Search results for: SMEs survival

Authors: Sabita Mahapatra

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‘Going green’ has been an emerging issue worldwide driving companies to continuously enhance their green capabilities and implement innovative green practices to protect the environment and improve business performance. Green has become a contemporary business environmental issue. The resource advantage theory is adopted in the present study to observe the impact of marketing orientation and green innovation practices on environmental and firm’s performance. The small and medium firms compared to large firms have different approach towards market orientation as a strategic tool. The present study proposes a conceptual framework regarding the impact of market orientation on environmental and firm’s performance through green innovation practices in the context of small and medium scale industries (SMEs). The propositions developed in the present paper would provide scope for future research study to validate the conceptual framework in the emerging economy like India.

Keywords: market orientation, green innovation practices, environment performance, corporate performance, emerging market

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Authors: M. I. Oshimagye, V. O. Ayuba, P. A. Annune

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The effect of Sublethal Concentrations of Parkia biglobosa pod extract on the growth and survival of Clarias gariepinus juveniles (mean weight 32.73g ± 0.0) were investigated under laboratory conditions for 8 weeks using the static renewal and continuous aeration system. Statistical analysis showed that fish exposed to various concentrations had significantly lower (P<0.05) growth rate than the control groups. The reduction in growth was observed to be directly proportional to increase in concentration. However, at 50 mg/L no significant depression in weight was observed.

Keywords: Clarias gariepinus, Parkia biglobosa, pod, weight

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Authors: Mohamed Haffar, Ramdane Djebarni, Russell Evans

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Despite a growth in literature on distributed leadership, the majority of studies are centred on large public organisations particularly within the health and education sectors. The purpose of this study is to fill the gap in the literature by exploring employee experiences of distributed leadership within two commercial consultancy SME businesses in the UK and USA. The aim of the study informed an exploratory method of research to gather qualitative data drawn from semi-structured interviews involving a sample of employees in each organisation. A series of broad, open questions were used to explore the employees’ experiences; evidence of distributed leadership; and extant barriers and practices in each organisation. Whilst some of our findings aligned with patterns and practices in the existing literature, it importantly discovered some emergent themes that have not previously been recognised in the previous studies. Our investigation identified that whilst distributed leadership was in evidence in both organisations, the interviewees’ experience reported that it was sporadic and inconsistent. Moreover, non-client focused projects were reported to be less important and distributed leadership was found to be inconsistent or non-existent.

Keywords: consultancy, distributed leadership, owner-manager, SME, entrepreneur

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Authors: Mike T. Wei, Douglas N. Mintz, Lisa A. Mandl, Arielle W. Fein, Jayme C. Burket, Yuo-Yu Lee, Wei-Ti Huang, Vivian P. Bykerk, Mark P. Figgie, Edward F. Di Carlo, Bruce N. Cronstein, Susan M. Goodman

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Background/Purpose: Rheumatoid arthritis (RA) patients have excellent total hip arthroplasty (THA) survival, and methotrexate (MTX), an anti-inflammatory disease modifying drug which may affect bone reabsorption, may play a role. The purpose of this study is to determine the diagnosis leading to revision THA (rTHA) in RA patients and to assess the association of radiographic lucency with MTX use. Methods: All patients with validated diagnosis of RA in the institution’s THA registry undergoing rTHA from May 2007 - February 2011 were eligible. Diagnosis leading to rTHA and medication use was determined by chart review. Osteolysis was evaluated on available radiographs by measuring maximum lucency in each Gruen zone. Differences within RA patients with/without MTX in osteolysis, demographics, and medications were assessed with chi-squared, Fisher's exact tests or Mann-Whitney U tests as appropriate. The error rate for multiple comparisons of lucency in the different Gruen zones was corrected via false discovery rate methods. A secondary analysis was performed to determine differences in diagnoses leading to revision between RA and matched OA controls (2:1 match by sex age +/- 5 years). OA exclusion criteria included presence of rheumatic diseases, use of MTX, and lack of records. Results: 51 RA rTHA were identified and compared with 103 OA. Mean age for RA was 57.7 v 59.4 years for OA (p = 0.240). 82.4% RA were female v 83.5% OA (p = 0.859). RA had lower BMI than OA (25.5 v 28.2; p = 0.166). There was no difference in diagnosis leading to rTHA, including infection (RA 3.9 v OA 6.8%; p = 0.719) or dislocation (RA 23.5 v OA 23.3%; p = 0.975). There was no significant difference in the length of time the implant was in before revision: RA 11.0 v OA 8.8 years (p = 0.060). Among RA with/without MTX, there was no difference in use of biologics (30.0 v 43.3%, p = 0.283), steroids (47.6 v 50.0%, p = 0.867) or bisphosphonates (23.8 v 33.3%, p = 0.543). There was no difference in rTHA diagnosis with/without MTX, including loosening (52.4 v 56.7%, p = 0.762). There was no significant difference in lucencies with MTX use in any Gruen zone. Patients with MTX had femoral stem subsidence of 3.7mm v no subsidence without MTX (p = 0.006). Conclusion: There was no difference in the diagnosis leading to rTHR in RA and OA, although RA trended longer prior to rTHA. In this small retrospective study, there were no significant differences associated with MTX exposure or radiographic lucency among RA patients. The significance of subsidence is not clear. Further study of arthroplasty survival in RA patients is warranted.

Keywords: hip arthroplasty, methotrexate, revision arthroplasty, rheumatoid arthritis

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Authors: Asifa Fitriani, Galih Prakoso

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This study aims to improve the design layout of a Micro, Small and Medium Enterprises (SMEs) to minimize material handling and redesigning the layout of production facilities based on the safety and health and standards of food production facilities. Problems layout in the one of chip making industry mushrooms in Indonesia is cross movement between work stations, work accidents, and the standard of facilities that do not conform with the standards of the food industry. Improvement layout design using CORELAP and 5S method to give recommendation and implementation of occupational health and safety standards of food production facilities. From the analysis, improved layout using CORELAP provide a smaller displacement distance is 155.84 meters from the initial displacement distance of 335.9 meters, and providing a shorter processing time than the original 112.726 seconds to 102.831 seconds. 5S method also has recommended the completion of occupational health and safety issues as well as the standard means of food production by changing the working environment better.

Keywords: Layout Design, Corelap, 5S

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Authors: Mohammadjavad Sotoudeheian

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Heart failure (HF) prevalence, as a global cardiovascular problem, is increasing gradually. A variety of molecular mechanisms contribute to HF. Proteins involved in cardiac contractility regulation, such as ion channels and calcium handling proteins, are altered. Additionally, epigenetic modifications and gene expression can lead to altered cardiac function. Moreover, inflammation and oxidative stress contribute to HF. The progression of HF can be attributed to mitochondrial dysfunction that impairs energy production and increases apoptosis. Molecular mechanisms such as these contribute to the development of cardiomyocyte defects and HF and can be therapeutically targeted. The heart's contractile function is controlled by cardiomyocytes. Calpain, and its related molecules, including Bax, VEGF, and AMPK, are among the proteins involved in regulating cardiomyocyte function. Apoptosis is facilitated by Bax. Cardiomyocyte apoptosis is regulated by this protein. Furthermore, cardiomyocyte survival, contractility, wound healing, and proliferation are all regulated by VEGF, which is produced by cardiomyocytes during inflammation and cytokine stress. Cardiomyocyte proliferation and survival are also influenced by AMPK, an enzyme that plays an active role in energy metabolism. They all play key roles in apoptosis, angiogenesis, hypertrophy, and metabolism during myocardial inflammation. The role of calpains has been linked to several molecular pathways. The calpain pathway plays an important role in signal transduction and apoptosis, as well as autophagy, endocytosis, and exocytosis. Cell death and survival are regulated by these calcium-dependent cysteine proteases that cleave proteins. As a result, protein fragments can be used for various cellular functions. By cleaving adhesion and motility proteins, calcium proteins also contribute to cell migration. HF may be brought about by calpain-mediated pathways. Many physiological processes are mediated by the calpain molecular pathways. Signal transduction, cell death, and cell migration are all regulated by these molecular pathways. Calpain is activated by calcium binding to calmodulin. In the presence of calcium, calmodulin activates calpain. Calpains are stimulated by calcium, which increases matrix metalloproteinases (MMPs). In order to develop novel treatments for these diseases, we must understand how this pathway works. A variety of myocardial remodeling processes involve calpains, including remodeling of the extracellular matrix and hypertrophy of cardiomyocytes. Calpains also play a role in maintaining cardiac homeostasis through apoptosis and autophagy. The development of HF may be in part due to calpain-mediated pathways promoting cardiomyocyte death. Numerous studies have suggested the importance of the Ca2+ -dependent protease calpain in cardiac physiology and pathology. Therefore, it is important to consider this pathway to develop and test therapeutic options in humans that targets calpain in HF. Apoptosis, autophagy, endocytosis, exocytosis, signal transduction, and disease progression all involve calpain molecular pathways. Therefore, it is conceivable that calpain inhibitors might have therapeutic potential as they have been investigated in preclinical models of several conditions in which the enzyme has been implicated that might be treated with them. Ca 2+ - dependent proteases and calpains contribute to adverse ventricular remodeling and HF in multiple experimental models. In this manuscript, we will discuss the calpain molecular pathway's important roles in HF development.

Keywords: calpain, heart failure, autophagy, apoptosis, cardiomyocyte

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Authors: Pongsiri Kamkankaew

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This paper experiments to consider brand equity thought in Thai academic works. This essay employs that the first emerging of brand equity in Thai academic works and the components of brand equity which explore the extent to the convoluted approach with other Thai social condition. In Thailand, brand equity is supposed to provide branding and brand management replacement. However, the commitment of brand equity imposes in its proposal for seemly application in Thai context – to develop the brand equity framework by the Thai social – culture and Thai utilization style which it is questionable whether the brand equity in western conception is useful for characterizing the brand equity in Thailand context. In this position, brand equity also aspects several major questions: How can western conception lead to apply in Thai business? How can diversification be given within Thai SMEs business running? Can corporate brand valuation approach adopt in real business doing? So this paper argues that Thai brand equity notion should reduce disturb over improvement of its self-restraint and business area. Instead, Thai academic who are interested in brand equity can harmonize different mature bodies of discipline and other investigative a frame of references to complete and open the recognizing of brand equity.

Keywords: Thai brand equity, knowledge critical, brand management, branding

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Authors: Maya Jaber

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Climate change is one of the biggest challenges that require immediate attention and mitigation for the continued prosperity of human existence. The transformation will need to occur that is top-down and bottom-up on holistic scales. A new way of thinking will need to be adopted that is innovative, human-centric, and global. Designers and researchers are vital leaders in this movement that can help guide other practitioners in the strategy development, critical thinking process, and alignment of transformative solutions. Holistic critical thinking strategies will be essential to change behaviors and cultures for future generations' survival. This paper will discuss these topics associated with Dr. Jaber's research.

Keywords: environmental social governance (ESG), integral design thinking (IDT), organizational transformation, sustainability management

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Authors: Jianming Cai

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Exposure to ionizing radiation causes severe damage to human body and an safe and effective radioprotector is urgently required for alleviating radiation damage. In 2008, flagellin, an agonist of TLR5, was found to exert radioprotective effects on radiation injury through activating NF-kB signaling pathway. From then, the radioprotective effects of TLR ligands has shed new lights on radiation protection. CpG-ODN is an unmethylated oligonucleotide which activates TLR9 signaling pathway. In this study, we demonstrated that CpG-ODN has therapeutic effects on radiation injuries induced by γ ray and 12C6+ heavy ion particles. Our data showed that CpG-ODN increased the survival rate of mice after whole body irradiation and increased the number of leukocytes as well as the bone marrow cells. CpG-ODN also alleviated radiation damage on intestinal crypt through regulating apoptosis signaling pathway including bcl2, bax, and caspase 3 etc. By using a radiation-induced pulmonary fibrosis model, we found that CpG-ODN could alleviate structural damage, within 20 week after whole–thorax 15Gy irradiation. In this model, Th1/Th2 imbalance induced by irradiation was also reversed by CpG-ODN. We also found that TGFβ-Smad signaling pathway was regulated by CpG-ODN, which accounts for the therapeutic effects of CpG-ODN in radiation-induced pulmonary injury. On another hand, for high LET radiation protection, we investigated protective effects of CpG-ODN against 12C6+ heavy ion irradiation and found that after CpG-ODN treatment, the apoptosis and cell cycle arrest induced by 12C6+ irradiation was reduced. CpG-ODN also reduced the expression of Bax and caspase 3, while increased the level of bcl2. Then we detected the effect of CpG-ODN on heavy ion induced immune dysfunction. Our data showed that CpG-ODN increased the survival rate of mice and also the leukocytes after 12C6+ irradiation. Besides, the structural damage of immune organ such as thymus and spleen was also alleviated by CpG-ODN treatment. In conclusion, we found that TLR9 ligand, CpG-ODN reduced radiation injuries in response to γ ray and 12C6+ heavy ion irradiation. On one hand, CpG-ODN inhibited the activation of apoptosis induced by radiation through regulating bcl2, bax and caspase 3. On another hand, through activating TLR9, CpG-ODN recruit MyD88-IRAK-TRAF6 complex, activating TAK1, IRF5 and NF-kB pathway, and thus alleviates radiation damage. This study provides novel insights into protection and therapy of radiation damages.

Keywords: TLR9, CpG-ODN, radiation injury, high LET radiation

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Authors: Ella Tyuryumina, Alexey Neznanov

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This paper is devoted to mathematical modelling of the progression and stages of breast cancer. We propose Consolidated mathematical growth model of primary tumor and secondary distant metastases growth in patients with lymph nodes metastases (CoM-III) as a new research tool. We are interested in: 1) modelling the whole natural history of primary tumor and secondary distant metastases growth in patients with lymph nodes metastases; 2) developing adequate and precise CoM-III which reflects relations between primary tumor and secondary distant metastases; 3) analyzing the CoM-III scope of application; 4) implementing the model as a software tool. Firstly, the CoM-III includes exponential tumor growth model as a system of determinate nonlinear and linear equations. Secondly, mathematical model corresponds to TNM classification. It allows to calculate different growth periods of primary tumor and secondary distant metastases growth in patients with lymph nodes metastases: 1) ‘non-visible period’ for primary tumor; 2) ‘non-visible period’ for secondary distant metastases growth in patients with lymph nodes metastases; 3) ‘visible period’ for secondary distant metastases growth in patients with lymph nodes metastases. The new predictive tool: 1) is a solid foundation to develop future studies of breast cancer models; 2) does not require any expensive diagnostic tests; 3) is the first predictor which makes forecast using only current patient data, the others are based on the additional statistical data. Thus, the CoM-III model and predictive software: a) detect different growth periods of primary tumor and secondary distant metastases growth in patients with lymph nodes metastases; b) make forecast of the period of the distant metastases appearance in patients with lymph nodes metastases; c) have higher average prediction accuracy than the other tools; d) can improve forecasts on survival of breast cancer and facilitate optimization of diagnostic tests. The following are calculated by CoM-III: the number of doublings for ‘non-visible’ and ‘visible’ growth period of secondary distant metastases; tumor volume doubling time (days) for ‘non-visible’ and ‘visible’ growth period of secondary distant metastases. The CoM-III enables, for the first time, to predict the whole natural history of primary tumor and secondary distant metastases growth on each stage (pT1, pT2, pT3, pT4) relying only on primary tumor sizes. Summarizing: a) CoM-III describes correctly primary tumor and secondary distant metastases growth of IA, IIA, IIB, IIIB (T1-4N1-3M0) stages in patients with lymph nodes metastases (N1-3); b) facilitates the understanding of the appearance period and inception of secondary distant metastases.

Keywords: breast cancer, exponential growth model, mathematical model, primary tumor, secondary metastases, survival

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Authors: Rihab Hentati, Younes Boujelbene

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Nowadays we realize more and more than the value of a company is not only a function of its means of production but depends essentially on the managerial aptitude and orientation to implement the material and human means for generating profitability. Indeed, a productive R&D activity, a good strategy, and innovation are originally supplementary benefits that increase the value of the business. Is this ‘value-added’ closely linked to innovation? The purpose of our research is to Meta-analyze the results of 56 empirical studies in order to explain the overall effect of innovation on performance of small and medium-sized enterprises. In order to justify the differences in the results, we look for the moderating factors that may affect the innovation-performance relationship. We find a positive and significant relationship between innovation and performance in small and medium-sized enterprises. The results also note a positive relationship between entrepreneurial orientation, research and development (R&D), and performance in SMEs. In addition, innovation has a strong impact on performance measured both with accounting and market index. The originality of the article is based on a rigorous synthesis, based on several statistical tools, of an important subject of research in finance.

Keywords: innovation, performance, entrepreneurial orientation, meta-analysis, moderator variables

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Authors: Nervana Elbakary, Sami Ouanes, Sadaf Riaz, Oraib Abdallah, Islam Mahran, Noriya Al-Khuzaei, Yassin Eltorki

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Major Depressive Disorder (MDD) requires therapeutic interventions during the initial month after being diagnosed for better disease outcomes. International guidelines recommend a duration of 4–12 weeks for an initial antidepressant (IAD) trial at an optimized dose to get a response. If depressive symptoms persist after this duration, guidelines recommend switching, augmenting, or combining strategies as the next step. Most patients with MDD in the mental health setting have been labeled incorrectly as treatment-resistant where in fact they have not been subjected to an adequate trial of guideline-recommended therapy. Premature discontinuation of IAD due to ineffectiveness can cause unfavorable consequences. Avoiding irrational practices such as subtherapeutic doses of IAD, premature switching between the ADs, and refraining from unjustified polypharmacy can help the disease to go into a remission phase We aimed to determine the prevalence and the patterns of strategies applied after an IAD was changed because of a suboptimal response as a primary outcome. Secondary outcomes included the median survival time on IAD before any change; and the predictors that were associated with IAD change. This was a retrospective cross- sectional study conducted in Mental Health Services in Qatar. A dataset between January 1, 2018, and December 31, 2019, was extracted from the electronic health records. Inclusion and exclusion criteria were defined and applied. The sample size was calculated to be at least 379 patients. Descriptive statistics were reported as frequencies and percentages, in addition, to mean and standard deviation. The median time of IAD to any change strategy was calculated using survival analysis. Associated predictors were examined using two unadjusted and adjusted cox regression models. A total of 487 patients met the inclusion criteria of the study. The average age for participants was 39.1 ± 12.3 years. Patients with first experience MDD episode 255 (52%) constituted a major part of our sample comparing to the relapse group 206(42%). About 431 (88%) of the patients had an occurrence of IAD change to any strategy before end of the study. Almost half of the sample (212 (49%); 95% CI [44–53%]) had their IAD changed less than or equal to 30 days. Switching was consistently more common than combination or augmentation at any timepoint. The median time to IAD change was 43 days with 95% CI [33.2–52.7]. Five independent variables (age, bothersome side effects, un-optimization of the dose before any change, comorbid anxiety, first onset episode) were significantly associated with the likelihood of IAD change in the unadjusted analysis. The factors statistically associated with higher hazard of IAD change in the adjusted analysis were: younger age, un-optimization of the IAD dose before any change, and comorbid anxiety. Because almost half of the patients in this study changed their IAD as early as within the first month, efforts to avoid treatment failure are needed to ensure patient-treatment targets are met. The findings of this study can have direct clinical guidance for health care professionals since an optimized, evidence-based use of AD medication can improve the clinical outcomes of patients with MDD; and also, to identify high-risk factors that could worsen the survival time on IAD such as young age and comorbid anxiety

Keywords: initial antidepressant, dose optimization, major depressive disorder, comorbid anxiety, combination, augmentation, switching, premature discontinuation

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Authors: Arturo J. Anci Alméstar, Jose D. Fernandez Huapaya, David Mauricio

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Companies make erroneous decisions by not evaluating the inherent difficulties of entering electronic commerce without a prior review of current digital and alternate means of payment. For this reason, it is very important for businesses to have reliable, complete and integrated information on the means of current digital and alternate payments that allow decisions to be made about which of these to use. However, there is no such consolidated information or criteria that companies use to make decisions about the means of payment according to their needs. In this paper, we propose a decision tree model based on a taxonomy that presents us with a categorization of digital and alternative means of payment, as well as the visualization of the flow of information at a high level from the company to obtain a recommendation. This will allow the company to make the most appropriate decision about the implementation of the digital means of payment or alternative ideal for their needs, which allows a reduction in costs and complexity of the payment process. Likewise, the efficiency of the proposed model was evaluated through a satisfaction survey presented to company personnel, confirming the satisfactory quality level of the recommendations obtained by the model.

Keywords: digital payment medium, decision tree, decision making, digital payments taxonomy

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Authors: Jiri Kysucan, Dusan Klos, Katherine Vomackova, Pavel Koranda, Martin Lovecek, Cestmir Neoral, Roman Havlik

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Aim: The prognosis of patients with pancreatic cancer is poor. The median of survival after establishing diagnosis is 3-11 months without surgical treatment, 13-20 months with surgical treatment depending on the disease stage, 5-year survival is less than 5%. Radical surgical resection remains the only hope of curing the disease. Early diagnosis with valid establishment of tumor resectability is, therefore, the most important aim for patients with pancreatic cancer. The aim of the work is to evaluate the contribution and define the role of 18F-FDG PET/CT in preoperative staging. Material and Methods: In 195 patients (103 males, 92 females, median age 66,7 years, 32-88 years) with a suspect pancreatic lesion, as part of the standard preoperative staging, in addition to standard examination methods (ultrasonography, contrast spiral CT, endoscopic ultrasonography, endoscopic ultrasonographic biopsy), a hybrid 18F-FDG PET/CT was performed. All PET/CT findings were subsequently compared with standard staging (CT, EUS, EUS FNA), with peroperative findings and definitive histology in the operated patients as reference standards. Interpretation defined the extent of the tumor according to TNM classification. Limitations of resectability were local advancement (T4) and presence of distant metastases (M1). Results: PET/CT was performed in a total of 195 patients with a suspect pancreatic lesion. In 153 patients, pancreatic carcinoma was confirmed and of these patients, 72 were not indicated for radical surgical procedure due to local inoperability or generalization of the disease. The sensitivity of PET/CT in detecting the primary lesion was 92.2%, specificity was 90.5%. A false negative finding in 12 patients, a false positive finding was seen in 4 cases, positive predictive value (PPV) 97.2%, negative predictive value (NPV) 76,0%. In evaluating regional lymph nodes, sensitivity was 51.9%, specificity 58.3%, PPV 58,3%, NPV 51.9%. In detecting distant metastases, PET/CT reached a sensitivity of 82.8%, specificity was 97.8%, PPV 96.9%, NPV 87.0%. PET/CT found distant metastases in 12 patients, which were not detected by standard methods. In 15 patients (15.6%) with potentially radically resectable findings, the procedure was contraindicated based on PET/CT findings and the treatment strategy was changed. Conclusion: PET/CT is a highly sensitive and specific method useful in preoperative staging of pancreatic cancer. It improves the selection of patients for radical surgical procedures, who can benefit from it and decreases the number of incorrectly indicated operations.

Keywords: cancer, PET/CT, staging, surgery

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Authors: Raphael Udeh, Luis García De Guadiana Romualdo, Xenia Dolje-Gore

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Background: Quite disturbing is the huge public health impact of COVID-19: As at today [25th March 2021, the COVID-19 global burden shows over 123 million cases and over 2.7 million deaths worldwide. Rationale: Recent evidence shows calprotectin’s potential as a therapeutic target, stating that tasquinimod, from the Quinoline-3-Carboxamide family is capable of blocking the interaction between calprotectin and TLR4. Hence preventing the cytokine release syndrome, that heralds the functional exhaustion in COVID-19. Early preclinical studies showed that tasquinimod inhibit tumor growth and prevent angiogenesis/cytokine storm. Phase I – III clinical studies in prostate cancer showed it has a good safety profile with good radiologic progression free survival but no effect on overall survival. Rationale/hypothesis: Strategic endeavors have been amplified globally to assess new therapeutic interventions for COVID-19 management – thus the clinical and antiviral efficacy of tasquinimod in COVID-19 remains to be explored. Hence the primary objective of this trial will be to evaluate the efficacy of tasquinimod in the treatment of adult patients with severe COVID-19 infections. Therefore, I hypothesise that among adults with COVID19 infection, tasquinimod will reduce the severe respiratory distress associated with COVID-19 compared to placebo, over a 28-day study period. Method: The setting is in Europe. Design – a randomized, placebo-controlled, phase II double-blinded trial. Trial lasts for 28 days from randomization, Tasquinimod capsule given as 0.5mg daily 1st fortnight, then 1mg daily 2nd fortnight. I0 outcome - assessed using six-point ordinal scale alongside eight 20 outcomes. 125 participants to be enrolled, data collection at baseline and subsequent data points, and safety reporting monitored via serological profile. Significance: This work could potentially establish tasquinimod as an effective and safe therapeutic agent for COVID-19 by reducing the severe respiratory distress, related time to recovery, time on oxygen/admission. It will also drive future research – as in larger multi-centre RCT.

Keywords: Calprotectin, COVID-19, Phase II Trial, Tasquinimod

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Authors: Rabah Iratni, Husain El Hasasna, Khawlah Athamneh, Halima Al Sameri, Nehla Benhalilou, Asma Al Rashedi

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Background: Cancer therapies have witnessed great advances in the recent past, however, cancer continues to be a leading cause of death, with colorectal cancer being the fourth cause of cancer-related deaths. Colorectal cancer affects both sexes equally with poor survival rate once it metastasizes. Phytochemicals, which are plant derived compounds, have been on a steady rise as anti-cancer drugs due to the accumulation of evidences that support their potential. Here, we investigated the anticancer effect of Rhus coriaria on colon cancer cells. Material and Method: Human colon cancer HT-29 cell line was used. Protein expression and protein phosphorylation were examined using Western blotting. Transcription activity was measure using Quantitative RT-PCR. Human tumoral clonogenic assay was used to assess cell survival. Senescence was assessed by the senescence-associated beta-galactosidase assay. Results: Rhus coriaria extract (RCE) was found to significantly inhibit the viability and colony growth of human HT-29 colon cancer cells. RCE induced senescence and cell cycle arrest at G1 phase. These changes were concomitant with upregulation of p21, p16, downregulation of cyclin D1, p27, c-myc and expression of Senescence-associated-β-Galactosidase activity. Moreover, RCE induced non-canonical beclin-1independent autophagy and subsequent apoptotic cell death through activation of activation caspase 8 and caspase 7. The blocking of autophagy by 3-methyladenine (3-MA) or chloroquine (CQ) reduced RCE-induced cell death. Further, RCE induced DNA damage, reduced mutant p53 protein level and downregulated phospho-AKT and phospho-mTOR, events that preceded autophagy. Mechanistically, we found that RCE inhibited the AKT and mTOR pathway, a regulator of autophagy, by promoting the proteasome-dependent degradation of both AKT and mTOR proteins. Conclusion: Our findings provide strong evidence that Rhus coriaria possesses strong anti-colon cancer activity through induction of senescence and autophagic cell death, making it a promising alternative or adjunct therapeutic candidate against colon cancer.

Keywords: autophagy, proteasome degradation, senescence, mTOR, apoptosis, Beclin-1

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Authors: Go Bong Choi, Shin Je Lee, Sung Jin Yoo, Gibaek Lee, Jong Min Lee

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In South Korea, it is difficult to obtain data for statistical pipe assessment. In this paper, to address these issues, we find that various statistical model presented before is how data mixed with noise and are whether apply in South Korea. Three major type of model is studied and if data is presented in the paper, we add noise to data, which affects how model response changes. Moreover, we generate data from model in paper and analyse effect of noise. From this we can find robustness and applicability in Korea of each model.

Keywords: proportional hazard model, survival model, water main deterioration, ecological sciences

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Authors: Jiraporn Rojtinnakorn

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ICAM-2 (intercellular adhesion molecule 2) or CD102 (Cluster of Differentiation 102) is type I trans-membrane glycoproteins, composing 2-9 immunoglobulin-like C2-type domains. ICAM-2 plays the particular role in immune response and cell surveillance. It is concerned in innate and specific immunity, cell survival signal, apoptosis, and anticancer. EST clone of ICAM-2, from P. gigas blood cell EST libraries, showed high identity to human ICAM-2 (92%) with conserve region of ICAM N-terminal domain and part of Ig superfamily. Gene and protein of ICAM-2 has been founded in mammals. This is the first report of ICAM-2 in fish.

Keywords: ICAM-2, CD102, Pangasianodon gigas, antitumor

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Authors: Sandro Nikolaishvili

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The end of the eleventh and the beginning of the twelfth century was a transitional period for the Byzantine empire as well as for the Caucasus. The empire was struggling for its survival under Alexios I Komnenos while Medieval Georgia was emerging as a dominant player in the Caucasus under Davit IV the Builder. The reigns of these two rulers were periods of renewal and transformation. I aim to compare the imperial image of Alexios I Komnenos with the renewed kingship ideology under Davit IV. I will hypothesize about the possible translation of the Byzantine political culture into the Medieval Georgia.

Keywords: Byzantium, Georgia, imperial, image

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Authors: Maria L. G. Lourenço, Keylla H. N. P. Pereira, Viviane Y. Hibaru, Fabiana F. Souza, João C. P. Ferreira, Simone B. Chiacchio, Luiz H. A. Machado

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Orphaned is a risk factor for mortality in newborns since it is a condition with total or partial absence of maternal care that is essential for neonatal survival, including nursing (nutrition, the transference of passive immunity and hydration), warmth, urination, and defecation stimuli, and protection. The most common causes of mortality in orphans are related to lack of assistance, handling mistakes and infections. This study aims to describe the orphans rates in neonatal puppies, the main causes, and the mortality rates. The study included 735 neonates admitted to the Sao Paulo State University (UNESP) Veterinary Hospital, Botucatu, Sao Paulo, Brazil, between January 2018 and November 2019. The orphans rate was 43.4% (319/735) of all neonates included, and the main causes for orphaned were related to maternal agalactia/hypogalactia (23.5%, 75/319); numerous litter (15.7%, 50/319), toxic milk syndrome due to maternal mastitis (14.4%, 46/319), absence of suction/weak neonate (12.2%, 39/319), maternal disease (9.4%, 30/319), cleft palate/lip (6.3%, 20/319), maternal death (5.9%, 19/319), prematurity (5.3%, 17/319), rejection/failure in maternal instinct (3.8%, 12/319) and abandonment by the owner/separation of mother and neonate (3.5%, 11/319). The main consequences of orphaned observed in the admitted neonates were hypoglycemia, hypothermia, dehydration, aspiration pneumonia, wasting syndrome, failure in the transference of passive immunity, infections and sepsis, which happened due to failure of identifying the problem early, lack of adequate assistance, negligence and handling mistakes by the owner. The total neonatal mortality rate was 8% (59/735) and the neonatal mortality rate among orphans was 18.5% (59/319). The orphaned and mortality rates were considered high, but even higher rates may be observed in locations without adequate neonatal assistance and owner orientation. The survival of these patients is related to constant monitoring of the litter, early diagnosis and assistance, and the implementation of effective handling for orphans. Understanding the correct handling for neonates and instructing the owners regarding proper handling are essential to minimize the consequences of orphaned and the mortality rates.

Keywords: orphans, neonatal care, puppies, newborn dogs

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Authors: Michal Kielbik, Izabela Szulc-Kielbik, Anna Brzostek, Jaroslaw Dziadek, Magdalena Klink

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The goal of many research groups in the world is to find new components that are important for survival of mycobacteria in the host cells. Mycobacterium tuberculosis (Mtb) possesses a number of enzymes degrading cholesterol that are considered to be an important factor for its survival and persistence in host macrophages. One of them - cholesterol oxidase (ChoD), although not being essential for cholesterol degradation, is discussed as a virulence compound, however its involvement in macrophages’ response to Mtb is still not sufficiently determined. The recognition of tubercle bacilli antigens by pathogen recognition receptors is crucial for the initiation of the host innate immune response. An important receptor that has been implicated in the recognition and/or uptake of Mtb is Toll-like receptor type 2 (TLR2). Engagement of TLR2 results in the activation and phosphorylation of intracellular signaling proteins including IRAK-1 and -4, TRAF-6, which in turn leads to the activation of target kinases and transcription factors responsible for bactericidal and pro-inflammatory response of macrophages. The aim of these studies was a detailed clarification of the role of Mtb cholesterol oxidase as a virulence factor affecting the TLR2 signaling pathway in human macrophages. As human macrophages the THP-1 differentiated cells were applied. The virulent wild-type Mtb strain (H37Rv), its mutant lacking a functional copy of gene encoding cholesterol oxidase (∆choD), as well as complimented strain (∆choD–choD) were used. We tested the impact of Mtb strains on the expression of TLR2-depended signaling proteins (mRNA level, cytosolic level and phosphorylation status). The cytokine and bactericidal response of THP-1 derived macrophages infected with Mtb strains in relation to TLR2 signaling pathway dependence was also determined. We found that during the 24-hours of infection process the wild-type and complemented Mtb significantly reduced the cytosolic level and phosphorylation status of IRAK-4 and TRAF-6 proteins in macrophages, that was not observed in the case of ΔchoD mutant. Decreasement of TLR2-dependent signaling proteins, induced by wild-type Mtb, was not dependent on the activity of proteasome. Blocking of TLR2 expression, before infection, effectively prevented the induced by wild-type strain reduction of cytosolic level and phosphorylation of IRAK-4. None of the strains affected the surface expression of TLR2. The mRNA level of IRAK-4 and TRAF-6 genes were significantly increased in macrophages 24 hours post-infection with either of tested strains. However, the impact of wild-type Mtb strain on both examined genes was significantly stronger than its ΔchoD mutant. We also found that wild-type strain stimulated macrophages to release high amount of immunosuppressive IL-10, accompanied by low amount of pro-inflammatory IL-8 and bactericidal nitric oxide in comparison to mutant lacking cholesterol oxidase. The influence of wild-type Mtb on this type of macrophages' response strongly dependent on fully active IRAK-1 and IRAK-4 signaling proteins. In conclusion, Mtb using cholesterol oxidase causes the over-activation of TLR2 signaling proteins leading to the reduction of their cytosolic level and activity resulting in the modulation of macrophages response to allow its intracellular survival. Supported by grant: 2014/15/B/NZ6/01565, National Science Center, Poland

Keywords: Mycobacterium tuberculosis, cholesterol oxidase, macrophages, TLR2-dependent signaling pathway

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Authors: Ella Tyuryumina, Alexey Neznanov

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Finding algorithms to predict the growth of tumors has piqued the interest of researchers ever since the early days of cancer research. A number of studies were carried out as an attempt to obtain reliable data on the natural history of breast cancer growth. Mathematical modeling can play a very important role in the prognosis of tumor process of breast cancer. However, mathematical models describe primary tumor growth and metastases growth separately. Consequently, we propose a mathematical growth model for primary tumor and primary metastases which may help to improve predicting accuracy of breast cancer progression using an original mathematical model referred to CoM-IV and corresponding software. We are interested in: 1) modelling the whole natural history of primary tumor and primary metastases; 2) developing adequate and precise CoM-IV which reflects relations between PT and MTS; 3) analyzing the CoM-IV scope of application; 4) implementing the model as a software tool. The CoM-IV is based on exponential tumor growth model and consists of a system of determinate nonlinear and linear equations; corresponds to TNM classification. It allows to calculate different growth periods of primary tumor and primary metastases: 1) ‘non-visible period’ for primary tumor; 2) ‘non-visible period’ for primary metastases; 3) ‘visible period’ for primary metastases. The new predictive tool: 1) is a solid foundation to develop future studies of breast cancer models; 2) does not require any expensive diagnostic tests; 3) is the first predictor which makes forecast using only current patient data, the others are based on the additional statistical data. Thus, the CoM-IV model and predictive software: a) detect different growth periods of primary tumor and primary metastases; b) make forecast of the period of primary metastases appearance; c) have higher average prediction accuracy than the other tools; d) can improve forecasts on survival of BC and facilitate optimization of diagnostic tests. The following are calculated by CoM-IV: the number of doublings for ‘nonvisible’ and ‘visible’ growth period of primary metastases; tumor volume doubling time (days) for ‘nonvisible’ and ‘visible’ growth period of primary metastases. The CoM-IV enables, for the first time, to predict the whole natural history of primary tumor and primary metastases growth on each stage (pT1, pT2, pT3, pT4) relying only on primary tumor sizes. Summarizing: a) CoM-IV describes correctly primary tumor and primary distant metastases growth of IV (T1-4N0-3M1) stage with (N1-3) or without regional metastases in lymph nodes (N0); b) facilitates the understanding of the appearance period and manifestation of primary metastases.

Keywords: breast cancer, exponential growth model, mathematical modelling, primary metastases, primary tumor, survival

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Authors: Vanessa Kummer, Maik Meusel

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Real estate demand estimates are typically derived from transaction data. However, in regions with excess demand, transactions are driven by supply and therefore do not indicate what people are actually looking for. To estimate the demand for housing in Switzerland, search subscriptions from all important Swiss real estate platforms are used. These data do, however, suffer from missing information—for example, many users do not specify how many rooms they would like or what price they would be willing to pay. In economic analyses, it is often the case that only complete data is used. Usually, however, the proportion of complete data is rather small which leads to most information being neglected. Also, the data might have a strong distortion if it is complete. In addition, the reason that data is missing might itself also contain information, which is however ignored with that approach. An interesting issue is, therefore, if for economic analyses such as the one at hand, there is an added value by using the whole data set with the imputed missing values compared to using the usually small percentage of complete data (baseline). Also, it is interesting to see how different algorithms affect that result. The imputation of the missing data is done using unsupervised learning. Out of the numerous unsupervised learning approaches, the most common ones, such as clustering, principal component analysis, or neural networks techniques are applied. By training the model iteratively on the imputed data and, thereby, including the information of all data into the model, the distortion of the first training set—the complete data—vanishes. In a next step, the performances of the algorithms are measured. This is done by randomly creating missing values in subsets of the data, estimating those values with the relevant algorithms and several parameter combinations, and comparing the estimates to the actual data. After having found the optimal parameter set for each algorithm, the missing values are being imputed. Using the resulting data sets, the next step is to estimate the willingness to pay for real estate. This is done by fitting price distributions for real estate properties with certain characteristics, such as the region or the number of rooms. Based on these distributions, survival functions are computed to obtain the functional relationship between characteristics and selling probabilities. Comparing the survival functions shows that estimates which are based on imputed data sets do not differ significantly from each other; however, the demand estimate that is derived from the baseline data does. This indicates that the baseline data set does not include all available information and is therefore not representative for the entire sample. Also, demand estimates derived from the whole data set are much more accurate than the baseline estimation. Thus, in order to obtain optimal results, it is important to make use of all available data, even though it involves additional procedures such as data imputation.

Keywords: demand estimate, missing-data imputation, real estate, unsupervised learning

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Authors: Kurotimi Maurice Fems, Abara Onu, Francis W. D. Poazi

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Scholars and development economists believe that the development of an economy depends largely on the creative and innovative ingenuity of its entrepreneurs. Others however, are of the opinion that the lack of entrepreneurs or entrepreneurial activities is not a constraint to economic development in any economy, particularly Nigeria. This paper sets out to explore the connectivity between entrepreneurship and economic development from a theoretical point of view, principally in Nigeria. A desk research approach was adopted where a conglomerate of literatures was reviewed on how entrepreneurship can spur economic growth or otherwise. The findings reveal that entrepreneurship is vital to the development of Nigeria and that, universities and other Higher Education Institutions must play the vital role of educating the people on entrepreneurship skills and competences. However, the problems and difficulties entrepreneurs face in Nigeria and the same problems suffocating the growth and development of its economy. Therefore, entrepreneurship cannot be said to be the sole cure for economic under-development in Nigeria but rather other factors such as empowering and granting the institutions autonomy and the provision of infrastructural capability, such as consistent electricity generation and supply, good system of transportation, implementing proposed economic policies in an effective and efficient manner etc., the cultural beliefs and mindset of the citizenry, was also found to be key in the development of any economy.

Keywords: economic underdevelopment, entrepreneurial, entrepreneurship, infrastructural under-development, oil boom, SMEs, unemployable

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Authors: Aulia F. Hadining, Atya Nur Aisha, Dimas Kurninatoro Aji

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Utilization of social media as a marketing tool is growing rapidly, including for SMEs. Social media allows the user to give product evaluation and recommendations to the public. In addition, the social media facilitate word-of-mouth marketing communication. One of the social media that can be used is Facebook, with Facebook Ads. This study aimed to evaluate the location of Facebook Ads, to obtain an appropriate advertising design. There are three alternatives location consist of desktop, right-hand column and mobile. The effectiveness and efficiency of advertising will be measured based on advertising metrics such as reach, click, Cost per Click (CUC) and Unique Click-Through-Rate (UCTR). Facebook's Ads Manager was used for seven days, targeted by age (18-24), location (Bandung), language (Indonesia) and keywords. The result was 13,999 total reach, as well as 342 clicks. Based on the results of comparison using ANOVA, there was a significant difference for each placement location based on advertising metrics. Mobile location was chosen to be successful ads, because it produces the lowest CUC, amounting to Rp 691,- per click and 14% UCTR. Results of this study showed Facebook Ads was useful and cost-effective media to promote the product of SME, because it could be view by many people in the same time.

Keywords: marketing communication, social media, Facebook Ads, mobile location

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Authors: Hanadi Al-Mubaraki, Michael Busler

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Both in the developed and developing countries as well as Gulf Cooperation Council (GCC), the small and medium-sized enterprises (SMEs) proven to be main drivers of jobs creation and tools to accelerate economic development and economic diversification. This paper seeks to investigate and identify the strengths and weakness of SME as a veritable tool in economic development. A survey method was used to gather data from 171 SME from Gulf Cooperation Council (GCC). The research methodology uses a quantitative approach (survey) while data were collected with a structured questionnaire and analyzed with several descriptive statistics. The results of the study, therefore, will present sets of the strengths of SME in GCC such as 1) government supported local products (59%), 2) promoting SME local products rather than international products (47%), 3) reduce the legal and administrative procedures of SME establishment (46%) and weakness of SME in GCC such as: 1) lack of funding during the initial phase of the project (46%), 2) lack of liquidity during project continuity (39%), and 3) strong competition in the domestic and global market (38%). The study findings will be guidelines for academia and practitioners such as governments, policymakers, funded organizations, universities and strategic institutions for successful implementation.

Keywords: SME, economic development, GCC, strengths and weaknesses

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Authors: Kolawole-Amao, Grace Titilayo

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Children are the most vulnerable members of the society. The child is a foundation of the society and he/she assures its continuity. Thus, the survival, continuity and the standard of development of human society depends upon the protection, preservation, nurture and development of the child. In other words, the rights of a child must be protected and guaranteed for the assurance of a healthy society. The law is an instrument of social change in any society as well as a potent weapon to combat crime, achieve justice for the people and protect their rights. In Nigeria, child marriage still occurs, though its prevalence varies from one region to another. This paper shall Centre on child rights under the law in Nigeria, child marriage and its impact on the child, obstacles in eliminating child marriages and measures that have been adopted as well as the role of the law and its effect in deterring child marriage in Nigeria.

Keywords: child rights, child marriage, law, Nigeria

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Authors: Naseem Fatima, A. N. Srivastava, Tasleem Raza, Vijay Kumar

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Introduction: Carcinoma gallbladder is third most common gastrointestinal lethal disease with the highest incidence and mortality rate among women in Northern India. Scientists have found several risk factors that make a person more likely to develop gallbladder cancer; among these risk factors, deregulation of miRNAs has been demonstrated to be one of the most crucial factors. The changes in the expression of specific miRNA genes result in the control of inflammation, cell cycle regulation, stress response, proliferation, differentiation, apoptosis and invasion thus mediate the process in tumorgenesis. The aim of this study was to investigate the role of MiRNA-335 and may as a molecular marker in early detection of gallbladder cancer in suspected cases. Material and Methods: A total of 20 consecutive patients with gallbladder cancer aged between 30-75 years were registered for the study. Total RNA was extracted from tissue by using the mirVANA MiRNA isolation Kit according to the manufacturer’s protocol. The MiRNA- 335 and U6 snRNA-specific cDNA were reverse-transcribed from total RNA using Taqman microRNA reverse-transcription kit according to the manufacturer’s protocol. TaqMan MiRNA probes hsa-miR-335 and Taqman Master Mix without AmpEase UNG, Individual real-time PCR assays were performed in a 20 μL reaction volume on a Real-Time PCR system (Applied Biosystems StepOnePlus™) to detect MiRNA-335 expression in tissue. Relative quantification of target MiRNA expression was evaluated using the comparative cycle threshold (CT) method. The correlation was done in between cycle threshold (CT Value) of target MiRNA in gallbladder cancer with respect to non-cancerous Cholelithiasis gallbladder. Each sample was examined in triplicate. The Newman-Keuls Multiple Comparison Test was used to determine the expression of miR-335. Results: MiRNA335 was found to be significantly downregulated in the gallbladder cancer tissue (P<0.001), when compared with non-cancerous Cholelithiasis gallbladder cases. Out of 20 cases, 75% showed reduced expression of MiRNA335, were at last stage of disease with low overall survival rate and remaining 25% were showed up-regulated expression of MiRNA335 with high survival rate. Conclusion: The present study showed that reduced expression of MiRNA335 is associated with the advancement of the disease, and its deregulation may provide important clues to understanding it as a prognostic marker and opportunities for future research.

Keywords: carcinoma gallbladder, downregulation, MiRNA-335, RT-PCR assay

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Authors: Karen Boaz, C. R. Charan

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Background: The infiltration of tumour stroma by eosinophils, Tumor-Associated Tissue Eosinophilia (TATE), is known to modulate the progression of Oral Squamous Cell Carcinoma (OSCC). Eosinophils have direct tumoricidal activity by release of cytotoxic proteins and indirectly they enhance permeability into tumor cells enabling penetration of tumoricidal cytokines. Also, eosinophils may promote tumor angiogenesis by production of several angiogenic factors. Identification of eosinophils in the inflammatory stroma has been proven to be an important prognosticator in cancers of mouth, oesophagus, larynx, pharynx, breast, lung, and intestine. Therefore, the study aimed to correlate TATE with clinical and histopathological variables, and blood eosinophil count to assess the role of TATE as a prognosticator in Oral Squamous Cell Carcinoma (OSCC). Methods: Seventy two biopsy-proven cases of OSCC formed the study cohort. Blood eosinophil counts and TNM stage were obtained from the medical records. Tissue sections (5µm thick) were stained with Haematoxylin and Eosin. The eosinophils were quantified at invasive tumour front (ITF) in 10HPF (40x magnification) with an ocular grid. Bryne’s grading of ITF was also performed. A subset of thirty cases was also assessed for association of TATE with recurrence, involvement of lymph nodes and surgical margins. Results: 1) No statistically significant correlation was found between TATE and TNM stage, blood eosinophil counts and most parameters of Bryne’s grading system. 2) Statistically significant relation of intense degree of TATE was associated with the absence of distant metastasis, increased lympho-plasmacytic response and increased survival (diseasefree and overall) of OSCC patients. 3) In the subset of 30 cases, tissue eosinophil counts were higher in cases with lymph node involvement, decreased survival, without margin involvement and in cases that did not recur. Conclusion: While the role of eosinophils in mediating immune responses seems ambiguous as eosinophils support cell-mediated tumour immunity in early stages while inhibiting the same in advanced stages, TATE may be used as a surrogate marker for determination of prognosis in oral squamous cell carcinoma.

Keywords: tumour-associated tissue eosinophilia, oral squamous cell carcinoma, prognosticator, tumoral immunity

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Authors: Javad Moghtader Kargaran

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Today, attention to knowledge and management Knowledge as a strategy is very important has taken with economy becoming knowledge-oriented, how and knowing the effective management and integration of different types Knowledge (obvious-implicit) to preserve and create advantage. Competition has become very important. Knowledge is a valuable resource for empowering organizations in the direction of innovation and competition. Due to the importance of human resources in the survival of organizations, extensive efforts are made to empower them. This knowledge can lead to awareness among employees. Employees and the knowledge that is in their minds are very valuable resources for the organization, which must be managed and developed. In fact, the ultimate goal of knowledge management is to increase the intelligence and productivity of employees and the organization.

Keywords: knowledge, management, productivity, human

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