Efficacy of Whole Cancer Stem Cell-Based Vaccines: A Systematic Review of Preclinical and Clinical Studies.

BACKGROUND: Despite the conventional cancer therapeutic, cancer treatment remains a medical challenge due to neoplasm metastasis and cancer recurrence; therefore, new approaches promoting therapeutic strategies are highly desirable. As a new therapy, the use of whole neoplastic stem cells or cancer stem cell (CSC)-based vaccines is one strategy to overcome these obstacles. We investigated the effects of whole CSC-based vaccines on the solid tumor development, metastasis, and survival rate. METHODS: Primary electronic databases (PubMed/MEDLINE, Scopus, Embase, and Web of Science) and a major clinical registry were searched. Interventional studies of whole CSC-based vaccines in rodent cancer models (38 studies) and human cancer patients (11 studies) were included; the vaccine preparation methodologies, effects, and overall outcomes were evaluated. RESULTS: Preclinical studies were divided into 4 groups: CSC-lysates/ inactivated-CSC-based vaccines, CSC-lysate-loaded dendritic cell (CSC-DC) vaccines, cytotoxic T-cell (CTL) vaccines generated with CSC-DC (CSC-DC-CTL), and combinatorial treatments carried out in the prophylactic and therapeutic experimental models. The majority of preclinical studies reported a promising effect on tumor growth, survival rate, and metastasis. Moreover, whole CSC-based vaccines induced several antitumor immune responses. A small number of clinical investigations suggested that the whole CSC-based vaccine treatment is beneficial; however, further research is required. CONCLUSIONS: This comprehensive review provides an overview of the available methods for assessing the efficacy of whole CSC-based vaccines on tumor development, metastasis, and survival rate. In addition, it presents a set of recommendations for designing high-quality clinical studies that may allow to determine the efficacy of whole CSC-based-vaccines in cancer therapy.

Clinical Significance of Talin-1 and HER-2 Status in Different Types of Gastric Carcinoma.

BACKGROUND: Talin-1 (TLN1) is crucial in cell migration, metastasis, and cancer development. This study evaluated Talin-1 expression and its clinical significance in gastric cancer (GC), along with human epidermal growth factor receptor-2 (HER-2) expression and its correlation with Talin-1. METHODS: Bioinformatics analysis assessed the potential prognostic value of Talin-1 and HER-2 in GC patients. The study included 223 GC patients (Signet Ring Cells and Intestinal subtypes) and 29 non-malignant tissue samples. Immunohistochemistry (IHC) on tissue microarray slides evaluated Talin-1 and HER-2 expression and clinical significance. Receiver operating characteristic (ROC) curves assessed their diagnostic value. RESULTS: Bioinformatics identified Talin-1 as a potential prognostic factor and HER-2 as an oncogene in GC. Talin-1 and HER-2 expression increased in SRC-type GC samples compared to non-malignant tissues. High cytoplasmic Talin-1 expression inversely correlated with tumor expansion and invasion in SRC-type GC. Increased HER-2 expression positively correlated with metastasis. ROC curves showed significant diagnostic values for both proteins. CONCLUSIONS: Higher cytoplasmic Talin-1 expression is associated with less invasive tumor behavior, while increased membranous HER-2 expression is associated with metastasis in SRC-type GC. These findings suggest potential use in assessing diagnosis and screening high-risk cancer patients, particularly those with SRC-type GC.

Circulating exosomal microRNAs as potential prognostic biomarkers in gastrointestinal cancers: a systematic review and meta-analysis.

BACKGROUND: Recent reports suggested that circulating exosomal microRNAs (exomiRs) may serve as non-invasive prediction biomarkers in gastrointestinal (GI) cancers, yet their clinicopathological and prognostic values need to be more clarified. Hence, the present meta-analysis was aimed to quantitatively assess the evidence regarding the association between circulating exomiRs and prognosis in GI cancer patients. METHODS: A comprehensive search was carried out in prominent literature databases, including PubMed, ISI Web of Science, Scopus, and Embase. Odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs) were gathered to evaluate the strength of the association. The quality assessment was investigated through the Newcastle-Ottawa Scale (NOS) and publication bias via Eggers' test and funnel plots. RESULTS: A total of 47 studies, comprising of 4881 patients, were considered eligible for this meta-analysis. Both up-regulated and down-regulated circulating exomiRs are significantly associated with differentiation (HR = 1.353, P = 0.015; HR = 1.504, P = 0.016), TNM stage (HR = 2.058, P < 0.001; HR = 2.745, P < 0.001), lymph node metastasis (HR = 1.527, P = 0.004; HR = 2.009, P = 0.002), distant metastasis (HR = 2.006, P < 0.001; HR = 2.799, P = 0.002), worse overall survival (OS) (HR = 2.053, P < 0.001; HR = 1.789, P = 0.001) and poorer disease/relapse/progression-free survival (DFS/RFS/PFS) (HR = 2.086, P < 0.001; HR = 1.607, P = 0.001) in GI cancer patients, respectively. In addition, subgroup analyses based on seven subcategories indicated the robustness of the association. The majority of findings were lack of publication bias except for the association between up-regulated exomiRs and OS or DFS/RFS/PFS and for the down-regulated exomiRs and TNM stage. CONCLUSION: This study supports that up- and down-regulated circulating exomiRs are associated with poorer survival outcomes and could be served as potential prognostic biomarkers in GI cancers. Given the limitations of the current findings, such as significant heterogeneity, more investigations are needed to fully clarify the exomiRs prognostic role.

Adoption of cytoreductive surgery in the management of peritoneal malignancies-Global trends.

Cytoreductive surgery (CRS) has now been accepted as an integral component in the management of gastrointestinal and gynecological cancers with peritoneal metastases. Since the adoption of CRS is influenced by access to advanced medical facilities, trained multidisciplinary teams, and funding, there is wide variability in incorporation of CRS into routine clinical practice between high- versus low- and middle-income countries. This review highlights the global trends in the adoption of CRS for peritoneal malignancies with a specific focus on the establishment of CRS programs and barriers to incorporate CRS into routine clinical care in low- and middle-income countries.

Noncoding RNAs and their therapeutics in paclitaxel chemotherapy: Mechanisms of initiation, progression, and drug sensitivity.

The identification of agents that can reverse drug resistance in cancer chemotherapy, and enhance the overall efficacy is of great interest. Paclitaxel (PTX) belongs to taxane family that exerts an antitumor effect by stabilizing microtubules and inhibiting cell cycle progression. However, PTX resistance often develops in tumors due to the overexpression of drug transporters and tumor-promoting pathways. Noncoding RNAs (ncRNAs) are modulators of many processes in cancer cells, such as apoptosis, migration, differentiation, and angiogenesis. In the present study, we summarize the effects of ncRNAs on PTX chemotherapy. MicroRNAs (miRNAs) can have opposite effects on PTX resistance (stimulation or inhibition) via influencing YES1, SK2, MRP1, and STAT3. Moreover, miRNAs modulate the growth and migration rates of tumor cells in regulating PTX efficacy. PIWI-interacting RNAs, small interfering RNAs, and short-hairpin RNAs are other members of ncRNAs regulating PTX sensitivity of cancer cells. Long noncoding RNAs (LncRNAs) are similar to miRNAs and can modulate PTX resistance/sensitivity by their influence on miRNAs and drug efflux transport. The cytotoxicity of PTX against tumor cells can also be affected by circular RNAs (circRNAs) and limitation is that oncogenic circRNAs have been emphasized and experiments should also focus on onco-suppressor circRNAs.

Oncogenic functions and clinical significances of DCLK1 isoforms in colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: The oncogenic role of doublecortin-like kinase 1 (DCLK1) as a putative cancer stem cell (CSC) marker has been clarified in colorectal cancer (CRC). Isoform-specific functions of DCLK1 have shed new light on different functions of DCLK1 short (DCLK1-S) and DCLK1 long (DCLK1-L) isoforms in tumor initiation, growth, and metastasis. Therefore, the current systematic review and meta-analysis aimed to review the available in vitro, in vivo, and clinical evidence on the oncogenic roles and clinical significance of DCLK1 isoforms in colorectal cancer. METHODS: The literature databases of PubMed, Scopus, ISI Web of Science, and Embase were searched to identify eligible articles. The description characteristics of in vitro and pre-clinical studies were extracted from identified reports. In addition, hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were recorded to determine the relationships between DCLK1-L and DCLK1-S expression and prognostic outcomes in patients with CRC. RESULTS: Both in vitro and in vivo evidence have emphasized the potential oncogenic functions of DCLK1 in tumor initiation, self-renewal ability, tumor invasion, epithelial-mesenchymal transition (EMT), and metastasis. However, the anti-DCLK1 antibodies generally utilized in these studies could detect sequence homology epitopes of both isoforms. Recent limited isoform-specific evidence has strongly supported the significant positive expression and rather oncogenic efficacy of DCLK1-S in tumorigenesis, EMT, and invasion compared with DCLK1-L in human CRC cell lines. Our meta-analysis findings of limited clinical studies indicated that only overexpression of DCLK1-S is associated with worse overall survival (OS) (HR = 7.930, 95% CI 2.252-27.924, p = 0.001). Increased expression of both DCLK1-S (HR = 1.610, 95% CI 1.020-2.541, p = 0.041) and DCLK1-L (HR = 5.890, 95% CI 1.219-28.453, p = 0.027) isoforms was closely associated with worse DSS/CSS in CRC patients. Furthermore, the high expression of DCLK1-S was found to be associated with poor DFS/RFS/PFS (HR = 1.913, 95% CI 1.230-2.973, p = 0.004). CONCLUSIONS: The current findings strongly supported that the DCLK1-S isoform may play a crucial role in the invasion, aggressive tumor behavior, and worsened survival outcomes of CRC patients. However, further critical investigations related to the potential preclinical and clinical utilities of DCLK1-S as a specific CRC-CSC marker are warranted.

The Interrelationship between Liver Function Test and the Coronavirus Disease 2019: A Systematic Review and Meta-Analysis.

Background: The outbreak of the coronavirus disease-2019 (COVID-19) has become a global public health challenge. Assessing the effect of COVID-19 on liver injury is of great importance. A systematic review and meta-analysis were conducted to establish the characteristics of liver function tests in COVID-19 patients. Methods: A systematic search of publications from December 2019 up to April 2020 in Web of Science, Scopus, and Medline (via PubMed) databases was performed. Both cross-sectional and case series studies reporting an association between liver injury and COVID-19 infection were included. The data were analyzed using the STATA software (version 11.0) and the random-effects model for I2>50% was used to pool the results. Results: In this meta-analysis, 42 articles comprising a total of 6,557 COVID-19 patients were studied. The prevalence of increase in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels was 30% and 21% in non-severe patients and 38% and 48% in severe patients, respectively. Patients with severe COVID-19 infection were 4.22, 4.96, and 4.13 times more likely to have elevated AST, ALT, and lactate dehydrogenase (LDH) levels, respectively. Conclusion: Elevation in liver function tests was higher in patients with severe than non-severe COVID-19 infection. Given the widespread use of drugs that increases the risk of hepatotoxicity, healthcare providers should be aware of changes in liver enzymes in COVID-19 patients. The inclusion of other studies from outside China could confirm the pattern of elevation in liver function tests in COVID-19 patients across the globe. Preprint of this article is available on medRxiv, https://www.medrxiv.org/content/10.1101/2020.05.20.20108357v1.

The potential therapeutic effects of curcumin on pregnancy complications: Novel insights into reproductive medicine.

Pregnancy complications including preeclampsia, preterm birth, intrauterine growth restriction, and gestational diabetes are the main adverse reproductive outcomes. Excessive inflammation and oxidative stress play crucial roles in the pathogenesis of pregnancy disorders. Curcumin, the main polyphenolic compound derived from Curcuma longa, is mainly known by its anti-inflammatory and antioxidant properties. There are in vitro and in vivo reports revealing the preventive and ameliorating effects of curcumin against pregnancy complications. Here, we aimed to seek mechanisms underlying the modulatory effects of curcumin on dysregulated inflammatory and oxidative responses in various pregnancy complications.

Higher Expression of Talin-1 is Associated With Less Aggressive Tumor Behavior in Pancreatic Cancer.

Talin-1 is one of the major scaffold proteins in focal adhesions playing a vital role in cell migration, metastasis, and cancer progression. Although studies regarding the importance of Talin-1 in cancer have rapidly developed, its prognostic and diagnostic value still remain unsatisfying in pancreatic cancer (PC). Therefore, the present study aims to investigate the expression, clinical significance, as well as the prognostic and diagnostic value of Talin-1 in different types of PC. Bioinformatic analysis was applied to determine the clinical importance and biological role of Talin-1 expression in PC tumors and the normal adjacent samples. The expression patterns, clinical significance, prognosis, and diagnosis value of Talin-1 were evaluated in tissue microarrays (TMAs) of 190 PC samples including 170 pancreatic ductal adenocarcinoma (PDAC), and 20 pancreatic neuroendocrine tumors (PNET), along with 24 adjacent normal tissues using immunohistochemistry (IHC). The results indicated that the expression of Talin-1 was upregulated in tumor cells compared with adjacent normal tissues. A statistically significant association was observed between the higher cytoplasmic expression of Talin-1 and lower histologic grade (P<0.001) in PDAC samples. Further, our findings indicated an inverse significant correlation between cytoplasmic expression of Talin-1 and recurrence (P=0.014) in PNET samples. No significant association was observed between the cytoplasmic expression of Talin-1 and survival outcomes as well as diagnostic accuracy. In conclusion, our observations demonstrated that a higher cytoplasmic level of Talin-1 protein was significantly associated with less aggressive tumor behaviors in PC samples. Nevertheless, further investigations are required to explore the prognostic plus diagnostic value, and mechanism of action of Talin-1 in pancreatic cancer.

The Prognostic Importance of Ki-67 in Gastrointestinal Carcinomas: A Meta-analysis and Multi-omics Approach.

PURPOSE: This study aimed to determine if Ki-67, a commonly used marker to measure tumor proliferation, is a reliable prognostic factor in various types of gastrointestinal (GI) cancers based on current high-quality multivariable evidence. METHODS: A comprehensive search was conducted in PubMed, Embase, Scopus, and ISI Web of Science databases to investigate the association between Ki-67 positivity and overall survival (OS) and disease/recurrence-free survival (DFS/RFS) in GI cancers. Heterogeneity was assessed using Chi-square-based Q and I2 analyses and publication bias using funnel plots and Egger's analysis. In addition, Ki-67 levels in different GI cancers were examined by different platforms. The prognostic capability of Ki-67, gene ontology (GO), and pathway enrichment analysis were obtained from GEPIA2 and STRING. RESULTS: Totally, 61 studies, involving 13,034 patients, were deemed eligible for our evaluation. The combined hazard ratios (HRs) demonstrated the prediction ability of overexpressed Ki-67 for a worse OS (HR: 1.67, P < 0.001; HR: 1.37, P = 0.021) and DFS/RFS (HR: 2.06, P < 0.001) in hepatocellular and pancreatic malignancies, respectively, as confirmed by multi-omics databases. However, similar correlation was not found in esophageal, gastric, and colorectal cancers. Furthermore, most of the associations were identified to be robust based on different subcategories and publication bias assessment. Finally, enriched Ki-67-related genes were found to be involved in various important signaling pathways, such as cell cycle, P53 signaling network, and DNA damage responses. CONCLUSION: This study supports that Ki-67 can serve as an independent prognostic biomarker for pancreatic and hepatocellular malignancies in clinical settings.

Regional Therapy Approaches for Gastric Cancer with Limited Peritoneal Disease.

PURPOSE: Despite advances in systemic therapy, outcomes of patients with gastric cancer (GC) peritoneal carcinomatosis (PC) remain poor, in part because of poor penetrance of systemic therapy into peritoneal metastasis due to the plasma-peritoneal barrier and anarchic intra-tumoral circulation. Hence, regional treatment approach with administration of chemotherapy directly into the peritoneal cavity (intraperitoneal, IP) under various conditions, combined with or without cytoreductive surgery (CRS) has remained an area of significant research interest. The purpose of this review is to provide high-level evidence for regional treatment approaches in the management of GCPC with limited peritoneal disease. METHODS: A review of the current literature and ongoing clinical trials for regional IP therapies for GCPC was performed. Studies included in this review comprise of phase III randomized controlled trials, non-randomized phase II studies, high-impact retrospective studies, and active ongoing clinical trials for each available IP modality. RESULTS: The three common IP approaches are heated intraperitoneal chemotherapy (HIPEC), normothermic intraperitoneal chemotherapy (NIPEC) and more recently introduced, pressurized intraperitoneal aerosolized chemotherapy (PIPAC). These IP approaches have been combined with systemic therapy and/or CRS with varying degrees of promising results, demonstrating evidence of improvements in survival rates and peritoneal disease control. Patient selection, optimization of systemic therapy, and completeness of cytoreduction have emerged as major factors influencing the design of contemporary and ongoing trials. CONCLUSION: IP chemotherapy has a clear role in the management of patients with GCPC, and when combined with CRS in appropriately selected patients has the potential to significantly improve survival. Ongoing and upcoming IP therapy clinical trials hold great promise to shape the treatment paradigm for GCPC.

Clinical significance of CD166 and HER-2 in different types of gastric cancer.

INTRODUCTION: Cluster of differentiation 166 (CD166), a cancer stem cell (CSC) marker, and human epidermal growth factor receptor 2 (HER-2) are expressed in a diversity of malignancies and is associated with tumor progression. Although studies regarding the importance of CSC markers and HER-2 in gastric cancer (GC) have rapidly developed, their clinicopathological, prognosis, and diagnosis value still remain unsatisfying in GC. Therefore, the present study aims to investigate the clinical, prognostic, and diagnostic significance of CD166 and HER-2 in different histological types of GC. MATERIALS AND METHODS: Bioinformatic analysis was applied to determine the clinical importance of CD166 and HER-2 expression based on their tissue localization in primary GC tumors and the normal adjacent samples. The expression patterns, clinical significance, prognosis, and diagnosis value of CD166 and HER-2 proteins in tissue microarrays (TMAs) of 206 GC samples, including Signet Ring Cell (SRC) and intestinal types and also 28 adjacent normal tissues were evaluated using immunohistochemistry (IHC). RESULTS: The results indicated that the expression of CD166 (membranous and cytoplasmic) and HER-2 were significantly up-regulated in tumor cells compared to adjacent normal tissues (P = 0.010, P < 0.001, and P = 0.011, respectively). A statistically significant association was detected between a high level of membranous expression of CD166 and lymphovascular invasion (P = 0.006); We also observed a statistically significant association between high cytoplasmic expression of CD166 protein and more invasion of the subserosa (P = 0.040) in the SRC type. In contrast, there was no correlation between the expression of HER-2 and clinicopathologic characteristics. Both CD166 and HER-2 showed reasonable accuracy and high specificity as diagnostic markers. CONCLUSION: Our results confirmed that increased membranous and cytoplasmic expression of CD166 showed clinical significance in the SRC type and is associated with the progression of the disease and more aggressive tumor behaviors. These findings can be used to assist in designating subgroups of patients that require different follow-up strategies, and also, they might be utilized as the prognostic or diagnostic biomarkers in these types of GC for prospective clinical application.

Expression and Clinical Significance of Ki-67, CD10, BCL6, MUM1, c-MYC, and EBV in Diffuse Large B Cell Lymphoma Patients.

INTRODUCTION: Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL) in adults. Although studies regarding the association between the expression of Ki-67, CD10, BCL6, and MUM1 proteins, as well as c-MYC amplification and EBV status with clinicopathologic characteristics have rapidly progressed, their co-expression and prognostic role remain unsatisfactory. Therefore, this study aimed to investigate the association between the expression of all markers and clinicopathologic features and their prognostic value in DLBCL. Also, the co-expression of markers was investigated. METHODS: The protein expression levels and prognostic significance of Ki-67, CD10, BCL6, and MUM1 were investigated with clinical follow-up in a total of 53 DLBCL specimens (including germinal center B [GCB] and activated B cell [ABC] subtypes) as well as adjacent normal samples using immunohistochemistry (IHC). Besides, the clinical significance and prognostic value of c-MYC and EBV status were also evaluated through chromogenic in situ hybridization (CISH), and their correlation with other markers was also assessed. RESULTS: The results demonstrated a positive correlation between CD10 and BCL6 expression, with both markers being associated with the GCB subtype ( P< 0.001 and P =0.001, respectively). Besides, we observe a statistically significant association between MUM1 protein expression and clinicopathologic type ( P< 0.005) as well as a positive association between c-MYC and recurrence ( P =0.028). Our survival analysis showed that patients who had responded to R-CHOP treatment had better overall survival (OS) and progression-free survival (PFS) than those who did not. CONCLUSION: Collectively, this study's results add these markers' value to the existing clinical understanding of DLBCL. However, further investigations are needed to explore markers' prognostic and biological roles in DLBCL patients.

Unraveling the potential of CD8, CD68, and VISTA as diagnostic and prognostic markers in patients with pancreatic ductal adenocarcinoma.

Introduction: Pancreatic cancer is a truculent disease with limited treatment options and a grim prognosis. Immunotherapy has shown promise in treating various types of cancer, but its effectiveness in pancreatic cancer has been lacking. As a result, it is crucial to identify markers associated with immunological pathways in order to improve the treatment outcomes for this deadly cancer. The purpose of this study was to investigate the diagnostic and prognostic significance of three markers, CD8, CD68, and VISTA, in pancreatic ductal adenocarcinoma (PDAC), the most common subtype of pancreatic cancer. Methods: We analyzed gene expression data from Gene Expression Omnibus (GEO) database using bioinformatics tools. We also utilized the STRING online tool and Funrich software to study the protein-protein interactions and transcription factors associated with CD8, CD68, and VISTA. In addition, tissue microarray (TMA) and immunohistochemistry (IHC) staining were performed on 228 samples of PDAC tissue and 10 samples of normal pancreatic tissue to assess the expression levels of the markers. We then correlated these expression levels with the clinicopathological characteristics of the patients and evaluated their survival rates. Results: The analysis of the GEO data revealed slightly elevated levels of VISTA in PDAC samples compared to normal tissues. However, there was a significant increase in CD68 expression and a notable reduction in CD8A expression in pancreatic cancer. Further investigation identified potential protein-protein interactions and transcription factors associated with these markers. The IHC staining of PDAC tissue samples showed an increased expression of VISTA, CD68, and CD8A in pancreatic cancer tissues. Moreover, we found correlations between the expression levels of these markers and certain clinicopathological features of the patients. Additionally, the survival analysis revealed that high expression of CD8 was associated with better disease-specific survival and progression-free survival in PDAC patients. Conclusion: These findings highlight the potential of CD8, CD68, and VISTA as diagnostic and prognostic indicators in PDAC.

Mentorship of Junior Surgical Faculty Across Academic Programs in Surgery.

Importance: Because mentorship is critical for professional development and career advancement, it is essential to examine the status of mentorship and identify challenges that junior surgical faculty (assistant and associate professors) face obtaining effective mentorship. Objective: To evaluate the mentorship experience for junior surgical faculty and highlight areas for improvement. Design, Setting, and Participants: This qualitative study was an explanatory sequential mixed-methods study including an anonymous survey on mentorship followed by semistructured interviews to expand on survey findings. Junior surgical faculty from 18 US academic surgery programs were included in the anonymous survey and interviews. Survey responses between "formal" (assigned by the department) vs "informal" (sought out by the faculty) mentors and male vs female junior faculty were compared using χ2 tests. Interview responses were analyzed for themes until thematic saturation was achieved. Survey responses were collected from November 2022 to August 2023, and interviews conducted from July to December 2023. Exposure: Mentorship from formal and/or informal mentors. Main Outcomes and Measures: Survey gauged the availability and satisfaction with formal and informal mentorship; interviews assessed broad themes regarding mentorship. Results: Of 825 survey recipients, 333 (40.4%) responded; 155 (51.7%) were male and 134 (44.6%) female. Nearly all respondents (319 [95.8%]) agreed or strongly agreed that mentorship is important to their surgical career, especially for professional networking (309 respondents [92.8%]), career advancement (301 [90.4%]), and research (294 [88.3%]). However, only 58 respondents (18.3%) had a formal mentor. More female than male faculty had informal mentors (123 [91.8%] vs 123 [79.4%]; P = .003). Overall satisfaction was higher with informal mentorship than formal mentorship (221 [85.0%] vs 40 [69.0%]; P = .01). Most male and female faculty reported no preferences in gender or race and ethnicity for their mentors. When asked if they had good mentor options if they wanted to change mentors, 141 (47.8%) responded no. From the interviews (n = 20), 6 themes were identified, including absence of mentorship infrastructure, preferred mentor characteristics, and optimizing mentorship. Conclusions and Relevance: Academic junior surgical faculty agree mentorship is vital to their careers. However, this study found that few had formal mentors and almost half need more satisfactory options if they want to change mentors. Academic surgical programs should adopt a framework for facilitating mentorship and optimize mentor-mentee relationships through alignment of mentor-mentee goals and needs.

A disastrous year that ends with corona outbreak: Effects on mental health of university students.

ObjectiveWe aimed to evaluate depression, anxiety and stress in university students of a large university in Tehran. Iranians witnessed an extraordinary combination of natural and man-made disasters last year; the last of which was the outbreak of COVID-19. Participants: 234 students from Iran University of Medical Sciences. Methods: We designed an online survey to gather data related to General Health Questionnaire (GHQ)-28, Depression, Anxiety, and Stress Scale (DASS)-21, and demographic data. Results: The mean score of GHQ-28 was 34.4 (SD = 15.5, n = 195), and 73.8% (n = 144) of the sample had a score of higher than cut-point (23). According to DASS-21, varying degrees of depression, anxiety, and stress existed in 51%, 32%, and 56% of the students. Conclusions: Negative effects of stressful life events on mental health seems to be additive. More often than not, students need some kind of mental health care at the time of COVID-19 outbreak.

COVID-19 pandemic impact on screening and diagnosis of prostate cancer: a systematic review.

INTRODUCTION: The healthcare level has been greatly affected by the COVID-19 pandemic compared with before the outbreak. This study aimed to review the impact of COVID-19 on the screening and diagnosis of prostate cancer (PCa). METHOD: The current study was designed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020. The keywords used to perform the search strategy were COVID-19 and prostate neoplasms. The four primary electronic databases comprising PubMed/MEDLINE, Web of Science, Scopus and Embase were searched until 1 September 2022. After screening and selecting studies through the EndNote software, data were extracted from each included study by two independent authors. All studies were evaluated according to Newcastle-Ottawa Scale quality assessment tool. RESULTS: As a result, 40 studies were included, categorised into two subjects. The majority of studies indicated a significant decrease in screening prostate-specific antibody tests during the COVID-19 pandemic compared with the pre-pandemic period, leading to delays in cancer diagnosis. The decrease in the number of diagnosed cases with low/intermediate stages to some extent was more than those with advanced stages. The PCa screening and diagnosis reduction ranged from nearly 0% to 78% and from 4.1% to 71.7%, respectively. CONCLUSION: Our findings showed that during the COVID-19 lockdown, delays in PCa screening tests and diagnoses led to the negative health effects on patients with PCa. Thus, it is highly recommended performing regular cancer screening to reduce the impact of the COVID-19 lockdown. PROSPERO REGISTRATION NUMBER: CRD42021291656.

Nuclear overexpression of DNA damage-inducible transcript 4 (DDIT4) is associated with aggressive tumor behavior in patients with pancreatic tumors.

DNA damage-inducible transcript 4 (DDIT4) is induced in various cellular stress conditions. Several studies showed that the dysregulation of DDIT4 is involved in different malignancies with paradoxical expressions and roles. Therefore, this study investigated the clinical significance, prognostic, and diagnostic value of DDIT4 in different types of pancreatic tumors (PT). The expression of DDIT4 and long non-coding RNA (TPTEP1) in mRNA level was examined in 27 fresh PT samples using Real-time quantitative PCR (RT-qPCR). Moreover, 200 formalin-fixed paraffin-embedded PT tissues, as well as 27 adjacent normal tissues, were collected to evaluate the clinical significance, prognostic, and diagnosis value of DDIT4 expression by immunohistochemistry (IHC) on tissue microarrays (TMA) slides. The results of RT-qPCR showed that the expression of DDIT4 in tumor samples was higher than in normal samples which was associated with high tumor grade (P = 0.015) and lymphovascular invasion (P = 0.048). Similar to this, IHC findings for nucleus, cytoplasm, and membrane localization showed higher expression of DDIT4 protein in PT samples rather than in nearby normal tissues. A statistically significant association was detected between a high level of nuclear expression of DDIT4 protein, and lymphovascular invasion (P = 0.025), as well as advanced TNM stage (P = 0.034) pancreatic ductal adenocarcinoma (PDAC) and in pancreatic neuroendocrine tumor (PNET), respectively. In contrast, a low level of membranous expression of DDIT4 protein showed a significant association with advanced histological grade (P = 0.011), margin involvement (P = 0.007), perineural invasion (P = 0.023), as well as lymphovascular invasion (P = 0.005) in PDAC. No significant association was found between survival outcomes and expression of DDIT4 in both types. It was found that DDIT4 has rational accuracy and high sensitivity as a diagnostic marker. Our results revealed a paradoxical role of DDIT4 expression protein based on the site of nuclear and membranous expression. The findings of this research indicated that there is a correlation between elevated nuclear expression of DDIT4 and the advancement and progression of disease in patients with PT. Conversely, high membranous expression of DDIT4 was associated with less aggressive tumor behavior in patients with PDAC. However, further studies into the prognostic value and biological function of DDIT4 are needed in future studies.

Low expression of isocitrate dehydrogenase 1 (IDH1) R132H is associated with advanced pathological features in laryngeal squamous cell carcinoma.

INTRODUCTION: Recent developments in genomic sequencing have led to the identification of somatic mutations in isocitrate dehydrogenase 1 (IDH1) in various malignancies. IDH1 R132H is the most common mutation of IDH1, which affects codon 132 and results in the conversion of amino acid residue arginine (R) to histidine (H). This study is designed to evaluate the association between the expression of IDH1 R132H and clinicopathological characteristics in laryngeal squamous cell carcinoma (LSCC). METHODS: The expression pattern and clinical significance of IDH1 R132H were investigated in tissue microarrays (TMAs) of 50 LSCC tumors as well as adjacent normal tissues using immunohistochemistry. Then the exons of the 12 tumor samples with negative/weak positive staining were sequenced by applying polymerase chain reaction (PCR). RESULTS: The results demonstrated that the cytoplasmic expression of IDH1 R132H was downregulated in tumor cells compared to adjacent normal tissues. A statistically significant association was found between a low level of cytoplasmic expression of IDH1 R132H protein and an increase in histological grade (p < 0.001), perineural invasion (p = 0.019), and lymph node involvement (p < 0.001). The exon4 sequencing results showed that only one sample was positive for IDH1 R132H mutation. IDH1 R132H expression was observed in 39 (78.0%) LSCC samples. CONCLUSION: These findings indicate that low cytoplasmic expression of IDH1 R132H may have clinical significance in LSCC patients and is associated with more aggressive tumor behavior and progression of the disease, which can help improve potential treatment in patients with LSCC. Further investigations are needed to understand the biological function of IDH1 R132H and larger sample size to confirm our findings.

The potential role of telemedicine in the infectious disease pandemic with an emphasis on COVID-19: A narrative review.

Background and Aims: Due of its low cost, rapid speed, data record, and vast communication coverage, information and communication technology might be useful for health-related fields in times of crisis. By providing medical or hygienic services to a patient who lives elsewhere using communication methods like email, fax, cellphones, applications, and wireless gadgets, telemedicine can aid in the better management of diseases. Reviewing the potential role of telemedicine in the pandemic of infectious diseases with a focus on the Coronavirus disease 2019 (COVID-19) epidemic was the main goal of this study. Methods: "Google Scholar," "PubMed," "Science Direct," and "Scopus" databases were searched to collect the papers that identify the advantages and disadvantages of telemedicine in the disease pandemic. Searched keywords include: telepharmacy, telemedicine, remote communication, pandemic(s), epidemic, distant care, distant communication, phone consulation, video conference communication and patient education. Results: Information and communication technology are crucial, especially when dealing with pandemics of infectious diseases like COVID-19. Less "in-person" patient visits to hospitals as a result of telemedicine eventually means less labor for the medical staff, less viral exposure for patients, and ultimately less disease spread. By establishing a bidirectional reciprocal relationship between patients and healthcare providers although they are in separate geographical areas, it can improve patient health status. Conclusion: Governments are currently facing a significant budgetary burden because to the COVID-19 pandemic. Since patients are not sent to medical facilities in person, which could be a source of infection, telemedicine reduces disease spread while saving money.