Differences in Clinicopathological Features, P16Ink4a and P57KIP2 Immunohistochemical Expressions, and Survival Between Colorectal Carcinoma in Rectosigmoid and Other Colonic Locations.

Background One unique criterion of colorectal carcinoma (CRC) is the different locations within the colorectum. Different CRC sidedness/locations could have distinct criteria, including risk factors, morphological features, genetic alterations, prognostic factors, and clinical outcomes. Nearly half of the CRC cases occur in the rectal-sigmoid locations, while other colonic locations constitute the other half. Investigating specific protein expression patterns in the rectosigmoid CRC (rsCRC) compared to other colonic (ocCRC) locations helps understand the disease pathogenesis, predict prognosis, and design personalized treatments. This study is the first to compare P16Ink4a and P57KIP2 immunohistochemical (IHC) expression in rsCRC to ocCRC and examine their relationship to disease outcomes in both locations. Materials and methods A comparative cross-sectional study used tissue microarray slides from rsCRC and ocCRC that were immunohistochemically stained by anti-P16Ink4a and P57KIP2 antibodies. A semi-quantitative scoring system classified each marker's expression as positive or negative. The statistical analysis compared clinicopathological features, P16Ink4a and P57KIP2 expressions, and their relationship to clinical outcomes in rsCRC and ocCRC cases. Results One hundred fifty CRCs were distributed into the rsCRC cases (n=86, 57.3%) and the ocCRC cases (n=64, 42.7%). The rsCRC cases had a significantly lower age <40 years (P=0.002), higher frequency of mismatch repair (MMR) proficient status (P=0.003), and perineural invasion (P=0.008), with lower disease-free (DFS) and overall survival (OS) (P=0.03, and P=0.015, respectively). Significantly higher positive P16Ink4a and P57KIP2 IHC expressions were found in the rsCRCs compared to the ocCRCs (P=0.02, and P=0.03, respectively); however, their relationship to the hazards (HR) of recurrence (HR=4.02, P=0.058, and HR=0.36, P=0.14, respectively) and mortality (HR=2.56, P=0.21, and HR=0.23, P=0.58, respectively) in the rsCRC group was statistically nonsignificant. In the ocCRC group, P16Ink4a positivity was significantly associated with a higher disease recurrence and mortality hazard (HR=8.19, P=0.007, and HR=5.57, P=0.037, respectively), while P57KIP2 positivity was significantly associated with a lower mortality hazard (HR=0.12, P=0.027). Conclusion The rsCRCs differ from ocCRCs in clinicopathological criteria and protein expression patterns. Though P16Ink4a and P57KIP2 IHC expressions are higher in the rsCRC than in the ocCRC, their value as outcome predictors is higher in the ocCRCs rather than the rsCRCs. P16Ink4a and P57KIP2 can act as prognostic markers and be suitable targets for therapy modulation in the ocCRC group.

Memes Adoption in Basic Medical Science Education as a Successful Learning Model: A Mixed Method Quasi-Experimental Study.

Purpose: Basic medical sciences are of a solid abstract nature. Pharmacology is a challenging discipline delivered in all healthcare-related curricula with different aims and goals. Memes are one of aiding instructional designs proved to surge students' performance and satisfaction with the educational process. Apart from assessing medical students' and faculty's perception of meme use in pharmacology learning, the current study aimed to explore the criteria of preferences and factors associated with successful memes' adoption in this discipline as one of the most challenging basic medical sciences. Methods: A biphasic study was conducted among second-year undergraduate medical students and faculty members. The study involved assessing the perceptions of staff and students, and thematic content analysis was performed on the narrative responses of the participants to explore factors contributing to the success of learning memes. Additionally, students' performance was also analyzed. Results: The use of memes in pharmacology was well perceived by medical students, with a mean satisfaction rating of 4.5/5 for high-achieving students and 4.33 for low-achieving students. Memes were associated with a performance surge (p = 0.022). Six themes emerged as criteria for a successful learning experience of meme use: previous scientific background on the meme topic, scenario context of the meme, learning concepts tackled by memes, the simplicity of meme's message, the relevance of meme's message to practice, and the modality of meme's use in the topic of education. Regarding the perception of meme use in pharmacology learning, four themes emerged: the mode and engagement of learning experience mode, the feasibility of meme use in pharmacology learning, students' attitudes towards further meme inclusion in their study, and the perceived impact of memes on students' cognitive skills. Conclusion: The use of memes in pharmacology yields positive learning outcomes. A careful selection of memes is required to ensure a successful learning experience.

Cytoplasmic PPARγ Significantly Correlates With P53 Immunohistochemical Expression and Tumor Size in Localized Tenosynovial Giant Cell Tumor.

BACKGROUND: Tenosynovial giant cell tumor (TGCT) is a monoarticular fibrohistiocytic benign or locally aggressive soft tissue tumor that originates from the synovium of joints, bursae, and tendon sheaths. It has an inflammatory neoplastic nature, with a clinical presentation ranging from pain, swelling, stiffness, and limited range of movement to joint instability and blockage. Its uncommon incidence leads to a poorly understood pathogenesis. Localized forms of TGCT (LTGCT) can cause significant morbidity, interfere with daily patient activities, and decrease the patient's quality of life in challenging cases. This study aimed to investigate the immunohistochemical expression of PPARγ (peroxisome proliferator-activated receptor gamma) and P53 in LTGCT to understand the disease better and offer potential therapeutic targets. METHODS: The study is cross-sectional, in which 27 LTGCT cases were collected from the Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt. Solitary and multiple LTGCT cases retrieved between January 2018 and December 2022 were included, and immunohistochemically stained with anti-PPARγ and P53 antibodies. The TGCT samples were excluded if they were insufficient for sectioning, processing, and interpretation, over-fixed, had process artifacts, or were of the diffuse TGCT type. Scoring of stain expression was performed by ImageJ (National Institutes of Health, Bethesda, MD) analysis using the threshold method and was expressed in percent area/high power field. Clinicopathological correlations were analyzed. RESULTS: All the 27 collected LTGCT cases were located in the small joints of patients' hands. Cases with solitary LGTCTs constituted 55.6% (n = 15), while 44.4% (n = 12) had multiple LTGCTs related to one affected site/case (e.g., multiple tumors in one finger). PPARγ was expressed in the cytoplasm of mononuclear and multinucleated tumor cells and foamy histiocytes, while P53 expression was mainly in mononuclear cells' nuclei. PPARγ significantly correlated with P53 expression (r = 0.9 and P = 0.000). PPARγ (r = 0.4 and P = 0.02) and P53 (r = 0.5 and P = 0.01) were positively correlated with tumor size. Only P53 expression was positively correlated with tumor multiplicity (r = 0.4 and P = 0.03). Using the receiver operating characteristic curve test, the P53 cutoff score detecting the multiplicity of TGCTs was ≥20.5%, with a 75% sensitivity and 80% specificity. CONCLUSION: PPARγ and P53 have a significant role in LTGCT growth, while P53 plays a role in tumor multiplicity. They can be possible targets in LTGCTs unfit for excision.

Diacerein provokes apoptosis, improves redox balance, and downregulates PCNA and TNF-α in a rat model of testosterone-induced benign prostatic hyperplasia: A new non-invasive approach.

One of the most prevalent chronic conditions affecting older men is benign prostatic hyperplasia (BPH), causing severe annoyance and embarrassment to patients. The pathogenesis of BPH has been connected to epithelial proliferation, inflammation, deranged redox balance, and apoptosis. Diacerein (DIA), the anthraquinone derivative, is a non-steroidal anti-inflammatory drug. This study intended to investigate the ameliorative effect of DIA on the prostatic histology in testosterone-induced BPH in rats. BPH was experimentally induced by daily subcutaneous injection of testosterone propionate for four weeks. The treated group received DIA daily for a further two weeks after induction of BPH. Rats' body and prostate weights, serum-free testosterone, dihydrotestosterone, and PSA were evaluated. Prostatic tissue was processed for measuring redox balance and histopathological examination. The BPH group had increased body and prostate weights, serum testosterone, dihydrotestosterone, PSA, and oxidative stress. Histologically, there were marked acinar epithelial and stromal hyperplasia, inflammatory infiltrates, and increased collagen deposition. An immunohistochemical study showed an increase in the inflammatory TNF-α and the proliferative PCNA markers. Treatment with DIA markedly decreased the prostate weight and plasma hormones, improved tissue redox balance, repaired the histological changes, and increased the proapoptotic caspase 3 expression besides the substantial reduction in TNF-α and PCNA expression. In conclusion, our study underscored DIA's potential to alleviate the prostatic hyperplastic and inflammatory changes in BPH through its antioxidant, anti-inflammatory, antiproliferative, and apoptosis-inducing effects, rendering it an effective, innovative treatment for BPH.

Inserting an Erroneous Element in the Answer Key of Grouped Team Readiness Assurance Test in Team-Based Learning: A Randomized Controlled Trial in Clinical Toxicology.

Purpose: Team-based learning (TBL) is an interactive instructional strategy designed to enhance student engagement. Few studies reported that TBL needs to be more interactive, concerns were raised regarding the insufficient instructor feedback, and students feel that TBL gets less attractive with time. One method of boosting students' interaction and performance is adding an element of challenge or positive stress. Therefore, we hypothesized that inserting an erroneous answer in the answer key would generate an observable improvement in the selected outcomes in terms of better satisfaction, interaction, interest in learning, better academic performance, and better development of competencies compared to traditional TBL. Methods: This randomized controlled trial aimed to determine if inserting an erroneous element in the answer key of a grouped team readiness assurance test (GRAT) would update TBL and whether this intervention would enhance students' performance and satisfaction. Results: A total of 55 medical students were recruited (88.7% response rate). Erroneous elements were inserted in the answer key of the experimental group and students enrolled in traditional TBL were considered as controls. Compared to the control group (p < 0.001), the experimental group revealed significantly higher academic performances in GRAT and team evaluation test (TET). Analysis of students' perception of the implemented TBL revealed better perception among the experimental group (33.7 ± 6.4) than the control group (30.1 ± 7.0). Moreover, significantly higher team dynamics were reported among the experimental group than the control group (33.0 ± 6.3 and 27.8 ± 7.6 for both groups, respectively; p = 0.005). The reported advantages were in-depth understanding, easier information retrieval, and development of problem-solving skills. Students considered time and effort as their main limitations. Conclusion: Adding a few erroneous answers in the GRAT is well perceived by students, enhances their learning competencies and overcomes some TBL challenges.

Screening a novel six critical gene-based system of diagnostic and prognostic biomarkers in prostate adenocarcinoma patients with different clinical variables.

The mechanisms behind prostate adenocarcinoma (PRAD) pathogenicity remain to be understood due to tumor heterogeneity. In the current study, we identified by microarray technology six eligible real hub genes from already identified hub genes through a systematic in silico approach that could be useful to lower the heterogenetic-specific barriers in PRAD patients for diagnosis, prognosis, and treatment. For this purpose, microarray technology-based, already-identified PRAD-associated hub genes were initially explored through extensive literature mining; then, a protein-protein interaction (PPI) network construction of those hub genes and its analysis helped us to identify six most critical genes (real hub genes). Various online available expression databases were then used to explore the tumor driving, diagnostic, and prognostic roles of real hub genes in PRAD patients with different clinicopathologic variables. In total, 124 hub genes were extracted from the literature, and among those genes, six, including CDC20, HMMR, AURKA, CDK1, ASF1B, and CCNB1 were identified as real hub genes by the degree method. Further expression analysis revealed the significant up-regulation of real hub genes in PRAD patients of different races, age groups, and nodal metastasis status relative to controls. Moreover, through correlational analyses, different valuable correlations between treal hub genes expression and different other data (promoter methylation status, genetic alterations, overall survival (OS), tumor purity, CD4+ T, CD8+ T immune cells infiltration, and different other mutant genes and a few more) across PRAD samples were also documented. Ultimately, from this study, a few important transcription factors (TFS), miRNAs, and chemotherapeutic drugs showing a great therapeutic potential were also identified. In conclusion, we have discovered a set of six real hub genes that might be utilized as new biomarkers for lowering heterogenetic-specific barriers in PRAD patients for diagnosis, prognosis, and treatment.

Decoding signal transducer and activator of transcription 1 across various cancers through data mining and integrative analysis.

OBJECTIVES: Using different online available databases and Bioinformatics tools, we extensively studied the role STAT1 across different cancers. METHODS: STAT1 mRNA, protein expression, and promoter methylation were analyzed and validated using UALCAN, GENT2, Human Protein Atlas (HPA), and MEXPRESS. Furthermore, the potential prognostic values were evaluated through KM plotter. Then, cBioPortal was utilized to examine the STAT1-related genetic mutations, while pathway enrichment analysis was performed using DAVID. To identify STAT1 targeted microRNAs (miRNAs) and transcription factors (TFs) we used Enricher. Moreover, a correlational analysis between STAT1 expression tumor purity and CD8+ T immune cells and a gene-drug interaction network analysis was performed using TIMER, CTD, and Cytoscape. RESULTS: In 23 major human cancers, STAT1 expression was notably up-regulated relative to corresponding controls. As well, the elevated expression of STAT1 was exclusively found to be associated with the reduced overall survival (OS) of Esophageal Carcinoma (ESCA), Kidney Renal Clear Cell Carcinoma (KIRC), and Lung adenocarcinoma (LUAD) patients. This implies that STAT1 plays a significant role in the development and progression of these three cancers. Further pathway analysis indicated that STAT1 enriched genes were involved in six critical pathways, while a few interesting correlations were also documented between STAT1 expression and promoter methylation level, tumor purity, CD8+ T immune cells infiltration, and genetic alteration. In addition, we have also predicted a few miRNAs, TFs, and chemotherapeutic drugs that could regulate the STAT1 expression. CONCLUSION: The current study revealed the shared oncogenic, diagnostic, and prognostic role of STAT1 in ESCA, KIRC, and LUAD.

Medical Community Perspectives Regarding the Egyptian Medical Licensing Exam: A Mixed-Method Study.

BACKGROUND: Although national licensing examinations (NLEs) may be a costly process, they can predict performance of medical practitioners for many years following graduation. The current licensing requirements do not fulfill this function as there are no clear performance criteria for them. Therefore, new requirements should be developed and announced. OBJECTIVE:  The study aims to develop a framework for the Egyptian Medical Licensing Exam (EMLE) by exploring the opinions and perceptions of Egyptian health practitioners and medical educators. METHODS: This study is a two-phase exploratory mixed-method study. An online discussion forum was conducted with medical practitioners and educators concerning the development of the EMLE. Then, an online survey was distributed to explore the opinions of medical practitioners and educators about the EMLE. RESULTS: Fifty medical practitioners and educators participated in the discussion forum about the development of the EMLE, while 266 participants responded to the online survey. The responses of the participants contributed to the development of a framework for the EMLE that is divided into two main sections, the exam logistics and the exam set up. The exam logistics included the exam committee, prerequisites for the exam, the admission criteria and fees, and validity of the license. The exam set up included exam setting, structure, pass marks, and exam retake policy. CONCLUSION: The study concluded that medical practitioners and educators could contribute greatly to the planning for the EMLE. Their opinions are based on their experiences and include the timing of the exam, blueprinting, assessment methods, psychometrics and retake.