Search results for: SMEs survival

Authors: Tadayuki Kyoutani, Shigeyuki Haruyama, Ken Kaminishi, Zefry Darmawan

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Japan’s semiconductor industries have developed greatly in recent years. Many were started from a Small and Medium-sized Enterprises (SMEs) that found at a good circumstance and now become the prosperous industries in the world. Sustainable growth factors that support the creation of spirit value inside the Japanese company were strongly embedded through performance. Those factors were not clearly defined among each company. A series of literature research conducted to explore quantitative text mining about the definition of sustainable growth factors. Sustainable criteria were developed from previous research to verify the definition of the factors. A typical frame work was proposed as a systematical approach to develop sustainable growth factor in a specific company. Result of approach was review in certain period shows that factors influenced in sustainable growth was importance for the company to achieve the goal.

Keywords: SME, manufacture, sustainable, growth factor

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Authors: Chiara Colarusso, Michela Terlizzi, Aldo Pinto, Rosalinda Sorrentino

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Cigarette smoking is the main cause and the most common risk factor for both COPD and lung cancer. In our previous studies, we proved that caspase-11 in mice and its human analogue, caspase-4, are involved in lung carcinogenesis and that AIM2 inflammasome might play a pro-cancerous role in lung cancer. Therefore, the aim of this study was to investigate potential crosstalk between COPD and lung cancer, focusing on AIM2 and caspase-11-dependent inflammasome signaling pathway. To mimic COPD, we took advantage of an experimental first-hand smoking mouse model and, to confirm what was observed in mice, we used human samples of lung adenocarcinoma patients stratified according to the smoking and COPD status. We demonstrated that smoke exposure led to emphysema-like features, bronchial tone impairment, and release of IL-1-like cytokines (IL-1α, IL-1β, IL-33, IL-18) in a caspase-1 independent manner in C57Bl/6N. Rather, a dysfunctional caspase-11 in smoke-exposed 129Sv mice was associated to lower bronchial inflammation, collagen deposition, and IL-1-like inflammation. In addition, for the first time, we found that AIM2 inflammasome is involved in lung inflammation in smoking and COPD, in that its expression was higher in smoke-exposed C57Bl/6N compared to 129Sv smoking mice, who instead did not show any alteration of AIM2 in both macrophages and dendritic cells. Moreover, we found that AIM2 expression in the cancerous tissue, albeit higher than non-cancerous tissue, was not statistically different according to the COPD and smoking status. Instead, the higher expression of AIM2 in non-cancerous tissue of smoker COPD patients than smokers who did not have COPD was correlated to a higher hazard ratio of poor survival rate than patients who presented lower levels of AIM2. In conclusion, our data highlight that caspase-11 in mice is associated to smoke-induced lung latent inflammation which could drive the establishment of lung cancer, and that AIM2 inflammasome plays a role at the crosstalk between smoking/COPD and lung adenocarcinoma in that its higher presence is correlated to lower survival rate of smoker COPD adenocarcinoma.

Keywords: COPD, inflammasome, lung cancer, lung inflammation, smoke

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Authors: Q. B. Maria de la Luz Ortega Juárez, Saúl Rojas Hernández, Itzel Berenice Rodríguez Mera, María Maricela Carrasco Yépez, Mara Gutierrez Sánchez

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Naegleria fowleri is a free-living amoeba found mainly in temperate freshwater and is the etiologic agent of primary amebic meningoencephalitis (PAM), a fatal acute disease with a mortality rate greater than 95%. At present, there are no treatments available for MAP, and the development of effective vaccines that generate long-term immunological memory allowing protection against MAP would be of great importance. The objective of this work was to analyze the effector and memory immune response in BALB/c mice immunized with total extract of N. fowleri co-administered with cholera toxin. In this study, BALB/c mice were immunized four times intranasally with ET of N. fowleri adjuvanted with CT with or without booster at three months and were challenged or not with the lethal dose of N. fowleri, determining survival, the humoral, effector and memory response, by ELISA and flow cytometry techniques. The results obtained showed that the survival of mice immunized with booster had 60% protection compared to the group without booster, which obtained 20% protection. Evaluating the humoral response, it was found that both IgG and IgA levels were higher in sera than in nasal washes in both treatments. In the cellular response, the increase in the percentage of positive cells was found for effector T and B lymphocytes in the nasal passages (NP) in the group with boost and nasopharynx-associated lymphoid tissue (NALT) in the group without boost and lymphocytes only. B in both treatments, as well as in memory cells treatment with boost T lymphocytes in PN and NALT and without boost in cervical lymph nodes (CG) with respect to B lymphocytes, in PN, GC and NALT in treatment with boost and NALT in treatment without booster. Therefore, the involvement of the effector immune response and memory play a fundamental role for protection against N. fowleri and for the development of vaccine candidates.

Keywords: immune response, immunological memory, naegleria fowleri, primary amebic meningoencephalitis

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Authors: Suphat Rittirat, Sutha Klaocheed, Kanchit Thammasiri

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The effects of thidiazuron (TDZ) and benzyladenine (BA) on protocorm-like bodies (PLBs) induction from leaf explants was investigated. It was found that TDZ was superior to BA. The highest percentage and number of PLBs per leaf explant at 30 and 5.3 respectively were obtained on ½ MS medium supplemented with 9µM TDZ. The regenerated plantlets were potted and acclimatized in the greenhouse. These plants grew well and developed into normal plants after 3 month of transplantation. The 100% survival of plantlets was achieved when planted on pots containing sphagnum moss.

Keywords: orchid, PLBs, sphagnum moss, thidiazuron

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Authors: Kim Kennedy, Daren Gibson, Stephanie Flukes, Chandra Diwakarla, Lisa Spalding, Leanne Pilkington, Andrew Redfern

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Introduction: The mortality gap in Aboriginal Head and Neck Cancer is well known, but the reasons for poorer survival are not well established. Aim: We aimed to evaluate the locoregional and metastatic involvement, and stage at diagnosis, in Aboriginal compared with non-Aboriginal patients. Methods: We performed a retrospective cohort analysis of 320 HNC patients from a single centre in Western Australia, identifying 80 Aboriginal patients and 240 non-Aboriginal patients matched on a 1:3 ratio by sites, histology, rurality, and age. We collected data on the patient characteristics, tumour features, regions involved, stage at diagnosis, treatment history, and survival and relapse patterns, including sites of metastatic and locoregional involvement. Results: Aboriginal patients had a significantly higher incidence of lung metastases (26.3% versus 13.7%, p=0.009). Aboriginal patients also had a numerically but non-statistically significant higher incidence of thoracic nodal involvement (10% vs 5.8%) and malignant pleural effusions (3.8% vs 2.5%). Aboriginal patients also had a numerically but not statistically significantly higher incidence of adrenal and bony involvement. Interestingly, non-Aboriginal patients had an increased rate of cutaneous (2.1% vs 0%) and liver metastases (4.6% vs 2.5%) compared with Aboriginal patients. In terms of locoregional involvement, Aboriginal patients were more than twice as likely to have contralateral neck involvement (58.8% vs 24.2%, p<0.00001), and 30% more likely to have ipsilateral neck lymph node involvement (78.8% vs 60%, p=0.002) than non-Aboriginal patients. Aboriginal patients had significantly more advanced disease at diagnosis (p=0.008). Aboriginal compared with non-Aboriginal patients were less likely to present with stage I (7.5% vs 22.5%), stage II (11.3% vs 13.8%), or stage III disease (13.8% vs 17.1%), and more likely to present with more advanced stage IVA (42.5% vs 34.6%), stage IVB (15% vs 7.1%), or stage IVC (10% vs 5%) disease (p=0.008). Number of regions of disease involvement was higher in Aboriginal patients (median 3, mean 3.64, range 1-10) compared with non-Aboriginal patients (median 2, mean 2.80, range 1-12). Conclusion: Aboriginal patients had a significantly higher incidence of lung metastases, and significantly more frequent involvement of ipsilateral and contralateral neck lymph nodes. Aboriginal patients also had significantly more advanced disease at presentation with a higher stage at diagnosis. We are performing further analyses to investigate explanations for these findings.

Keywords: head and neck cancer, Aboriginal, metastases, locoregional, pattern of relapse, sites of disease

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Authors: Angelica Alvarez-Lee, Sergio Martinez-Diaz, Jose Luis Garcia-Corona, Humberto Lanz-Mendoza

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World aquaculture is always looking for improvements to achieve productions with high yields avoiding the infection by pathogenic agents. The best way to achieve this is to know the biological model to create alternative treatments that could be applied in the hatcheries, which results in greater economic gains and improvements in human public health. In the last decade, immunomodulation in shrimp culture with probiotics, organic acids and different carbon sources has gained great interest, mainly in larval and juvenile stages. Immune priming is associated with a strong protective effect against a later pathogen challenge. This work provides another perspective about immunostimulation from spawning until hatching. The stimulation happens during development embryos and generates resistance to infection by pathogenic bacteria. Massive spawnings of white shrimp L. vannamei were obtained and placed in experimental units with 700 mL of sterile seawater at 30 °C, salinity of 28 ppm and continuous aeration at a density of 8 embryos.mL⁻¹. The immunostimulating effect of three death strains of non-pathogenic bacterial (Escherichia coli, Staphylococcus aureus and Bacillus subtilis) and a pathogenic strain for white shrimp (Vibrio parahaemolyticus) was evaluated. The strains killed by heat were adjusted to O.D. 0.5, at A 600 nm, and directly added to the seawater of each unit at a ratio of 1/100 (v/v). A control group of embryos without inoculum of dead bacteria was kept under the same physicochemical conditions as the rest of the treatments throughout the experiment and used as reference. The duration of the stimulus was 12 hours, then, the larvae that hatched were collected, counted and transferred to a new experimental unit (same physicochemical conditions but at a salinity of 28 ppm) to carry out a challenge of infection against the pathogen V. parahaemolyticus, adding directly to seawater an amount 1/100 (v/v) of the live strain adjusted to an OD 0.5; at A 600 nm. Subsequently, 24 hrs after infection, nauplii survival was evaluated. The results of this work shows that, after 24 hrs, the hatching rates of immunostimulated shrimp embryos with the dead strains of B. subtillis and V. parahaemolyticus are significantly higher compared to the rest of the treatments and the control. Furthermore, survival of L. vanammei after a challenge of infection of 24 hrs against the live strain of V. parahaemolyticus is greater (P < 0.05) in the larvae immunostimulated during the embryonic development with the dead strains B. subtillis and V. parahaemolyticus, followed by those that were treated with E. coli. In summary superficial antigens can stimulate the development cells to promote hatching and can have normal development in agreeing with the optical observations, plus exist a differential response effect between each treatment post-infection. This research provides evidence of the immunostimulant effect of death pathogenic and non-pathogenic bacterial strains in the rate of hatching and oversight of shrimp L. vannamei during embryonic and larval development. This research continues evaluating the effect of these death strains on the expression of genes related to the defense priming in larvae of L. vannamei that come from massive spawning in hatcheries before and after the infection challenge against V. parahaemolyticus.

Keywords: immunostimulation, L. vannamei, hatching, survival

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Authors: A. Boudiaf

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The purpose of this paper is to analyze and apprehend, through four case studies, the interest of the project of the implementation of the quality management system (QMS) at four Moroccan small and medium-sized enterprises (SMEs). This project could generate significant organizational change to improve the functioning of the organization. In fact, quality is becoming a necessity in the current business world. It is considered to be a major component in companies’ competitive strategies. It should be noted that quality management is characterized by a set of methods and techniques that can be used to solve malfunctions and reorganize companies. It is useful to point out that the choice of the adoption of the quality approach could be influenced by the circumstances of the business context, it could also be derived from its strategic vision; this means that this choice can be characterized as either a strategic aspect or a reactive aspect. This would probably have a major impact on the functioning of the QMS and also on the perception of the quality issue by company managers and their employees.

Keywords: business context, organizational change, quality, reorganization

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Authors: Sohaib Raza, Parvez Mantry

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Frailty is a multi-system impairment associated with stressors such as age, disease, and invasive surgical procedures. This multi-system impairment can lead to increased post-transplant mortality and functional decline. Additionally, the prevalence and/or severity of frailty increases when patient pre-habilitation is unsatisfactory or lacking. We conducted a retrospective study to examine whether the COVID-19 Pandemic, and subsequent lack of patient access to pre-habilitation and physical therapy resources, led to an increase in the prevalence and severity of frailty, sarcopenia, and other comorbidities including diabetes, hypertension, and COPD. Secondarily, we examined the correlation between patient survival rate and liver frailty index as well as muscle wasting/sarcopenia. Data were analyzed in order to correlate variables associated with these parameters. Three hundred sixty-nine liver transplant candidates at Methodist Dallas Medical Center were administered pre-transplant frailty assessments, which consisted of chair stands, grip strength, and position balance time. A frailty score less than 3.2 indicated a robust condition, a score from 3.3 to 4.4 indicated a pre-frail condition, and a score greater than 4.5 indicated a frail condition. Greater than 50 percent of patients were found to have muscle wasting in the COVID-19 period (March 13, 2020 to February 28, 2022), an increase of 16.5 percent from the pre-COVID period (April 1st, 2018 to March 12, 2020). Additionally, sarcopenia was associated with a two-fold increase in patient mortality rate. Furthermore, high liver frailty index scores were associated with increased patient mortality. However, there was no significant difference in liver frailty index or number of comorbidities between patients in the two cohorts. Conclusion: The COVID-19 Pandemic exacerbated sarcopenia-related muscle wasting in liver transplant candidates, and patient survival rate was directly correlated with liver frailty index score and the presence of sarcopenia.

Keywords: frailty, sarcopenia, covid-19, patient mortality, pre-habilitation, liver transplant candidates

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Authors: Tarana Siddika, Ilka U. Heinemann, Patrick O’Donoghue

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Protein kinase B (AKT1) is a serine/threonine kinase and central transducer of cell survival pathways. Typical approaches to study AKT1 biology in cells rely on growth factor or insulin stimulation that activates AKT1 via phosphorylation at two key regulatory sites (Threonine308, Serine473), yet cell stimulation also activates many other kinases and fails to differentiate the effect of the two main activating sites of AKT1 on downstream substrate phosphorylation and cell growth. While both AKT1 activating sites are associated with disease and used as clinical markers, in some cancers, high levels of Threonine308 phosphorylation are associated with poor prognosis while in others poor survival correlates with high Serine473 levels. To produce cells with specific AKT1 activity, a system was developed to deliver active AKT1 to human cells. AKT1 phospho-variants were produced from Escherichia coli with programmed phosphorylation by genetic code expansion. Tagging of AKT1 with an N-terminal cell penetrating peptide tag derived from the human immunodeficiency virus trans-activator of transcription (TAT) helped to enter AKT1 proteins in mammalian cells. The TAT-tag did not alter AKT1 kinase activity and was necessary and sufficient to rapidly deliver AKT1 protein variants that persisted in human cells for 24 h without the need to use transfection reagents. TAT-pAKT1T308, TAT-pAKT1S473 and TAT-pAKT1T308S473 proteins induced selective phosphorylation of the known AKT1 substrate GSK-3αβ, and downstream stimulation of the AKT1 pathway as evidenced by phosphorylation of ribosomal protein S6 at Serine240/244 in transfected cells. Increase in cell growth and proliferation was observed due to the transfection of different phosphorylated AKT1 protein variants compared to cells with TAT-AKT1 protein. The data demonstrate efficient delivery of AKT1 with programmed phosphorylation to human cells, thus establishing a cell-based model system to investigate signaling that is dependent on specific AKT1 activity and phosphorylation.

Keywords: cell penetrating peptide, cell signaling, protein kinase b (AKT1), phosphorylation

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Authors: Ayon Mukherjee

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Covariate-adjusted response-adaptive (CARA) designs use the available responses to skew the treatment allocation in a clinical trial in towards treatment found at an interim stage to be best for a given patient's covariate profile. Extensive research has been done on various aspects of CARA designs with the patient responses assumed to follow a parametric model. However, ranges of application for such designs are limited in real-life clinical trials where the responses infrequently fit a certain parametric form. On the other hand, robust estimates for the covariate-adjusted treatment effects are obtained from the parametric assumption. To balance these two requirements, designs are developed which are free from distributional assumptions about the survival responses, relying only on the assumption of proportional hazards for the two treatment arms. The proposed designs are developed by deriving two types of optimum allocation designs, and also by using a distribution function to link the past allocation, covariate and response histories to the present allocation. The optimal designs are based on biased coin procedures, with a bias towards the better treatment arm. These are the doubly-adaptive biased coin design (DBCD) and the efficient randomized adaptive design (ERADE). The treatment allocation proportions for these designs converge to the expected target values, which are functions of the Cox regression coefficients that are estimated sequentially. These expected target values are derived based on constrained optimization problems and are updated as information accrues with sequential arrival of patients. The design based on the link function is derived using the distribution function of a probit model whose parameters are adjusted based on the covariate profile of the incoming patient. To apply such designs, the treatment allocation probabilities are sequentially modified based on the treatment allocation history, response history, previous patients’ covariates and also the covariates of the incoming patient. Given these information, an expression is obtained for the conditional probability of a patient allocation to a treatment arm. Based on simulation studies, it is found that the ERADE is preferable to the DBCD when the main aim is to minimize the variance of the observed allocation proportion and to maximize the power of the Wald test for a treatment difference. However, the former procedure being discrete tends to be slower in converging towards the expected target allocation proportion. The link function based design achieves the highest skewness of patient allocation to the best treatment arm and thus ethically is the best design. Other comparative merits of the proposed designs have been highlighted and their preferred areas of application are discussed. It is concluded that the proposed CARA designs can be considered as suitable alternatives to the traditional balanced randomization designs in survival trials in terms of the power of the Wald test, provided that response data are available during the recruitment phase of the trial to enable adaptations to the designs. Moreover, the proposed designs enable more patients to get treated with the better treatment during the trial thus making the designs more ethically attractive to the patients. An existing clinical trial has been redesigned using these methods.

Keywords: censored response, Cox regression, efficiency, ethics, optimal allocation, power, variability

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Authors: Kiana Taheri

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Rural tourism has garnered significant attention as a catalyst for rural development and sustainability, particularly in regions like Tuscany, Italy, where the convergence of cultural heritage, picturesque landscapes, and agricultural traditions provides a fertile ground for tourism activities. This paper investigates the pivotal role of women entrepreneurs in driving sustainable rural tourism development, with a specific focus on Tuscany. Drawing upon a synthesis of literature on rural tourism, entrepreneurship, and gender studies, this research offers insights into how women entrepreneurs contribute to the economic, social, and environmental dimensions of rural tourism in Tuscany. The conceptual framework of this study is rooted in the evolving landscape of rural development, shaped by shifting paradigms in agricultural policies, such as the Common Agricultural Policy (CAP) of the European Union. This framework underscores the transition from traditional agrarian economies to dynamic rural tourism destinations characterized by a consumer-centric approach and a focus on sustainable development. Against this backdrop, the study delves into the multifaceted contributions of women entrepreneurs within the rural tourism sector. Central to the analysis is the recognition of rural tourism as a nexus of social, cultural, economic, and environmental interactions, wherein women entrepreneurs play a pivotal role in leveraging local resources, preserving cultural heritage, and fostering community engagement. By capitalizing on their unique perspectives, skills, and networks, women entrepreneurs drive innovation, diversification, and inclusivity within the tourism sector, thereby enhancing its resilience and long-term viability. Moreover, the study highlights the symbiotic relationship between rural tourism development and women's empowerment, as evidenced by the increasing prominence of women entrepreneurs in Tuscany's rural economy. Through their leadership roles in small and medium enterprises (SMEs) and agritourism ventures, women entrepreneurs not only contribute to economic growth but also challenge traditional gender norms and empower local communities. A key empirical focus of this research is a comprehensive case study of Tuscany, renowned for its successful rural tourism model and vibrant entrepreneurial ecosystem. Through qualitative interviews, surveys, and archival analysis, the study elucidates the strategies, challenges, and impacts of women entrepreneurs on sustainable rural tourism development in Tuscany. By examining the experiences of women entrepreneurs across diverse sectors of rural tourism, including hospitality, gastronomy, and cultural heritage, the study offers nuanced insights into their contributions to regional development and empowerment. In conclusion, this research contributes to the burgeoning scholarship on rural tourism, entrepreneurship, and gender studies by shedding light on the transformative role of women entrepreneurs in driving sustainable development agendas in rural areas. By elucidating the interplay between gender dynamics, entrepreneurial activities, and tourism development, this study seeks to inform policy interventions and strategic initiatives aimed at fostering inclusive and sustainable rural tourism ecosystems.

Keywords: rural tourism, women empowerment, entrepreneurship, sustainable development, small and medium-sized enterprises (SMEs)

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

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

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

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Authors: Liu Yao, B. T. Wan Maseri, Wan Mohd, B. T. Nurul Izzah, Mohd Shah, Wei Wei

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Effectively managing knowledge has become a vital weapon for businesses to survive or to succeed in the increasingly competitive market. But do they perform environmental analysis when managing knowledge? If yes, how is the level and significance? This paper established a conceptual framework covering the basic knowledge management activities (KMA) to examine their contribution towards organizational performance (OP). Environmental analysis (EA) was then investigated from both internal and external aspects, to identify its effects on that contribution. Data was collected from 400 Chinese SMEs by questionnaires. Cronbach's α and factor analysis were conducted. Regression results show that the external analysis presents higher level than internal analysis. However, the internal analysis mediates the effects of external analysis on the KMA-OP relation and plays more significant role in the relation comparing with the external analysis. Thus, firms shall improve environmental analysis especially the internal analysis to enhance their KM practices.

Keywords: knowledge management, environmental analysis, performance, mediating, small sized enterprises, medium sized enterprises

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Authors: Nguyen Thi Hoang Hieu

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Mergers and Acquisitions (M&A) activities have increasingly become popular in both developed and developing countries. It is also an attractive topic for researchers to exploit in various sectors such as business, economies or finance. However, activities of Small and Medium Enterprises (SMEs) in M&A activities for a long time have not been sufficiently studied to provide the complete picture of what has been really, particularly in the developing market like Vietnam. The study employs semi-structured in-depth interviews with experts who have worked for years in the M&A sector to explore the participation motivation of both buy side and sell side of M&A activities. In addition, through the interviews, the study attempts to explain how firms finance their M&A deals. The collected data then will be content-analyzed to reflect the study's expectations based on the theories and practices reviews. In addition, limitations and recommendations are given in the hope that the M&A performance in Vietnam can be improved in the future.

Keywords: mergers and acquisitions, Vietnam, small and medium enterprises, content-analysis, semi-structure in-depth interview

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Authors: Akinsola Oluwatosin, Udofia Samuel, Odofin Mayowa

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The study is aimed at assessing the Geographic Information System (GIS)-based spatial analysis of Survival Pattern and Treatment Outcomes of Multi-Drug Resistant Tuberculosis (MDR-TB) cases for Lagos, Nigeria, with an objective to inform priority areas for public health planning and resource allocation. Multi-drug resistant tuberculosis (MDR-TB) develops due to problems such as irregular drug supply, poor drug quality, inappropriate prescription, and poor adherence to treatment. The shapefile(s) for this study were already georeferenced to Minna datum. The patient’s information was acquired on MS Excel and later converted to . CSV file for easy processing to ArcMap from various hospitals. To superimpose the patient’s information the spatial data, the addresses was geocoded to generate the longitude and latitude of the patients. The database was used for the SQL query to the various pattern of the treatment. To show the pattern of disease spread, spatial autocorrelation analysis was used. The result was displayed in a graphical format showing the areas of dispersing, random and clustered of patients in the study area. Hot and cold spot analysis was analyzed to show high-density areas. The distance between these patients and the closest health facility was examined using the buffer analysis. The result shows that 22% of the points were successfully matched, while 15% were tied. However, the result table shows that a greater percentage of it was unmatched; this is evident in the fact that most of the streets within the State are unnamed, and then again, most of the patients are likely to supply the wrong addresses. MDR-TB patients of all age groups are concentrated within Lagos-Mainland, Shomolu, Mushin, Surulere, Oshodi-Isolo, and Ifelodun LGAs. MDR-TB patients between the age group of 30-47 years had the highest number and were identified to be about 184 in number. The outcome of patients on ART treatment revealed that a high number of patients (300) were not ART treatment while a paltry 45 patients were on ART treatment. The result shows the Z-score of the distribution is greater than 1 (>2.58), which means that the distribution is highly clustered at a significance level of 0.01.

Keywords: tuberculosis, patients, treatment, GIS, MDR-TB

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Authors: Moustafa Osman

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The paper describes and analyses different good practice examples of protective levels, and initiatives actions (“framework conditions”) and encourages the uptake of environmental management systems (EMSs) to small and medium-sized enterprises (SMEs). Most of industries tend to take EMS as tools leading towards sustainability planning. The application of these tools has numerous environmental obligations that neither suggests decision nor recommends what a company should achieve ultimately. These set up clearly defined criteria to evaluate environmental protective action (EEPA) into sustainability indicators. The physical integration will evaluate how to incorporate traditional knowledge into baseline information, preparing impact prediction, and planning mitigation measures in monitoring conditions. Thereby efforts between the government, industry and community led protective action to concern with present needs for future generations, meeting the goal of sustainable development. The paper discusses how to set out distinct aspects of sustainable indicators and reflects inputs, outputs, and modes of impact on the environment.

Keywords: environmental management, sustainability, indicators, protective action

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Authors: Romain Ben Taleb, Aurélie Montarnal, Matthieu Lauras, Mathieu Dahan, Romain Miclo

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To be competitive and sustainable, any company has to maximize its value. However, unlike listed companies that can assess their values based on market shares, most Small and Medium Enterprises (SMEs) which are non-listed cannot have direct and live access to this critical information. Traditional accounting reports only give limited insights to SME decision-makers about the real impact of their day-to-day decisions on the company’s performance and value. Most of the time, an SME’s financial valuation is made one time a year as the associated process is time and resource-consuming, requiring several months and external expertise to be completed. To solve this issue, we propose in this paper a value-oriented metamodel that enables real-time and dynamic assessment of the SME’s value based on the large definition of their assets. These assets cover a wider scope of resources of the company and better account for immaterial assets. The proposal, which is illustrated in a case study, discusses the benefits of incorporating assets in the SME valuation.

Keywords: SME, metamodel, decision support system, financial valuation, assets

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Authors: Soodabeh Shahid Sales, Azam Rastgar Moghadam, Mehrane Mehramiz, Malihe Entezari, Kazem Anvari, Mohammad Sadegh Khorrami, Saeideh Ahmadi Simab, Ali Moradi, Seyed Mahdi Hassanian, Majid Ghayour-Mobarhan, Gordon A. Ferns, Amir Avan

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Background Esophageal cancer has been reported as the eighth most common cancer universal and the seventh cause of cancer-related death in men .recent studies have revealed that cytochrome P450, family 1, subfamily B, polypeptide 1, which plays a role in metabolizing xenobiotics, is associated with different cancers. Therefore in the present study, we investigated the impact of CYP1B1-rs1056836 on esophagus squamous cell carcinoma (ESCC) patients. Method: 317 subjects, with and without ESCC were recruited. DNA was extracted and genotyped via Real-time PCR-Based Taq Man. Kaplan Meier curves were utilized to assess overall and progression-free survival. To evaluate the relationship between patients clinicopathological data, genotypic frequencies, disease prognosis, and patients survival, Pearson chi-square and t-test were used. Logistic regression was utilized to assess the association between the risk of ESCC and genotypes. Results: the genotypic frequency for GG, GC, and CC are respectively 58.6% , 29.8%, 11.5% in the healthy group and 51.8%, 36.14% and 12% in ESCC group. With respect to the recessive genetic inheritance model, an association between the GG genotype and stage of ESCC were found. Also, statistically significant results were not found for this variation and risk of ESCC. Patients with GG genotype had a decreased risk of nodal metastasis in comparison with patients with CC/CG genotype, although this link was not statistically significant. Conclusion: Our findings illustrated the correlation of CYP1B1-rs1056836 as a potential biomarker for ESCC patients, supporting further studies in larger populations in different ethnic groups. Moreover, further investigations are warranted to evaluate the association of emerging marker with dietary intake and lifestyle.

Keywords: Cytochrome P450, esophagus squamous cell carcinoma, dietary intake, lifestyle

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Authors: Esther Friedlander, Philip Friedlander

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The use of immunotherapy that inhibits programmed death-1 (PD-1) or its ligand PD-L1 confers survival benefits in patients with non-small cell lung cancer (NSCLC). However, approximately 45% of patients experience primary treatment resistance, necessitating the development of strategies to improve efficacy. While the renin-angiotensin system (RAS) has systemic hemodynamic effects, tissue-specific regulation exists along with modulation of immune activity in part through regulation of myeloid cell activity, leading to the hypothesis that RAS inhibition may improve anti-PD-1/L-1 efficacy. A retrospective analysis was conducted that included 173 advanced solid tumor cancer patients treated at Valley Hospital, a community Hospital in New Jersey, USA, who were treated with a PD-1/L-1 inhibitor in a defined time period showing a statistically significant relationship between RAS pathway inhibition (RASi through concomitant treatment with an ACE inhibitor or angiotensin receptor blocker) and positive efficacy to the immunotherapy that was independent of age, gender and cancer type. Subset analysis revealed strong numerical benefit for efficacy in both patients with squamous and nonsquamous NSCLC as determined by documented clinician assessment of efficacy and by duration of therapy. A PUBMED literature search was now conducted to identify studies assessing the effect of RAS pathway inhibition on anti-PD-1/L1 efficacy in advanced solid tumor patients and compare these findings to those seen in the Valley Hospital retrospective study with a focus on NSCLC specifically. A total of 11 articles were identified assessing the effects of RAS pathway inhibition on the efficacy of checkpoint inhibitor immunotherapy in advanced cancer patients. Of the 11 studies, 10 assessed the effect on survival of RASi in the context of treatment with anti-PD-1/PD-L1, while one assessed the effect on CTLA-4 inhibition. Eight of the studies included patients with NSCLC, while the remaining 2 were specific to genitourinary malignancies. Of the 8 studies, two were specific to NSCLC patients, with the remaining 6 studies including a range of cancer types, of which NSCLC was one. Of these 6 studies, only 2 reported specific survival data for the NSCLC subpopulation. Patient characteristics, multivariate analysis data and efficacy data seen in the 2 NSLCLC specific studies and in the 2 basket studies, which provided data on the NSCLC subpopulation, were compared to that seen in the Valley Hospital retrospective study supporting a broader effect of RASi on anti-PD-1/L1 efficacy in advanced NSLCLC with the majority of studies showing statistically significant benefit or strong statistical trends but with one study demonstrating worsened outcomes. This comparison of studies extends published findings to the community hospital setting and supports prospective assessment through randomized clinical trials of efficacy in NSCLC patients with pharmacodynamic components to determine the effect on immune cell activity in tumors and on the composition of the tumor microenvironment.

Keywords: immunotherapy, cancer, angiotensin, efficacy, PD-1, lung cancer, NSCLC

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Authors: Golson Mohamed, Yasmine Gamasy, Khaled EL-Khatib, Anas Al-Natour, Shady Fadel, Haytham Rashwan, Haytham Badawy, Nadia Farghaly

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Introduction: Wilm's tumor is the most common malignant renal tumor in children. Much progress has been made in the management of patients with this malignancy over the last 3 decades. Today treatments are based on several trials and studies conducted by the International Society of Pediatric Oncology (SIOP) in Europe and National Wilm's Tumor Study Group (NWTS) in the USA. It is necessary for us to understand why do we follow either of the protocols, NWTS which follows the upfront surgery principle or the SIOP which follows the upfront chemotherapy principle in all stages of the disease. Objective: The aim of is to assess outcome in patients treated with preoperative chemotherapy and patients treated with upfront surgery to compare their effect on overall survival. Study design: to decide which protocol to follow, study was carried out on records for patients aged 1 day to 18 years old suffering from Wilm's tumor who were admitted to Alexandria University Hospital, pediatric oncology, pediatric urology and pediatric surgery departments, with a retrospective survey records from 2010 to 2015, Design and editing of the transfer sheet with a (PRISMA flow study) Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Data were fed to the computer and analyzed using IBM SPSS software package version 20.0. (11) Qualitative data were described using number and percent. Quantitative data were described using Range (minimum and maximum), mean, standard deviation and median. Comparison between different groups regarding categorical variables was tested using Chi-square test. When more than 20% of the cells have expected count less than 5, correction for chi-square was conducted using Fisher’s Exact test or Monte Carlo correction. The distributions of quantitative variables were tested for normality using Kolmogorov-Smirnov test, Shapiro-Wilk test, and D'Agstino test, if it reveals normal data distribution, parametric tests were applied. If the data were abnormally distributed, non-parametric tests were used. For normally distributed data, a comparison between two independent populations was done using independent t-test. For abnormally distributed data, comparison between two independent populations was done using Mann-Whitney test. Significance of the obtained results was judged at the 5% level. Results: A significantly statistical difference was observed for survival between the two studied groups favoring the upfront chemotherapy(86.4%)as compared to the upfront surgery group (59.3%) where P=0.009. As regard complication, 20 cases (74.1%) out of 27 were complicated in the group of patients treated with upfront surgery. Meanwhile, 30 cases (68.2%) out of 44 had complications in patients treated with upfront chemotherapy. Also, the incidence of intraoperative complication (rupture) was less in upfront chemotherapy group as compared to upfront surgery group. Conclusion: Upfront chemotherapy has superiority over upfront surgery.As the patient who started with upfront chemotherapy shown, higher survival rate, less percent in complication, less percent needed for radiotherapy, and less rate in recurrence.

Keywords: Wilm's tumor, renal tumor, chemotherapy, surgery

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Authors: María-José Palacin-Sanchez, Filippo Di Pietro, Reyes Samaniego-Medina

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This article examines, in an institutional context such as Spanish one, the corporate board structure characteristics and determinants in entrepreneurial firms to go public. Specifically, it explores these issues through all the initial public offerings in the Spanish Alternative Equity Market (MAB), which is a market segment for smaller growing companies. The results show that: a) firm size, age of the company, and the reputation of the auditor and the nominated advisor and Corporate Governance Code favour a larger and more independent board structure that enhances its monitoring functions; and b) leverage, opportunities of growth, sector risk and ownership by executive directors all lead towards a smaller broad of directors where the role of entrepreneurship provided by executive directors remains crucial. This reflects the delicate balance of power between small-business entrepreneurs and financial equity market forces, which demand more transparency and monitoring in the companies.

Keywords: board composition, board size, corporate governance, IPO, SMEs

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Authors: Vrushali Guhe, Shailza Singh

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Cutaneous leishmaniasis is neglected tropical disease present worldwide caused by the protozoan parasite Leishmania major, the therapeutic armamentarium for leishmaniasis are showing several limitations as drugs are showing toxic effects with increasing resistance by a parasite. Thus identification of novel therapeutic targets is of paramount importance. Previous studies have shown that autophagy, a cellular process, can either facilitate infection or aid in the elimination of the parasite, depending on the specific parasite species and host background in leishmaniasis. In the present study, our objective was to target the essential autophagy protein ATG8, which plays a crucial role in the survival, infection dynamics, and differentiation of the Leishmania parasite. ATG8 in Leishmania major and its homologue, LC3, in Homo sapiens, act as autophagic markers. Present study manifested the crucial role of ATG8 protein as a potential target for combating Leishmania major infection. Through bioinformatics analysis, we identified non-conserved motifs within the ATG8 protein of Leishmania major, which are not present in LC3 of Homo sapiens. Against these two non-conserved motifs, we generated a peptide library of 60 peptides on the basis of physicochemical properties. These peptides underwent a filtering process based on various parameters, including feasibility of synthesis and purification, compatibility with Selective Reaction Monitoring (SRM)/Multiple reaction monitoring (MRM), hydrophobicity, hydropathy index, average molecular weight (Mw average), monoisotopic molecular weight (Mw monoisotopic), theoretical isoelectric point (pI), and half-life. Further filtering criterion shortlisted three peptides by using molecular docking and molecular dynamics simulations. The direct interaction between ATG8 and the shortlisted peptides was confirmed through Surface Plasmon Resonance (SPR) experiments. Notably, these peptides exhibited the remarkable ability to penetrate the parasite membrane and exert profound effects on Leishmania major. The treatment with these peptides significantly impacted parasite survival, leading to alterations in the cell cycle and morphology. Furthermore, the peptides were found to modulate autophagosome formation, particularly under starved conditions, suggesting their involvement in disrupting the regulation of autophagy within Leishmania major. In vitro, studies demonstrated that the selected peptides effectively reduced the parasite load within infected host cells. Encouragingly, these findings were corroborated by in vivo experiments, which showed a reduction in parasite burden upon peptide administration. Additionally, the peptides were observed to affect the levels of LC3II within host cells. In conclusion, our findings highlight the efficacy of these novel peptides in targeting Leishmania major’s ATG8 and disrupting parasite survival. These results provide valuable insights into the development of innovative therapeutic strategies against leishmaniasis via targeting autophagy protein ATG8 of Leishmania major.

Keywords: ATG8, leishmaniasis, surface plasmon resonance, MD simulation, molecular docking, peptide designing, therapeutics

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Authors: Masoud Swalehe, Semra Günay

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Developed countries are losing many lives to non-communicable diseases as compared to their developing counterparts. The effects of these diseases are mostly sudden and manifest at a very short time prior to death or a dangerous attack and this has consolidated the significance of emergency medical system (EMS) as one of the vital areas of healthcare service delivery. The primary objective of this research is to reduce ambulance response times (RT) of Eskişehir province EMS since a number of studies have established a relationship between ambulance response times and survival chances of patients especially out of hospital cardiac arrest (OHCA) victims. It has been found out that patients who receive out of hospital medical attention in few (4) minutes after cardiac arrest because of low ambulance response times stand higher chances of survival than their counterparts who take longer times (more than 12 minutes) to receive out of hospital medical care because of higher ambulance response times. The study will make use of geographic information systems (GIS) technology to dynamically reallocate ambulance resources according to demand and time so as to reduce ambulance response times. Geospatial-time distribution of ambulance calls (demand) will be used as a basis for optimal ambulance deployment using system status management (SSM) strategy to achieve much demand coverage with the same number of ambulance resources to cause response time reduction. Drive-time polygons will be used to come up with time specific facility coverage areas and suggesting additional facility candidate sites where ambulance resources can be moved to serve higher demands making use of network analysis techniques. Emergency Ambulance calls’ data from 1st January 2014 to 31st December 2014 obtained from Eskişehir province health directorate will be used in this study. This study will focus on the reduction of ambulance response times which is a key Emergency Medical Services performance indicator.

Keywords: emergency medical services, system status management, ambulance response times, geographic information system, geospatial-time distribution, out of hospital cardiac arrest

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Authors: Ruqayya Naheed Khan, Awais Amjad Malik, Awais Naeem, Amina Khan, Asad Parvaiz

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Introduction: Axillary nodal status in breast cancer patients is a paramount prognosticator, next to primary tumor size and grade. It has been well established that patients with negative sentinel lymph node biopsy can safely avoid axillary lymph node dissection. A positive sentinel lymph node has traditionally required subsequent axillary dissection. According to ACOSOG Z11 trial, patients who underwent axillary dissection with 3 or more positive sentinel nodes or opted for observation in case of negative sentinel lymph node, did not find any difference in Overall Survival (OS) and Disease Free Survival (DFS). The Z11 trial included patients who underwent breast conserving surgery and excluded patients with mastectomies. The purpose of this study is to determine whether Z0011 can be applied to mastectomy patients as well in 1-3 positive sentinel lymph nodes and avoid unnecessary ALND. Methods: A retrospective review was conducted at Shaukat Khanam Memorial Cancer Hospital Pakistan from Jan 2015 to Dec 2017 including patients who were treated for invasive breast cancer and required upfront mastectomy. They were clinically node negative, so sentinel lymph node biopsy was performed. Patients underwent ALND with positive sentinel lymph node. A total of 156 breast cancer patients with mastectomies were reviewed. Results: 95% of the patients were female while 3% were male. Average age was 44 years. There was no difference in race, comorbidities, histology, T stage, N stage, and overall stage, use of adjuvant chemotherapy and radiation therapy. 64 patients underwent ALND for positive lymph node while 92 patients were spared of axillary dissection due to negative sentinel lymph node biopsy. Out of 64 patients, 38 patients (59%) had only 1 lymph node positive which was the sentinel node. 18 patients (28%) had 2 lymph nodes positive including the sentinel node while only 8 patients (13%) had 3 or more positive nodes. Conclusion: Keeping in mind the complications related to ALND, above results clearly show that ALND could have been avoided in 87% of patients in the setting of adjuvant radiation, possibly avoiding the morbidity associated with axillary lymphadenectomy although a prospective randomized trial needs to confirm these results.

Keywords: mastectomy, sentinel lymph node biopsy, axillary lymph node dissection, breast cancer

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Authors: Yang-Ho Jang, Soon-Ok Jee, Hae-Chul Park, Jeong-Woo Kang, Byung-Jae So, Sung-Shik Shin, Kyu-Sung Ahn, Kwang-Jick Lee

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Introduction: Antibiotics have been used as feed additives for the growth promotion and performance in food-producing animals. However, the possibility of selection of antimicrobial resistance and the concerns of residue in animal products led to ban the use of antibiotics in farm animals at 2011 in Korea. This strategy is also adjusted to anticoccidial drugs soon but these are still allowed for the time being to use in a diet for the treatment and control for the enteric necrosis in poultry. Therefore substantial focus has been given to find alternatives to antimicrobial agents. Several phytogenic materials have been reported to have positive effects on coccidiosis. This study was to evaluate the effects on anti-coccidial effect of oregano oil based herb mixture on Eimeria spp. in poultry. Materials and Methods: A total of one day-old boiler chickens divided into six groups (each group=30 chkckens) were used in this study. The herbal mixture was fed with water freely as follows: two groups, one infected with Eimeria spp. and the other group served as controls without herbal mixture respectively; 0.2ml/L of oregano oil; 0.2ml/L of oregano oil and Sanguisorbae radix; 0.2ml/L of Sanguisorbae radix; last group was fed with dichlazuril diet as positive control. Sporulated Eimeria spp. was infected at 14 day-old. Following infection, survival rate, bloody diarrhea, OPG (oocyst per gram) and feed conversion ratios were determined. The experimental period was lasted for 4 weeks. Results: Herbal mixture feeding groups (Group 3,4,5) showed low feed conversion ratio comparing with negative control. Oregano oil group and positive control group recorded the highest survival rate. The grade of bloody diarrhea was scored 0 to 5. Herbal mixture feeding groups showed 2, 3 and 1 score respectively however, group 2 (infection and no-treatment) showed 4. OPG results in herbal mixture feeding group were 3 to 4 times higher than diclazuril diet feeding group. Conclusions: These results showed that oregano oil and Sanguisorbae radix mixture may have an anti-coccidial effect and also affect chick performance.

Keywords: anticoccidial effects, oregano oil based herb mixture, herbal mixture, antibiotics

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Authors: Satoshi Furukawa, Satomu Morita, Katsuji Nishi, Masahito Hitosugi

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A 75-year-old woman took thyroidectomy forty years previously. Enlarged masses were seen at autopsy just above and below the left clavicle. We proved the diagnosis of papillary thyroid cancer (PTC) and lung metastasis by histological examinations. The prognosis of PTC is excellent; the 10-year survival rate ranges between 85 and 99%. Lung metastases may be found in 10% of the patients with PTC. We report an unusual case of recurrence of PTC with metastasis to the lung.

Keywords: papillary thyroid cancer, lung metastasis, autopsy, histopathological findings

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Authors: Vijaya Madhuri Devraj, Swarnalatha Guditi, Kiran Kumar Bokara, Gangadhar Taduri

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Cell-based strategies may open therapeutic approaches that promote tolerance through manipulation of macrophages to increase long-term transplant survival rates and minimize side effects of the current immune suppressive regimens. The aim of the present study was, therefore, to test and compare the therapeutic potential of MSC and Tregs on macrophage polarization to develop an alternate cell-based treatment option in kidney transplantation. In the current protocol, macrophages from kidney transplant recipients with graft dysfunction were co-cultured with MSCs and Treg cells with and without cell-cell contact on transwell plates, further to quantitatively assess macrophage polarization in response to MSC and Treg treatment over time, M1 and M2 cell surface markers were used. Additionally, multiple soluble analytes were analyzed in cell supernatant by using bead-based immunoassays. Furthermore, to confirm our findings, gene expression analysis was done. MSCs induced the formation of M2 macrophages more than Tregs when macrophages M0 were cultured in transwell without cell contact. From this, we deduced the mechanism that soluble factors present in the MSCs condition media are involved in skewing of macrophages towards type 2 macrophages; similarly, in co-culture with cell-cell contact, MSCs resulted in more M2 type macrophages than Tregs. And an important finding of this study is the combination of both MSC-Treg showed significantly effective and consistent results in both with and without cell contact setups. Hence, it is suggestive to prefer MSCs over Tregs for secretome-based therapy and a combination of both for either therapy for effective transplantation outcomes. Our findings underline a key role of Tregs and MSCs in promoting macrophage polarization towards anti-inflammatory type. The study has great importance in prolongation of allograft and patient survival without any rejection by cell-based therapy, which induce self-tolerance and controlling infection.

Keywords: graft rejection, graft tolerance, macrophage polarization, mesenchymal stem cells, regulatory T cells, transplant immunology

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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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