Investigation of Epstein-Barr virus, Cytomegalovirus, Human herpesvirus 6, and Polyoma viruses (JC virus, BK virus) among Gastric cancer patients: A cross sectional study.

Background and Aims: Gastric cancer is a significant global issue with a high death rate. This malignancy could be associated with several viral agents such as EBV, CMV, HHV-6, JCV, and BKV. Objective: Evaluation of EBV, CMV, HHV-6 ,and JCV, BKV frequency among gastric cancer patients. Methods: In this cross-sectional study, a total number of 60 gastric cancer specimens (32 male, 28 female) were retrieved from the pathology lab. Formalin-fixed paraffin-embedded tissue was used for molecular testing. DNA was extracted from samples, according to protocol, and used for PCR reaction. Polymerase chain reactions were used to assess CMV, EBV, HHV-6, JCV, and BKV frequency. Results and Conclusion: The mean age of the participants was 61 years and 53.3% (32) of the participants were Male. A total number of 5 samples (8.34%) were infected with viral agents. Four male gastric samples were infected with EBV (6.67%) and only one female sample contained the BKV genome (1.67%). Totally 8.34% of the samples were infected with EBV and BKV. The CMV, HHV-6, and JCV genome was not detected in the samples. In conclusion, the presence of two viral agents including EBV and BKV among male and female samples respectively, and the genome of other viruses were not detected.

Perceived Stress and Level of Uncertainty Among Hospitalized COVID-19 Patients.

Introduction: Disease uncertainty refers to the inability to assign meaning to events related to the illness. Uncertainty of the disease can affect various aspects of human life such as psychological aspects. Objectives: This study aims to examine the relationship between disease uncertainty and perceived stress in COVID-19 patients. Methods: An analytical cross-sectional study was conducted on 212 hospitalized COVID-19 patients who were initially admitted to the intensive care units (ICUs) and later transferred to general wards within the same hospitals. Three instruments were utilized to collect data for this study. The Demographic Information Questionnaire, Mishel Uncertainty in Illness Scale (MUIS) for disease uncertainty, and Perceived Stress Questionnaire. For data analysis, both descriptive and inferential statistics were employed using IBM SPSS Statistics version 25. Results: The Pearson correlation coefficient matrix results showed a positive and significant relationship between uncertainty about the illness (P < .001, r = 0.829), ambiguity (P < .001, r = 0.795), complexity (P < .001, r = 0.835), inconsistency or instability (P < .001, r = 0.787), and unpredictability (P < .001, r = 0.776) with perceived stress in COVID-19 patients transferred from the intensive care units. Conclusion: Based on the findings of the current study, both uncertainty and perceived stress are elevated among COVID-19 patients, and a significant and direct relationship exists between these two variables. Healthcare providers, particularly nurses, should address the uncertainties surrounding emerging diseases, both at the hospital and community levels.

Self-management interventions for people with multiple sclerosis: A systematic review and meta-analysis protocol.

Background and Aims: Educational self-management interventions (SMI) have an important role in improving symptom management, preventing relapse of multiple sclerosis (MS) and promoting quality of life (QoL) of these patients; since there is little knowledge about overall effectiveness of MS self-management programs and which types of SMI improves the outcomes, this research aims to assess the efficacy of structured SMI in improving health outcomes in people with MS (PwMS) by synthesizing and compare outcomes from related randomized controlled trials. Methods: In the present systematic review protocol, the keywords related to self-management and MS will be searched in electronic databases including (PubMed, Web of Science, Scopus, EMBASE, Cochrane Central Register of Controlled Trials [CENTRAL]), gray literature resources and key journals from 2000 to July 2023. Research-related articles will be collected and after removing duplicate articles, will be included in the study. In the screening step, titles and abstracts of articles will be reviewed and after deleting irrelevant articles, the full text of related articles will be evaluated independently by two researchers and data will be extracted from final articles and the findings will be categorized in an extraction table. Risk of bias will be assessed by using the Cochrane collaboration's tool. If possible, the data will be analyzed using random effect models and the statistical analysis will be performed using STATA software (version 14.2) developed by StataCorp. Discussion: Comparative effectiveness of SMI is currently unknown. We will analyze outcome measures used to assess effectiveness of self-management education in improving QoL, depression, self-efficacy, pain, and fatigue. These findings will help identify the most promising components of SMIs, guiding targeted interventions for specific subpopulations, and facilitating the design of better interventions.

Design and validation of the presenteeism scale in nursing.

BACKGROUND: The instruments used to measure presenteeism are all flawed and only incompletely measure the concept of presenteeism in employees of the general population. As a result, the concept of presenteeism is not measured, and in most of these instruments, the population for which the instrument has been developed differs from the nursing population. The present research was conducted to design and validate the instrument for evaluating presenteeism in nursing. METHODS: The present study was part of an exploratory sequential mixed study. In this study, the instrument for measuring the level of presenteeism among nurses was developed and validated based on the results of the qualitative stage. To this end, the instrument's psychometric properties were investigated using face, content, and construct validity, as well as reliability through internal consistency and stability. RESULTS: In this study, an instrument containing 17 items and three dimensions (imperfect cognitive presence, imperfect emotional presence, and imperfect movement presence) with favorable validation characteristics was developed. Therefore, the instrument was able to explain 56.375% of the total variance. Furthermore, Cronbach's alpha and McDonald's omega coefficients were 0.881 and 0.815, respectively. The intra-cluster correlation coefficient (ICC) was also reported as 0.972 for the entire instrument, with a 95% confidence interval of 0.941 to 0.987. CONCLUSION: Based this study, it was possible to measure the level of nurses' presenteeism through an instrument with favorable psychometric properties. This study helps health managers lay the groundwork for designing a system for measuring presenteeism among Iranian nurses using the developed instrument.

The relationship between health-related quality of life of students at Tehran University of Medical Sciences and their knowledge, attitudes, and practices regarding COVID-19 in 2020.

BACKGROUND: Present study attempts to investigate health-related quality of life (HRQoL) and its relation with knowledge, attitudes, and practices (KAP) of students of Tehran University of Medical Sciences (TUMS) during this pandemic. MATERIALS AND METHODS: In this cross-sectional study which was conducted between 23 may to 21 June 2020, 470 students in different levels of TUMS were included to the study randomly. participants completed validate, designed online questionnaire which assessed KAP towards coronavirus disease 2019 (COVID-19) and HRQoL. All statistical tests were applied, including Chi-square and Fisher's exact test, Partial correlation, analysis of variance, multiple linear regression, multiple binary and multinomial logistic regression models (P < 0.05) and were performed in SPSS 16, R 4.0.2, and GraphPad Prism 6.0 softwares. RESULTS: A total of 470 students were included in the study. The overall correct answer rate of the COVID-19 knowledge questionnaire was 74.43% and total score of the HRQoL was 72.50 (14.85). 61.7% of the students were agreed that COVID-19 will finally be successfully controlled, 44.3% had confidence that Iran can win the battle against the COVID-19, and 92.6% agreed that Quarantine will reduce the prevalence of COVID-19. Most of them adhered to health protocols and about a relation between HRQoL and knowledge we have a weak positive and unsignificant correlation between them (r = 0.05, P = 0.27). CONCLUSIONS: TUMS students showed expected levels of knowledge, proper attitudes, and preemptive practices regarding COVID-19, whereas COVID-19 outbreak substantially affected the physical and mental health but, the students were in a way better physical health rather than mental. Therefore, motivational planning and other related intervention to improve mental health can be noticeable.

The nurse without a nurse: the antecedents of presenteeism in nursing.

BACKGROUND: Presenteeism describes the state in which staff who lack the conditions for being present at work and need rest and leave for various reasons (such as illness, low spirits, fatigue, etc.) are present at the workplace. Due to the lack of knowledge about the antecedents of presenteeism in nurses and the context-based nature of this concept, the present study was conducted to explain the reasons for presenteeism in nurses. METHODS: This qualitative study was performed using the qualitative content analysis method. The study population consisted of 17 nurses working in different wards of hospitals. In this regard, data were collected from February to June 2020 using individual, face-to-face, in-depth, semi-structured interviews and were analyzed using qualitative content analysis. RESULTS: The nurse without a nurse was a category introduced as an antecedent of presenteeism. In this respect, nurses experienced limited power, injustice, compulsory presence, inadequate structural facilities, damaged professional identity, manager-nurse disconnect, insufficient knowledge, physical and mental health complications, job stress, job burnout, multitasking, and impaired communication. CONCLUSION: The nurse, who has been responsible for caring, supporting, advising, advocating, and educating the patient, has now been left without a nurse. In other words, not nursing the nurse has given rise to the emergence of presenteeism. It is recommended that the results of this study be used in making health policies. The results of this study can make nurses' voices heard by health leaders and managers. A voice that has never been heard as it deserves.

Patients' Experiences of Life Challenges After Liver Transplantation: A Qualitative Study.

Patients experience a new life with different challenges after liver transplantation (LT). Identifying these challenges can facilitate the improvement of their quality of life. This study aimed to explore patients' experiences of post-LT life challenges. This qualitative study was performed in 2019 through the content analysis approach. Participants were liver transplant recipients purposively recruited from a LT clinic. Semistructured interviews were conducted for data collection. Data were analyzed through Graneheim and Lundman's conventional content analysis approach. Meaning units were identified and coded, and the codes were grouped into subcategories and categories according to their similarities. In total, 18 transplant recipients were interviewed. Their age mean was 51 years and their transplant age ranged from 4 months to 12 years. Their post-LT life challenges were categorized into 4 main categories, that is, self-care deficit, the need for seeking information, fears and concerns, and hope-despair duality. Nurses and members of LT team are recommended to assess transplant recipients' life challenges and develop comprehensive plans for managing their challenges and problems and improving their quality of life.

SMAD4 Expression in Renal Cell Carcinomas Correlates With a Stem-Cell Phenotype and Poor Clinical Outcomes.

Renal cell carcinoma (RCC) is the most lethal neoplasm of common urologic cancers with poor prognoses. SMAD4 has a principal role in TGF-ß (Transformis growth factorß)-induced epithelial to mesenchymal transition (EMT) as a key factor in gaining cancer stem cell (CSC) features and tumor aggressiveness. This study aimed to evaluate the expression patterns and clinical significance of SMAD4 in RCC and the impact of its targeting on stem cell/mesenchymal cells and EMT characteristics in renal spheroid derived cells (SDCs) compared to parental cells (PCs) in RCC. The expression pattern and clinical significance of SMAD4 was evaluated in RCC. SDCs were enriched using a sphere culture system. Then SDCs and their PCs were compared with respect to their sphere and colony formation, expression of putative CSC markers, invasiveness as well as expression of genes, including stemness/mesenchymal, SMAD4 and TGFß1genes. Finally, the effect of SMAD4 knockdown on SDCs was analyzed. We demonstrated that SMAD4 is positively correlated with decreased disease specific survival (DSS) in RCC patients and clear cell RCC (ccRCC) subtype and associates with poor DSS in patients with RCC, especially in ccRCC as the most metastatic RCC subtype. SDCs exhibited higher stem cell/mesenchymal properties. Inhibition of SMAD4 in PCs accelerated the dissociation of SDCs and decreased their clonogenicity, invasiveness, expression of mesenchymal markers and expression of SMAD4 and TGFß1 genes compared to SDCs before transfection. We suggest that targeting SMAD4 may be useful against renal CSCs and may improve RCC prognosis.

Exploring the concept of presenteeism in nursing: A hybrid concept analysis.

PURPOSE: To explore the concept of presenteeism in nursing. METHOD: A three-phase concept analysis using a hybrid model was used. In the theoretical phase (first phase), a literature review was conducted using PubMed, Web of Science, Proquest, EBSCO, Scopus, OVID, Cochrane Library, PsycINFO, Google Scholar, SID, and Iranmedex. In the fieldwork phase (second phase), semistructured interviews with 17 nurses were used. In the final analytical phase (third phase), the results of the previous phases were combined. FINDINGS: In the final definition, presenteeism can be considered as a kind of fall from balance, in whose nature lies the non-actualization of capacities. If the imbalance of presence is due to the body, we are faced with the non-actualization of movement capacity, and regarding the imbalance caused by the soul, cognitive and emotional actualization is challenged. CONCLUSION: Exploration of the concept of presenteeism in the nursing is the basis for identifying this concept in a profession that deals with health as the most valuable human property. IMPLICATIONS FOR NURSING PRACTICE: The identified attributes of presenteeism provide a deep insight for nurse managers into the nature of presenteeism. Nurse managers cannot deal with a destructive phenomenon without exploring and identifying its exact meaning.

Cytoplasmic expression of B7-H3 and membranous EpCAM expression are associated with higher grade and survival outcomes in patients with clear cell renal cell carcinoma.

B7-H3 and EpCAM are overexpressed in cancer and play a role in tumorigenesis and metastasis. In this study, the membranous, cytoplasmic and nuclear expression levels of B7-H3 and EpCAM biomarkers were mapped in three major subtypes of renal cell carcinoma (RCC). Expression of B7-H3 and EpCAM were evaluated using immunohistochemistry in RCC samples on tissue microarrays (TMAs), including clear cell RCCs (ccRCCs), type I and II papillary RCCs (pRCCs), and chromophobe RCCs (chRCCs). The association between B7-H3 and EpCAM expression and clinicopathological features as well as survival outcomes was determined. There was a statistically significant difference between B7-H3 and EpCAM expression among the different RCC subtypes. In ccRCC, higher cytoplasmic expression of B7-H3 was significantly associated with increase in nucleolar grade, lymph node invasion (LNI), invasion of the Gerota's fascia, and tumor necrosis, while no association was found with the membranous and nuclear expression. Moreover tumors with cytoplasmic expression of B7-H3 tended to have a worse prognosis for disease-specific survival (DSS) than those with membranous expression. In case of EpCAM, increased membranous expression of EpCAM was associated with nucleolar grade and tumor necrosis in ccRCC. Additionally, membranous EpCAM expression added prognostic value in patients with ccRCC who had high nucleolar grade versus low nucleolar grade. Moreover, membranous EpCAM expression was found to be an independent favorable prognostic marker for progression-free survival (PFS) in ccRCC. Our results demonstrated that higher cytoplasmic B7-H3 and membranous EpCAM expression are clinically significant in ccRCC and are associated with more aggressiveness tumor behavior.

Spheroid-Derived Cells From Renal Adenocarcinoma Have Low Telomerase Activity and High Stem-Like and Invasive Characteristics.

Cancer stem cells (CSCs) are a theorized small subpopulation of cells within tumors thought to be responsible for metastasis, tumor development, disease progression, treatment-resistance, and recurrence. The identification, isolation, and biological characterization of CSCs may therefore facilitate the development of efficient therapeutic strategies targeting CSCs. This study aims to compare the biology and telomerase activity of CSCs to parental cells (PCs) in renal cancer. Renal CSCs were enriched from the ACHN cell line using a sphere culture system. Spheroid-derived cells (SDCs) and their adherent counterparts were compared with respect to their colony and sphere formation, expression of putative CSC markers, tumorigenicity in non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, and invasiveness. The expression of genes associated with CSCs, stemness, EMT, apoptosis, and ABC transporters was also compared between the two populations using quantitative real-time PCR (qRT-PCR). Finally, telomerase activity, hTERT expression, and sensitivity to MST-312, a telomerase inhibitor, was investigated between the two populations. We demonstrated that a subpopulation of ACHN cells was capable of growing as spheroids with many properties similar to CSCs, including higher clonogenicity, superior colony- and sphere-forming ability, and stronger tumorigenicity and invasiveness. In addition, SDCs demonstrated a higher expression of markers for CSCs, stemness, EMT, apoptosis, and ABC transporter genes compared to PCs. The expression of hTERT and telomerase activity in SDCs was significantly lower than PCs; however, the SDC population was more sensitive to MST-312 compared to PCs. These findings indicate that the SDC population exhibits stem-like potential and invasive characteristics. Moreover, the reduced expression of hTERT and telomerase activity in SDCs demonstrated that the expressions of hTERT and telomerase activity are not always higher in CSCs. Our results also showed that MST-312 treatment inhibited SDCs more strongly than PCs and may therefore be useful as a complementary targeted therapy against renal CSCs in the future.

Human telomerase reverse transcriptase protein expression predicts tumour aggressiveness and survival in patients with clear cell renal cell carcinoma.

Human telomerase reverse transcriptase (hTERT) is an active component of telomerase and responsible for its catalytic activity, associated with cell proliferation and differentiation. For the first time, the present study was conducted to evaluate the expression and prognostic significance of hTERT in different histological subtypes of renal cell carcinoma (RCC). Expression of hTERT was examined in 176 well-defined renal tumour samples including clear cell RCCs (ccRCCs), papillary and chromophobe RCCs using immunohistochemistry on tissue microarrays. The association between hTERT expression and clinicopathological parameters as well as survival outcomes were then analysed. There was a statistically significant difference in terms of hTERT expression among various RCC subtypes. In ccRCC, increased expression of hTERT was significantly associated with advanced stage, higher grade, presence of microvascular invasion, lymph node invasion, and metastasis. Moreover, in the multivariate analysis, tumour stage and tumour size were independent predictors of the disease-specific survival (DSS). Additionally, expression of hTERT was found to be a significant predictor of worse DSS (p = 0.012) in the univariate analysis. In papillary carcinoma samples (type I and II), significant association was detected between hTERT expression and the tumour stage (p = 0.010, p = 0.050), respectively. In chromophobe RCC, no significant association was detected between expression of hTERT and clinicopathological parameters and survival data. We showed that hTERT protein expression was associated with more aggressive tumour behaviour and more advanced disease in ccRCC patients. Also, hTERT may be a novel poor prognostic indicator of DSS, if the patients are followed for more prolonged time periods.

Co-expression of Cancer Stem Cell Markers OCT4 and NANOG Predicts Poor Prognosis in Renal Cell Carcinomas.

Many renal cancer patients experience disease recurrence after combined treatments or immunotherapy due to permanence of cancer stem cells (CSCs). This study was conducted to evaluate the expression patterns and clinical significance of octamer-binding transcription factor 4 (OCT4) and NANOG as the key stem cell factors in renal cell carcinoma (RCC). A total of 186 RCC tissues were immunostained on a tissue microarray (TMA) for the putative CSC markers OCT4 and NANOG. Subsequently, the correlation among the expression of these markers, the clinicopathological variables and survival outcomes were determined. OCT4 and NANOG were expressed in both the nucleus and the cytoplasm of RCC cells. Coexpression of OCT4 and NANOG in renal cancer was significantly associated with RCC subtypes. A significant association was found among nuclear coexpression of OCT4 and NANOG, worse PFS in RCC, and the clear cell renal cell carcinomas (ccRCC) subtype. The OCT4-nuclear high/NANOG-nuclear high phenotype in RCC and ccRCC subtype indicated aggressive tumor behavior and predicted a worse clinical outcome, which may be a useful biomarker to identify patients at high risk of postoperative recurrence and metastasis. Cytoplasmic expression of NANOG could be considered as a novel independent prognostic predictor in patients with renal cancer.

Expression of CD105 cancer stem cell marker in three subtypes of renal cell carcinoma.

BACKGROUND: CD105 is recently described as a cancer stem cell (CSC) marker. OBJECTIVE: The present study was aimed to investigate the expression and prognostic significance of the CSC marker CD105 in different histological subtypes of renal cell carcinoma (RCC). METHODS: Expression of CD105 was evaluated using immunohistochemistry in RCC samples on tissue microarrays including clear cell RCCs (ccRCCs), papillary, and chromophobe RCCs. The association between CD105 expression and clinicopathological features as well as survival outcomes was determined. RESULTS: In ccRCC, increased tumoral cytoplasmic and endothelial expression of CD105 were significantly associated with advanced stage, renal vein invasion, and microvascular invasion (MVI). In addition, MVI was associated with a worse overall survival (OS). Moreover, in multivariate analysis tumor stage and nuclear grade were independent prognostic factors for OS both in case of tumoral cytoplasmic and endothelial CD105 expression. Additionally, CD105 expression was found to be a predictor of worse OS in univariate analysis. However, in papillary and chromophobe RCC, no significant association was found between CD105 expression and clinicopathological parameters or prognosis. CONCLUSIONS: We showed that CD105 expression was associated with more aggressive tumor behavior, more advanced disease, and worse prognosis in ccRCC but not in the other RCC subtypes.

Cytoplasmic expression of Twist1, an EMT-related transcription factor, is associated with higher grades renal cell carcinomas and worse progression-free survival in clear cell renal cell carcinoma.

Twist1 is a key transcription factor, which confers tumor cells with cancer stem cell (CSC)-like characteristics and enhances epithelial-mesenchymal transition in pathological conditions including tumor malignancy and metastasis. This study aimed to evaluate the expression patterns and clinical significance of Twist1 in renal cell carcinoma (RCC). The cytoplasmic and nuclear expression of Twist1 were examined in 252 well-defined renal tumor tissues, including 173 (68.7%) clear cell renal cell carcinomas (ccRCC), 45 (17.9%) papillary renal cell carcinomas (pRCC) and 34 (13.5%) chromophobe renal cell carcinoma, by immunohistochemistry on a tissue microarray. The association between expression of this marker and clinicopathologic parameters and survival outcomes were then analyzed. Twist1 was mainly localized to the cytoplasm of tumor cells (98.8%). Increased cytoplasmic expression of Twist1 was associated with higher grade tumors (P = 0.045), renal vein invasion (P = 0.031) and microvascular invasion (P = 0.044) in RCC. It was positively correlated with higher grade tumors (P = 0.026), shorter progression-free survival time (P = 0.027) in patients with ccRCC, and also with higher stage in pRCC patients (P = 0.036). Significantly higher cytoplasmic expression levels of Twist1 were found in ccRCC and pRCC subtypes, due to their more aggressive tumor behavior. Increased cytoplasmic expression of Twist1 had a critical role in worse prognosis in ccRCC. These findings suggest that cytoplasmic, rather than nuclear expression of Twist1 can be considered as a prognostic and therapeutic marker for targeted therapy of RCC, especially for ccRCC patients.

Increased expression of CD44 is associated with more aggressive behavior in clear cell renal cell carcinoma.

AIM: Although CD44 has been suggested as a prognostic marker in renal cell carcinoma (RCC), the prognostic significance of this marker in three main subtypes of RCC is still unclear. Thus, the present study was conducted to evaluate the expression and prognostic significance of CD44 as a cancer stem cell marker in different histological subtypes of RCC. Methodology & results: CD44 expression was evaluated in 206 well-defined renal tumor samples using immunohistochemistry on tissue microarrays. Higher CD44 expression was associated with more aggressive behavior, tumor progression and worse prognosis in clear cell RCC (ccRCC) but not in papillary and chromophobe RCC subtypes. DISCUSSION & CONCLUSION: Cancer stem cell marker CD44 may be a promising target for cancer treatment only in ccRCC.

Prevalence of vitamin D deficiency in healthy Iranian children: A systematic review and meta-analysis.

Background: Vitamin D deficiency is related to rickets in children, and it can increase the risk of osteoporosis in adulthood. The aim of our study was to estimate the prevalence of vitamin D deficiency among healthy Iranian children and adolescents. Vitamin D levels less than 20ng/ml and between 20 and 30ng/ml was considered as vitamin D deficiency and insufficiency, respectively. Methods: Relevant observational studies evaluating the prevalence of vitamin D deficiency through 1 January 1990 to 28 Dec 2016, were searched in several electronic databases including Iran-Medex, Scientific Information Database (SID), Irandoc, PubMed and NLM Gateway (for MEDLINE), Web of Science, and Scopus with no restriction on language. Only full-text articles were used for data extraction and synthesis after considering the inclusion/exclusion criteria. Results: 11 studies included; the data of four studies of Iranian newborns were withdrawn because of their high heterogeneity. The prevalence of vitamin D deficiency in Iranian boys and girls were 35% (CI 95% 34-37) and 61% (CI 95% 60-63), respectively. The prevalence of vitamin D insufficiency in Iranian children and adolescents was 31% (CI 95% 30-31). Conclusion: It seems that the prevalence of vitamin D deficiency is very high among Iranian children and adolescents. The present findings could provide practical information for healthcare decision makers.

Circulating cancer stem cell markers in breast carcinomas: a systematic review protocol.

BACKGROUND: Breast cancer is one of the most common types of cancer in women worldwide. Recent studies have provided strong support for the cancer stem cell (CSC) hypothesis, which suggests that many cancers, including breast cancer, are driven by a subpopulation of cells that display stem cell-like properties. The hypothesis that a subpopulation of circulating tumor cells (CTCs) possesses many CSC-like hallmarks is reinforced by the expression of related molecular markers between these two cell populations. The aim of this study is to systematically review primary studies and identify circulating CSC markers in breast cancer patients. METHODS AND DESIGN: Relevant observational studies evaluating the expression of circulating breast cancer stem cell markers through October 31, 2016, will be searched in PubMed, SCOPUS, Embase, ISI Web of Science, and Google Scholar with no restriction on language. Full copies of articles identified by the search and considered to meet the inclusion criteria will be obtained for data extraction and synthesis. Two quality assessment tools will be used for evaluating observational studies like case control, which are the Hoy et al. suggested tool and Newcastle-Ottawa Scale (NOS), respectively. Publication bias will be assessed by funnel plots or Egger's test (i.e., plots of study results against precision), and data synthesis will be performed using Stata software (Stata Corp V.12, TX, USA).This systematic review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). DISCUSSION: Detecting cancer stem cells in blood will help clinicians to monitor cancer patients by obtaining as many samples as needed with a non-invasive method and in any stages; it is not possible to repeat sampling on working on tissue samples. By identifying cancer stem cells early in blood, it will be possible to distinguish metastasis in early stages. SYSTEMATIC REVIEW REGISTRATION: CRD42016043810.

Exosomal microRNAs as potential circulating biomarkers in gastrointestinal tract cancers: a systematic review protocol.

BACKGROUND: Metastasis is the most frequent type of recurrence in gastrointestinal (GI) cancers, and there is an emerging potential for new diagnostic and therapeutic approaches, especially in the cases of metastatic GI carcinomas. The expression profiles of circulating exosomal microRNAs are of particular interest as novel non-invasive diagnostic and prognostic biomarkers for improved detection of GI cancers in body fluids, especially in the serum of patients with recurrent cancers. The aim of this study is to systematically review primary studies and identify the miRNA profiles of serum exosomes of GI cancers. METHODS AND DESIGN: This systematic review will be reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidance. Relevant studies will be identified through a comprehensive search of the following main electronic databases: PubMed, Web of Science, Embase, Scopus, and Google Scholar, with no language restrictions (up to July 2017). Full copies of articles will be identified by a defined search strategy and will be considered for inclusion against pre-defined criteria. The quality assessment of the included studies will be performed by the Newcastle-Ottawa Scale (NOS). Data will be analyzed using Stata software V.12. Publication bias will be assessed by funnel plots, Beggs' and Eggers' tests. The levels of evidence for primary outcomes will be evaluated using the GRADE criteria. DISCUSSION: The analysis of circulating exosomal miRNA profiles provides attractive screening and non-invasive diagnostic tools for the majority of solid tumors including GI cancers. There is limited information regarding the relationship between serum exosomal miRNA profiles and the pathological condition of patients with different GI cancers. Since there is no specific biomarker for GI cancers, we aim to suggest a number of circulating exosomal miRNA candidates as potential multifaceted GI cancer biomarkers for clinical utility. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017057129.