Multiple independent studies have shown that tumor-infiltrating lymphocytes (TIL) are prognostic in breast cancer with potential relevance for response to immune-checkpoint inhibitor therapy. ...Although many groups are currently evaluating TIL, there is no standardized system for diagnostic applications. This study reports the results of two ring studies investigating TIL conducted by the International Working Group on Immuno-oncology Biomarkers. The study aim was to determine the intraclass correlation coefficient (ICC) for evaluation of TIL by different pathologists. A total of 120 slides were evaluated by a large group of pathologists with a web-based system in ring study 1 and a more advanced software-system in ring study 2 that included an integrated feedback with standardized reference images. The predefined aim for successful ring studies 1 and 2 was an ICC above 0.7 (lower limit of 95% confidence interval (CI)). In ring study 1 the prespecified endpoint was not reached (ICC: 0.70; 95% CI: 0.62–0.78). On the basis of an analysis of sources of variation, we developed a more advanced digital image evaluation system for ring study 2, which improved the ICC to 0.89 (95% CI: 0.85–0.92). The Fleiss' kappa value for <60 vs ≥60% TIL improved from 0.45 (ring study 1) to 0.63 in RS2 and the mean concordance improved from 88 to 92%. This large international standardization project shows that reproducible evaluation of TIL is feasible in breast cancer. This opens the way for standardized reporting of tumor immunological parameters in clinical studies and diagnostic practice. The software-guided image evaluation approach used in ring study 2 may be of value as a tool for evaluation of TIL in clinical trials and diagnostic practice. The experience gained from this approach might be applicable to the standardization of other diagnostic parameters in histopathology.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•The mobile suitcase lab is a portable system for molecular diagnosis in the field, especially in poor resource settings.•The recombinase aided amplification assay based on the RdRP gene is robust ...and accurate for SARS-CoV-2 detection.•Diagnostic accuracy across different sites depends not only on the assay itself, but also on other external factors such as implementation of standardized operation procedure, enhanced quality control measures and importantly, in-person continuous staff training.
The COVID-19 pandemic led to severe health systems collapse, as well as logistics and supply delivery shortages across sectors. Delivery of PCR related healthcare supplies continue to be hindered. There is the need for a rapid and accessible SARS-CoV-2 molecular detection method in low resource settings.
To validate a novel isothermal amplification method for rapid detection of SARS-CoV-2 across seven sub-Sharan African countries.
In this multi-country phase 2 diagnostic study, 3,231 clinical samples in seven African sites were tested with two reverse transcription Recombinase-Aided Amplification (RT-RAA) assays (based on SARS-CoV-2 Nucleocapsid (N) gene and RNA-dependent RNA polymerase (RdRP) gene). The test was performed in a mobile suitcase laboratory within 15 min. All results were compared to a real-time RT-PCR assay. Extraction kits based on silica gel or magnetic beads were applied.
Four sites demonstrated good to excellent agreement, while three sites showed fair to moderate results. The RdRP gene assay exhibited an overall PPV of 0.92 and a NPV of 0.88. The N gene assay exhibited an overall PPV of 0.93 and a NPV 0.88. The sensitivity of both RT-RAA assays varied depending on the sample Ct values. When comparing sensitivity between sites, values differed considerably. For high viral load samples, the RT-RAA assay sensitivity ranges were between 60.5 and 100% (RdRP assay) and 25 and 98.6 (N assay).
Overall, the RdRP based RT-RAA test showed the best assay accuracy. This study highlights the challenges of implementing rapid molecular assays in field conditions. Factors that are important for successful deployment across countries include the implementation of standardized operation procedures, in-person continuous training for staff, and enhanced quality control measures.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In a cross-sectional survey in Omdurman, Sudan, during March-April 2021, we estimated that 54.6% of the population had detectable severe acute respiratory syndrome coronavirus 2 antibodies. Overall ...population death rates among those >50 years of age increased 74% over the first coronavirus disease pandemic year.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Breast cancer is the most common malignancy accounting for 25% of all cancers in females. In Africa, breast cancer prevalence and mortality are steadily increasing. Knowledge of hormone receptors and ...human epidermal growth factor receptor-2 (HER-2) expressions are vital for breast cancer management plans and decision making. There is wide regional variation in the proportion of these biomarkers, especially in African countries. Hormone receptors positivity in indigenous African and African American women is considered to be low and triple negative breast cancer is a dominant phenotype. There is paucity of data regarding hormone receptors (ER and PR) and HER2 expressions in North-eastern Africa (Eritrea and Sudan). The purpose of this study was to evaluate the expression of ER, PR and HER2 in Eritrean and Sudanese case series and correlate these biomarkers with the clinicopathological profile.
Clinicopathologic data of patients were collected from clinical records. Immunohistochemistry biomarkers (ER, PR, and HER2) were assessed in consecutive female patients who had been diagnosed with invasive breast cancer from 2011 to 2015 in Gezira University Pathology Laboratory, the Sudan and National Health laboratory, Asmara, Eritrea.
There were 678 cases involved in this study. The mean age was 48.8 years with ±0.53 standard error of the mean. Two-thirds of the case were ≤50 years. Invasive ductal carcinoma, no special type was the most dominant histologic type (86%) in both study groups. The majority of cases (70%) had tumour stage pT2 and pT3 and about 50% had lymph node involvement. Less than 5% of the cases had well-differentiated tumours. The ER, PR and HER2 positive rates were 45%, 32%, and 29%, respectively. The proportion of luminal-A like, luminal-B like, HER2 enriched and TNBC were 37%, 13%, 16% and 34%, respectively. Fisher extract analysis showed age (p = .015), tumour size (p = .041), and histologic grade (p = .000) were significantly associated with intrinsic subtypes. Furthermore, Logistic regression analysis stratified by origin, age, tumour size, lymph-node metastasis and grade indicated that younger women age (≤50 years) and grade III tumours were more likely to be diagnosed with ER negative breast cancer.
Most of Sudanese and Eritrean women were diagnosed at younger age and with unfavourable prognostic clinicopathologic prognostic markers. TNBC is more frequent in this cohort study; patients with grade III tumours and young age are more likely to be hormone receptors negative. Therefore, routine determination of hormone receptors is warranted for appropriate targeted therapy.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Epstein-Barr virus (EBV) is a well-characterized oncovirus, associated with several malignancies. The complex and heterogeneous nature of colorectal cancer (CRC) has led to many epidemiological ...causal associations with CRC. However, a direct causal link between microbial infections and CRC has not been established yet. Our review indicates that the current evidence for the presence and role in EBV in CRC is insufficient and contradictory. The design of the analyzed studies, sample size as well as methodology used for EBV detection varied markedly and consequently may not lead to meaningful conclusions. The presence of EBV in other colorectal tumors (lymphomas, smooth muscle tumors) is in line with their status at other anatomic locations and may have therapeutic implications with EBV-specific vaccines. On the other hand, studies exploring EBV in colorectal adenoma-carcinoma sequence and its molecular genetic characteristics are largely missing and may significantly contribute to a better understanding of the role of EBV in CRC.
Abstract
Background
Advances in our understanding of the tumor microenvironment have radically changed the cancer field, highlighting the emerging need for biomarkers of an active, favorable tumor ...immune phenotype to aid treatment stratification and clinical prognostication. Numerous immune-related gene signatures have been defined; however, their prognostic value is often limited to one or few cancer types. Moreover, the area of non-coding RNA as biomarkers remains largely unexplored although their number and biological roles are rapidly expanding.
Methods
We developed a multi-step process to identify immune-related long non-coding RNA signatures with prognostic connotation in multiple TCGA solid cancer datasets.
Results
Using the breast cancer dataset as a discovery cohort we found 2988 differentially expressed lncRNAs between immune favorable and unfavorable tumors, as defined by the immunologic constant of rejection (ICR) gene signature. Mapping of the lncRNAs to a coding-non-coding network identified 127 proxy protein-coding genes that are enriched in immune-related diseases and functions. Next, we defined two distinct 20-lncRNA prognostic signatures that show a stronger effect on overall survival than the ICR signature in multiple solid cancers. Furthermore, we found a 3 lncRNA signature that demonstrated prognostic significance across 5 solid cancer types with a stronger association with clinical outcome than ICR. Moreover, this 3 lncRNA signature showed additional prognostic significance in uterine corpus endometrial carcinoma and cervical squamous cell carcinoma and endocervical adenocarcinoma as compared to ICR.
Conclusion
We identified an immune-related 3-lncRNA signature with prognostic connotation in multiple solid cancer types which performed equally well and in some cases better than the 20-gene ICR signature, indicating that it could be used as a minimal informative signature for clinical implementation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Breast cancer largely dominates the global cancer burden statistics; however, there are striking disparities in mortality rates across countries. While socioeconomic factors contribute to ...population-based differences in mortality, they do not fully explain disparity among women of African ancestry (AA) and Arab ancestry (ArA) compared to women of European ancestry (EA). In this study, we sought to identify molecular differences that could provide insight into the biology of ancestry-associated disparities in clinical outcomes. We applied a unique approach that combines the use of curated survival data from The Cancer Genome Atlas (TCGA) Pan-Cancer clinical data resource, improved single-nucleotide polymorphism-based inferred ancestry assignment, and a novel breast cancer subtype classification to interrogate the TCGA and a local Arab breast cancer dataset. We observed an enrichment of BasalMyo tumors in AA patients (38 vs 16.5% in EA, p = 1.30E - 10), associated with a significant worse overall (hazard ratio (HR) = 2.39, p = 0.02) and disease-specific survival (HR = 2.57, p = 0.03). Gene set enrichment analysis of BasalMyo AA and EA samples revealed differences in the abundance of T-regulatory and T-helper type 2 cells, and enrichment of cancer-related pathways with prognostic implications (AA: PI3K-Akt-mTOR and ErbB signaling; EA: EGF, estrogen-dependent and DNA repair signaling). Strikingly, AMPK signaling was associated with opposing prognostic connotation (AA: 10-year HR = 2.79, EA: 10-year HR = 0.34). Analysis of ArA patients suggests enrichment of BasalMyo tumors with a trend for differential enrichment of T-regulatory cells and AMPK signaling. Together, our findings suggest that the disparity in the clinical outcome of AA breast cancer patients is likely related to differences in cancer-related and microenvironmental features.
Culture of
remains the gold standard in mycobacteriology laboratories, constrained by the very high risk of contamination; therefore, contamination rate is an important key performance indicator ...(KPI) for laboratory monitoring and evaluation processes.
This study aimed to investigate the factors that contribute to elevated contamination rates in the Sudan National Tuberculosis Reference Laboratory.
A laboratory-based retrospective study was applied; a TB culture register-book was carefully reviewed and data from 2 January 2019 to 31 December 2019 were entered, cleaned, and analyzed using IBM SPSS 20. A multivariate logistic regression model was performed to examine two dependent variables, the massive contamination, and the single tube contamination against predictors of reason for cultivation, type of specimen, experiment team, and the quarter of cultivation.
It has been found that in 2019 contamination rates were frequently higher; the highest rates were recorded in January and November, 28.2 and 25.2%, respectively. August is an exception with an accepted contamination rate of 4.6%. Of 1,149 specimens requested for culture, 945 (82.2%) samples were eligible to be included in multivariate logistic regression analysis. The team conducting the experiment was significantly associated with a high single tube contamination
0.007; adjusted odds ratio AOR 3.570 (1.415-9.005). The correlation between the single tube contamination and the massive contamination is significant;
0.01.
The study concludes that high culture contamination is the greatest risk to the quality of laboratory service and can end in either the loss of specimens or delay in the decisions of initiating patient treatment. In addition, the low quality or incompleteness of data increases the uncertainty and undermines the measurement of key performance indicators.
Background: The role of vitamin D in the development, progression, and prognosis of breast cancer, though widely studied worldwide, has been inconclusive. This study intended to assess the role of ...some factors (including serum vitamin D level, sun-exposed area, dietary factors, and physical activity) as predictors of the development of invasive breast cancer (IBC) among Sudanese women. Methods: A case-control study was conducted on 200 Sudanese women (100 with newly diagnosed IBC and 100 matched healthy females). Serum 25-hydroxyvitamin D was measured through a competitive electrochemiluminescence immunoassay. Matching analysis was adopted by R version 3.4.1 making use of the "MatchIt" package for calculating propensity scores to build a confounder-adjusted, multiple generalized, linear logistic regression model. Results: Participants' age ranged from 28 to 85 years with a mean ±standard deviation (SD) of 48.10 (±12.11) years. The mean (±SD) serum vitamin D level was 12.97 (±8.60) and 13.79 (±6.79) ng/mL in breast cancer and noncancer Sudanese women, respectively P = 0.013; odds ratio (OR) 0.862; 95% confidence interval (CI) 0.766-0.969; β = 0.149). Sun-exposed area (P = 0.038; OR 0.013; 95% CI 0.000-0.782; β = 4.339) is significantly and negatively associated with breast cancer development. While moderate physical activity (P = 0.0008; OR 2625.430; 95% CI 26.647-258673.001; β = 7.873) is significantly and positively associated with IBC risk. Occasional consumption of milk, dairy products, eggs, and fish reduces the risk of developing IBC by 78.1%, 75.0%, 78.4%, and 76.4%, respectively. Conclusion: The higher the plasma vitamin D level by one unit, the lower the risk of breast cancer by 13.84%. Sedentary lifestyle, reduced sun-exposed skin area, and low serum vitamin D levels can be considered as predictors of IBC. Encouraging moderate physical activity and consumption of certain foods may, in part, decrease the precipitating risks of breast cancer. More studies and research are needed to confirm these findings.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background: Vitamin D deficiency is a worldwide concern. The aim of the current study was to determine the vitamin D level and its contributing factors in Sudanese women. Methods: In this ...cross-sectional study, 251 Sudanese women attending Family Health Centers in Khartoum, Sudan were interviewed. Following the exclusion of confounding factors, samples from 190 women were analzsed. Serum 25 hydroxyvitamin D "25(OH) D" was quantified using competitive electrochemiluminescence immunoassay. Results: Participants' age ranged from 18 to 85 years with a mean age (±SD) of 40.2 (±14.06) years. The mean (±SD) vitamin D level was 13.4 (±6.72) ng/ml, ranged 3.00-36.5 ng/ml and the median was 12.7 ng/mL. In total, 157 out of 190 (82.6%) had vitamin D serum levels below 20 ng/ml (deficient); of whom, 52 (27.4%) were in the age group 21-30 years (P value = 0.228). The correlation between vitamin D level and residence outside Khartoum, sun-exposed face and hands, and face and limbs in comparison with being completely covered were found to be statistically significant (p values 0.008, 0.023, and 0.036). Conclusion: This study displayed a high percentage (82.6%.) of vitamin D deficiency among women in Sudan, and this in part may indicate that sunshine alone cannot guarantee vitamin D sufficiency in the tropics. Family physicians in tropical countries should screen those with clinical presentations related to vitamin D deficiency.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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