cancer. Although it significantly decreases the tumor recurrence rate and provides an overall benefit, as much as 20–30% of women still relapse during or after long-term therapy. 3-Bromopyruvate (3-BP) is a promising agent with impressive antitumor effects in several models of animal tumors and cell lines. Aim: This study was designed to investigate the combined effect of (TAM) and (3-BP) in breast cancer cells and to explore their molecular interaction via assessment of apoptotic, angiogenic, and metastatic markers. Methods: In vitro cytotoxicity study was carried out for both compounds to determine the combination regimen producing a synergistic effect and mechanistic pathways were studied using RT-PCR and western techniques. Moreover, the anti-oncolytic and anti-angiogenic potentials were assessed in mice bearing solid Ehrlich carcinoma (SEC). Results: The combined treatment significantly increased the expressions and protein levels of caspase 7, 9, and 3 and decreased of angiogenic markers VEGF, HIF-1α, and HK2 compared to cells treated with either drug individually. However, there were no significant changes in MMP-2 and MMP-9 protein levels. Interestingly, the in vivo results supported the in vitro findings; there was a decrease in the tumor volume and VEFG using immunohistochemistry in the combination-treated groups compared to either TAM or 3-BP treated one. Conclusion: 3-BP synergizes the cytotoxic effect of TAM by increasing apoptosis and decreasing angiogenesis which makes this combination a promising regimen to be applied clinically.

Keywords: tamoxifen, 3-bromopyruvate, breast cancer, cytotoxicity, angiogenesis

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Authors: Javier Enciso-Benavides, Fredy Fabian, Carlos Castaneda, Luis Alfaro, Alex Choque, Aparicio Aguilar, Javier Enciso

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Background: The use of biomarkers in breast cancer diagnosis, therapy, and prognosis has gained increasing interest. Cancer stem cells (CSCs) are a subpopulation of tumor cells that can drive tumor initiation and may cause relapse. Therefore, due to the importance of diagnosis, therapy, and prognosis, several biomarkers that characterize CSCs have been identified; however, in treatment-naïve triple-negative breast tumors, there is an urgent need to identify new biomarkers and therapeutic targets. According to this, the aim of this study was to identify serum proteins associated with cancer stem cells and pluripotency in women with triple-negative breast tumors in order to subsequently identify a biomarker for this type of breast tumor. Material and Methods: Whole blood samples from 12 women with histopathologically diagnosed triple-negative breast tumors were used after obtaining informed consent from the patient. Blood serum was obtained by conventional procedure and frozen at -80ºC. Identification of cancer stem cell-associated proteins was performed by matrix-assisted laser desorption/ionisation-assisted laser desorption/ionisation mass spectrometry (MALDI-TOF MS), protein analysis was obtained using the AB Sciex TOF/TOF™ 5800 system (AB Sciex, USA). Sequences not aligned by ProteinPilot™ software were analyzed by Protein BLAST. Results: The following proteins related to pluripotency and cancer stem cells were identified by MALDI TOF/TOF mass spectrometry: A-chain, Serpin A12 [Homo sapiens], AIEBP [Homo sapiens], Alpha-one antitrypsin, AT {internal fragment} [human, partial peptide, 20 aa] [Homo sapiens], collagen alpha 1 chain precursor variant [Homo sapiens], retinoblastoma-associated protein variant [Homo sapiens], insulin receptor, CRA_c isoform [Homo sapiens], Hydroxyisourate hydrolase [Streptomyces scopuliridis], MUCIN-6 [Macaca mulatta], Alpha-actinin-3 [Chrysochloris asiatica], Polyprotein M, CRA_d isoform, partial [Homo sapiens], Transcription factor SOX-12 [Homo sapiens]. Recommendations: The serum proteins identified in this study should be investigated in the exosome of triple-negative breast cancer stem cells and in the blood serum of women without breast cancer. Subsequently, proteins found only in the blood serum of women with triple-negative breast cancer should be identified in situ in triple-negative breast cancer tissue in order to identify a biomarker to study the evolution of this type of cancer, or that could be a therapeutic target. Conclusions: Eleven cancer stem cell-related serum proteins were identified in 12 women with triple-negative breast cancer, of which MUCIN-6, retinoblastoma-associated protein variant, transcription factor SOX-12, and collagen alpha 1 chain are the most representative and have not been studied so far in this type of breast tumor. Acknowledgement: This work was supported by Proyecto CONCYTEC–Banco Mundial “Mejoramiento y Ampliacion de los Servicios del Sistema Nacional de Ciencia Tecnología e Innovacion Tecnologica” 8682-PE (104-2018-FONDECYT-BM-IADT-AV).

Keywords: triple-negative breast cancer, MALDI TOF/TOF MS, serum proteins, cancer stem cells

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Authors: Fatma Al-Maadheed

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Following an ethnographic approach this study explored bilingual programmes offered by two types of primary schools in Qatar: international and Independent schools. Qatar with its unique linguistic and socio-economic situation launched a new initiative for educatiobnal development in 2001 but with hardly any research linked to theses changes. The study reveals that the Qatari bilingual schools context was one of heteroglossia, with three codes in operation: Modern Standard Arabic, Colloquial Arabic dialects and English. The two schools adopted different models of bilingualism. The international school adopted a strict separation policy between the two languages following a monoglossic belief. The independent school was found to apply a flexible language policy. The study also highlighted the daily challnges produced from the diglossia situation in Qatar, the difference between students and teacher dialect as well as acquiring literacy in the formal language. In addition to an abscence of a clear language policy in Schools, the study brought attention to the instructional methods utilised in language teaching which are mostly associated with successful bilingual education.

Keywords: diglossia, instructional methods, language policy, qatari primary schools

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Authors: Md. Rifat-Ur- Rahman

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Dhamairnagar, Sirajganj, Bangladesh, local villagers describe the peculiar mounds spotted scattered among the nearby villages as “Buruj”. Among these, a mound was explored in one of these mounds, in Khirtala village, in early 2019. Primary archaeological surveys and map making has been conducted in this site, where suspect lays the remains of an 8 square miles city, at least 1200 years old. In the government gazettes of Bangladesh from 1990, this place has been linked with a mythical kind from the Indian epic, Mahabharata. In the primary explorations, found bricks, mortars, different kinds of potteries and terracotta pieces. Assumable observation is that this city was a flourishing establishment during the early Pala dynasty of Bengal (800 AD to 1200 AD). At present there are four indigenous groups live around this site and they are known as Mahato, Teli, Oraon and Santals. These four indigenous groups are considered as the core four of Bengali ethnicity. In the folklore of these groups we find stories of ancient kingdoms which have not been documented through archaeological findings yet. So, a question rises about the population that was used to reside in this archaeological site. Were they the ancestors of these indigenous tribes that are dwelling in this area? With such primary information, the aim is to conduct a comparative study of the physiology; osteology and cultural practices of this civilization.

Keywords: Archaeology, Heritage, Indigenous Peoples, Physiology

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Authors: Nikolaos Katsoulas, Ioannis Naounoulis, Sofia Faliagka

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Cascade hydroponic systems have the potential to minimize environmental impact and improve resource efficiency by recycling the nutrient solution drained from a hydroponic (primary-donor) crop to irrigate another (secondary-receiver), less sensitive to salinity crop. However, it remains unclear if the drained solution from the primary crop can fully meet the nutritional requirements of a secondary crop and whether the productivity of the secondary crop is affected. To address this question, a prototype cascade hydroponic system was designed and tested using a cucumber crop as the donor crop and a melon as secondary crop. The performance of the system in terms of productivity and water and nutrient use efficiency was evaluated by measuring plant growth, fresh and dry matter production, nutrients content, and photosynthesis rate in the secondary crop. The amount of water and nutrients used for the primary and secondary crops was also recorded. This work was carried out under the ECONUTRI project that has received funding from the European Union’s Horizon 2020 research and innovation programme under the Horizon Europe Grant agreement: 101081858.

Keywords: hydroponics, salinity, water use efficiencu, nutrients use efficiency

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Authors: Saeed Musaid H. Alzahrani

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The role of middle leaders, especially in primary schools, is a multi-faced role that has been subject to changes in nature over recent decades, with claims for more distributed leadership practices. This research examines the way 18 middle leaders in Saudi and English primary schools conceptualise their roles and responsibilities, and different factors influencing those roles and responsibilities. It begins from the premise that both the power of the role and the values of middle leaders are grounded in cultural and political bases, a belief held by the researcher as an 'insider' within the Saudi educational leadership context. The study consisted of a comparative analysis of the role and the responsibilities of middle leaders in Saudi primary schools and their equivalents in English primary schools. A purely qualitative methodological stance was adopted, using in-depth face-to-face semi-structured interviews, observations and document analysis. Middle leaders were asked to reflect deeply on their perceptions and understanding of their roles and explain what they thought influenced their daily practices and responsibilities. The findings suggest that the concept of middle leadership has been influenced by power imposed from above by political authority, via internal and external hierarchical structures, which shapes the nature of the role of the middle leaders and forces them to comply. Middle leaders seem to believe they have the power to make decisions and promote change, but these findings suggest that this is illusory. The power that keeps middle leaders performing is the power of their cultural and religious values. Those values are the resource to which they turn in their search for more energy when they lack support and are short of time taken. Middle leaders in Saudi, just like their equivalents in English schools must comply with the requirements of their role. However, Saudi middle leaders are given no leeway to make decisions or implement change, neither do they have the culture of collegiality that seems to give middle leaders in England more power over their resources and decisions. However, in neither educational setting have middle leaders been given the power to lead, so they remain managers rather than leaders. The findings of this research suggest that there are more similarities between the educational settings of Saudi and England than differences; and in the light of different factors identified in the study, suggest the establishment of a framework for middle leadership, in the hope of enhancing the way the role is practiced.

Keywords: middle leader, primary school, power, educational leadership, value, culture, model, Saudi Arabia, England

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Authors: Sayed Ali Garossi, Azar Heidarizadi, Shahla Mohammad Ganji

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Context: Colorectal cancer is the second type of cancer-related mortality globally. Expression of cas8 (caspase 8) is closely connected to growth and metastasis of colorectal cancer.Cas8/Rip1 plays a vital role in the apoptosis pathway and resistance to chemotherapy. The aim of the present study is to investigate the pattern of gene expression in colorectal cancer and compare the differences using Real-Time PCR to find a potential biomarker candidate for colorectal cancer. Methodology: This study conducted real-time PCR to evaluate gene expression of Cas8 in colorectal cancer patients. The gene-specific primer sequences exon–exon junction was designed by OLIGO7 software for the expression of the gene under investigation. Forty-six patient samples without any chemotherapy were selected, including tumoral tissue and adjacent normal tissue samples. The age of the patients was 50 and the size of the tumors was 5.5 cm. The categories were before and after age 50. Findings: Here, we found that Caspase 8 was overexpressed in CRC tissues compared to corresponding adjacent colon tissues (Cas8: 5.2 vs. 1 ratio); high expression of Cas8 was associated with poor overall survival and independent risk factors for the prognosis of CRC patients. Conclusion: In conclusion, our study pioneered the reporting of high Casp8 expression as a predictor of poor prognosis and chemical resistance in CRC patients.Cas8 overexpression suppressed Cas 8 / Rip1-dependent apoptosis and activated the proliferation of tumor cells by activating necroptosis. The necroptosis pathway has also emerged as a new approach to anti-tumor in cancer treatment.

Keywords: Cas8, necroptosis, apoptosis, Real-Time PCR

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Authors: Riffat Iqbal, Sidra Ihsan, Andleeb Batool, Maryam Mukhtar

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Glaucoma is a gathering of optic neuropathies described by dynamic degeneration of retinal ganglionic cells. It is clinically and innately heterogenous illness containing a couple of particular forms each with various causes and severities. Primary open-angle glaucoma (POAG) is the most generally perceived kind of glaucoma. This study investigated the genetic association of single nucleotide polymorphisms (SNPs; rs10483727 and rs33912345) at the SIX1/SIX6 locus with primary open-angle glaucoma (POAG) in the Pakistani population. The SIX6 gene plays an important role in ocular development and has been associated with morphology of the optic nerve. A total of 100 patients clinically diagnosed with glaucoma and 100 control individuals of age over 40 were enrolled in the study. Genomic DNA was extracted by organic extraction method. The SNP genotyping was done by (i) PCR based restriction fragment length polymorphism (RFLP) and sequencing method. Significant genetic associations were observed for rs10483727 (risk allele T) and rs33912345 (risk allele C) with POAG. Hence, it was concluded that Six6 gene is genetically associated with pathogenesis of Glaucoma in Pakistan.

Keywords: genotyping, Pakistani population, primary open-angle glaucoma, SIX6 gene

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