Introduction Discrimination in education is commonly associated with face-to-face interactions between teachers and students. However, e-learning environments can also foster discrimination. Despite existing research on discrimination in traditional education, limited studies address this issue in virtual education, particularly in nursing education. Objectives This study aimed to explore the factors contributing to perceived discrimination in e-learning among nursing and midwifery students, focusing on the underlying causes and conditions that shape these experiences. Methods A qualitative design was employed at the nursing and midwifery school of Isfahan University of Medical Sciences. Thirteen nursing and midwifery students were selected using purposeful and convenient sampling. Data were collected through semi-structured, in-depth interviews, and analyzed using content analysis. Results Factors contributing to perceived discrimination in e-learning were categorized into four themes: (1) the nature of e-learning (e.g., limited teacher availability, reduced interaction); (2) professor-related factors (e.g., experience, age, technology skills, and inattention to feedback); (3) student-related factors (e.g., gender, financial issues, and varying technology skills); and (4) inadequate resources (e.g., internet connectivity and limited access to study materials). Conclusions This study highlights multiple factors influencing students’ perceptions of discrimination in e-learning. Addressing these issues can improve virtual education quality in nursing programs. Further research is needed to explore these factors in broader educational contexts

Background Genetic germline testing is restricted for African patients. Lack of ancestrally relevant genomic data perpetuated by African diversity has resulted in European-biased curated clinical variant databases and pathogenic prediction guidelines. While numerous variant pathogenicity prediction tools (VPPTs) exist, their performance has yet to be established within the context of African diversity. Methods To address this limitation, we assessed 54 VPPTs for predictive performance (sensitivity, specificity, false positive and negative rates) across 145,291 known pathogenic or benign variants derived from 50 Southern African and 50 European men matched for advanced prostate cancer. Prioritising VPPTs for optimal ancestral performance, we screened 5.3 million variants of unknown significance for predicted functional and oncogenic potential. Results We observe a 2.1- and 4.1-fold increase in the number of known and predicted rare pathogenic or benign variants, respectively, against a 1.6-fold decrease in the number of available interrogated variants in our European over African data. Although sensitivity was significantly lower for our African data overall (0.66 vs 0.71, p = 9.86E-06), MetaSVM, CADD, Eigen-raw, BayesDel-noAF, phyloP100way-vertebrate and MVP outperformed irrespective of ancestry. Conversely, MutationTaster, DANN, LRT and GERP-RS were African-specific top performers, while MutationAssessor, PROVEAN, LIST-S2 and REVEL are European-specific. Using these pathogenic prediction workflows, we narrow the ancestral gap for potentially deleterious and oncogenic variant prediction in favour of our African data by 1.15- and 1.1-fold, respectively. Conclusion Although VPPT sensitivity favours European data, our findings provide guidelines for VPPT selection to maximise rare pathogenic variant prediction for African disease studies.

Background:Studies of germline variants in prostate cancer (PCa) have largely focused on their connections to cancer predisposition. However, an understanding of how heritable factors contribute to cancer progression and metastasis remain limited. Objective:To identify low frequency to rare germline nonsynonymous variants associated with increased risk for metastatic PCa (mPCa), while providing functional validation. Design:We assembled an extreme phenotype cohort (EPC) of 52 patients diagnosed with predominantly high-grade (Gleason Score (GS) ≥ 8) PCa and > 7 years of follow-up for which localized treatment naïve tumor tissues were available. In half of the cases, the tumor had metastasized to bone, providing an even distribution of bone mPCa and non mPCa cases. Tumor and matched distant benign DNA samples were exome sequenced and analyzed for germline variants with population-wide minor allelic frequencies ≤ 2%. Findings were validated using two independent PCa germline cohorts, including a closely matched Australian study biased to aggressive disease (n = 53) and Pan Prostate Cancer Group (PPCG, n = 976). Two mPCa-promoting candidate variants in KDM6B and BRCA2 were engineered into cell lines and functionalized. Results:Germline nonsynonymous rare variants (gnsRVs) identified in 25 DNA Damage Repair (DDR) genes were significantly enriched in the mPCa patients (p=4.57e-06). Conversely, the prevalence of synonymous variants at minor allele frequencies of ≤ 2% were similar between the mPCa and non mPCa patients. The predictive power of variants in 53 non-DDR genes was validated in the Australian cohort (p=0.028) and correlated with high-risk PCa in PPCG (p=0.03). KDM6B K973Q showed functional significance despite being annotated as benign in ClinVar, while BRCA2 I1962T showed sensitivity to Olaparib. In total, six EPC variants related to DNA repair or epigenetics were found to alter enzymatic activity. Conclusions:EPCs coupled with low frequency/rare variant analyses may advance understanding of interactions between the germline and tumor in PCa. We identified a series of germline variants that were enriched among mPCa patients. Moreover, we showed that one of these variants confers a metastatic phenotype. Our findings suggest that germline testing at diagnosis may improve treatment stratification in PCa. Patient summary:The presence of specific genetic variants among men with PCa may elevate the risk of mPCa once PCa develops. Knowledge of the variant burden at time of diagnosis may enable accurate stratification of some patients for aggressive therapeutic interventions.

Prostate cancer (PCa) is highly heritable, with men of African ancestry at greatest risk and associated lethality. Lack of representation in genomic data means germline testing guidelines exclude for Africans. Established that structural variations (SVs) are major contributors to human disease and prostate tumourigenesis, their role is under-appreciated in familial and therapeutic testing. Utilising clinico-methodologically matched deep-sequenced whole-genome data for 113 African versus 57 European PCa patients, we interrogate 42,966 high-quality germline SVs using a best-fit pathogenicity prediction workflow. We identify 15 potentially pathogenic SVs representing 12.4% African and 7.0% European patients, of which 72% and 86% met germline testing standard-of-care recommendations, respectively. Notable African-specific loss-of-function gene candidates include DNA damage repair MLH1 and BARD1 and tumour suppressors FOXP1, WASF1 and RB1. Representing only a fraction of the vast African diaspora, this study raises considerations with respect to the contribution of kilo-to-mega-base rare variants to PCa pathogenicity and African-associated disparity.

Prostate cancer (PCa) germline testing, while gaining momentum, is ancestry restrictive and African exclusive. Through whole genome sequencing for 217 African ancestral cases (186 southern African, 31 Pan representative), we identify 172 potentially pathogenic variants in 78 DNA damage repair or PCa related genes. Prevalence for reported (13/217, 5.99%) and cumulative predicted (24/217, 11.06%) variants of significance (11 genes) falls below that reported for non-Africans. Conversely, BRCA1, HOXB13, CDK12, MLH1, MSH2, and BRIP1 remain unimpacted. Through pathogenic ranking based on variant frequency and functionality, clinical presentation and tumour-matched biallelic inactivation, top-ranked candidates include PREX2, POLE, FAT1, BRCA2, POLQ, LRP1B and ATM. Besides notable impact of DNA polymerases, including POLG, Fanconi anaemia genes include FANCD2, FANCA, FANCG, ERCC4, FANCE and FANCI, while DNA mismatch repair genes MSH3 and PMS1 outranked known namesakes MSH6 and PMS2. This study provides insights into the spectrum of African-relevant potentially pathogenic PCa variants, highlighting much-needed gene candidates for ancestry-inclusive germline testing.

African ancestry is a significant risk factor for prostate cancer and advanced disease. Yet, genetic studies have largely been conducted outside the context of Sub-Saharan Africa, identifying 278 common risk variants contributing to a multiethnic polygenic risk score, with rare variants focused on a panel of roughly 20 pathogenic genes. Based on this knowledge, we are unable to determine polygenic risk or differentiate prostate cancer status interrogating whole genome data for 113 Black South African men. To further assess for potentially functional common and rare variant associations, here we interrogate 247,780 exomic variants for 798 Black South African men using a case versus control or aggressive versus non-aggressive study design. Notable genes of interest include HCP5, RFX6 and H3C1 for risk, and MKI67 and KLF5 for aggressive disease. Our study highlights the need for further inclusion across the African diaspora to establish African-relevant risk models aimed at reducing prostate cancer health disparities.

BackgroundAlthough survival from colorectal cancer (CRC) has improved substantially in recent decades, people with advanced age still have a high likelihood of mortality from this disease. Nonetheless, few studies have investigated how cancer stage, subsite and comorbidities contribute collectively to poor prognosis of older people with CRC. Here, we decided to explore the association of age with mortality measures and how other variables influenced this association.MethodsUsing linkage of several administrative datasets, we investigated the risk of death among CRC cases during 2003–2014. Different models were used to explore the association of age with mortality measures and how other variables influenced this association.ResultsOur results indicated that people diagnosed at a young age and with lower comorbidity had a lower likelihood of all-cause and CRC-specific mortality. Aging had a greater association with mortality in early-stage CRC, and in rectal cancer, compared that seen with advanced-stage CRC and right colon cancer, respectively. Meanwhile, people with different levels of comorbidity were not significantly different in terms of their increased likelihood of mortality with advanced age. We also found that while most comorbidities were associated with all-cause mortality, only dementia [SHR = 1.43 (1.24–1.64)], Peptic ulcer disease [SHR = 1.12 (1.02–1.24)], kidney disease [SHR = 1.11 (1.04–1.20)] and liver disease [SHR = 1.65 (1.38–1.98)] were risk factors for CRC-specific mortality.ConclusionThis study showed that the positive association of advanced age with mortality in CRC depended on stage and subsite of the disease. We also found only a limited number of comorbidities to be associated with CRC-specific mortality. These novel findings implicate the need for more attention on factors that cause poor prognosis in older people.

BACKGROUND:Germline testing for prostate cancer is on the increase, with clinical implications for risk assessment, treatment, and management. Regardless of family history, NCCN recommends germline testing for patients with metastatic, regional, very-high-risk localized, and high-risk localized prostate cancer. Although African ancestry is a significant risk factor for aggressive prostate cancer, due to a lack of available data no testing criteria have been established for ethnic minorities.PATIENTS AND METHODS:Through deep sequencing, we interrogated the 20 most common germline testing panel genes in 113 Black South African males presenting with largely advanced prostate cancer. Bioinformatic tools were then used to identify the pathogenicity of the variants.RESULTS:After we identified 39 predicted deleterious variants (16 genes), further computational annotation classified 17 variants as potentially oncogenic (12 genes; 17.7% of patients). Rare pathogenic variants included CHEK2 Arg95Ter, BRCA2 Trp31Arg, ATM Arg3047Ter (2 patients), and TP53 Arg282Trp. Notable oncogenic variants of unknown pathogenicity included novel BRCA2 Leu3038Ile in a patient with early-onset disease, whereas patients with FANCA Arg504Cys and RAD51C Arg260Gln reported a family history of prostate cancer. Overall, rare pathogenic and early-onset or familial-associated oncogenic variants were identified in 6.9% (5/72) and 9.2% (8/87) of patients presenting with a Gleason score ≥8 or ≥4 + 3 prostate cancer, respectively.CONCLUSIONS:In this first-of-its-kind study of southern African males, we provide support of African inclusion for advanced, early-onset, and familial prostate cancer genetic testing, indicating clinical value for 30% of current gene panels. Recognizing current panel limitations highlights an urgent need to establish testing guidelines for men of African ancestry. We provide a rationale for considering lowering the pathologic diagnostic inclusion criteria and call for further genome-wide interrogation to ensure the best possible African-relevant prostate cancer gene panel.

Prostate cancer (PCa) is a significant health burden in Sub-Saharan Africa, with mortality rates loosely linked to African ancestry. Yet studies aimed at identifying contributing risk factors are lacking within the continent and as such exclude for significant ancestral diversity. Here, we investigate a series of epidemiological demographic and lifestyle risk factors for 1387 men recruited as part of the multi-ethnic Southern African Prostate Cancer Study (SAPCS). We found poverty to be a decisive factor for disease grade and age at diagnosis, with other notably significant PCa associated risk factors including sexually transmitted diseases, erectile dysfunction, gynaecomastia, and vertex or complete pattern balding. Aligned with African American data, Black ethnicity showed significant risk for PCa diagnosis (OR = 1.44, 95% CI 1.05–2.00), and aggressive disease presentation (ISUP ≥ 4: OR = 2.25, 95% CI 1.49–3.40). New to this study, we demonstrate African ancestral population substructure associated PCa disparity, observing increased risk for advanced disease for the southern African Tsonga people (ISUP ≥ 4: OR = 3.43, 95% CI 1.62–7.27). Conversely, South African Coloured were less likely to be diagnosed with aggressive disease overall (ISUP ≥ 3: OR = 0.38, 95% 0.17–0.85). Understanding the basis for PCa health disparities calls for African inclusion, however, lack of available data has limited the power to begin discussions. Here, focusing on arguably the largest study of its kind for the African continent, we draw attention to the contribution of within African ancestral diversity as a contributing factor to PCa health disparities within the genetically diverse region of southern Africa.

Background: Advanced age is associated with decreased likelihood of colorectal cancer treatment. Here, we investigated the extent to which comorbidities are accountable for this lesser treatment. Methods: Using population-based datasets, the pattern of care among CRC cases in South Australia during 2004-2013 was investigated. Models were used to investigate associations of age with each treatment type, and differences in these associations were explored by comorbidity and cancer site. Results: The presence of comorbidity was associated with a significantly weaker relationship of age with surgery and chemotherapy. The association of age with surgery also varied for colon and rectal primary cancer sites. Individual comorbidity types varied in their associations with each treatment category. For example, dementia was associated with less chemotherapy provision, however, it was not significantly related to the likelihood of surgery. Conclusion: This study indicates that the association of age with surgical treatment differed significantly by the CRC subsite. Comorbidity moderated the negative association of age with chemotherapy, and less so, with extent of surgery. Results were novel in indicating associations of multiple individual comorbidity types with CRC treatment modalities. The data suggest that different individual comorbidity types may have different effects on treatment and should be studied separately.

BACKGROUND While age and stage at diagnosis are known to affect treatment choices and survival from colorectal cancer (CRC), few studies have investigated the extent to which these effects are influenced by comorbidity. In this study, we describe the occurrence of comorbidity in CRC cases in South Australia and associations of comorbidity with age, stage and the age-stage relationship. Furthermore, we report on the association of individual comorbidities with age and stage at diagnosis. METHODS The South Australian Cancer Registry (SACR) provided CRC data (C18-C20, ICD-10) for 2004-2013 diagnoses. CRC data were linked with comorbidity data drawn from hospital records and health insurance claims. Logistic regression was used to model associations of comorbidity with age and stage. RESULTS For the 8462 CRC cases in this study, diabetes, peptic ulcer disease, and previous cancers were the most commonly recorded co-existing conditions. Most comorbidities were associated with older age, although some presented more frequently in younger people. Patients at both ends of the age spectrum (<50 and 80 + years) had an increased likelihood of CRC diagnosis at an advanced stage compared with other ages (50-79 years old). Adjusting for comorbidities moderated the association of older age with advanced stage. Conditions associated with advanced stage included dementia (OR = 1.25 (1.01-1.55)), severe liver disease (OR = 1.68 (1.04-2.70)), and a previous cancer (OR = 1.18 (1.08-1.28)). CONCLUSION Comorbidities are prevalent with CRC, especially in older people. These comorbidities differ in their associations with age at diagnosis and stage. Dementia and chronic heart failure were associated with older age whereas inflammatory bowel disease and alcohol access were associated with younger onset of the disease. Severe liver disease and dementia were associated with more advanced stage and rheumatic disease with less advanced stage. Comorbidities also interact with age at diagnosis and appear to vary the likelihood of advanced-stage disease. CRC patient have different association of age with stage depending on their comorbidity status.

Background Although the need for justice and the elimination of injustice (or discrimination) is now a universally accepted principle, discrimination is still an unpleasant experience for many nursing students. This study aimed to explain the experiences of nursing students of educational discrimination and find out the main factors that cause this feeling. Methods This is a qualitative study conducted in the nursing faculty of Shahr-e-Kord and the Iran university of medical science (IUMS) in Iran. Twelve nursing students were selected by purposeful sampling method and data were collected through face-to-face and in-depth interviews with semi-structured questions. All interviews were analyzed according to the content analysis method. Results Three main themes and ten subcategories appeared. Extracted themes include: "inappropriate behavior of nursing professors (or instructors) " with 3 subcategories (1- discriminatory behavior by nursing professors (or instructors), 2- lack of sufficient self-confidence in nursing professors and transferring it to the student, and 3- the educator role in motivating or eliminating motivation); "Strict rules" with 3 subcategories (1- inequality in implementation of rights and rules among students of different disciplines, 2- differences in compliance with laws and regulations, and 3- nurses are being strictly monitored), and " Lack of nursing professional independence " with 4 subcategories (1- lack of authority, 2- lack of supportive organizations for nurses, 3- lack of proper social status of nursing in society, and 4- the high authority and power of physicians over other disciplines). Conclusions In our study, it was shown that nursing students feel the most discrimination in front of medical students. Feelings of discrimination reduce self-confidence in nursing students. Therefore, nursing educators and professors must think of a solution, or at least they should not cause this feeling in them through inappropriate behavior and discriminatory speech and words.

Abstract Background Virtual and e-learning have taken on a more prominent role since the inception of the coronavirus. One of the disadvantages that are less addressed is the feeling of discrimination in this type of education. So, this study aims to explain nursing students' experiences of educational discrimination in e-learning education. Methods This is a qualitative study conducted in the Isfahan nursing and midwifery faculty in Iran in 2021. Thirteen nursing and midwifery students were selected by purposeful sampling method and were interviewed and data were collected through face-to-face and in-depth interviews with semi-structured questions. All interviews were analyzed according to the content analysis method. Results The factors that caused the feeling of discrimination in the virtual education were into four major categories: 1 - The nature of virtual education (With two subclasses: 1 — less teacher availability and 2 — reduction interaction between the professor and student); 2 - Factors related to the professor (With five subcategories: 1 - professor's experience, 2 — professor's age, 3 — a type of professor's field of work, 4 — professor's skill in using technology and 5 — insignificance of protest and criticisms); 3 - Factors related to students (With four subcategories: 1 - Student gender, 2 - Student field of study, 3 - Student economic problems and 4 - Differences in students' ability to use technology) and 4- Inadequate resources (divided into two sub-categories: 1- Inadequate internet and 2- Lack of access to study and library resources) Conclusions Nursing educators and professors must be aware of the factors that cause this feeling before starting this type of training, investigate all suitable platforms such as high-speed internet, train educators, professors, and students in using educational applications, etc.

Introduction Australians have a high incidence of Colorectal cancer (CRC) and it is the second leading cause of cancer death. CRC patients experience more comorbid conditions such as diabetes and heart diseases than expected from population norms. It is anticipated that older patients with CRC will have even more comorbidities. Approach Data from South Australia Cancer Registry were linked with hospital inpatient separations (public and private) and Pharmaceutical Benefit Scheme data to acquire a detailed dataset of CRC patients in South Australia. We have investigated the prevalence of different comorbidities by age and subsite (colon vs rectal) in the 12 months period prior to CRC diagnosis using the chronic comorbid conditions used by Charlson and RX-risk indices. Results Of 11,656 CRCs diagnosed in 2003-2013, a significant higher prevalence of comorbidity presented in colon than rectal cancer patients using either indices. The most prevalent comorbidities for colon and rectal cancers respectively were: hypertension (25.9%, 22.0%), diabetes (17.3%, 15.6%) and gastric disease (11.4%, 12.4%). Common medications for colon and rectal cancers respectively were: hyperlipidaemia (38.4%, 33.7%), hypertension (38.0%, 31.7%) and gastroesophageal reflux diseases (36.2%, 26.8%). In younger patients (<50 years) with colon and rectal cancer anaemia (9.1%) and diabetes (7.4%) were the most prevalent comorbidities and gastroesophageal reflux medications (17.1%) and opioids (14.5%) were used most frequently whereas, in older patients (>79 years) hypertension (36.7%, 32.7%) was the most prevalent comorbid condition and hypertensive drugs (52.23%, 51,72%)were the most frequently used medication respectively. Conclusion Although often regarded as a single disease (CRC), colon and rectal cancers have different predisposing factors and clinical features. As expected, older patients have a higher prevalence of comorbid chronic diseases. We observe, however, that colon and rectal cancer have different comorbidity patterns by age.

We are delighted to share with you our sixth Journal Club and highlight some of the most interesting papers published recently [...].

Background: Asthma and allergic diseases are raised as a major health problem. The prevalence of these diseases are increasing in Iran and all over the world. Based on this, the present study assessed to prevalence of these diseases in Assalouyeh region, Bushehr Province. Material and Methods: This study was performed on 190 school children aged 6-7 years and 223 girl student aged 13-14 years in Assalouyeh city in 2014 based on ISAAC standard questionnaires Phase I and III which examined prevalence and risk factors for these diseases. Results: The prevalence of atopic eczema, allergic rhinitis and asthma among 6-7 year-old students were 11.6%, 13.7% and 5.8%, respectively. While, the prevalence of these diseases among 13-14 year-old students were 14.3%, 21.5% and 15.2%, respectively. Also, there were a significant association between risk factors such as exposure to tobacco smoke, pet keeping, consumption of fast and sea foods with prevalence of these diseases (P<0.05). Conclusion: Asthma and allergic diseases were high among school children in Assalouyeh and it seems that this increasing prevalenc can be associated with risk factors such as exposure to tobacco smoke, pet keeping, consumption of fast and sea foods.

BACKGROUND:T regulatory cells (Tregs) are known to negatively control immune response. The frequency of these cells was inversely correlated with clinical outcomes of breast cancer. CD19+CD24hiCD38hi cells also play a critical role in inflammation and autoimmune disease. However, their function in tumor immune response is less studied. In this study we aimed to determine the role of CD19+CD24hiCD38hi cells and some other clinicopathological variables in increasing the proportion of Tregs in breast cancer patients.METHODS:We selected 47 patients with invasive ductal breast carcinoma and 50 healthy controls and obtained their blood samples.RESULTS:The proportion of circulating CD4+CD25+Foxp3+ Tregs and CD19+CD24hiCD38hi cells was significantly increased in breast cancer patients. We also found that increased proportion of Tregs in breast cancer is correlated with HER2 amplification, advanced clinical stages, serum TGF-β1 and increased CD19+CD24hiCD38hi cells in the peripheral blood.CONCLUSION:Altogether, our data suggest that as much as Tregs, CD19+CD24hiCD38hi B cells could also have a part in the suppression of immune response in breast cancer.

Background: Patients with β-thalassemia major (TM) develop iron overload through increased iron absorption and transfusional therapy and it’s the most important complication of TM. Thalassemia is common in coastal regions and lands with low altitudes. The aim of this study is to determine the effect of high and low altitude on serum ferritin and treatment requirement in two groups of β-thalassemia major (TM) patients. Subjects and Methods: Patients were divided into two groups, the first group (No: 50) living at sea level (in the port of Bushehr, Iran) and the second group (No: 40) living at the altitude of 2061 m (in the city of Shahrekord, Iran). All patient’s clinical history, blood transfusion and laboratory tests including complete blood count and hemoglobin electrophoresis were reviewed. Results: There were no significant difference in ferritin levels, transfusion period and diabetes incidence of the two cities patients (P> 0.05). Patient’s cardiac function and liver condition were significantly better in patients of Bushehr (P<0.05). Patients under 20 years in Bushehr were less splenectomized in comparison with Shahrekord (P<0.05). Conclusion: Our result showed that some of clinical manifestations of patients in low altitude such as cardiac and liver condition were better. But it did not affect ferritin level probably due to transfusion and chelating therapy. Totally patients of Bushehr had better conditions and had longer survivals.