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118 result(s) for "Helou, Khalil"
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Validity and reliability of an adapted arabic version of the long international physical activity questionnaire
Background The International Physical Actvity Questionnaire (IPAQ) is a validated tool for physical activity assessment used in many countries however no Arabic version of the long-form of this questionnaire exists to this date. Hence, the aim of this study was to cross-culturally adapt and validate an Arabic version of the long International Physical Activity Questionnaire (AIPAQ) equivalent to the French version (F-IPAQ) in a Lebanese population. Methods The guidelines for cross-cultural adaptation provided by the World Health Organization and the International Physical Activity Questionnaire committee were followed. One hundred fifty-nine students and staff members from Saint Joseph University of Beirut were randomly recruited to participate in the study. Items of the A-IPAQ were compared to those from the F-IPAQ for concurrent validity using Spearman’s correlation coefficient. Content validity of the questionnaire was assessed using factor analysis for the A-IPAQ’s items. The physical activity indicators derived from the A-IPAQ were compared with the body mass index (BMI) of the participants for construct validity. The instrument was also evaluated for internal consistency reliability using Cronbach’s alpha and Intraclass Correlation Coefficient (ICC). Finally, thirty-one participants were asked to complete the A-IPAQ on two occasions three weeks apart to examine its test–retest reliability. Bland-Altman analyses were performed to evaluate the extent of agreement between the two versions of the questionnaire and its repeated administrations. Results A high correlation was observed between answers of the F-IPAQ and those of the A-IPAQ, with Spearman’s correlation coefficients ranging from 0.91 to 1.00 ( p  < 0.05). Bland-Altman analysis showed a high level of agreement between the two versions with all values scattered around the mean for total physical activity (mean difference = 5.3 min/week, 95% limits of agreement = −145.2 to 155.8). Negative correlations were observed between MET values and BMI, independent of age, gender or university campus. The A-IPAQ showed a high internal consistency reliability with Cronbach’s alpha ranging from 0.769–1.00 ( p  < 0.001) and intraclass correlation coefficient (ICC) ranging from 0.625–0.999 ( p  < 0.001), except for a moderate agreement with the moderate garden/yard activity (alpha = 0.682; ICC = 0.518; p  < 0.001). The A-IPAQ had moderate-to-good test-retest reliability for most of its items (ICC ranging from 0.66–0.96; p  < 0.001) and the Bland-Altman analysis showed a satisfactory agreement between the two administrations of the A-IPAQ for total physical activity (mean difference = 99.8 min/week, 95% limits of agreement = −1105.3; 1304.9) and total vigorous and moderate physical activity (mean difference = −29.7 min/week, 95% limits of agreement = −777.6; 718.2). Conclusion The modified Arabic version of the IPAQ showed acceptable validity and reliability for the assessment of physical activity among Lebanese adults. More studies are necessary in the future to assess its validity compared to a gold-standard criterion measure.
Optimization of cell viability assays to improve replicability and reproducibility of cancer drug sensitivity screens
Cancer drug development has been riddled with high attrition rates, in part, due to poor reproducibility of preclinical models for drug discovery. Poor experimental design and lack of scientific transparency may cause experimental biases that in turn affect data quality, robustness and reproducibility. Here, we pinpoint sources of experimental variability in conventional 2D cell-based cancer drug screens to determine the effect of confounders on cell viability for MCF7 and HCC38 breast cancer cell lines treated with platinum agents (cisplatin and carboplatin) and a proteasome inhibitor (bortezomib). Variance component analysis demonstrated that variations in cell viability were primarily associated with the choice of pharmaceutical drug and cell line, and less likely to be due to the type of growth medium or assay incubation time. Furthermore, careful consideration should be given to different methods of storing diluted pharmaceutical drugs and use of DMSO controls due to the potential risk of evaporation and the subsequent effect on dose-response curves. Optimization of experimental parameters not only improved data quality substantially but also resulted in reproducible results for bortezomib- and cisplatin-treated HCC38, MCF7, MCF-10A, and MDA-MB-436 cells. Taken together, these findings indicate that replicability (the same analyst re-performs the same experiment multiple times) and reproducibility (different analysts perform the same experiment using different experimental conditions) for cell-based drug screens can be improved by identifying potential confounders and subsequent optimization of experimental parameters for each cell line.
Pan-cancer analysis identifies BIRC5 as a prognostic biomarker
Background The BIRC5 gene encodes for the Survivin protein, which is a member of the inhibitor of apoptosis family. Survivin is found in humans during fetal development, but generally not in adult cells thereafter. Previous studies have shown that Survivin is abundant in most cancer cells, thereby making it a promising target for anti-cancer drugs and a potential prognostic tool. Methods To assess genetic alterations and mutations in the BIRC5 gene as well as BIRC5 co-expression with other genes, genomic and transcriptomic data were downloaded via cBioPortal for approximately 9000 samples from The Cancer Genome Atlas (TCGA) representing 33 different cancer types and 11 pan-cancer organ systems, and validated using the ICGC Data Portal and COSMIC. TCGA BIRC5 RNA sequencing data from 33 different cancer types and matching normal tissue samples for 16 cancer types were downloaded from Broad GDAC Firehose and validated using breast cancer microarray data from our previous work and data sets from the GENT2 web-based tool. Survival data were analyzed with multivariable Cox proportional hazards regression analysis and validated using KM plotter for breast-, ovarian-, lung- and gastric cancer. Results Although genetic alterations in BIRC5 were not common in cancer, BIRC5 expression was significantly higher in cancer tissue compared to normal tissue in the 16 different cancer types. For 14/33 cancer types, higher BIRC5 expression was linked to worse overall survival (OS, 4/14 after adjusting for both age and tumor grade and 10/14 after adjusting only for age). Interestingly, higher BIRC5 expression was associated with better OS in lung squamous cell carcinoma and ovarian serous cystadenocarcinoma. Higher BIRC5 expression was also linked to shorter progressive-free interval (PFI) for 14/33 cancer types (4/14 after adjusting for both age and tumor grade and 10/14 after adjusting only for age). External validation showed that high BIRC5 expression was significantly associated with worse OS for breast-, lung-, and gastric cancer. Conclusions Our findings suggest that BIRC5 overexpression is associated with the initiation and progression of several cancer types, and thereby a promising prognostic biomarker.
Age and sex effects across the blood proteome after ionizing radiation exposure can bias biomarker screening and risk assessment
Molecular biomarkers of ionizing radiation (IR) exposure are a promising new tool in various disciplines: they can give necessary information for adaptive treatment planning in cancer radiotherapy, enable risk projection for radiation-induced survivorship diseases, or facilitate triage and intervention in radiation hazard events. However, radiation biomarker discovery has not yet resolved the most basic features of personalized medicine: age and sex. To overcome this critical bias in biomarker identification, we quantitated age and sex effects and assessed their relevance in the radiation response across the blood proteome. We used high-throughput mass spectrometry on blood plasma collected 24 h after 0.5 Gy total body irradiation (15 MV nominal photon energy) from male and female C57BL/6 N mice at juvenile (7-weeks-old) or adult (18-weeks-old) age. We also assessed sex and strain effects using juvenile male and female BALB/c nude mice. We showed that age and sex created significant effects in the proteomic response regarding both extent and functional quality of IR-induced responses. Furthermore, we found that age and sex effects appeared non-linear and were often end-point specific. Overall, age contributed more to differences in the proteomic response than sex, most notably in immune responses , oxidative stress , and apoptotic cell death . Interestingly, sex effects were pronounced for DNA damage and repair pathways and associated cellular outcome (pro-survival vs. pro-apoptotic). Only one protein (AHSP) was identified as a potential general biomarker candidate across age and sex, while GMNN, REG3B, and SNCA indicated some response similarity across age. This low yield advocated that unisex or uniage biomarker screening approaches are not feasible. In conclusion, age- and sex-specific screening approaches should be implemented as standard protocol to ensure robustness and diagnostic power of biomarker candidates. Bias-free molecular biomarkers are a necessary progression towards personalized medicine and integral for advanced adaptive cancer radiotherapy and risk assessment.
Development and validation of a quantitative food frequency questionnaire to assess dietary intake among Lebanese adults
Background The food frequency questionnaire (FFQ) is the most frequently used method to assess dietary intake in epidemiological studies evaluating diet-disease association. The objective of this study was to validate a FFQ for use among Lebanese adults by evaluating various facets of validity and reproducibility. Methods The quantitative 164-items FFQ was validated against the average of six 24-h dietary recalls (DRs) in a sample of 238 Lebanese adults. Reproducibility of the FFQ was assessed by administering it twice within 1 month’ time interval. Results Positive statistically significant Pearson correlations were observed in most macro and micronutrients between the FFQ and the six 24-h DRs, ranging from 0.16 to 0.65, with two thirds of the correlation coefficients exceeding 0.3. Energy, gender, and age-adjusted statistically significant Pearson correlation coefficients ranged from 0.14 to 0.64, with two thirds of the coefficients exceeding 0.2. Intakes from the FFQ were mostly higher than those of the 24-h DRs. Mean percent difference between nutrient intakes from both dietary methods decreased remarkably after using energy-adjusted mean intakes. Values were acceptable to good for all macronutrients and several micronutrients. Cross-classification analysis revealed that around 64.3 to 83.9% of participants were classified into the same and adjacent quartile whereas grossly misclassified proportions ranged from 3.7 to 12.2%. Weighted kappa values ranged from 0.02 to 0.36 with most of them exceeding 0.2. In indirect validity analysis, key nutrient mean intakes estimated from the six 24-h DRs were significantly positively associated with tertiles of food groups derived from the FFQ. Bland Altman plots showed that the majority of data points fell within the limits of agreement (LOA) for all nutrients. As for reproducibility analysis, ICC values were all statistically significant ranging from 0.645 to 0.959 and Bland Altman plots confirmed these results. Conclusions Based on various aspects of validity and reproducibility, and an extensive range of statistical tests, the present FFQ developed for a Lebanese community is an acceptable tool for dietary assessment and is useful for evaluating diet-disease associations in future studies.
Age-related long-term response in rat thyroid tissue and plasma after internal low dose exposure to 131I
131 I is used clinically for therapy, and may be released during nuclear accidents. After the Chernobyl accident papillary thyroid carcinoma incidence increased in children, but not adults. The aims of this study were to compare 131 I irradiation-dependent differences in RNA and protein expression in the thyroid and plasma of young and adult rats, and identify potential age-dependent biomarkers for 131 I exposure. Twelve young (5 weeks) and twelve adult Sprague Dawley rats (17 weeks) were i.v. injected with 50 kBq 131 I (absorbed dose to thyroid = 0.1 Gy), and sixteen unexposed age-matched rats were used as controls. The rats were killed 3–9 months after administration. Microarray analysis was performed using RNA from thyroid samples, while LC–MS/MS analysis was performed on proteins extracted from thyroid tissue and plasma. Canonical pathways, biological functions and upstream regulators were analysed for the identified transcripts and proteins. Distinct age-dependent differences in gene and protein expression were observed. Novel biomarkers for thyroid 131 I exposure were identified: (PTH), age-dependent dose response (CA1, FTL1, PVALB (youngsters) and HSPB6 (adults)), thyroid function ( Vegfb (adults)). Further validation using clinical samples are needed to explore the role of the identified biomarkers.
Investigating PCBs and OCPs in Lebanese Yogurt: National Contamination Patterns and Health Risk Assessment
This study investigates the presence of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in 165 yogurt samples collected from farms across 11 Lebanese regions. As the first nationwide assessment of these contaminants in yogurt, it addresses a critical gap in Lebanon’s food safety monitoring. Levels of PCBs, ΣDDTs, ΣHCH, HCB, endosulfan, methoxychlor, and dieldrin were quantified, revealing widespread contamination. A total of 40.6% of samples recorded total PCB concentrations exceeding European maximum residue limits (MRLs), with a national mean of 39.26 ng/g fat. Keserwan, and North and South Lebanon showed the highest PCB contamination, likely linked to thermal power generation activities. For OCPs, mean concentrations of all tested compounds exceeded their respective MRLs across all regions. Levels of ΣDDTs surpassed the MRL in 100% of samples with the highest mean concentration at 376.79 ng/g fat, followed by endosulfan (70.32 ng/g fat) and β-HCH (65.32 ng/g fat). Elevated OCP levels were especially noted in Bekaa, Baalbek-Hermel, and South and North Lebanon, likely reflecting intensive agricultural practices and the ongoing use of contaminants. Estimated daily intakes (EDIs) indicated potential dietary exposure risks, particularly from PCBs, ΣDDTs, and ΣHCH. These findings underscore the urgent need for regulatory oversight and national food safety monitoring to ensure public health protection.
Occurrence and Health Risk Assessment of Per- and Polyfluoroalkyl Substances in Yogurt Across Lebanese Governorates
Per- and polyfluoroalkyl substances (PFAS) are persistent environmental pollutants of emerging concern due to their widespread use and potential adverse health effects. This study assessed the concentrations of key PFAS compounds in yogurt samples collected from eleven Lebanese governorates. Results revealed notable geographic variability, with the Bekaa region exhibiting the highest PFAS levels, particularly PFHpA, PFOA, PFHxS, PFOS, and PFPeA, while Jbeil showed the lowest concentrations. Health risk assessment using estimated daily intake (EDI), risk quotients (RQ), and cumulative hazard index (HI) indicated all individual compound exposures below established safety thresholds. However, elevated RQs for PFOS and PFOA and an average HI of 0.71 suggest potential chronic exposure concerns in high-burden regions. These findings emphasize the importance of continued monitoring and risk management to protect public health and inform environmental policies addressing PFAS contamination in Lebanon.
Patient-derived scaffolds representing breast cancer microenvironments influence chemotherapy responses in adapted cancer cells consistent with clinical features
Background The tumor microenvironment clearly influences cancer progressing properties but less is known about how individual cancer microenvironments potentially moderate cancer treatment effects. By cultivating and treating cancer cell lines in patient-derived scaffolds (PDS), the impact of specific characteristics of individual cancer microenvironments can be incorporated in human-like growth modelling and cancer drug treatment testing. Methods PDSs from 78 biobanked primary breast cancer samples with known patient outcomes, were prepared and repopulated with donor breast cancer cell lines, followed by treatment with 5-fluorouracil or doxorubicin after cellular adaption to the various microenvironments. Cancer cell responses to the treatments were monitored by RNA-analyses, highlighting changes in gene sets representative for crucial tumor biological processes such as proliferation, cancer stem cell features, differentiation and epithelial-to-mesenchymal transition. Results The chemotherapy treatments induced distinct gene expression patterns in adapted cancer cells with clusters of similar treatment responses depending on the patient-derived cancer microenvironment used as growth substrate. The doxorubicin treatment displayed a favorable gene signature among surviving cancer cells with low proliferation ( MKI67 ) and pluripotency features ( NANOG , POU5F1 ), in comparison to 5-fluorouracil showing low proliferation but increased pluripotency. Specific gene changes monitored post-treatment were also significantly correlated with clinical data, including histological grade ( NANOG ), lymph node metastasis ( SLUG ) and disease-free patient survival ( CD44 ). Conclusions This laboratory-based treatment study using patient-derived scaffolds repopulated with cancer cell lines, clearly illustrates that the human cancer microenvironment influences chemotherapy responses. The differences in treatment responses defined by scaffold-cultures have potential prognostic and treatment predictive values.
Immunohistochemical validation of COL3A1, GPR158 and PITHD1 as prognostic biomarkers in early-stage ovarian carcinomas
Background Ovarian cancer is the main cause of gynecological cancer-associated death. However, 5-year survival rates differ dramatically between the five main ovarian carcinoma histotypes. Therefore, we need to have a better understanding of the mechanisms that promote histotype-specific ovarian carcinogenesis and identify novel prognostic biomarkers. Methods Here, we evaluated the prognostic role of 29 genes for early-stage (I and II) ovarian carcinomas ( n  = 206) using immunohistochemistry (IHC). Results We provide evidence of aberrant protein expression patterns for Collagen type III alpha 1 chain (COL3A1), G protein-coupled receptor 158 (GPR158) and PITH domain containing 1 (PITHD1). Kaplan-Meier survival analysis revealed that COL3A1 expression was associated with shorter overall survival in the four major histotypes of epithelial ovarian carcinoma patients ( P value = 0.026, HR = 2.99 (95% CI 1.089–8.19)). Furthermore, GPR158 and PITHD1 were shown to be histotype-specific prognostic biomarkers, with elevated GPR158 expression patterns in mucinous ovarian carcinoma patients with unfavorable overall survival ( P value = 0.00043, HR = 6.13 (95% CI 1.98–18.98)), and an association with lower PITHD1 protein expression and unfavorable overall and disease-specific survival in clear-cell ovarian carcinoma patients ( P value = 0.012, HR = 0.22 (95% CI 0.058–0.80); P value = 0.003, HR = 0.17 (95% CI 0.043–0.64)). Conclusions The novel biomarkers identified here may improve prognostication at the time of diagnosis and may assist in the development of future individualized therapeutic strategies for ovarian carcinoma patients.