Search results for: cell survival

Authors: Sazzad Hossain Talukder

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Survival in the competitive international market with unforeseen environmental contingencies has always been a concern of the firms that led to adopting different strategies to deal with different situations. Language strategy is considered to enhance the international performance of a firm by organizing language diversity and fostering communications within and outside the firm. Yet there is a lack of theoretical attention or model development on the role of language strategy on firm international survival. From resource dependence perspective, the adoption of language strategy and its relationship with firm survival are determined by the firm´s capability to prevent dependency concentration and/or increase relative power on the external environment. However, the impact of language strategy on firm survival is complex and multifaceted as the strategy influence firm performance indirectly through communication, coordination, learning and value creation. The evidence of various types of language strategies and different forms of firm survival also bring in complexities to understand the effects of a language strategy on the international survival of a firm. Based on language literatures and resource dependence logic, certain propositions are developed to conceptualize the relationship between language strategy and firm international survival in this conceptual paper. For the purpose of this paper, a conceptual model is proposed to examine how different kinds of language strategy foster reduction of resource dependency that lead to firm international survival in respond to local responsiveness and global integration. In this proposed model, it is theorized that language strategy has a positive relationship with the international survival of the firm, as the strategy is likely to reduce external resource dependency and increase the ability to continue independent operations both in short and long term.

Keywords: language strategy, language diversity, firm international survival, resource dependence logic

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Authors: Dibyakanta Seth, Hari Niwas Mishra, Sankar Chandra Deka

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Microencapsulation is an established method of protecting bacteria from the adverse conditions. An improved extrusion spraying technique was used to encapsulate mixed bacteria culture of S. thermophilus and L. bulgaricus using sodium alginate as the coating material. The effect of nozzle air pressure (200, 300, 400 and 500 kPa), sodium alginate concentration (1%, 1.5%, 2%, 2.5% and 3% w/v), different concentration of calcium chloride (0.1, 0.2, 1 M) and initial cell loads (10⁷, 10⁸, 10⁹ cfu/ml) on the viability of encapsulated bacteria were investigated. With the increase in air pressure the size of microcapsules decreased, however the effect was non-significant. There was no significant difference (p > 0.05) in the viability of encapsulated cells when the concentration of calcium chloride was increased. Increased level of sodium alginate significantly increased the survival ratio of encapsulated bacteria (P < 0.01). Encapsulation with 3% alginate was treated as optimum since a higher concentration of alginate increased the gel strength of the solution and thus was difficult to spray. Under optimal conditions 3% alginate, 10⁹ cfu/ml cell load, 20 min hardening time in 0.1 M CaCl2 and 400 kPa nozzle air pressure, the viability of bacteria cells was maximum compared to the free cells. The microcapsules made at the optimal condition when mixed with yoghurt and subjected to spray drying at 148°C, the survival ratio was 2.48×10⁻¹ for S. thermophilus and 7.26×10⁻¹ for L. bulgaricus. In contrast, the survival ratio of free cells of S. thermophilus and L. bulgaricus were 2.36×10⁻³ and 8.27×10⁻³, respectively. This study showed a decline in viable cells count of about 0.5 log over a period of 7 weeks while there was a decline of about 1 log in cultures which were incorporated as free cells in yoghurt. Microencapsulation provided better protection at higher acidity compared to free cells. This study demonstrated that microencapsulation of yoghurt culture in sodium alginate is an effective technique of protection against extreme drying conditions.

Keywords: extrusion, microencapsulation, spray drying, sweetened yoghurt

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Authors: Md. M. Hossain, Regan Roat, Jenica Christopherson, Colette Free, Zhiguang Guo

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Long noncoding RNA (lncRNA) mediated post-transcriptional gene regulation, and their epigenetic landscapes have been shown to be involved in many human diseases. However, their regulation in diabetes through governing islet’s β-cell function and survival needs to be elucidated. Due to the technical and ethical constraints, it is difficult to study their role in β-cell function and survival in human under in vivo condition. In this study, humanized mice have been developed through transplanting human pancreatic islet under the kidney capsule of NOD.SCID mice and induced β-cell death leading to diabetes condition to study lncRNA mediated regulation. For this, human islets from 3 donors (3000 IEQ, purity > 80%) were transplanted under the kidney capsule of STZ induced diabetic NOD.scid mice. After at least 2 weeks of normoglycecemia, lymphocytes from diabetic NOD mice were adoptively transferred and islet grafts were collected once blood glucose reached > 200 mg/dl. RNA from human donor islets, islet grafts from humanized mice with either adoptive lymphocyte transfer (ALT) or PBS control (CTL) were ribodepleted; barcoded fragment libraries were constructed and sequenced on the Ion Proton sequencer. lncRNA expression in isolated human islets, islet grafts from humanized mice with and without induced β-cell death and their regulation in human islets function in vitro under glucose challenge, cytokine mediated inflammation and induced apoptotic condition were investigated. Out of 3155 detected lncRNAs, 299 that highly expressed in islets were found to be significantly downregulated and 224 upregulated in ALT compared to CTL. Most of these are found to be collocated within 5 kb upstream and 1 kb downstream of 788 up- and 624 down-regulated mRNAs. Genomic Regions Enrichment of Annotations Analysis revealed deregulated and collocated genes are related to pancreas endocrine development; insulin synthesis, processing, and secretion; pancreatitis and diabetes. Many of them, that found to be located within enhancer domains for islet specific gene activity, are associated to the deregulation of known islet/βcell specific transcription factors and genes that are important for β-cell differentiation, identity, and function. RNA sequencing analysis revealed aberrant lncRNA expression which is associated to the deregulated mRNAs in β-cell function as well as in molecular pathways related to diabetes. A distinct set of candidate lncRNA isoforms were identified as highly enriched and specific to human islets, which are deregulated in human islets from donors with different BMIs and with type 2 diabetes. These RNAs show an interesting regulation in cultured human islets under glucose stimulation and with induced β-cell death by cytokines. Aberrant expression of these lncRNAs was detected in the exosomes from the media of islets cultured with cytokines. Results of this study suggest that the islet specific lncRNAs are deregulated in human islet with β-cell death, hence important in diabetes. These lncRNAs might be important for human β-cell function and survival thus could be used as biomarkers and novel therapeutic targets for diabetes.

Keywords: β-cell, humanized mouse, pancreatic islet, LncRNAs

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Authors: Madaki Umar Yusuf, Mohd Rizam B. Abubakar

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The survival censored data with incomplete covariate data is a common occurrence in many studies in which the outcome is survival time. With model when the missing covariates are categorical, a useful technique for obtaining parameter estimates is the EM by the method of weights. The survival outcome for the class of generalized linear model is applied and this method requires the estimation of the parameters of the distribution of the covariates. In this paper, we propose some clinical trials with ve covariates, four of which have some missing values which clearly show that they were fully censored data.

Keywords: EM algorithm, incomplete categorical covariates, ignorable missing data, missing at random (MAR), Weibull Distribution

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Authors: Gerard Bray, Arya Bahadori, Sachinka Ranasinghe

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Renal cell carcinoma (RCC) is among the top 10 most common cancers worldwide, where metastatic disease carries a poor prognosis. Herein, we present a 74-year-old male presenting with asymptomatic solitary metachronous metastasis to the gall bladder 4 years following nephrectomy for clear cell RCC. Solitary RCC metastasis to the gall bladder following nephrectomy is rarely reported in the literature and brings with it a clinical conundrum of whether surgical resection or systemic therapy should be utilized. In this case, surgical excision with cholecystectomy was employed without systemic therapy. We, therefore, contribute a rare and interesting case that highlights that metastasectomy of a solitary metastasis can improve survival according to current literature.

Keywords: renal cell carcinoma, gall bladder metastasis, solitary metastasectomy, metachronous

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Authors: Taleb Lotfi, Benarbia Maheidine, Allam Hamza, Boutira Fatima, Boukerche Abdelbaki

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Introduction and purpose of the study: This is a retrospective single-center study with an analytical aim to determine the prognostic factors for relapse in patients treated with radiotherapy after total laryngectomy with lymph node dissection for laryngeal cancer at the Emir Abdelkader cancer center in Oran (Algeria). Material and methods: During the study period from January 2014 to December 2018, eighty-nine patients (n=89) with squamous cell carcinoma of the larynx were treated with postoperative radiotherapy. Relapse-free survival was studied in the univariate analysis according to pre-treatment criteria using Kaplan-Meier survival curves. We performed a univariate analysis to identify relapse factors. Statistically significant factors have been studied in the multifactorial analysis according to the Cox model. Results and statistical analysis: The average age was 62.7 years (40-86 years). It was a squamous cell carcinoma in all cases. Postoperatively, the tumor was classified as pT3 and pT4 in 93.3% of patients. Histological lymph node involvement was found in 36 cases (40.4%), with capsule rupture in 39% of cases, while the limits of surgical excision were microscopically infiltrated in 11 patients (12.3%). Chemotherapy concomitant with radiotherapy was used in 67.4% of patients. With a median follow-up of 57 months (23 to 104 months), the probabilities of relapse-free survival and five-year overall survival are 71.2% and 72.4%, respectively. The factors correlated with a high risk of relapse were locally advanced tumor stage pT4 (p=0.001), tumor site in case of subglottic extension (p=0.0003), infiltrated surgical limits R1 (p=0.001), l lymph node involvement (p=0.002), particularly in the event of lymph node capsular rupture (p=0.0003) as well as the time between surgery and adjuvant radiotherapy (p=0.001). However, in the subgroup analysis, the major prognostic factors for disease-free survival were subglottic tumor extension (p=0.001) and time from surgery to adjuvant radiotherapy (p=0.005). Conclusion: Combined surgery and postoperative radiation therapy are effective treatment modalities in the management of laryngeal cancer. Close cooperation of the entire cervicofacial oncology team is essential, expressed during a multidisciplinary consultation meeting, with the need to respect the time between surgery and radiotherapy.

Keywords: laryngeal cancer, laryngectomy, postoperative radiotherapy, survival

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Authors: Mekni Sabrine, Nouira Mariem

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Background and aim: Allogeneic hematopoietic stem cell transplantation is a curative treatment for several hematological diseases; however, it has a non-negligible morbidity and mortality depending on several prognostic factors, including pre-transplant hyperferritinemia. The aim of our study was to estimate the impact of hyperferritinemia on survivals and on the occurrence of post-transplant complications. Methods: It was a longitudinal study conducted over 8 years and including all patients who had a first allograft. The impact of pretransplant hyperferritinemia (ferritinemia ≥1500) on survivals was studied using the Kaplan Meier method and the COX model for uni- and multivariate analysis. The Khi-deux test and binary logistic regression were used to study the association between pretransplant ferritinemia and post-transplant complications. Results: One hundred forty patients were included with an average age of 26.6 years and a sex ratio (M/F)=1.4. Hyperferritinemia was found in 33% of patients. It had no significant impact on either overall survival (p=0.9) or event -free survival (p=0.6). In multivariate analysis, only the type of disease was independently associated with overall survival (p=0.04) and event-free survival (p=0.002). For post-allograft complications: The occurrence of early documented infections was independently associated with pretransplant hyperferritinemia (p=0.02) and the presence of acute graft versus host disease( GVHD) (p<10-3). The occurrence of acute GVHD was associated with early documented infection (p=0.002) and Cytomegalovirus reactivation (p<10-3). The occurrence of chronic GVHD was associated with the presence of Cytomegalovirus reactivation (p=0.006) and graft source (p=0.009). Conclusion: Our study showed the significant impact of pre-transplant hyperferritinemia on the occurrence of early infections but not on survivals. Early and more accurate assessment iron overload by other tests such as liver magnetic resonance imaging with initiation of chelating treatment could prevent the occurrence of such complications after transplantation.

Keywords: allogeneic, transplants, ferritin, survival

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Authors: Hossein Pourbashash

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Recent experimental studies have shown that HIV can be transmitted directly from cell to cell when structures called virological synapses form during interactions between T cells. In this article, we describe a new within-host model of HIV infection that incorporates two mechanisms: infection by free virions and the direct cell-to-cell transmission. We conduct the local and global stability analysis of the model. We show that if the basic reproduction number R0 1, the virus is cleared and the disease dies out; if R0 > 1, the virus persists in the host. We also prove that the unique positive equilibrium attracts all positive solutions under additional assumptions on the parameters.

Keywords: HIV virus model, cell-to-cell transmission, global stability, Lyapunov function, second compound matrices

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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: Mais Khader, Xingjie Wei

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This research sheds light on female entrepreneurs by providing new insights on the survival predictions of companies led by females in the UK. This study aims to build a predictive machine learning model of the survival of female-led & co-led small & medium enterprises (SMEs) in the UK over the period 2000-2020. The predictive model built utilised a combination of financial and non-financial features related to both companies and their directors to predict SMEs' survival. These features were studied in terms of their contribution to the resultant predictive model. Five machine learning models are used in the modelling: Decision tree, AdaBoost, Naïve Bayes, Logistic regression and SVM. The AdaBoost model had the highest performance of the five models, with an accuracy of 73% and an AUC of 80%. The results show high feature importance in predicting companies' survival for company size, management experience, financial performance, industry, region, and females' percentage in management.

Keywords: company survival, entrepreneurship, females, machine learning, SMEs

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Authors: Shi-xia Xu, Zai-wen Zhang, Ru-xue Chen, Shan Zhou, Xiang-feng Tang

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Objective: The clinical influence of HLA-DPB1 mismatches on clinical outcome of HSCT is less clear. This is the first meta-analysis to study the HLA-DPB1 matching statues on clinical outcomes after unrelated donor HSCT. Methods: We searched the CIBMTR, Cochrane Central Register of Controlled Trials (CENTRAL) and related databases (1995.01–2017.06) for all relevant articles. Comparative studies were used to investigate the HLA-DPB1 loci mismatches on clinical outcomes after unrelated donor HSCT, such as the disease-free survival (DFS), overall survival, GVHD, relapse, and transplant-related mortality (TRM). We performed meta-analysis using Review Manager 5.2 software and funnel plot to assess the bias. Results: At first, 1246 articles were retrieved, and 18 studies totaling 26368 patients analyzed. Pooled comparisons of studies found that the HLA-DPB1 mismatched group had a lower rate of DFS than the DPB1-matched group, and lower OS in non-T cell depleted transplantation. The DPB1 mismatched group has a higher incidence of aGVHD and more severe ( ≥ III degree) aGvHD, lower rate of relapse and higher TRM. Moreover, compared with 1-antigen mismatch, 2-antigen mismatched led to a higher risk of TRM and lower relapse rate. Conclusions: This meta-analysis indicated HLA-DPB1 has important influence on survival and transplant-related complications during unrelated donor HSCT and HLA-DPB1 donor selection strategies have been proposed based on a personalized algorithm.

Keywords: human leukocyte antigen, DPB1, transplant, meta-analysis, outcome

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Authors: Ashok K. Gupta

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Over the past few decades, since the bio-engineering revolution, autologous cell therapy (ACT) has become a rapidly evolving field. Currently, this form of therapy has broad applications in modern medicine and plastic surgery, ranging from the treatment/improvement of wound healing to life-saving operations. A study was conducted on 50 patients having to disfigure, and deform post burn scars and was treated by injection of extracted, refined adipose tissue grafts with their unique stem cell properties. To compare the outcome, a control of 20 such patients was treated with conventional skin or soft-tissue flaps or skin grafting, and a control of 10 was treated with more advanced microsurgical techniques such as Pre-fabricated flaps/pre laminated flaps / free flaps. Assessment of fat volume and survival post- follow up period was done by radiological aid, using MRI and clinically (Survival of the autograft and objective parameters for scar elasticity were evaluated skin elasticity parameters 3 to 9 months postoperatively). Recently, an enzyme that is involved in collagen crosslinking in fibrotic tissue, lysyl hydroxylase (LH2), was identified. This enzyme is normally active in bone and cartilage but hardly in the skin. It has been found that this enzyme is highly expressed in scar tissue and subcutaneous fat; this is in contrast to the dermis, where the enzyme is hardly expressed. Adipose tissue-derived stem cell injections are an effective method in the treatment of various extensive post-burn scar deformities that makes it possible to re-create the lost sub-dermal tissue for improvement in the function of involved joint movements.

Keywords: adipose tissue-derived stem cell injections, treatment of various extensive post-burn scar deformities, re-create the lost sub-dermal tissue, improvement in function of involved joint movements

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Authors: Renata Checiches, Thierry Coche, Nicolas F. Delahaye, Albert Linder, Fernando Ulloa Montoya, Olivier Gruselle, Karen Langfeld, An de Creus, Bart Spiessens, Vincent G. Brichard, Jamila Louahed, Frédéric F. Lehmann

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Background: The RNA-expression levels of cancer-testis antigens MAGE A3 and PRAME were determined in resected tissue from patients with primary non-small-cell lung cancer (NSCLC) and related to clinical outcome. EGFR, KRAS and BRAF mutation status was determined in a subset to investigate associations with MAGE A3 and PRAME expression. Methods: We conducted a single-centre, uncontrolled, retrospective study of 1260 tissue-bank samples from stage IA-III resected NSCLC. The prognostic value of antigen expression (qRT-PCR) was determined by hazard-ratio and Kaplan-Meier curves. Results: Thirty-seven percent (314/844) of tumours expressed MAGE-A3, 66% (723/1092) expressed PRAME and 31% (239/839) expressed both. Respective frequencies in squamous-cell tumours and adenocarcinomas were 43%/30% for MAGE A3 and 80%/44% for PRAME. No correlation with stage, tumour size or patient age was found. Overall, no prognostic value was identified for either antigen. A trend to poorer overall survival was associated with MAGE-A3 in stage IIIB and with PRAME in stage IB. EGFR and KRAS mutations were found in 10.1% (28/311) and 33.8% (97/311) of tumours, respectively. EGFR (but not KRAS) mutation status was negatively associated with PRAME expression. Conclusion: No clear prognostic value for either PRAME or MAGE A3 was observed in the overall population, although some observed trends may warrant further investigation.

Keywords: MAGE A3, PRAME, cancer-testis gene, NSCLC, survival, EGFR

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Authors: Danni Cheng

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Background: Preclinical and epidemiological studies have reported potential protective effects of low-density lipoprotein cholesterol (LDL-C) lowering drugs on head and neck squamous cell cancer (HNSCC) survival, but the causality was not consistent. Genetic variants associated with LDL-C lowering drug targets can predict the effects of their therapeutic inhibition on disease outcomes. Objective: We aimed to evaluate the causal association of genetically proxied cholesterol-lowering drug targets and circulating lipid traits with cancer survival in HNSCC patients stratified by human papillomavirus (HPV) status using two-sample Mendelian randomization (MR) analyses. Method: Single-nucleotide polymorphisms (SNPs) in gene region of LDL-C lowering drug targets (HMGCR, NPC1L1, CETP, PCSK9, and LDLR) associated with LDL-C levels in genome-wide association study (GWAS) from the Global Lipids Genetics Consortium (GLGC) were used to proxy LDL-C lowering drug action. SNPs proxy circulating lipids (LDL-C, HDL-C, total cholesterol, triglycerides, apoprotein A and apoprotein B) were also derived from the GLGC data. Genetic associations of these SNPs and cancer survivals were derived from 1,120 HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) and 2,570 non-HPV-driven HNSCC patients in VOYAGER program. We estimated the causal associations of LDL-C lowering drugs and circulating lipids with HNSCC survival using the inverse-variance weighted method. Results: Genetically proxied HMGCR inhibition was significantly associated with worse overall survival (OS) in non-HPV-drive HNSCC patients (inverse variance-weighted hazard ratio (HR IVW), 2.64[95%CI,1.28-5.43]; P = 0.01) but better OS in HPV-positive OPSCC patients (HR IVW,0.11[95%CI,0.02-0.56]; P = 0.01). Estimates for NPC1L1 were strongly associated with worse OS in both total HNSCC (HR IVW,4.17[95%CI,1.06-16.36]; P = 0.04) and non-HPV-driven HNSCC patients (HR IVW,7.33[95%CI,1.63-32.97]; P = 0.01). A similar result was found that genetically proxied PSCK9 inhibitors were significantly associated with poor OS in non-HPV-driven HNSCC (HR IVW,1.56[95%CI,1.02 to 2.39]). Conclusion: Genetically proxied long-term HMGCR inhibition was significantly associated with decreased OS in non-HPV-driven HNSCC and increased OS in HPV-positive OPSCC. While genetically proxied NPC1L1 and PCSK9 had associations with worse OS in total and non-HPV-driven HNSCC patients. Further research is needed to understand whether these drugs have consistent associations with head and neck tumor outcomes.

Keywords: Mendelian randomization analysis, head and neck cancer, cancer survival, cholesterol, statin

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Authors: Zahra Shokrolahi, Mohammad Reza Atashzar

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The goals of treating patients with breast cancer are to cure the disease, prolong survival, and improve quality of life. Immune cells in the tumor microenvironment have an important role in regulating tumor progression. The term of cellular immunotherapy refers to the administration of living cells to a patient; this type of immunotherapy can be active, such as a dendritic cell (DC) vaccine, in that the cells can stimulate an anti-tumour response in the patient, or the therapy can be passive, whereby the cells have intrinsic anti-tumour activity; this is known as adoptive cell transfer (ACT) and includes the use of autologous or allogeneic lymphocytes that may, or may not, be modified. The most important breast cancer cellular immunotherapies involving the use of T cells and natural killer (NK) cells in adoptive cell transfer, as well as dendritic cells vaccines. T cell-based therapies including tumour-infiltrating lymphocytes (TILs), engineered TCR-T cells, chimeric antigen receptor (CAR T cell), Gamma-delta (γδ) T cells, natural killer T (NKT) cells. NK cell-based therapies including lymphokine-activated killers (LAK), cytokine-induced killer (CIK) cells, CAR-NK cells. Adoptive cell therapy has some advantages and disadvantages some. TILs cell strictly directed against tumor-specific antigens but are inactive against tumor changes due to immunoediting. CIK cell have MHC-independent cytotoxic effect and also need concurrent high dose IL-2 administration. CAR T cell are MHC-independent; overcome tumor MHC molecule downregulation; potent in recognizing any cell surface antigen (protein, carbohydrate or glycolipid); applicable to a broad range of patients and T cell populations; production of large numbers of tumor-specific cells in a moderately short period of time. Meanwhile CAR T cells capable of targeting only cell surface antigens; lethal toxicity due to cytokine storm reported. Here we present the most popular cancer cellular immunotherapy approaches and discuss their clinical relevance referring to data acquired from clinical trials .To date, clinical experience and efficacy suggest that combining more than one immunotherapy interventions, in conjunction with other treatment options like chemotherapy, radiotherapy and targeted or epigenetic therapy, should guide the way to cancer cure.

Keywords: breast cancer , cell therapy , CAR T cell , CIK cells

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Authors: Sarpong Boateng, Rohit Balasundaram, Akua Afrah Amoah

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Introduction: Racial and Gender disparities have been found to be independently associated with Salivary Gland Cancers (SGCs) survival; however, to our best knowledge, there are no previous studies on the interplay of these social determinants on the prognosis of SGCs. The objective of this study was to examine the joint effect of race and gender on the survival of SGCs. Methods: We analyzed survival outcomes of 13,547 histologically confirmed cases of SGCs using the Surveillance Epidemiology and End Results (SEER) database (2004 to 2015). Multivariable Cox regression analysis and Kaplan-Meier curves were used to estimate hazard ratios (HR) after controlling for age, tumor characteristics, treatment type and year of diagnosis. Results: 73.5% of the participants were whites, 8.5% were blacks, 10.1% were Hispanics and 58.5% were males. Overall, males had poorer survival than females (HR = 1.16, p=0.003). In the adjusted multivariable model, there were no significant differences in survival by race. However, the interaction of gender and race was statistically significant (p=0.01) in Hispanic males. Thus, compared to White females (reference), Hispanic females had significantly better survival (HR=0.53), whiles Hispanic males had worse survival outcomes (HR=1.82) for SGCs. Conclusions: Our results show significant interactions between race and gender, with racial disparities varying across the different genders for SGCs survival. This study indicates that racial and gender differences are crucial factors to be considered in the prognostic counseling and management of patients with SGCs. Biologic factors, tumor genetic characteristics, chemotherapy, lifestyle, environmental exposures, and socioeconomic and dietary factors are potential yet proven reasons that could account for racial and gender differences in the survival of SGCs.

Keywords: salivary, cancer, survival, disparity, race, gender, SEER

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Authors: Zhenqiu Liu

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Visualizing the heterogeneity within cell-populations for single-cell RNA-seq data is crucial for studying the functional diversity of a cell. However, because of the high level of noises, outlier, and dropouts, it is very challenging to measure the cell-to-cell similarity (distance), visualize and cluster the data in a low-dimension. Minimum volume embedding (MVE) projects the data into a lower-dimensional space and is a promising tool for data visualization. However, it is computationally inefficient to solve a semi-definite programming (SDP) when the sample size is large. Therefore, it is not applicable to single-cell RNA-seq data with thousands of samples. In this paper, we develop an efficient algorithm with an accelerated proximal gradient method and visualize the single-cell RNA-seq data efficiently. We demonstrate that the proposed approach separates known subpopulations more accurately in single-cell data sets than other existing dimension reduction methods.

Keywords: single-cell RNA-seq, minimum volume embedding, visualization, accelerated proximal gradient method

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Authors: Sudeshna Mukherjee, Leena Fageria, R. Venkataramana Dilip, Rajdeep Chowdhury, Jitendra Panwar

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Metal nanoparticles in recent years have gained importance in cancer therapy due to their enhanced permeability retention effect. Among various nanomaterials, silver nanoparticles (AgNPs) have received considerable attention due to their unique properties like conductivity, chemical stability, relative lower toxicity and outstanding therapeutic potential, such as anti-inflammatory, antimicrobial and anti-cancerous activities. In this study, we took a greener approach to synthesize silver nanoparticle from fungus and analyze its effects on both epithelial and mesenchymal derived cancer cells. Much research has been done on nanoparticle-induced apoptosis, but little is known about its role in autophagy. In our study, the silver nanoparticles were seen to induce autophagy which was analyzed by studying the expression of several autophagy markers like, LC3B-II and ATG genes. Monodansylcadaverine (MDC) assay also revealed the induction of autophagy upon treatment with AgNPs. Inhibition of autophagy by chloroquine resulted in increased cell death suggesting autophagy as a survival strategy adopted by the cells. In parallel to autophagy induction, silver nanoparticles induced ROS accumulation. Interestingly, autophagy inhibition by chloroquine increased ROS level, resulting in enhanced cell death. We further analyzed MAPK signaling upon AgNP treatment. It was observed that along with autophagy, activation of JNK signaling served as pro-survival while ERK signaling served as a pro-death signal. Our results provide valuable insights into the role of autophagy upon AgNP exposure and provide cues to probabilistic strategies to effectively sensitize cancer cells.

Keywords: autophagy, JNK signalling, reactive oxygen species, silver nanoparticles

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Authors: A. Hayrapetyan, A. Simon, P. Marques, G. Renart

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Business survival is a question of greatest interest for any economy. Firm characteristics that can explain or predict performance and, ultimately, business survival become of the greatest significance, as the sustainable longevity of any business can mean health for the future of the country. Family Firms (FFs) are one of the most ubiquitous forms of business worldwide, as more than half of European firms (60%) are considered as family firms. Therefore, the inherent characteristics of FFs are one of the possible explanatory variables for firm survival because FFs have strategic goals that differentiate them from other types of businesses. Although there is literature on the performance of FFs across generations, there are fewer studies on the factors that impact the survival of family and non-family FFs, as there is a lack of data on failed firms. To address this gap, this paper explores the differential survival of family firms versus non-family firms with a representative sample of companies of the region of Catalonia (Northeast of Spain) that were adhoc classified as family or nonfamily firms, as well as classified as failed or surviving, since no census data for family firms or for failed firms is available in Spain. By using the COX regression model on a representative sample of 629 family and non-family firms, this study investigates to what extent financial ratios, such as Liquidity, Solvency Rate can impact business survival, taking into consideration the socioemotional side of family firms, as well as revealing the differences between family and non-family firms. The findings show that the liquidity rate is significant for non-family firm survival, whereas not for family firms. On the other hand, FFs can benefit while having a higher solvency rate. Ultimately, this paper discovers that FFs increase their chances of survival when they are small, as the growth in size starts negatively impacting the socioemotional objectives of the firm. This study proves the existence of significant differences between family and non-family firms’ survival during economic crises, suggesting that the prioritization of emotional wealth creates distinct conditions for both types of firms.

Keywords: COX regression, economy crises, family firm, non-family firm, survival

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Authors: Raheela Akhtar, Zafar Iqbal Chaudhary, Yongqun Oliver He, Muhammad Younus, Aftab Ahmad Anjum

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Brucella abortus is an intracellular pathogen affecting macrophages. Macrophages release some components such as lysozymes (LZ), reactive oxygen species (ROS) and reactive nitrite intermediates (RNI) which are important tools against intracellular survival of Brucella. The antibrucella activity of bovine and murine macrophages was compared following stimulation with Brucella abortus lipopolysaccharides. Our results revealed that murine macrophages were ten times more potent to produce antibrucella components than bovine macrophages. The differential production of these components explained the differential Brucella killing ability of these species that was measured in terms of intramacrophagic survival of Brucella in murine and bovine macrophages.

Keywords: bovine macrophages, Brucella abortus, cell stimulation, cytokines, Murine macrophages

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Authors: Trenten Theis, Trevor Daubert, Kennedy Kluthe, Austin Nuxoll

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Staphylococcus aureus is a gram-positive bacterium responsible for an estimated 23,000 deaths in the United States and 25,000 deaths in the European Union annually. Recurring S. aureus bacteremia is associated with biofilm-mediated infections and can occur in 5 - 20% of cases, even with the use of antibiotics. Despite these infections being caused by drug-susceptible pathogens, they are surprisingly difficult to eradicate. One potential explanation for this is the presence of persister cells—a dormant type of cell that shows a high tolerance to antibiotic treatment. Recent studies have shown a connection between low intracellular ATP and persister cell formation. Specifically, this decrease in ATP, and therefore increase in persister cell formation, is due to an interrupted tricarboxylic acid (TCA) cycle. However, S. aureus persister cells’ role in pathogenesis remains unclear. Initial studies have shown that a fumC (TCA cycle gene) knockout survives challenge from aspects of the innate immune system better than wild-type S. aureus. Specifically, challenges from two antimicrobial peptides--LL-37 and hBD-3—show a log increase in survival of the fumC::N∑ strain compared to wild type S. aureus after 18 hours. Furthermore, preliminary studies show that the fumC knockout has a log more survival within a macrophage. These data lead us to hypothesize that the fumC knockout is better suited to other aspects of the innate immune system compared to wild-type S. aureus. To further investigate the mechanism for increased survival of fumC::N∑ within a macrophage, we tested bacterial growth in the presence of reactive oxygen species (ROS), reactive nitrogen species (RNS), and a low pH. Preliminary results suggest that the fumC knockout has increased growth compared to wild-type S. aureus in the presence of all three antimicrobial factors; however, no difference was observed in any single factor alone. To investigate survival within a host, a nine-day biofilm-associated catheter infection was performed on 6–8-week-old male and female C57Bl/6 mice. Although both sexes struggled to clear the infection, female mice were trending toward more frequently clearing the HG003 wild-type infection compared to the fumC::N∑ infection. One possible reason for the inability to reduce the bacterial burden is that biofilms are largely composed of persister cells. To test this hypothesis further, flow cytometry in conjunction with a persister cell marker was used to measure persister cells within a biofilm. Cap5A (a known persister cell marker) expression was found to be increased in a maturing biofilm, with the lowest levels of expression seen in immature biofilms and the highest expression exhibited by the 48-hour biofilm. Additionally, bacterial cells in a biofilm state closely resemble persister cells and exhibit reduced membrane potential compared to cells in planktonic culture, further suggesting biofilms are largely made up of persister cells. These data may provide an explanation as to why infections caused by antibiotic-susceptible strains remain difficult to treat.

Keywords: antibiotic tolerance, Staphylococcus aureus, host-pathogen interactions, microbial pathogenesis

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Authors: Hanish Mohammed, C. H. Muthukumar Muthuchamy

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The advancement in the science and technology has made it possible to convert electrical energy into any desired form. It has given electrical energy a place of pride in the modern world. The survival of industrial undertakings and our social structure depends primarily upon low cost and uninterrupted supply of electrical energy. Microbial fuel cell (MFC) is a promising and emerging technique for sustainable bioelectricity generation and wastewater treatment. MFCs are devices which are capable of converting organic matter to electricity/hydrogen with help of microorganisms. Different kinds of wastewater could be used in this technique, distillery effluent is one of the most troublesome and complex and strong organic effluent with high chemical oxygen demand of 1,53,846 mg/L. A single cell MFC unit was designed and fabricated for the distillery effluent treatment and to generate electricity. Due to the high COD value of the distillery effluent helped in the production of energy for 74 days. The highest voltage got from the fuel cell is 206 mV on the 30th day. A maximum power density obtained from the MFC was 9.8 mW, treatment efficiency was evaluated in terms of COD removal and other parameters. COD removal efficiencies were around 68.5 % and other parameters such as Total Hardness (81.5%), turbidity (70 %), chloride (66%), phosphate (79.5%), Nitrate (77%) and sulphate (71%). MFC using distillery effluent is a promising new unexplored substrate for the power generation and sustainable treatment technique through harnessing of bioelectricity.

Keywords: microbial fuel cell (MFC), bioelectricity, distillery effluent, wastewater treatment

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Authors: Rahul Kumar

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Background: Under-FiveMortality Rate(U5MR)ofanationiswidelyacceptedandlong-standing indicators of well-beingofherchildren.They measuredtheprobability of dying before theageoffive(expressedper1000livebirths).TheU5MRisanappropriate indicator of the cumulative exposure totheriskofdeathduringthefirstfiveyearsoflife, and accepted globalindicator ofthehealthandsocioeconomicstatusofagiven population.Itisalsousefulforassessing theimpactofvariousintervention programmes aimed at improving child survival.Under-fivemortalitytrendsconstitutealeadingindicatorofthelevel ofchildhealthandoveralldevelopmentincountries. Objectives: The first aim of our research is to study the level, trends, and Pattern of Under-five mortality using different sources of data. The second objective is to examine the survival pattern of Under-five mortality by different background characteristics. Data Source and Methodology: SRS and NFHS data have been used forobservingthelevelandtrendofUnder-Five mortality rate. Kaplan Meier Estimate has been used to understand the survival Pattern of Under-five mortality. Result: WefindthatallmostallthestatesmadesomeprogressbyreducingU5MRin recent decades.During1992-93highestU5MR(per thousand live birth) was observed in Assam(142)followed by up(141),Odisha(131),MP(130),andBihar(127.5).While the least U5MR(perthousandlive birth)wasobservedinRajasthan(102). The highestU5MR(per thousandlive birth)isobservedinUP(78.1), followed by MP(64.9)and Chhattisgarh(63.7)which are far away from the national level(50). Among them, Uttarakhand(46.7)hadleastU5MR(perthousandlivebirth), followed by Odisha(48.6). TheU5MR(perthousandlivebirth)ofcombinedhighfocusstateis63.7whichisfar away fromthenationallevel(50). Weidentified thatthesurvivalprobability ofunder-fivechildrenfromadolescentmotherislessin comparisontootherchildrenbornby differentagegroupofmothers. thatduringneonatalperiodusually male mortality exceedsthefemale mortality butthisdifferentialreversedinthepostneonatalperiod. Astheirageincreasesand approachingtofiveyears,weidentifiedthatthesurvivalprobability ofbothsexdecreasesbut female’s survival probabilitydecrement is more than male as their ageincreases. The poorer children’s survival probability is minimum. Children using improved toilet facility has more survival probability throughout thefiveyearsthan who uses unimproved. The survival probability of children under five who got Full ANCis more than the survival probability of children under five who doesn’t get any ANC. Conclusions: Improvement of maternal education is an urgent need to improve their health seeking behavior and thus the health of their children. Awareness on reproductive health and environmental sanitation should be strengthened.

Keywords: under-five mortality, survival pattern, ANC, trend

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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: Marta Fernández Olmos, Ana Gargallo Castel, Alice Salami

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The literature has shown the importance of studying the issue of business survival in highly competitive environments. In particular, the wine sector has certain characteristics that make it interesting to study factors that increase the possibility of wineries' survival, such as individual productivity, winery size, age, innovation efforts or the maturity of the industry itself, among others. Due to the importance of these factors, this research aims to analyze whether the possibility of wineries' survival increases if they are family businesses or if there is gender diversity in senior management. To this end, a nationwide survey was carried out. The sample was made up of wineries from all the Spanish appellations of origin, using this sample to analyze the survival of the diverse types of wineries according to the factors to be studied. The main results indicate that family wineries survive longer, suggesting that this may be due to the fact that the main objective of family wineries is the continuity of the business in the long term. Regarding gender diversity, wineries that have a female presence in top roles in management, adding gender diversity, survive more than those with a predominantly male presence. Based on these results, it is advisable to consider the importance of family businesses, especially in this type of sector. In addition, support should be provided for the inclusion of a female labor force to improve the possibility of survival.

Keywords: gender, family business, wine industry, survival

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Authors: Hirowati Ali, Aisyah Ellyanti, Dewi Rusnita, Septelia Inawati Wanandi

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Stem cell has been known for its potency to be differentiated in many cells. Recently stem cell has been used for many treatment of degenerative medicine. It is still controversy whether stem cell can be used for therapy or these cells can activate cancer stem cell. SCUBE2 is a novel secreted and membrane-anchored protein which has been reported to its role in better prognosis and inhibition of cancer cell proliferation. Our study aims to observe whether stem cell can up-regulate SCUBE2 gene in MCF7 breast cancer cell line. We used in vitro study using MCF-7 cell treated with stem cell derived from placenta Wharton's jelly which has been known for its stemness and widely used. Our results showed that MCF-7 cell line grows up rapidly in 6-well culture dish. Stem cell was cultured in 6-well dish. After 50%-60% MCF-7 confluence, we co-cultured these cells with stem cells for 24 hours and 48 hours. We hypothesize SCUBE2 gene which is previously known for its higher expression in better prognosis of breast cancer, is up-regulated after stem cells addition in MCF7 culture dishes.

Keywords: breast cancer cells, inhibition of cancer cells, mesenchymal stem cells, SCUBE2

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Authors: Xiaoyuan Chen

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Background: This study aimed to characterize the epidemiological and clinical features of five rare subtypes of hepatocellular carcinoma (HCC) and to create a competing risk nomogram for predicting cancer-specific survival. Methods: This study used the Surveillance, Epidemiology, and End Results database to analyze the clinicopathological data of 50,218 patients with classic HCC and five rare subtypes (ICD-O-3 Histology Code=8170/3-8175/3) between 2004 and 2018. The annual percent change (APC) was calculated using Joinpoint regression, and a nomogram was developed based on multivariable competing risk survival analyses. The prognostic performance of the nomogram was evaluated using the Akaike information criterion, Bayesian information criterion, C-index, calibration curve, and area under the receiver operating characteristic curve. Decision curve analysis was used to assess the clinical value of the models. Results: The incidence of scirrhous carcinoma showed a decreasing trend (APC=-6.8%, P=0.025), while the morbidity of other rare subtypes remained stable from 2004 to 2018. The incidence-based mortality plateau in all subtypes during the period. Clear cell carcinoma was the most common subtype (n=551, 1.1%), followed by fibrolamellar (n=241, 0.5%), scirrhous (n=82, 0.2%), spindle cell (n=61, 0.1%), and pleomorphic (n=17, ~0%) carcinomas. Patients with fibrolamellar carcinoma were younger and more likely to have non-cirrhotic liver and better prognoses. Scirrhous carcinoma shared almost the same macro clinical characteristics and outcomes as classic HCC. Clear cell carcinoma tended to occur in the Asia-Pacific elderly male population, and more than half of them were large HCC (Size>5cm). Sarcomatoid (including spindle cell and pleomorphic) carcinoma was associated with larger tumor size, poorer differentiation, and more dismal prognoses. The pathological subtype, T stage, M stage, surgery, alpha-fetoprotein, and cancer history were identified as independent predictors in patients with rare subtypes. The nomogram showed good calibration, discrimination, and net benefits in clinical practice. Conclusion: The rare subtypes of HCC had distinct clinicopathological features and biological behaviors compared with classic HCC. Our findings could provide a valuable reference for clinicians. The constructed nomogram could accurately predict prognoses, which is beneficial for individualized management.

Keywords: hepatocellular carcinoma, pathological subtype, fibrolamellar carcinoma, scirrhous carcinoma, clear cell carcinoma, spindle cell carcinoma, pleomorphic carcinoma

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Authors: Jannika Dombrowski, Sabine Ambros, Ulrich Kulozik

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Due to the increasing popularity of healthy products, probiotics are still of rising importance in food manufacturing. With the aim to amplify the field of probiotic application to non-chilled products, the cultures have to be preserved by drying. Microwave drying has proved to be a suitable technique to achieve relatively high survival rates, resulting from drying at gentle temperatures, among others. However, diffusion limitation due to compaction of cell suspension during drying can prolong drying times as well as deteriorate product properties (grindability, rehydration performance). Therefore, we aimed to embed probiotics in an aerated matrix of whey proteins (surfactants) and di-/polysaccharides (foam stabilization, probiotic protection) during drying. As a result of the manifold increased inner surface of the cell suspension, drying performance was enhanced significantly as compared to non-foamed suspensions. This work comprises investigations on suitable foam matrices, being stable under vacuum (variation of protein concentration, type and concentration of di-/polysaccharide) as well as development of an applicable microwave drying process in terms of microwave power, chamber pressure and maximum product temperatures. Performed analyses included foam characteristics (overrun, drainage, firmness, bubble sizes), and properties of the dried cultures (survival, activity). In addition, efficiency of the drying process was evaluated.

Keywords: foam structure, microwave drying, polysaccharides, probiotics

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Authors: Hsin-Lien Lin, Ju-Hui Fu

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Dendritic cells (DCs) are the major professional antigen-presenting cells for the development of optimal T-cell immunity. DCs can be used as pharmacological targets to screen novel biological modifiers for the treatment of harmful immune responses, such as transplantation rejection. Dryopteris crassirhizoma Nakai (Aspiadaceae) is used for traditional herbal medicine in the region of East Asia. The root of this fern plant has been listed for treating inflammatory diseases. Dryocrassin is the tetrameric phlorophenone component derived from Dryopteris. Here, we tested the immunomodulatory potential of dryocrassin on lipopolysaccharide (LPS)-stimulated activation of mouse bone marrow-derived DCs in vitro and in skin allograft transplantation in vivo. Results demonstrated that dryocrassin reduced the secretion of tumor necrosis factor-α, interleukin-6, and interleukin-12p70 by LPS-stimulated DCs. The expression of LPS-induced major histocompatibility complex class II, CD40, and CD86 on DCs was also blocked by dryocrassin. Moreover, LPS-stimulated DC-elicited allogeneic T-cell proliferation was lessened by dryocrassin. In addition, dryocrassin inhibited LPS-induced activation of IϰB kinase, JNK/p38 mitogen-activated protein kinase, as well as the translocation of NF-ϰB. Treatment with dryocrassin obviously diminished 2,4-dinitro-1-fluorobenzene- induced delayed-type hypersensitivity and prolonged skin allograft survival. Dryocrassin may be one of the potent immunosuppressive agents for transplant rejection through the destruction of DC maturation and function.

Keywords: dryocrassin, dendritic cells, immunosuppression, skin allograft

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Authors: Dalia Rimawi, Walid Salameh, Amal Al-Omari, Hadeel AbdelKhaleq

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Predication of Survival time of patients with cancer, is a core factor that influences oncologist decisions in different aspects; such as offered treatment plans, patients’ quality of life and medications development. For a long time proportional hazards Cox regression (ph. Cox) was and still the most well-known statistical method to predict survival outcome. But due to the revolution of data sciences; new predication models were employed and proved to be more flexible and provided higher accuracy in that type of studies. Artificial neural network is one of those models that is suitable to handle time to event predication. In this study we aim to compare ph Cox regression with artificial neural network method according to data handling and Accuracy of each model.

Keywords: Cox regression, neural networks, survival, cancer.

Procedia PDF Downloads 157