Nunezsparks6243

In parallel, iron application inhibited the activation, expansion and survival of cytotoxic CD8+ T cells and of CD4+ T helper cells type 1 and significantly reduced the efficacy of the investigated anti-cancer treatments. Our results indicate that iron administration has a tumor growth promoting effect and impairs anti-cancer responses of tumor infiltrating T lymphocytes along with a reduced efficacy of anti-cancer therapies. Iron supplementation in cancer patients, especially in those treated with immunotherapies in a curative setting, may be thus used cautiously and prospective studies have to clarify the impact of such intervention on the outcome of patients.Copy number aberrations (CNV/CNA) represent a major contribution to the somatic mutation landscapes in cancers, and their identification can lead to the discovery of oncogenetic targets as well as improved disease (sub-) classification. Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma in Western Countries and up to 40% of the affected individuals still succumb to the disease. DLBCL is an heterogenous group of disorders, and we call DLBCL today is not necessarily the same disease of a few years ago. This review focuses on types and frequencies of regional DNA CNVs in DLBCL, not otherwise specified, and in two particular conditions, the transformation from indolent lymphomas and the DLBCL in individuals with immunodeficiency.Colorectal cancer (CRC) is a disease with constantly increasing incidence and high mortality. The treatment efficacy could be curtailed by drug resistance resulting from poor drug penetration into tumor tissue and the tumor-specific microenvironment, such as hypoxia and acidosis. Furthermore, CRC tumors can be exposed to different pH depending on the position in the intestinal tract. CRC tumors often share upregulation of the Akt signaling pathway. In this study, we investigated the role of external pH in control of cytotoxicity of perifosine, the Akt signaling pathway inhibitor, to CRC cells using 2D and 3D tumor models. In 3D settings, we employed an innovative strategy for simultaneous detection of spatial drug distribution and biological markers of proliferation/apoptosis using a combination of mass spectrometry imaging and immunohistochemistry. In 3D conditions, low and heterogeneous penetration of perifosine into the inner parts of the spheroids was observed. The depth of penetration depended on the treatment duration but not on the external pH. However, pH alteration in the tumor microenvironment affected the distribution of proliferation- and apoptosis-specific markers in the perifosine-treated spheroid. Accurate co-registration of perifosine distribution and biological response in the same spheroid section revealed dynamic changes in apoptotic and proliferative markers occurring not only in the perifosine-exposed cells, but also in the perifosine-free regions. Cytotoxicity of perifosine to both 2D and 3D cultures decreased in an acidic environment below pH 6.7. External pH affects cytotoxicity of the other Akt inhibitor, MK-2206, in a similar way. Our innovative approach for accurate determination of drug efficiency in 3D tumor tissue revealed that cytotoxicity of Akt inhibitors to CRC cells is strongly dependent on pH of the tumor microenvironment. Therefore, the effect of pH should be considered during the design and pre-clinical/clinical testing of the Akt-targeted cancer therapy.

Metastatic breast cancer (MBC) is a highly heterogeneous disease and bone is one of the most common metastatic sites. This retrospective study was conducted to investigate the clinical features, prognostic factors and benefits of surgery of breast cancer patients with initial bone metastases.

From 2010 to 2015, 6,860 breast cancer patients diagnosed with initial bone metastasis were analyzed from Surveillance, Epidemiology, and End Results (SEER) database. Univariate and Multivariable analysis were used to identify prognostic factors. A nomogram was performed based on the factors selected from cox regression result. Survival curves were plotted according to different subtypes, metastatic burdens and risk groups differentiated by nomogram.

Hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2) positive patients showed the best outcome compared to other subtypes. Patients of younger age (<60 years old), white race, lower grade, lower T stage (<=T2), not combining visceral mets in patients with initial bone metastatic breast cancer and constructed a predicting nomogram with good accuracy. The finding of potential benefit of surgery to overall survival will cast some lights on the treatment tactics of this group of patients.

Many primary tumors have insufficient supply of molecular oxygen, called hypoxia. Hypoxia is one of the leading characteristics of solid tumors resulting in a higher risk of local failure and distant metastasis. It is quite necessary toinvestigate the hypoxia associated molecular hallmarks in breast cancer.

According to the published studies, we selected 13 hypoxia related gene expression signature to define the hypoxia status of breast cancer using ConsensusClusterPlus package based on the data from The Cancer Genome Atlas (TCGA). Subsequently, we characterized the infiltration of 24 immune cell types under different hypoxic conditions. Furthermore, the differentially expressed hypoxia associated microRNAs, mRNAs and related signaling pathways were analyzed and depicted. On this basis, a series of prognostic markers related to hypoxia were identified and ceRNA co-expression networks were constructed.

Two subgroups (cluster1 and cluster2) were identified and the 13 hypoxia related gene signature were alpectively.

Hypoxia plays an important role in the initiation and progression of breast cancer. Our research provides potential mechanisms into molecular-level understanding of tumor hypoxia.

Hypoxia plays an important role in the initiation and progression of breast cancer. Our research provides potential mechanisms into molecular-level understanding of tumor hypoxia.

We evaluated the impact of 3 months of mFOLFOX6 adjuvant chemotherapy or surgery alone in comparison with 6 months of mFOLFOX6 on disease-free survival (DFS) in deficient mismatch repair (dMMR) colon cancer (CC) patients.

This retrospective study identified a cohort of patients with high-risk stage II and III dMMR CC who underwent curative surgery between May 2011 and July 2019. DFS was compared using the Kaplan-Meier survival methods and Cox proportional hazards models. Propensity-score matching was performed to reduce imbalance in baseline characteristics.

A total of 242 dMMR CC patients were identified; 66 patients received 6 months of mFOLFOX6, 87 patients received 3 months of mFOLFOX6, and 89 patients were treated with surgery alone. The 3-year DFS rate was 72.8% in 3-month therapy group and 86.1% in 6-month therapy group, with a hazard ratio (HR) of 2.78 (95CI%, 1.18 to 6.47; P= 0.019). The difference in DFS between surgery alone group and 6-month therapy group was also observed but was nonsignificant (HR= 2.30, 95%CI, 0.99 to 5.38; P=0.054). The benefit of 6-month therapy in DFS compared with 3-month therapy group was pronounced for patients with stage III (HR=2.81, 95%CI, 1.03 to 7.67; P=0.044) but not for high-risk stage II patients. Propensity score matched analysis confirmed a DFS benefit in the 6-month therapy group.

This study suggested that a 6-month duration of mFOLFOX6 adjuvant chemotherapy in dMMR CC patients may be associated with improved DFS compared with 3-month therapy, particularly in patients with stage III. The observational nature of the study implies caution should be taken in the interpretation of these results.

This study suggested that a 6-month duration of mFOLFOX6 adjuvant chemotherapy in dMMR CC patients may be associated with improved DFS compared with 3-month therapy, particularly in patients with stage III. The observational nature of the study implies caution should be taken in the interpretation of these results.The mechanism of liver hepatocellular carcinoma (LIHC) development in correlation with tumor microenvironments and somatic mutations is still being elucidated. This study aims to identify the potential molecular mechanisms and candidate biomarkers in response to tumor microenvironments and somatic mutations. Multiple bioinformatics analysis methods were applied to assess the tumor immunological microenvironment, differentially expressed genes, genetic function enrichment, immunocyte infiltration, regulatory network construction, and tumor mutational burden, and to identify DNA methylation sites. The immunological microenvironment features of ESTIMATE score (OS p = 0.017, HR = 0.64; RFS HR = 0.43, p less then 0.001) have an important impact on the prognosis of LIHC patients. Cut-off by ESTIMATE score and prognostic information identified 666 DEGs (45 downregulated and 621 upregulated) that were linked with leukocyte migration and lymphocyte activation. In immunocyte infiltration analysis, NK cells (resting), M1 macrophages, CD8+ T cells, and regulatory T cells (Tregs), which are considered core immunoregulatory cells, exhibited significant differences between higher and lower ESTIMATE scores (overall survival and recurrence-free survival p-values less then 0.01). Subsequently, further analysis of immunocyte-hub gene identification illustrated that the expression levels of CXCL12 and IL7R significantly correlated with core immunoregulatory cells and somatic mutations (CXCL12 p = 2.1E-06; IL7R p = 0.001). This study provides new insight into our understanding of the mechanisms of immunocyte regulation and microenvironment involved in LIHC development as well as the effective biomarkers of CXCL12 and IL7R and core immunoregulatory cells, which may emerge as novel therapies for LIHC patients.The calcium-permeable cation channel TRPM8 (transient receptor potential melastatin 8) is a member of the TRP superfamily of cation channels that is upregulated in various types of cancer with high levels of autophagy, including prostate, pancreatic, breast, lung, and colon cancers. Autophagy is closely regulated by AMP-activated protein kinase (AMPK) and plays an important role in tumor growth by generating nutrients through degradation of intracellular structures. Additionally, AMPK activity is regulated by intracellular Ca2+ concentration. Considering that TRPM8 is a non-selective Ca2+-permeable cation channel and plays a key role in calcium homoeostasis, we hypothesized that TRPM8 may control AMPK activity thus modulating cellular autophagy to regulate the proliferation and migration of breast cancer cells. In this study, overexpression of TRPM8 enhanced the level of basal autophagy, whereas TRPM8 knockdown reduced the level of basal autophagy in several types of mammalian cancer cells. Moreover, the activity of the TRPM8 channel modulated the level of basal autophagy. The mechanism of regulation of autophagy by TRPM8 involves autophagy-associated signaling pathways for activation of AMPK and ULK1 and phagophore formation. Impaired AMPK abolished TRPM8-dependent regulation of autophagy. TRPM8 interacts with AMPK in a protein complex, and cytoplasmic C-terminus of TRPM8 mediates the TRPM8-AMPK interaction. Finally, basal autophagy mediates the regulatory effects of TRPM8 on the proliferation and migration of breast cancer cells. Thus, this study identifies TRPM8 as a novel regulator of basal autophagy in cancer cells acting by interacting with AMPK, which in turn activates AMPK to activate ULK1 in a coordinated cascade of TRPM8-mediated breast cancer progression.

The aim of this work is to introduce the 2019 International Planning Competition and to analyze its results.

A locally advanced non-small cell lung cancer (LA-NSCLC) case using the simultaneous integrated boost approach was selected. The plan quality was evaluated by using a ranking system in accordance with practice guidelines. Planners used their clinical Treatment Planning System (TPS) to generate the best possible plan along with a survey, designed to obtain medical physics aspects information. We investigated the quality of the large population of plans designed by worldwide planners using different planning and delivery systems. The correlations of plan quality with relevant planner characteristics (work experience, department scale, and competition experience) and with technological parameters (TPS and modality) were examined.

The number of the qualified plans was 287 with a wide range of scores (38.61-97.99). The scores showed statistically significant differences by the following factors 1) depied out successfully, and its results were analyzed. Plan quality was not correlated with work experiences or the TPS used, but it was correlated with department scale, modality, and competition experience. These findings differed from those reported in previous studies.

The 2019 international planning competition was carried out successfully, and its results were analyzed. Plan quality was not correlated with work experiences or the TPS used, but it was correlated with department scale, modality, and competition experience. These findings differed from those reported in previous studies.

This study aimed to evaluate the diagnostic value of telomerase activity (TA) for bladder cancer (BC) by meta-analysis.

We conducted a systematic search of studies published on PubMed, Embase, and Web of Science up to June 1, 2019. We used Stata 15 and Review Manager 5.3 for calculations and statistical analysis.

To evaluate the diagnostic value of TA for BC, we performed a meta-analysis on 22 studies, with a total of 2,867 individuals, including sensitivity, specificity, positive and negative likelihood ratio (PLR, NLR), diagnostic odds ratio (DOR), and 95% confidence intervals (CIs). The pooled parameters were calculated from all studies, and we found a sensitivity of 0.79 (95% CI 0.72-0.84), a specificity of 0.91 (95% CI 0.87-0.94), a PLR of 8.91 (95% CI 5.91-13.43), an NLR of 0.24 (95% CI 0.15-0.37), a DOR of 37.90 (95% CI 23.32-61.59), and an AUC of 0.92 (95% CI 0.90-0.94). We also conducted a subgroup analysis based on the different stages and grades of BC. Results from the subgroup analysis showed that there was no significant difference in TA in either high and low stages of BC, but that low-grade tumors had a lower TA than high-grade tumours.

TA can be used as a potential biomarker for the diagnosis of bladder cancer with its high specificity. Rigorous and high-quality prospective studies are required to verify our conclusion.

TA can be used as a potential biomarker for the diagnosis of bladder cancer with its high specificity. Rigorous and high-quality prospective studies are required to verify our conclusion.Immune checkpoint inhibitors (ICIs) represent one of the most promising therapeutic approaches in metastatic non-small cell lung cancer (M-NSCLC). Unfortunately, approximately 50-75% of patients do not respond to this treatment modality. Intratumor heterogeneity (ITH) at the genetic and phenotypic level is considered as a major cause of anticancer therapy failure, including resistance to ICIs. Recent observations suggest that spatial heterogeneity in the composition and spatial organization of the tumor microenvironment plays a major role in the response of M-NSCLC patients to ICIs. In this mini review, we first present a brief overview of the use of ICIs in M-NSCLC. We then discuss the role of genetic and non-genetic ITH on the efficacy of ICIs in patients with M-NSCLC.Meningiomas, the most common brain tumor, inevitably require surgical treatment. However, the efficacy of prophylactic antiepileptic drugs (AEDs), in reducing the frequency of new-onset seizures during the perioperative period remains controversial. To further clarify if prophylactic antiepileptic drug treatment for patients with meningioma had value, we reviewed the medical records of 186 supratentorial meningioma patients who were operated at our hospital between 2016 and 2018. SPSS 24.0 software was used for statistical analysis. The results of univariate analysis showed that factors including age, sex, the course of the disease (years), maximum cross-sectional area of the tumor, location of the tumor, multiple or single tumors, adjacent to the cortex, peritumoral brain edema, World Health Organization classification, and peritumoral adhesion were not associated with perioperative seizures (P >0.05). Furthermore, the results of multivariate analysis revealed hydrocephalus (OR 4.87 P = 0.05) and non-skull base location (OR 1.88 P = 0.04) were significant risk factors for perioperative in-hospital seizures. Prophylactic valproic acid treatment did not contribute to the alleviation of perioperative seizures (OR 1.76 P = 0.04). However, Multivariate logistic regression analyses excluding the patients with seizures before operation confirmed prophylactic valproic acid treatment did not reduce the frequency of seizures during the perioperative period (OR 1.84 P = 0.04). Taken together, the data suggest that prophylactic valproic acid treatment for patients with supratentorial meningioma does not reduce the rate of perioperative seizures.PD-1 blockade represents a promising treatment in patients with head and neck squamous cell carcinoma (HNSCC). We analyzed results of a neoadjuvant randomized window-of-opportunity trial of nivolumab plus/minus tadalafil to investigate whether immunotherapy-mediated treatment effects vary by site of involvement (primary tumor, lymph nodes) and determine how radiographic tumor shrinkage correlates with pathologic treatment effect.

Forty-four patients enrolled in trial NCT03238365 were treated with nivolumab 240 mg intravenously on days 1 and 15 with or without oral tadalafil, as determined by random assignment, followed by surgery on day 31. Radiographic volumetric response (RVR) was defined as percent change in tumor volume from pretreatment to posttreatment CT scan. Responders were defined as those with a 10% reduction in the volume of the primary tumor or lymph nodes (LN). Pathologic treatment effect (PTE) was defined as the area showing fibrosis or lymphohistiocytic inflammation divided by total tumor arepport the use of early radiographic response to assess immunotherapy treatment effect inHNSCC.

Nivolumab often induces discordant treatment effects between primary tumor sites and metastatic lymph nodes within subjects. This treatment discordance was also demonstrated in adjacent lymph nodes, which may correlate with local immune cell makeup. Finally, although these data were generated by a relatively small population size, our data support the use of early radiographic response to assess immunotherapy treatment effect in HNSCC.MicroRNAs (miRNAs) have been reported to play critical roles in the pathological development of hepatocellular carcinoma (HCC), one of the most common cancers in the world. Our study aims to explore the expression, function and mechanism of miR-631 in HCC. Our findings are that expression of miR-631 is significantly down-regulated in HCC tissue compared with that in adjacent non-cancerous tissue, and low expression of miR-631 in HCC tissue is associated with cirrhosis, multiple tumors, incomplete tumor encapsulation, poor tumor differentiation, and high TNM stage. Our test results showed that miR-631 could inhibit migration, invasion, epithelial-mesenchymal transition (EMT) and intrahepatic metastasis of HCC. Receptor-type protein tyrosine phosphatase epsilon (PTPRE) as a downstream target of miR-631 could promote migration, invasion and EMT of HCC cells. Besides, the expression of PTPRE had a negative correlation with the expression of miR-631 both in vivo and in vitro, and increasing expression of PTPRE could reverse inhibitory effects of miR-631 in HCC cells. In sum, our study first demonstrated that miR-631 targeted PTPRE to inhibit intrahepatic metastasis in HCC. We gain insights from these findings into the mechanism of miRNAs regulation in HCC metastasis and further introduce a novel therapeutic target for HCC treatment.

Early prediction of recurrence and death risks is significant to the treatment of hepatocellular carcinoma (HCC) patients. We aimed to develop and validate prognosis nomogram models based on the gamma-glutamyl transpeptidase (GGT)-to-platelet (PLT) ratio (GPR) for HCC and to explore the relationship between the GPR and inflammation-related signaling pathways.

All data were obtained from 2000 to 2012 in the Affiliated Hospital of Qingdao University. In the training cohort, factors included in the nomograms were determined by univariate and multivariate analyses. In the training and validation cohorts, the concordance index (C-index) and calibration curves were used to assess predictive accuracy, and receiver operating characteristic curves were used to assess discriminative ability. Clinical utility was evaluated using decision curve analysis. Moreover, improvement of the predictive accuracy of the nomograms was evaluated by calculating the decision curve analysis, the integrated discrimination improvementPLT levels (P = 0.063). And we found that P38MAPK can regulate the expression of GGT by quantitative real-time PCR and Western blotting experiments.

The dynamic nomogram based on the GPR provides accurate and effective prognostic predictions for HCC, and P38MAPK-GGT may be a suitable therapeutic target to improve the prognosis of HCC patients.

The dynamic nomogram based on the GPR provides accurate and effective prognostic predictions for HCC, and P38MAPK-GGT may be a suitable therapeutic target to improve the prognosis of HCC patients.The ever-increasing morbidity and mortality of clear cell renal cell carcinoma (ccRCC) urgently demands updated biomarkers. MicroRNAs (miRNAs) are involved in diverse biological processes such as cell proliferation, differentiation, apoptosis by regulating their target genes' expression. In kidney cancers, miRNAs have been reported to be involved in tumorigenesis and to be the diagnostic, prognostic, and therapeutic response biomarkers. Here, we performed a systematic analysis for ccRCC-related miRNAs as biomarkers by searching keywords in the NCBI PubMed database and found 118 miRNAs as diagnostic biomarkers, 28 miRNAs as prognostic biomarkers, and 80 miRNAs as therapeutic biomarkers in ccRCC. miRNA-21, miRNA-155, miRNA-141, miRNA-126, and miRNA-221, as significantly differentially expressed miRNAs between cancer and normal tissues, play extensive roles in the cell proliferation, differentiation, apoptosis of ccRCC. GO and KEGG enrichment analysis of these miRNAs' target genes through Metascape showed these target genes are enriched in Protein Domain Specific Binding (GO0019904). In this paper, we identified highly specific miRNAs in the pathogenesis of ccRCC and explored their potential applications for diagnosis, prognosis, and treatment of ccRCC.Melatonin exerts anti-cancer roles in various types of cancers. However, to the best of our knowledge, its role in oral squamous cell carcinoma (OSCC) is unknown. The present study aimed to investigate the role of melatonin and its underlying mechanism in OSCC. MTT, colony formation, wound healing, and transwell invasion assays proved that melatonin played anti-tumor effects in OSCC cells by inhibiting cell viability, proliferation, migration, and invasion in a concentration-dependent manner. The RT-qPCR analysis showed that miR-25-5p was significantly upregulated after melatonin treatment. Further, miR-25-5p might be involved in melatonin-induced inhibitory effects on the biological behavior of OSCC. The expression of miR-25-5p was decreased in tumor tissues and OSCC cells detected by RT-qPCR. MTT assay, colony formation assay, and TUNEL staining indicated miR-25-5p overexpression inhibited OSCC cell viability, proliferation, and induced OSCC cell apoptosis. Furthermore, wound healing, transwell invasion assay, and animal experiments suggested that miR-25-5p might exert suppressive effects on the migration, invasion, and tumor formation of OSCC cells, while miR-25-5p knockdown exhibited the opposite effects in OSCC cells. Bioinformatics analysis, western blot analysis, and luciferase reporter assay suggested that neural precursor cell expressed developmentally downregulated protein 9 (NEDD9) was proved to be a putative target for miR-25-5p. The role of NEDD9 in inhibiting OSCC cell proliferation, invasion, and migration was verified with NEDD9 siRNA transfection. Thus, melatonin exerted anti-proliferative, anti-invasive, and anti-migrative effects on OSCC via miR-25-5p/NEDD9 pathway. Melatonin could be applied as a potential novel drug on treating OSCC.With millions of cases diagnosed annually and high economic burden to cover expensive costs, cancer is one of the most difficult diseases to treat due to late diagnosis and severe adverse effects from conventional therapy. This creates an urgent need to find new targets for early diagnosis and therapy. Progress in research revealed the key steps of carcinogenesis. They are called cancer hallmarks. Zooming in, cancer hallmarks are characterized by ligands binding to their cognate receptor and so triggering signaling cascade within cell to make response for stimulus. Accordingly, understanding membrane topology is vital. In this review, we shall discuss one type of transmembrane proteins Glycosylphosphatidylinositol-Anchored Proteins (GPI-APs), with specific emphasis on those involved in tumor cells by evading immune surveillance and future applications for diagnosis and immune targeted therapy.PIK3CA is a key component of phosphatidylinositol 3-kinase (PI3K) pathway that its involvement in tumorigenesis has been revealed by previous research. However, its functions and potential mechanisms in bladder cancer are still largely undiscovered. Tissue microarray (TMA) with 66 bladder cancer patients was surveyed via immunohistochemistry to evaluate the level of PIK3CA and CUX1 and we found upregulation of PIK3CA in bladder cancer tissue and patients with higher level of PIK3CA presented with poorer prognosis. Overly expressed PIK3CA promoted growth, migration, invasion, and metastasis of bladder cancer cells and knockdown of PIK3CA had the opposite effect. Gain-of-function and loss-of-function studies showed that PIK3CA expression was facilitated by CUX1, leading to activation of epithelial-mesenchymal transition (EMT), accompanied by upregulated expression of Snail, β-catenin, Vimentin and downregulated expression of E-cadherin in the bladder cancer cell lines. Besides, over-expressed CUX1 could restore the expression of downregulated Snail, β-catenin, Vimentin and E-cadherin which was induced by PIK3CA knockdown. These results revealed that PIK3CA overexpression in bladder cancer was regulated by the transcription factor CUX1, and PIK3CA exerted its biological effects by activating EMT.Clear cell renal cell carcinoma represents the most common type of kidney cancer. Precision medicine approach to ccRCC requires an accurate stratification of patients that can predict prognosis and guide therapeutic decision. Transcription factors are implicated in the initiation and progression of human carcinogenesis. However, no comprehensive analysis of transcription factor activity has been proposed so far to realize patient stratification. Here we propose a novel approach to determine the subtypes of ccRCC patients based on global transcription factor activity landscape. Using the TCGA cohort dataset, we identified different subtypes that have distinct up-regulated biomarkers and altered biological pathways. More important, this subtype information can be used to predict the overall survival of ccRCC patients. Our results suggest that transcription factor activity can be harnessed to perform patient stratification.

Previous studies have shown the value in studying lineage tracing in slices of human tumors. However, a tumor is not a two-dimensional structure and to better understand how a tumor, and its corresponding metastasis grow, a three-dimensional (3-D) view is necessary.

Using somatic mitochondrial mutations as a marker for lineage tracing, it is possible to identify and follow tumor specific cell lineages. Using cycling temperature capillary electrophoresis (CTCE) a total of 8 tissues from 5 patients (4 primary tumors and 4 metastasis) containing clear mitochondrial markers of tumor lineages were selected. From these 8 tissues over 9,500 laser capture microdisection (LCM) samples were taken and analyzed, in a way that allows 3-D rendering of the observations.

Using CTCE combined with LCM makes it possible to study the 3-D patterns formed by tumors and metastasis as they grow. These results clearly show that the majority of the volume occupied by a tumor is not composed of tumor derived cells. These cells are most likely recruited from the neighboring tissue.

Using CTCE combined with LCM makes it possible to study the 3-D patterns formed by tumors and metastasis as they grow. These results clearly show that the majority of the volume occupied by a tumor is not composed of tumor derived cells. These cells are most likely recruited from the neighboring tissue.

Many diabetes educators in Iran do not have the necessary skills and competence for performing a needs assessment, and thus, cannot provide Diabetes Self-Management Education (DSME) to suit individual educational needs and conditions. The purpose of the present study was to explore and analyze needs assessment implementation in DSME and evaluate the barriers and the appropriate strategies from educators' viewpoints.

The present qualitative study was conducted using a conventional content analysis approach with semi-structured and in-depth interviews and using a purposeful sampling method on 20 nurses, physicians, and endocrinologists. The data of this study were collected from April to October 2018. The interviews were analyzed using the content analysis method of Graneheim and Lundman.

Qualitative data analysis resulted in the emergence of two main categories of educational challenges of needs assessment and managerial challenges of needs assessment and four subcategories (lack of structured educational planning, lack of needs assessment practical patterns, managers' insufficient support and supervision, and managers' insufficient attention to motivational factors).

Educational strategic planning, managers' obligation and support in designing practical patterns, and supervision tools to evaluate educators' performance in the needs assessment domain can result in the promotion of DSME needs assessment, the efficiency of plans, and the promotion of society's health.

Educational strategic planning, managers' obligation and support in designing practical patterns, and supervision tools to evaluate educators' performance in the needs assessment domain can result in the promotion of DSME needs assessment, the efficiency of plans, and the promotion of society's health.

There are no proper tools for measuring pregnancy-specific stress in Iranian population. The aim of this study was psychometric evaluation of the Persian version of Revised Prenatal Distress Questionnaire (NuPDQ) for the first time in Iranian society.

In a descriptive-analytic study, 269 pregnant women completed the NUPDQ at Obstetrics clinics of Mazanderan Province, Iran. The reliability of the 12-item NuPDQ and 17-item NuPDQ was reevaluated using Cronbach's alpha and internal consistency. Concurrent validity was assessed using the Spielberger state-anxiety Inventory. Moreover, exploratory factor analysis was used to assess the structural factors of the questionnaire.

Factor analysis revealed that the 12-item NuPDQ consisted of four areas in the second trimester including medical and financial problem, physical symptoms, infant health, and parenting with the explained variance of 64.15%. The Persian version of 17-item NuPDQ consisted of 5 areas in the third trimester, including medical and financial problems, physical symptoms, infant health, parenting, and labor and delivery with an explained variance of 61.94%. In addition, interclass correlation coefficient in all 4 areas and overall scale score exceeded 0.90. Finally, the reliability was high based on Cronbach's alpha of 0.78 for 12-item NuPDQ and 0.79 for 17-item NuPDQ.

The Persian version of 12-item NuPDQ in the second trimester and 17-item NuPDQ in the third trimester, as well as all the extracted subscales, had a good validity and reliability for assessing pregnancy-specific stress in Iranian society and can be used in clinical practice.

The Persian version of 12-item NuPDQ in the second trimester and 17-item NuPDQ in the third trimester, as well as all the extracted subscales, had a good validity and reliability for assessing pregnancy-specific stress in Iranian society and can be used in clinical practice.

Painful care procedures are the most common cause of stress in patients admitted to Intensive Care Units (ICUs). Tracheal suctioning is the most painful experience for ICU patients. The present study was conducted to compare open and closed endotracheal suctioning in terms of their effect in pain in mechanically ventilated patients.

The present clinical trial recruited 70 mechanically ventilated patients with tracheostomy in 2019. The eligible patients were randomly divided into open and closed suctioning groups. The pain was measured in the patients using the Critical Pain Observational Tool (CPOT) before and during suctioning as well as 10 and 30 min later. The data were analyzed using the repeated measures Analysis Of Variance (ANOVA), paired

-test, and Chi-squared test.

The pain score was significantly higher in the open suctioning group during (t = 2.59,

= 0.01) and 10 min after suctioning (t = 3.02,

= 0.004). No significant differences were observed in the pain score between the two groups 30 min after suctioning (t = 0.32,

= 0.75). The post hoc Least Significant Difference (LSD) test showed that the CPOT scores 10 min after suctioning was significantly higher than that before suctioning and significantly lower than that during suctioning (

= 0.001). The CPOT score 30 min after suctioning was also significantly lower than that 10 min after suctioning (

< 0.001).

The present findings suggested a lower pain in the patients with closed suctioning compared to those with open suctioning.

The present findings suggested a lower pain in the patients with closed suctioning compared to those with open suctioning.

Prenatal care providers play an important role during pregnancy. Because healthcare providers provide comprehensive support to pregnant women, they must pay attention to pregnant women's expectations and efforts to meet their expectations. Understanding of pregnant women's expectations is associated with continuation of care and improving the health of the community. The present study is carried out to investigate the viewpoints of Iranian gynecologists and midwives on the expectations of pregnant women.

This qualitative study was carried out on 10 prenatal care providers in Shiraz in 2018. Sampling method was purposive. Sampling continued until data saturation. Structured, face to face and in-depth interviews were used for data collection. Implementation and coding of interviews were performed simultaneously with data collection. The data were analyzed using conventional content analysis approach. The Lincoln and Guba criteria were used to increase the trustworthiness of the data.

Two main categories were emerged after analyzing of the data. The main category of "competent prenatal care providers" consisted of three subcategories professional skills, communication skills, and individual characteristics. Another main category was the "appropriate pregnancy and childbirth centers" that included two subcategories of personnel-facilities and management system.

According to the results, prenatal care providers have been aware that women during pregnancy period expect to have competent providers. Also, they tend that receive pregnancy care and delivery from appropriate pregnancy and childbirth centers.

According to the results, prenatal care providers have been aware that women during pregnancy period expect to have competent providers. Also, they tend that receive pregnancy care and delivery from appropriate pregnancy and childbirth centers.

Near-Death Experience (NDE) refers to a broad range of subjective experiences associated with forthcoming death. The majority of Cardiopulmonary Resuscitation (CPR) survivors experience NDEs. It seems that near-death events are experienced differently by people with different cultural and religious viewpoints. Thus, this study aimed to explain NDEs in Iranian Muslim CPR survivors.

A qualitative hermeneutic phenomenological approach influenced by Ricoeur was used to understand the meaning of CPR survivors' NDEs. Eight survivors were interviewed in private. The study was conducted in southeast Iran. In-depth, semi-structured interviews were used for data collection, and probing questions were added when necessary. The duration of the interviews was between 40 and 65 min. According to Lindseth and Norberg, in the naive understanding phase, we read the interviews several times for achieving naive understanding. In the structural analysis phase, the whole text is divided into meaningful units. Finally, the researchers formulated a comprehensive understanding of the contextualization of the text.

Four main themes emerged including 1) pleasing experiences along with flying and seeing light, 2) the experience of transport to the beyond, 3) out-of-body experience, and 4) reviewing life and memories in a religious context.

Iranian Muslim CPR survivors, reported NDEs, much similar to those reported by survivors in Western countries with different theistic religions. This means that medical professionals dealing with these patients need to be aware of such experiences in Iranian Muslims.

Iranian Muslim CPR survivors, reported NDEs, much similar to those reported by survivors in Western countries with different theistic religions. This means that medical professionals dealing with these patients need to be aware of such experiences in Iranian Muslims.

Aging causes major changes that affect the performance of all senses, and as a result, a critical change in the quality of life is expected. Falling and the fear of falling is one of the major health risks that affect the quality of life among elderly, threatening their independent living. This study was conducted to determine the role of sensory stimulation on the quality of life and self-efficacy in coping with fear in the elderly population.

During this randomized controlled trial, 80 elderly volunteers from healthcare centers were divided into four intervention groups (music, photo album, aromatherapy, and hand massage) and one control group. Data collection was performed using the Older People's Quality of Life Questionnaire and Falls Efficacy Scale-International tools. Data were analyzed using the Statistical Package for the Social Sciences (SPSS) software program, version 16.0.

Comparing the scores of the quality of life and self-efficacy questionnaires, no statistically significant difference was reported among the groups (

< 0.05).

Sensory stimulation seems to have no impressive effect on the improvement of self-efficacy in coping with the fear of falling and the quality of life in the older population.

Sensory stimulation seems to have no impressive effect on the improvement of self-efficacy in coping with the fear of falling and the quality of life in the older population.

Nausea and vomiting are almost inevitable features of pregnancy which have a serious impact on the quality of life of pregnant women. This study aimed to determine the effects of combined inhalation aromatherapy with lemon and peppermint on nausea and vomiting of pregnancy.

The parallel randomized clinical trial was conducted on 90 pregnant women suffering from nausea and vomiting of pregnancy referred to health centers in Birjand-Iran- from February 2015 to August 2016. Participants were randomly divided into two groups. The combined lemon and peppermint essential oils were used as an inhaler for the intervention and the placebo for the control group. Both groups were trained to place three drops of the solution onto a cotton ball and keep it in a 3-cm distance of their nose. The intensity of nausea, vomiting and fatigue was assessed through 24-hour Pregnancy Unique Quantization of Emesis (PUQE-24) questionnaire and Fatigue Severity Scale (FSS), respectively.

Mean (SD) scores of nausea and vomiting intensity before the intervention and on the first day of intervention were not significantly different between the two groups, but became significant on the second, third, and fourth days of intervention. The results showed that the effect of time on the mean intensity of nausea and vomiting was significant in the aromatherapy group (F

= 22.92,

< 0.001) but was not significant in the placebo group (F

= 0.26,

= 0.836).

The combined lemon and peppermint aromatherapy could reduce mild to moderate intensity of nausea and vomiting during pregnancy.

The combined lemon and peppermint aromatherapy could reduce mild to moderate intensity of nausea and vomiting during pregnancy.

Providing care for patients in Persistent Vegetative State (PVS) by family caregivers without enough training and knowledge may be problematic both for the patients and for the caregivers. Therefore, the present study tries to explain the experiences of family caregivers of patients with PVS of seeking information needed to provide adequate care.

Twenty two participants, including 17 family caregivers and 5 professional caregivers were enrolled by purposive sampling into this qualitative content analysis study, carried out between 2013 and 2015. Unstructured interviews and field notes were used to gather the data. Data collection was stopped when data saturation was achieved. Data analysis was performed by content analysis based on Graneheim and Lundman's approach.

As a result of the analysis of the collected data a main theme emerged labeled as "Seeking constructive education" with three categories including "Neglected requisite education," "Greedy search for useful education" and "Dynamic independence in care."

In this study, information seeking by family caregivers of patients with PVS was constructive. Family caregivers insistently sought needed information from various sources. Ultimately, they found these insistent efforts beneficial and fruitful, because their efforts made them independent in providing care for their patients.

In this study, information seeking by family caregivers of patients with PVS was constructive. Family caregivers insistently sought needed information from various sources. Ultimately, they found these insistent efforts beneficial and fruitful, because their efforts made them independent in providing care for their patients.

Since endothelial dysfunction is related to atherosclerosis, this study was planned to determine the effect of type of delivery on Nitric Oxide (NO) metabolites and endothelial function.

This Cohort study was conducted in 2015 in selected hospitals of Isfahan. 88 nulliparous women with gestational age of 39 weeks and above were enrolled in this study using convenience sampling method and finally, after giving birth, 51 mothers with vaginal delivery, 21 with urgent C-section and 13 with elective C-section were considered for data analysis. The serum levels of NO metabolites were measured in the laboratory with standard kits and data was analyzed using student and paired

-test, one-way ANOVA, and Chi-square test. The significance level was considered less than 0.05 for all tests.

The NO metabolites levels in mothers who had vaginal delivery or urgent C-section showed a significant difference before and after delivery (normal vaginal delivery (NVD) t

= 5.61,

< 0.001, Urgent C-section t

= 5.38,

< 0.001). But those with elective C-section showed no significant difference in the nitrate and total nitrite levels before and after delivery (

> 0.05).

Since reduction in serum levels of NO metabolites may possibly indicate endothelial dysfunction and predict cardiovascular disease, especially atherosclerosis in the future, it could be concluded that, childbirth, regardless of the type of delivery, could damage the endothelial cells but C-section (urgent or elective) could cause more disruption than vaginal delivery.

Since reduction in serum levels of NO metabolites may possibly indicate endothelial dysfunction and predict cardiovascular disease, especially atherosclerosis in the future, it could be concluded that, childbirth, regardless of the type of delivery, could damage the endothelial cells but C-section (urgent or elective) could cause more disruption than vaginal delivery.

Emergency department is among the most crowded hospital units. The function of this department considerably affects the functions of other hospital units as well as patient satisfaction. The Stabilization Model is a strategy with potential effectiveness in managing overcrowding in emergency department. This study aimed to determine the effects of overcrowding management based on the stabilization model on patient safety in emergency department.

This pretest-posttest quasi-experimental was conducted in 2015 in the emergency department of a teaching hospital located in Tehran, Iran. Primarily, the perceived safety of 35 patients was assessed using the Patient Safety Assessment Questionnaire. Then, an overcrowding management intervention was implemented based on the stabilization model. Finally, the perceived safety of 35 newly recruited patients was assessed after the intervention. The SPSS software (v. 16.0) was employed for data analysis through the Chi-square, the Kolmogorov-Smirnov, and the independent-sample t tests.

The mean (SD) score of patient safety was 27.45 (8.43) in the control group and 34.45 (4.04) in the intervention group and the between-group difference was statistically significant (t

= 50.37,

< 0.001). The rate of patient safety increased from 65% at baseline to 82% after the intervention.

Overcrowding management based on the stabilization model can significantly enhance patients' perceived safety. Therefore, this strategy can be used to ease emergency department overcrowding and enhance patient safety and care quality.

Overcrowding management based on the stabilization model can significantly enhance patients' perceived safety. Therefore, this strategy can be used to ease emergency department overcrowding and enhance patient safety and care quality.

Professional responsibility is important for bachelor degree nursing students, but it has not been measured specifically among these students and findings of the studies on its related factors are inconsistent. This study aimed to determine the level of professional responsibility and its related factors among bachelor degree nursing students in selected public nursing schools in Iran.

For this cross-sectional study, 388 bachelor degree nursing students from 8 selected public nursing schools in Iran were selected through convenience sampling (2018-2019). The participants completed the demographic questionnaire and Responsibility among Bachelor Degree Nursing Students Scale (RABDNSS). This valid and reliable scale consists of 45 items that determine professional responsibility and its 5 subscales. Data were analyzed using descriptive and inferential methods in SPSS software.

The mean (SD) total score of professional responsibility was 175.26 (23.58), indicating a high level of responsibility. The highest and lowest mean (SD) scores were obtained in the subscales of situational self-mandatory 4.20 (0.52) and positive professional attitude 3.71 (0.82), respectively. Students' educational grade average and level of interest in nursing were significantly correlated with professional responsibility and its subscales (

< 0.05).

The relationship of students' interest in nursing and students' educational grade average with professional responsibility can be useful for planning admission policies and evaluating and promoting professional responsibility related behaviors among nursing students. However, further research in these areas is recommended.

The relationship of students' interest in nursing and students' educational grade average with professional responsibility can be useful for planning admission policies and evaluating and promoting professional responsibility related behaviors among nursing students. However, further research in these areas is recommended.

Ventilator-Associated Pneumonia (VAP) is a recognized nosocomial infection and a leading cause of high morbidity and mortality. Intensive Care Unit (ICU) nurses are in the best position to put the known evidence-based strategies into practice to prevent VAP. The aim of the present study is to assess the knowledge and practices of ICU nurses related to prevention of VAP in selected ICUs of a tertiary care centre in India (2013-2014) and to find out the association between knowledge and practices.

A descriptive survey was conducted in the different ICUs of a tertiary care hospital in India. Purposive sampling technique was used and 108 ICU staff nurses were enrolled during the period of data collection. The tool used for data collection was a self-developed valid and reliable knowledge-based questionnaire and an observational checklist. The descriptive (frequency and percentages) and inferential (Chi-square test) statistics was used.

Out of the 108 nurses enrolled in the study, 82 (75.93%) had average, 24 (22.22%) had good and only 2 (1.85%) of the ICU nurses had poor knowledge. Assessment of the practices revealed that 68 (94.44%) nurses had average and only 4 (5.55%) nurses had good practice. There was no association between the knowledge and practices of ICU nurses related to prevention of VAP. (χ

= 0.14,

= 0.710).

Although the nurses were having good to average knowledge scores, their practices were not associated with knowledge scores. There is a need to find out the ways that would help the nurses to adhere to good practices.

Although the nurses were having good to average knowledge scores, their practices were not associated with knowledge scores. There is a need to find out the ways that would help the nurses to adhere to good practices.

Hospitalization in the Intensive Care Unit (ICU) brings about psychological and physical symptoms in patients' family members. Family Intensive Care Unit Syndrome (FICUS) is a term used to explain the psychological symptoms of the family of a patient in response to the patient's admission to the ICU. The purpose of this study was to define FICUS along with its symptoms and predictors.

The Web of Science, PubMed, Scopus, Google Scholar, and SID databases were searched for literature published in 2005-2018 with the keywords "FICUS," "intensive care unit," "family," "caregivers," "anxiety," "depression," and "post-traumatic stress disorder" in their title and abstract. The strategy for conducting an integrative review provided by Whittemore and Knafl (2005) was used in this study.

Twenty articles were included in the final data analysis. Following the patient's admission to the ICU, family members experience multiple psychological symptoms such as FICUS. The most commonly reported symptoms were anxiety, depression, post-traumatic stress disorder (PTSD), complicated grief, sleep disorder, stress, and fatigue.