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Samir Al Bashir,1 Nosayba Al-Azzam,2 Lina Elsalem,3 Aya Al Smerat,2 Husam K Haddad,4 Jomana Alsulaiman,5 Khalid A Kheirallah,6 Karem H Alzoubi7,8 1Department of Pathology and Microbiology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 2Department of Physiology and Biochemistry, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 3Department of Pharmacology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 4Department of Pathology and Laboratory Medicine, Ministry of Health, Amman, Jordan; 5Department of Pediatrics, Medical School of Yarmouk University, Irbid, Jordan; 6Department of Public Health, Community Medicine and Family Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 7Department of Pharmacy Practice and Pharmacotherapeutics, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates; 8Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, JordanCorrespondence: Samir Al Bashir, Department of Pathology and Microbiology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, 22110, Jordan, Email smalbashir9@just.edu.joBackground: The COVID-19 pandemic has disrupted the scope of healthcare education and shifted the teaching methods from on-campus to virtual. The impact of such a shift has rarely been investigated, and limited evidence exists about students’ experience in terms of effort made and time spent, especially for laboratory sessions. Assessing students’ experiences will provide paramount evidence to fine-tune laboratory virtual learning sessions.Objective: To assess students’ experience of virtual (online) laboratory sessions versus on-campus laboratory sessions, including preference, time spent, the effort made, ability to remember instructions, and preference for future teaching.Methods: A cross-sectional study was utilized. A Google Forms questionnaire was prepared and sent to medicine, dentistry, and nursing school students registered at Jordan University of Science and Technology (JUST) during the 2019/2020 academic year. Self-reported preference, time spent, efforts made, ability to remember instructions and preference for future teaching were assessed for virtual versus on-campus anatomy, pathology, microbiology, histology, and physiology laboratory sessions.Results: A total of 455 students participated in this questionnaire. More students in histology (55.2%), pathology (57.4%), and microbiology (55.3%) laboratories, but not anatomy (39.6%) physiology (443.95), reported preferring virtual sessions over on-campus sessions. More students from histology (35.6%) and microbiology (37.0%) reported spending less effort than on-campus sessions. More than half of the participants agreed that virtual laboratory sessions consumed less time than on-campus sessions. Participants reported that they cannot remember the instruction given during virtual teaching compared to on-campus teaching. Differences in students’ experiences were detected by gender, major, and year of study.Conclusion: The COVID-19 pandemic has the potential to change the future of healthcare education, and preparation for future crises is paramount. Effort made, time spent, ability to remember, and preference for virtual education should be considered in terms of gender, major of study, and year. These differences should also be reflected in the planning of virtual sessions for effective implementation.Keywords: medical students, COVID-19, laboratory sessions, virtual environment, on-campus sessions, Jordan

Najla Aldaoud,1,2 Ashley Graboski-Bauer,3 Nour Abdo,4 Samir Al Bashir,1,2 Ashraf O Oweis,5 Hanadi Ebwaini,1 Yousef Hasen,1–2,6 Rami Alazab,7 Kiril Trpkov81Department of Pathology and Microbiology, King Abdullah University Hospital, Irbid, Jordan; 2Jordan University of Science and Technology, Irbid, Jordan; 3Department of Teacher Education, University of Texas, El Paso, TX, USA; 4Department of Public Health, Jordan University of Science and Technology, Irbid, Jordan; 5Division of Nephrology, Department of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 6Attasami Diagnostic Center, Tripoli, Libya; 7Division of Urology, Jordan University of Science and Technology, Irbid, Irbid; 8Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, CanadaBackground: High-grade prostatic intraepithelial neoplasia (HGPIN) is the most likely precancerous lesion for prostatic adenocarcinoma (PCa). Recent molecular studies have shown that HGPIN can harbor TMPRSS2-ERG fusion, a genetic marker also associated with PCa, which may provide an additional risk stratification tool for HGPIN, especially when present as an isolated lesion. Our aim was to assess the frequency of HGPIN and ERG expression in a cohort of prostatic needle core biopsies from Jordanian-Arab patients with PCa.Materials and methods: We studied 109 needle core biopsies from patients with PCa. Clinical data, including age and preoperative prostate specific antigen (PSA) level, were obtained from patients’ medical records.Results: HGPIN was present in 31 (28.4 %) of the 109 cases. Of the HGPIN cases, 13 (41.9%) expressed ERG immunostain. ERG expression in HGPIN was independent of patient age at presentation (P=0.4), pre-operative PSA (P=0.9), and the grade, using the novel Grade Groups (P=0.5).Conclusion: The frequency of HGPIN in our cohort appears similar to the one found in the Western patient populations and demonstrates a comparable frequency of ERG expression in these lesions.Keywords: high-grade prostatic intraepithelial neoplasia, prostate carcinoma, ERG, immunohistochemistry

OBJECTIVE: Though tumor-infiltrating lymphocytes (TILs) have a predictive impact in cancer patients, their association with presentation and prognosis in breast cancer is less consistent. This study aimed to assess the level of infiltrating cytotoxic T lymphocytes (CTLs) and regulatory T lymphocytes (Tregs) and their association with the clinicopathological features of breast cancer. PATIENTS AND METHODS: Tissue samples from female patients (n=153) diagnosed with primary invasive breast cancer were stained with CD8 (a CTL marker) and Foxp3 (a Treg marker) using immunohistochemistry. RESULTS: CTLs were distributed between tumor bed and stroma whereas Treg cells were mainly located in the stroma. The level of intratumoral CTLs correlated positively with Tregs in both tumor and stroma (rho=0.312, p<0.001 and rho=0.176, p=0.031; respectively). Stromal CTLs correlated positively with stromal Tregs (rho=0.319, p=0.005). Tumor size correlated inversely with the number of Treg cells in the tumor bed (rho= - 0.179, p=0.028). Tregs were associated with lymphovascular invasion status in the tumor bed (p=0.042). The ratio of intratumoral CTLs to Tregs was associated with estrogen receptor positivity and luminal subtype (p=0.029 and p=0.045, respectively). The median number of CTLs was significantly lower in patients using aspirin or antihypertensive medications compared to nonusers (p=0.024 and p=0.03, respectively). CONCLUSIONS: TILs were distributed differently in tumor tissues of breast cancer patients. CTLs infiltrates were found in both tumor bed and stroma while Tregs were dominant in the stroma. TILs were also distinctly associated with tumor features. The impact of TILs on prognosis and treatment outcomes in Jordanian breast cancer patients needs further investigation. [ABSTRACT FROM AUTHOR]

Nehad M Ayoub,1 Mona Fares,1 Raya Marji,2 Samir M Al Bashir,2 Rami J Yaghan3 1Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology (JUST), Irbid, 22110, Jordan; 2Department of Pathology and Microbiology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, 22110, Jordan; 3Department of Surgery, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, BahrainCorrespondence: Nehad M AyoubDepartment of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology (JUST), Irbid, 22110, JordanTel +962-2-7201000 Ext. 23809Fax +962-2-7095123Email nmayoub@just.edu.joPurpose: Tumor expression of programmed death-ligand 1 (PD-L1) is associated with evasion of immune response in several types of malignancies and such expression may render patients eligible for PD-L1 inhibitors. The use of immune checkpoint blockade therapy has been recently approved for the treatment of breast cancer. However, PD-L1 expression data are lacking among Jordanian breast cancer patients. In this study, the tumor PD-L1 expression was characterized in breast cancer patients to assess their eligibility for immune checkpoint blockade therapy. The study also aimed to explore the association between tumoral PD-L1 expression and the clinicopathologic characteristics and the prognostic factors in patients with breast cancer.Patients and Methods: Tissue samples were available from 153 female patients with primary invasive breast cancer. Immunohistochemistry was performed on paraffin-embedded tumor sections that were stained with a PD-L1 antibody. Expression of tumor PD-L1 was correlated with demographics, clinicopathologic characteristics, and prognosis.Results: The mean age at diagnosis was 54.2± 12.8 years (median 52, interquartile range 45– 65). The percentage of PD-L1-positive tumors was 26.1%. PD-L1 expression on tumor cells significantly and positively correlated with tumor size (rho=0.174, p=0.032). PD-L1 positivity was significantly associated with the grade of carcinoma (p=0.001), HER2-positivity (p=0.015), and lymphovascular invasion (p=0.036). PD-L1 intensity was significantly associated with tumor stage (p=0.046). No significant associations were observed for the PD-L1 expression status or intensity with patient menopausal status, hormone receptor expression, and molecular subtypes. PD-L1 expression significantly correlated with a worse prognosis of breast cancer patients at the time of diagnosis (rho=0.230, p=0.005).Conclusion: Tumor PD-L1 expression was associated with advanced clinicopathologic features and worse prognosis in this cohort of Jordanian breast cancer patients. Future studies are needed to better understand the impact of PD-L1 blockade therapy on treatment outcomes in eligible breast cancer patients in Jordan.Keywords: breast cancer, PD-L1, immunohistochemistry, clinicopathologic, prognosis

Rawan A Obeidat,1 Abdelwahab J Aleshawi,2 Hasan A Obeidat,2 Samir M Al Bashir3 1Department of Obstetrics & Gynecology, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan; 2Department of General Surgery and Urology, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan; 3Department of Pathology, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan Abstract: Fibromas/fibrothecomas are considered to be benign ovarian tumors. We describe a rare case of recurrent fibrothecoma with a clinically malignant course. A 42-year-old woman, with no family history of malignancy, operated multiple times for tumor that recurred three times within 4 years despite radical surgical removal. Initially, she presented with 9×7×10 cm right ovarian mass, frozen section was consistent with fibrothecoma and thus right salpingoophorectomy was performed. At the last two recurrences, she was found to have recurrent multiple abdomino-pelvic fibrothecomas and two long major operations were performed. This malignant behavior of a benign tumor is very rare. Further genetic analysis and immunohistochemistry studies are recommended to be conducted. Furthermore, new modalities of treatment should be considered, eg, high-intensity focused ultrasound and/or hormonal treatment. Keywords: recurrent fibrothecoma, ovarian tumor, radical surgery, sex cord-stromal tumors

Context. Idiopathic male infertility is evident in half of infertile males. Vitamin D receptors are expressed throughout male reproductive tract, including spermatozoa, promoting motility. Epidemiological studies revealed the positive association between serum vitamin D and semen quality. However, there are no clinical studies examining the differential role of vitamin D in idiopathic male infertility. Objectives. 1) To investigate the association between vitamin D deficiency and idiopathic male infertility, and 2) To determine whether vitamin D deficient males would show restoration of semen quality parameters upon supplementation with vitamin D. Design. This was a year-long case-control study from November 2015 to November 2016. A therapeutic intervention cohort for 2 months was also performed. Subjects and Methods. 117 Jordanian males were enrolled. Following a clinical evaluation by a urologist, baseline serum vitamin D and semen fluid analyses were collected. Participants were stratified into 3 groups: controls (n=30), idiopathic infertility (n=67), and secondary infertility (n=20). Idiopathic infertility patients with low vitamin D (n= 45) were supplemented with oral vitamin D, 5000 IU, once daily for two months. Thereafter, serum vitamin D and semen fluid analyses were reassessed (n= 34; 11 patients were lost to follow up). Results. Vitamin D was significantly lower in patients with idiopathic infertility than in both controls and men with secondary infertility. Significant improvement of progressive and total sperm motility was observed after vitamin D treatment. Vitamin D correlated significantly with semen quality in the study population. However, no correlation was found between vitamin D and any of the semen quality parameters in the idiopathic infertility group. Conclusions. Vitamin D supplementation improves sperm motility in idiopathic male infertility patients with low vitamin D. Larger and longer clinical trials are warranted to validate the use of vitamin D in these cases. [ABSTRACT FROM AUTHOR]

The AKT1 oncogene is related to various cancers due to its critical role in the PIC3CA/AKT1 pathway; however, most of the studies screened the hotspot mutation AKT1 (E17K) with various incidences. Low frequency or lack of AKT1 (E17K) mutation was reported in prostate cancer (PC) patients. This study aims to explore genetic alterations in the AKT1 PH domain by extending the sequencing to include AKT1 gene exons 3 and 4. Genomic DNA was extracted from 84 Formalin-Fixed Paraffin-Embedded samples of PC patients in Jordan, and then subjected to PCR and sequencing for the targeted exons. This study revealed the presence of two novel mutations (N53Y and Q59K) and a high frequency of mutations in exon 4, with a lack of mutations in the E17K hotspot. Nine missense and two synonymous mutations were detected in exon 4 (Phe27Tyr, Phe27Leu, Ala58Thr, Ser56Phe, Arg41Trp, Phe35Leu, Asp32Glu, Phe35Tyr, and Gln43Lys) and (Ser56 and Glu40), respectively. Two synonymous mutations were detected in exon 3 (Leu12 and Ser2). It is concluded that there is a high frequency of AKT1 mutation in PC patients in Jordan with two novel missense mutations in the Pleckstrin homology (PH) domain. E17K hotspot mutation was not detected in any tested samples, which underlined the significant role of mutations in other AKT1 exons in PC development.

The purpose of this study was to assess the clinicopathological features of oropharyngeal cancer patients in Jordan based on their HPV status. Sixty-nine biopsies from two hospitals were included. Tissue microarrays were prepared from formalin-fixed paraffin-embedded (FFPE) specimens and stained with antibodies for CDKN2A/P16, EGFR, PI3K, PTEN, AKT, pS473AKT, PS2mTOR, and TIMAP. The cohort was divided according to P16 expression. Chi-square test and survival analyses were employed to evaluate the variations among the study variables and determine the prognostic factors, respectively. P16 expression was found in 55.1% of patients; however, there was no significant association between P16 expression and the patients' clinicopathological features. The Kaplan-Meier test revealed that smoking in P16-positive group and younger age (< 58 years) negatively impacted disease-free survival (DFS) (P = 0.04 and P = 0.003, respectively). Multivariate Cox regression test indicated that smoking, age, PI3K, and AKT were negative predictors of DFS (P = 0.021, P = 0.002, P = 0.021, and P = 0.009, respectively), while TIMAP was a positive predictor (P = 0.045). Elevated P16 expression is found in more than half of the patients' specimens. DFS is negatively affected by younger age and the combined effect of smoking and P16 overexpression. TIMAP is overexpressed in P16-positive oropharyngeal cancer, and it is a favorable predictor of DFS., (© 2024. The Author(s) under exclusive licence to The Japanese Society for Clinical Molecular Morphology.)

The delayed presentation of cancer patients to healthcare facilities for diagnosis is a pressing issue, as late-stage cancer cases are often more challenging to treat effectively. In low-resource settings, such as those with limited access to healthcare facilities, the impact of inadequate awareness of cancer signs and symptoms can be particularly severe. Therefore, this study aimed to evaluate public knowledge of cancer signs and symptoms and risk factors in the context of Jordan. This cross-sectional study was conducted among participants from all settings. Data was obtained from an Arabic version of the cancer awareness measure (CAM), which was answered online. It described demographic data and knowledge of cancer prevalence, age-related risk, signs, symptoms, and risk factors in recall and recognition-type questions. Participants (n = 1998) completed the questionnaire with a Median age of 35 and an interquartile range of 24. About half (n = 1070) thought that cancer is unrelated to age. Most participants identified breast cancer as the most common cancer among women (81%). Awareness of cancer signs/symptoms significantly differed in the level of knowledge in favor of females. The symptom "unexplained weight loss" was most commonly recognized (66.3%) and "persistent difficulty swallowing" the least (42.6%). As for risk factors, "smoking" was the most identified (76.9%) and "eating less than 5 portions of fruits and vegetables a day" was the least (19%), and "doing <30 minutes of moderate physical activity 5 times a week" as a close second least (19.95%). Females identified "smoking," "passive smoking," "HPV infection," and "having a close relative with cancer" as risk factors significantly more than males. Those with good economic status were more aware that smoking is a cancer risk factor by 1.51 times compared to those with poor economic status. To enhance early diagnosis and presentation in Jordan, there is a need for increased public awareness of the signs, symptoms, and risk factors of cancer. One effective strategy to achieve this goal is to conduct targeted public campaigns that cater to different population groups, such as the youth, to improve their understanding and ensure that the message resonates., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Objectives : Prognostic biomarkers in prostate cancer (PCa) include PTEN, ERG, SPINK1, and TFF3. Their relationships and patterns of expression in PCa in developing countries, including Jordan, have not yet been investigated. Materials and Methods : A tissue microarray (TMA) of PCa patients was taken from paraffin-embedded tissue blocks for 130 patients. PTEN, ERG, SPINK1, and TFF3 expression profiles were examined using immunohistochemistry (IHC) and correlated with each other and other clinicopathological factors. Results : PTEN loss of any degree was observed in 42.9% of PCa cases. ERG and TFF3 were expressed in 59.3% and 46.5% of PCa cases, respectively. SPINK1 expression was observed in 6 out of 104 PCa cases (5.4%). Among all PCa cases ( n = 104), 3.8% ( n = 4) showed SPINK1+/ERG+ phenotype, 1.9% ( n = 2) showed SPINK1+/ERG- phenotype, 56.7% ( n = 59) showed SPINK1-/ERG+ phenotype, and 37.5% showed SPINK1-/ERG- phenotype ( n = 39). Among ERG positive cases ( n = 63), 6.3% were SPINK1 positive. Among SPINK1 positive cases ( n = 6), 66.7% were ERG positive. SPINK1 expression was predominantly observed in a subgroup of cancers that expressed TFF3 (6/6). Additionally, a statistically significant loss of PTEN expression was observed from Gleason Score 6 (GS6) (Grade Group 1 (GG1)) to GS9-10 (GG5); ( p -value 0.019). Conclusions : This is the first study to look at the status of the PTEN, ERG, SPINK1, and TFF3 genes in a Jordanian Arab population. Loss of PTEN has been linked to more aggressive prostate cancer with high GSs/GGs. SPINK1 expression was predominantly observed in a subgroup of cancers that expressed TFF3. Our results call for screening these biomarkers for grading and molecular subtyping of the disease.

Malignancies rarely occur in somatic parts of mature cystic teratoma of the ovary. Squamous cell carcinoma is the most common form of cancer that can develop in mature cystic teratoma. Other less frequent malignancies include melanoma, sarcoma, carcinoid, and germ cell neoplasms. Only three cases have been reported as papillary thyroid carcinoma arising in struma ovarii. We present a unique case of a 31-year-old female patient who presented with a left ovarian cyst and underwent conservative surgical management in the form of cystectomy. Histopathological examination confirmed the diagnosis of a tall cell subtype of papillary thyroid carcinoma arising from a small focus of thyroid tissue in a mature cystic teratoma of the ovary. The patient was followed up for 60 months with an uneventful clinical course. For a better understanding of such rare cancers, collaborative retrospective studies on large databases with other medical centers are required., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Androgen deprivation therapy (ADT) remains the principal treatment of advanced prostate cancer. However, most patients eventually experience treatment failure, resulting in castrate-resistant prostate cancer (CRPC). Loss of the tumor suppressor gene phosphatase and tensin homolog ( PTEN ) has been linked to poor survival in prostate cancer. We have recently shown that PTEN loss is evident in approximately 60% of prostate cancer cases in Jordan. However, the correlation between PTEN loss and response to ADT remains unclear. This study aimed to determine the relationship between PTEN loss and time to CRPC in Jordan. We conducted a retrospective analysis of confirmed CRPC cases at our institution from 2005 to 2019 (N=104). PTEN expression was assessed using immunohistochemistry. Time to CRPC was calculated from the initiation of ADT to the confirmed diagnosis of CRPC. Combination/sequential ADT was defined as the use of two or more classes of ADT concomitantly or switching from one class to another. We found that PTEN loss was evident in 60.6% of CRPC. Mean time to CRPC was not different between patients with PTEN loss (24.8 months) and those with intact PTEN (24.2 months; p=0.9). However, patients receiving combination/sequential ADT had a significantly delayed onset of CRPC compared to patients on monotherapy ADT (log-rank Mantel-Cox p=0.000). In conclusion, PTEN loss is not a major determinant of time to CRPC in Jordan. The use of combination/sequential ADT procures a significant therapeutic advantage over monotherapy regimens, delaying the onset of CRPC., Competing Interests: The authors declare no conflict of interest., (©2023 JOURNAL of MEDICINE and LIFE.)

Bladder cancer (BC) is the 10th most common cancer worldwide. Genetic studies estimated 30% heritability in BC risk. Adiponectin is an adipocytokine that has important roles in the regulation of energy metabolism. Recent evidence suggests dysregulation of adiponectin levels in BC tissues. Serum level of adiponectin is influenced by single nucleotide polymorphisms (SNPs) in the ADIPOQ gene. However, limited evidence is available regarding the association between adiponectin serum levels or SNPs in ADIPOQ and BC risk. This study aimed to assess whether adiponectin serum levels or SNPs in ADIPOQ may modify BC risk. In this case-control study, 114 BC patients were recruited along with 114 controls. Study subjects were genotyped for variations in ADIPOQ SNPs, namely rs17300539, rs266729, rs2241766, and rs1501299. Adiponectin levels were measured from the serum of study subjects. Our analysis showed that the G allele and the GG genotype of rs1501299 were significantly more frequent in BC patients compared to those in the control group (p-value < 0.05). Moreover, two ADIPOQ haplotypes containing the above G allele were associated with increased BC risk (p-value < 0.05). Multivariate analysis showed that increased serum adiponectin, smoking or age were all significant predictors of BC (p-value < 0.05). The data supports use of serum adiponectin and the G allele of rs1501299 SNP in ADIPOQ as potential biomarkers and/or targets in BC. To further validate findings in this study, larger populations of various ethnicities and/or genetic backgrounds are required. More investigations on the functional role of adiponectin in BC will also provide better understanding of potential targeting adiponectin for BC treatment., Competing Interests: The authors report no conflicts of interest in this work.

Papillary renal cell carcinoma (PRCC) classification has traditionally been divided into two histologic types, type 1 and type 2. A new biological stratification system has recently been proposed based on comprehensive morphologic and genomic analysis. The predominant molecular marker in this 4-tiered stratification is the renal drug transporter ABCC2. In this study, we assessed and validated the value of the biological grouping in a PRCC cohort of 176 patients and provided a comprehensive assessment of clinicopathological variables. Tissue microarrays (TMAs) were constructed from nephrectomy specimens. The TMAs were stained with ABCC2 and GATA3 antibodies, and the PRCC cohort was stratified into four groups PRCC1-PRCC4: PRCC1 25%, PRCC2 37%, PRCC3 36%, and PRCC4 2%. PRCC1 demonstrated lower disease stage (p = 0.041) than PRCC2 and PRCC3. The biological stratification was significant on univariate analysis when analyzing both overall survival (p = 0.039) and disease-free survival (p = 0.011). The biological groups maintained the significance of predicting overall survival after adjusting for WHO/ISUP grade, age, pathological stage, and necrosis (p = 0.049, hazard ratio: 5.008, 95% confidence interval: 1.007 to 24.909). In contrast, WHO/ISUP grade did not maintain its significance on multivariate survival analysis. ABCC2 expression profile also separated cases ≤ 4 cm, based on disease-free survival (p = 0.038). None of the patients in the PRCC1 group died of disease during the follow-up period. The proposed biologic stratification adds molecular markers to the traditional morphologic assessment to better stratify patients' prognosis. ABCC2 expression can also potentially serve as a predictive biomarker owing to its known implication in cancer biology and drug resistance., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Stem cell science is rapidly developing with the potential to alleviate many non-treatable diseases. Medical students, as future physicians, should be equipped with the proper knowledge and attitude regarding this hopeful field. Interactive teaching, whereby the teachers actively involve the students in the learning process, is a promising approach to improve their interest, knowledge, and team spirit. This study aims to evaluate the effectiveness of an interactive teaching intervention on medical students' knowledge and attitudes about stem cell research and therapy., Methods: A pre-post test study design was employed. A six-session interactive teaching course was conducted for a duration of six weeks as an intervention. Pre- and post-intervention surveys were used. The differences in the mean scores of students' knowledge and attitudes were examined using paired t-test, while gender differences were examined using an independent t-test., Results: Out of 71 sixth-year medical students from different nationalities invited to participate in this study, the interactive teaching course was initiated by 58 students resulting in a participation rate of 81.7%. Out of 58 students, 48 (82.8%) completed the entire course. The mean age (standard deviation) of students was 24 (1.2) years, and 32 (66.7%) were males. The results showed poor knowledge about stem cells among the medical students in the pre-intervention phase. Total scores of stem cell-related knowledge and attitudes significantly improved post-intervention. Gender differences in knowledge and attitudes scores were not statistically significant post-intervention., Conclusions: Integrating stem cell science into medical curricula coupled with interactive learning approaches effectively increased students' knowledge about recent advances in stem cell research and therapy and improved attitudes toward stem cell research and applications., Competing Interests: The authors declare there are no competing interests., (©2022 Abdulrazeq et al.)

Background: Scabies is one of the prevalent dermatological conditions, accounting for a substantial proportion of skin diseases in developing countries. It represents a significant health challenge when an outbreak appears in homecare and refugee camps as it may lead to enormous morbidity and high treatment costs. Because Scabies can be easily prevented through education, the purpose of this study was to assess the impact of socio-demographic factors on the level of knowledge, attitude, and practices among Syrian refugees in Jordan's northern region., Methods: A prospective cross-sectional study was conducted among Syrian refugees attending primary health centers in northern Jordan, Ramtha, Mafraq, and Irbid, from February 2021 to May 2021. The targeted population was adult Syrian refugees above the age of 18. Two thousand participants were included in this study using simple random selection. The study questionnaire included socio-demographic characteristics and knowledge questions such as hearing about Scabies, causes of Scabies, signs and symptoms of Scabies, and its way of transmission. The data was analyzed using (SPSS) version 25., Results: Females with a mean age of 37.9 years old comprised the majority of the participants. The majority of the participants were married and had intermediate levels of education. The knowledge about Scabies lacked among the majority of the respondents (N = 1259); 321 respondents had moderate knowledge, while only 650 had good knowledge. A statistically significant association was found between knowledge scores and all demographic characteristics, including gender, marital status, income, and educational level., Conclusion: The general knowledge about Scabies among Syrian refugees is relatively low, with 1259 out of 2000 participants having a bad knowledge score. Moreover, the level of knowledge, attitude, and practices toward Scabies is highly affected by the demographic factors of the Syrian refugees' Health education for refugees is needed to improve their knowledge and help implement prevention programs., (© 2021 Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd.)

Background: Emotional distress is a major impact of COVID-19 among not only the general public but also healthcare workers including medical students. This study aimed at describing self-reported changes in emotional reactions associated with COVID-19 among medical students in Jordan and to assessing the potential effect of social media utilization on emotional distress among this group. Methods: A cross-sectional design was utilized to collect data early on during the outbreak in Jordan. All medical students in Jordan were eligible to complete an online questionnaire assessing self-reported emotional reactions to COVID-19 that covered four main domains: negative emotion (anxiety, worry, depression, panic, loneliness, and nervousness), positive emotion (happiness, joy, and excitement), sleep disorders (insomnia, shallow sleep, nightmares, and insufficient sleep), and aggression (verbal argument and physical fighting). The frequency of social media utilization as a main source of COVID-19 information was also assessed. Results: 59.9% of participants were females, 64.9% were enrolled at the two major medical schools in Jordan, and 59.6% were in the pre-clinical stage (years). A significant proportion of participants self-reported increased negative emotional levels of anxiety (49.2%), worry (72.4%), depression (23.1%), panic (22.6%), and nervousness (38.2%) and decreased positive emotional levels of happiness (44.8%), joy (47.3%), and feelings of excitement (45.1%). Self-reported sleep disorders were not as common (less than 15% for any of the four items), while arguing with others was at 26.7%. Significant differences by gender and academic year were detected. Almost half of participants reported using social media as a main source of COVID-19 information "most/all-the-times" with a significant effect of such on reducing emotional distress. Conclusion: The results suggest a potential effect of COVID-19 on the emotional distress of medical students. Addressing and mitigating such effects is crucial. The buffering effect of social media should be further investigated., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Kheirallah K et al.)

Background: The COVID-19 pandemic had many implications on healthcare services, including cellular pathology. The pandemic-related lockdown was applied in Jordan from March to May 2020. King Abdullah University Hospital (KAUH) was chosen to provide care for COVID-19 patients during that period. Since there was no experience in dealing with COVID-19 patients, the hospital maintained some essential services but canceled elective surgeries and procedures. The rationale was to prioritize care for COVID-19 patients and to provide better adherence to infection control policies and protect non-infected patients and healthcare workers. The purpose of the present study is to investigate the impact of COVID-19 pandemic restrictions on cellular pathology practice patterns at KAUH., Methods: This is a retrospective observational study conducted at KAUH. All cellular pathology reports during the 2020 national lockdown were retrieved. The total numbers of specimens including types and procedures were recorded. Data were compared with the corresponding data in 2019 when there was no pandemic and when hospital and laboratory services were run in full capacity., Results: 2020 lockdown period showed a 57.9% reduction in the total number of specimens received at the cellular pathology laboratory as compared to the corresponding period of 2019 (1400 versus 3322). Emergency procedures have represented 99.1% of the service during the lockdown with a remarkable diversity shift., Conclusion: There was a significant drop in the number of specimens dealt with at KAUH cellular pathology laboratory during the COVID-19 pandemic-related national lockdown. We learned from this pandemic how to adapt to such circumstances by adjusting our way of working to reach the best level of staff safety while maintaining highly productive work. Implementing digital pathology platforms, working from home strategies and alternative training methodologies have emerged as an essential need., Competing Interests: All authors declare that they have no conflicts of interest., (© 2021 The Authors.)

Recent advances in molecular biology make the identification of prostate cancer (PC) subsets a priority for more understanding of the molecular pathogenesis and treatment options. Genetic alterations in many genes such as TP53, SPOP and PIK3CA genes have been reported in PC with variable frequencies worldwide. We aimed to investigate genetic alterations in the hotspot lesions of TP53, SPOP and PIK3CA genes by direct sequencing and the expression of TP53 and PIK3CA by RT-PCR in prostate cancer, and to explore the correlation between TP53, SPOP and PIK3CA alterations and tumorigenesis of prostate cancer. Seventy-nine FFPE prostate samples from patients who underwent radical prostatectomy were obtained, subjected to genomic DNA extraction and sequenced for mutations in exons 5, 6, 7 and 8 of TP53 gene, exons 4 and 5 of SPOP gene and exons 9 and 20 of PIK3CA gene. RT-PCR was performed for the expression evaluation of the PIK3CA gene. Our results showed a high frequency of TP53 mutations (11/79, 13.9 %) in the selected population. On the other hand, SPOP and PIK3CA genes did not show any genetic alteration in the sequenced exons. PIK3CA gene overexpression was detected in 6% of the cohort by RT-PCR. TP53 mutation is the most frequent genetic alteration and likely has a major role in the pathogenesis of PC in the Jordanian population., .

Deletion of phosphatase and tensin homolog (PTEN) in prostate cancer has been associated with early biochemical recurrence, increased metastatic potential, and androgen independence. We evaluated the status of PTEN loss in a cohort of prostate cancer patients from Jordan. We investigated 71 patients with prostate cancer and 52 control subjects with benign prostatic hyperplasia (BPH). PTEN status was assessed by immunohistochemistry. PTEN mutations on exons 1, 2, 5, and 8 were also evaluated by polymerase chain reaction single-stranded conformation polymorphism (PCR-SSCP). We found PTEN loss in 42 of 71 (59.2%) evaluated prostate cancer cases by immunohistochemistry. In contrast, 51 of 52 BPH (98.1%) cases had an intact PTEN. In a subset of 24 prostate cancer cases evaluated by PCR-SSCP, we found PTEN mutations in 15 (62.5%) cases, whereas 22 (91.7%) of BPH controls lacked PTEN mutations. Exon 5 was the most frequently mutated exon (37.5%). Although the loss of PTEN was not significantly correlated with the Gleason Score (GS) or the World Health Organization (WHO)-International Society of Urological Pathology (ISUP) Grade Group (GG), we found higher frequency of PTEN loss (64%) in patients with GS≥4+3/GG≥3, compared with patients with GS≤3+4/GG≤2 (47.6%). In this first study to address the question of PTEN loss in a predominantly Arab population, we documented the frequency of PTEN loss in prostate cancer patients from Jordan, which was found to be higher than in comparable cohorts from East Asia, and was at the higher end of the range of reported frequency of PTEN loss in respective cohorts from North America and Western Europe. Although there was more frequent PTEN loss in cancers with higher GS/GG, this was not statistically significant.

Prostate intraepithelial neoplasia is described as a precursor lesion to prostatic adenocarcinoma. High-grade prostate intraepithelial neoplasia (HGPIN) is classified as both grade 2 and 3 prostate intraepithelial neoplasia due to inconsistency between pathologists' findings. In our study, we assessed the interobserver variability in the diagnosis of HGPIN among genitourinary and nongenitourinary pathologists. All cases with prostate adenocarcinoma diagnosis on needle core biopsy, radical prostatectomy, and transurethral resection of prostate (TURP) between the years 2005 and 2014 were included. In total, 191 prostate cancer cases were included: 109 needle core biopsies, 45 radical prostatectomies, and 37 TURP. All were independently reviewed by 2 urologic pathologists for the presence of HGPIN. High-grade prostate intraepithelial neoplasia was diagnosed in 65 cases (34%), among which the lesion was recognized by the reporting pathologists in 36 (55%) of the cases and was missed in 29 (45%) of the cases with a κ coefficient of 0.53. There was a moderate interobserver agreement in the diagnosis of HGPIN. Consultation with genitourinary pathologist can improve HGPIN diagnosis., Competing Interests: Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

TMPRSS2/ERG fusion was found to be the most common genetic event in prostate adenocarcinoma. There is a strong correlation between the fusion and ERG-positive immunostaining. Many studies showed racial variation in ERG expression in prostate cancer patients. There is no data however on the rate of ERG-positive cancer in Jordanian or Arab population. We evaluated the frequency and the significance of ERG fusion in Jordanian-Arab population using immunohistochemistry for ERG. The cohort included 193 prostate cancer specimens: 109 needle core biopsies, 45 radical prostatectomies, 37 transurethral resections of prostate, and 2 enucleation specimens. We found ERG reactivity in 64 (33.2%) of evaluated cases. The observed ERG frequency in the Jordanian-Arab population is lower than the one documented in North America, but it is higher than in Asian patient cohorts. The ERG positivity was significantly associated with lower baseline prostate-specific antigen but was unrelated to patient age, Gleason Score, or the novel Gleason Grade Groups. In the 45 prostatectomy cases, ERG did not correlate with the pathologic stage, margin, nodal status, and the biochemical recurrence, and it did not appear to represent an important prognosticator.

Purpose: Our study aims to assess the clinical relevance of fluorine-18 fluorodeoxyglucose (F-FDG) negative osteoblastic metastatic bone lesions noted on PET/computed tomography (CT) in breast cancer patients., Patients and Methods: The medical records of breast cancer patients were reviewed retrospectively from January 2012 until April 2015. We included the patients who had metastatic bone disease evaluated by F-FDG-PET/CT. Group 1 included patients with newly diagnosed metastatic bone disease at the time of imaging and group 2 included patients with a history of treated metastatic bone disease at the time of imaging. Functional and structural bone abnormality was monitored on F-FDG-PET/CT scans., Results: Fifty-three patients, median age 47.1 years (range 27-80 years), were included. Group 1 included 35 patients. Of those, 88% had predominantly F-FDG-avid osteolytic and mixed lesions (destructive pattern). Complete response was noted in 65% of the patients after treatment, evidenced by disappearance of bony focal activity with partial or total ossification of most osteolytic lesions converting into mixed and 'secondary' osteoblastic lesions. In addition, more ossified lesions were noted in some patients whose lesions were left untreated for long time (aged lesions). The remaining 12% of group 1 patients had pure 'primary' osteoblastic lesions (nondestructive pattern), which started small and expanded with time and tend to be F-FDG-negative. Group 2 included 18 patients who had predominantly mixed and 'secondary' osteoblastic lesions., Conclusion: We described two types of osteoblastic metastatic bone lesions in breast cancer patients: 'primary' and 'secondary'. 'Secondary' lesions (88%) are totally ossified (healed) osteolytic lesions and are almost always F-FDG-negative on PET/CT. These lesions are of no clinical importance. Healing is potentially seen after treatment or if the lesions are left untreated for a long time (aged lesions). 'Primary' lesions (12%) are seen without previous bone destruction and tend to be F-FDG-negative, although they contain tumor cells. Hence, sequential CT is more helpful than sequential FDG-PET in following 'primary' lesions.

Cysteine- rich secretory protein 3 (CRISP3) prognostic significance in prostate cancer (PCA) has generated mixed result. Herein, we investigated and independently validated CRISP3 expression in relation to ERG and PTEN genomic aberrations and clinical outcome. CRISP3 protein expression was examined by immunohistochemistry using a cohort of patients with localized PCA (n = 215) and castration resistant PCA (CRPC) (n = 46). The Memorial Sloan Kettering (MSKCC) and Swedish cohorts were used for prognostic validation. Results showed, CRISP3 protein intensity to be significantly associated with neoplastic epithelium, being highest in CRPC vs. benign prostate tissue (p < 0.0001), but was not related to Gleason score (GS). CRISP3 mRNA was significantly associated with higher GS (p = 0.022 in MSKCC, p = 1.1e-4 in Swedish). Significant association between CRISP3 expression and clinical outcome was documented at the mRNA but not the protein expression levels. CRISP3 mRNA expression was related to biochemical recurrence in the MSKCC (p = 0.038) and lethal disease in the Swedish cohort (p = 0.0086) and retained its prognostic value in the subgroup of patients with GS 6 & 7. Furthermore, CRISP3 protein and mRNA expression was significantly associated with positive ERG status and with PTEN deletions. Functional biology analysis documented phenylalanine metabolism as the most significant pathway governing high CRISP3 and ERG expression in this subtype of PCA. In conclusion, the combined status of CRISP3, ERG and PTEN define a molecular subtype of PCA with poorest and lethal outcome. Assessing their combined value may be of added value in stratifying patients into different prognostic groups and identify those with poorest clinical outcome.

Dynamin 2 (Dyn2) is essential for intracellular vesicle formation and trafficking, cytokinesis, and receptor endocytosis. In this study, we investigated the implication of Dyn2 as a prognostic marker and therapeutic target for progressive prostate cancer (PCA). We evaluated Dyn2 protein expression by immunohistochemistry in two cohorts: men with localized PCA treated by retropubic radical prostatectomy (n = 226), and men with advanced/castrate-resistant PCA (CRPC) treated by transurethral resection of prostate (TURP) (n = 253). The role of Dyn2 in cell invasiveness was assessed by in vitro and in vivo experiments using androgen-responsive and refractory PCA preclinical models. Dyn2 expression was significantly increased across advanced stages of PCA compared to benign prostate tissue (P < 0.0001). In the CRPC cohort, high Dyn2 was associated with higher Gleason score (P = 0.004) and marginally with cancer-specific mortality (P = 0.052). In preclinical models, Dyn2 gene silencing significantly reduced cell migration and invasion in vitro, as well as tumor size and lymph node metastases in vivo. In isolated PCA cells, Dyn2 was found to regulate focal adhesion turnover, which is critical for cell migration; this mechanism requires full Dyn2 compared to mutants deficient in GTPase activity. In conclusion, Dyn2 overexpression is associated with neoplastic prostate epithelium and is associated with poor prognosis. Inhibition of Dyn2 prevents cell invasiveness in androgen-responsive and -refractory PCA models, supporting the potential benefit of Dyn2 to serve as a therapeutic target for advanced PCA., (© 2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The aim of this study was to investigate the long term outcome of primary urothelial papilloma (UP). We retrieved 41 primary UP, diagnosed between January 2000 and December 2009. Follow-up was obtained by searching pathology and clinical electronic databases. Mean patient age was 57 years (range 30-84 years), with a male-to-female ratio of 1.9:1. Mean follow-up was 81 months (range 3-127 months). In 37 (90.2%) patients, no recurrence and/or progression were documented and no subsequent higher grade neoplasms were diagnosed. Three male patients were diagnosed with UP at 1, 31, and 43 months after the initial resection; the repeat diagnosis of UP at 1 month likely represented an incomplete resection. Thus, only two of 41 patients (4.9%) had a recurrent UP. One of these patients had a subsequent papillary urothelial neoplasm of low malignant potential (PUNLMP), 17 months after the recurrent UP (48 months after the initial UP). Only one additional male had a subsequent PUNLMP, 76 months after the initial UP. Thus, only two of 41 patients (4.9%) had a subsequent PUNLMP, both presenting with haematuria. Primary UP does not progress to UC when diagnosed using strict criteria, when no previous or concurrent neoplasms are documented, and when complete initial resection is performed.

C. difficile is a Gram-positive spore-forming anaerobic bacterium that is the leading cause of nosocomial diarrhea in the developed world. The pathogenesis of C. difficile infections (CDI) is driven by toxin A (TcdA) and toxin B (TcdB), secreted factors that trigger the release of inflammatory mediators and contribute to disruption of the intestinal epithelial barrier. Neutrophils play a key role in the inflammatory response and the induction of pseudomembranous colitis in CDI. TcdA and TcdB alter cytoskeletal signaling and trigger the release of CXCL8/IL-8, a potent neutrophil chemoattractant, from intestinal epithelial cells; however, little is known about the surface receptor(s) that mediate these events. In the current study, we sought to assess whether toxin-induced CXCL8/IL-8 release and barrier dysfunction are driven by the activation of the P2Y6 receptor following the release of UDP, a danger signal, from intoxicated Caco-2 cells. Caco-2 cells express a functional P2Y6 receptor and release measurable amounts of UDP upon exposure to TcdA/B. Toxin-induced CXCL8/IL-8 production and release were attenuated in the presence of a selective P2Y6 inhibitor (MRS2578). This was associated with inhibition of TcdA/B-induced activation of NFκB. Blockade of the P2Y6 receptor also attenuated toxin-induced barrier dysfunction in polarized Caco-2 cells. Lastly, pretreating mice with the P2Y6 receptor antagonists (MSR2578) attenuated TcdA/B-induced inflammation and intestinal permeability in an intrarectal toxin exposure model. Taken together these data outline a novel role for the P2Y6 receptor in the induction of CXCL8/IL-8 production and barrier dysfunction in response to C. difficile toxin exposure and may provide a new therapeutic target for the treatment of CDI.

Background: Melanosis is defined as an abnormal or excessive deposition of melanin within cells and/or tissues. It typically presents as a cutaneous or buccal mucosal lesion, but rare cases of bladder melanosis have also been documented. Melanosis of the urinary bladder is typically considered a benign condition, but it has also been described in association with malignant melanoma and urothelial carcinoma., Cases: We report the cases of 2 patients who presented with melanosis of the urinary bladder. One patient presented with melanosis of the urinary bladder together with urothelial dysplasia. Melanosis was incidentally identified during a cystoscopy for ureteral stones. A second patient presented with hematuria and was found to have a muscle invasive urothelial carcinoma with focal small nested morphology together with melanosis. We also present a literature review of the bladder melanosis and an overview of other bladder melanocytic lesions, which include primary and metastatic melanoma and blue nevus., Conclusion: Initial evaluation for bladder melanosis should include cystoscopy and upper urinary tract imaging. Biopsy is essential to establish the diagnosis and rule out associated malignancy.

Clostridium difficile, a major cause of hospital-acquired diarrhea, triggers disease through the release of two toxins, toxin A (TcdA) and toxin B (TcdB). These toxins disrupt the cytoskeleton of the intestinal epithelial cell, increasing intestinal permeability and triggering the release of inflammatory mediators resulting in intestinal injury and inflammation. The most prevalent animal model to study TcdA/TcdB-induced intestinal injury involves injecting toxin into the lumen of a surgically generated "ileal loop." This model is time-consuming and exhibits variability depending on the expertise of the surgeon. Furthermore, the target organ of C. difficile infection (CDI) in humans is the colon, not the ileum. In the current study, we describe a new model of CDI that involves intrarectal instillation of TcdA/TcdB into the mouse colon. The administration of TcdA/TcdB triggered colonic inflammation and neutrophil and macrophage infiltration as well as increased epithelial barrier permeability and intestinal epithelial cell death. The damage and inflammation triggered by TcdA/TcdB isolates from the VPI and 630 strains correlated with the concentration of TcdA and TcdB produced. TcdA/TcdB exposure increased the expression of a number of inflammatory mediators associated with human CDI, including interleukin-6 (IL-6), gamma interferon (IFN-γ), and IL-1β. Finally, we were able to demonstrate that TcdA was much more potent at inducing colonic injury than was TcdB but TcdB could act synergistically with TcdA to exacerbate injury. Taken together, our data indicate that the intrarectal murine model provides a robust and efficient system to examine the effects of TcdA/TcdB on the induction of inflammation and colonic tissue damage in the context of human CDI.

Background & Aims: International consensus guidelines, aimed at predicting malignancy, are available for surgical resection of mucinous cysts but not for other cystic lesions of the pancreas. We sought to determine whether the consensus guidelines can be applied to all cystic lesions of the pancreas., Methods: We identified all patients who underwent surgical resection of pancreatic cysts from 2001-2007. Pathology analyses of surgical specimens served as the reference standard. Surgical resection criteria proposed by the Sendai Guidelines and 5 modifications of these criteria were tested to determine their accuracy for diagnosis of malignant cysts., Results: Patients with cystic lesions of the pancreas (n = 154; mean age, 59.8 years; 64% women) underwent resection and met prespecified study criteria. Twenty-one patients had a malignancy. The classification cyst size > or = 3 cm had an accuracy of 56%, negative predictive value of 84%, and identified only 57% of the malignant cysts. The classification cyst size > or = 3 cm or cyst with main pancreatic duct > or = 10 mm had an accuracy of 55%, negative predictive value of 86%, and identified 66% of malignant cysts. The modified criterion of cyst size > or = 3 cm or cyst with main pancreatic duct > 3 mm had an accuracy of 48%, negative predictive value of 94%, and identified 91% (19/21) of the malignancies. Cyst size (odds ratio, 1.05) and pancreatic duct dilation > 3 mm (odds ratio, 10.5) were strong and independent predictors of malignancy., Conclusions: When applied to all cystic lesions of the pancreas, the international consensus criteria cause some malignant cysts to be missed. Modified criteria could identify most malignant cysts, although overall accuracy remains low.