Glutathione and Xanthine Metabolic Changes in Tamoxifen Resistant Breast Cancer Cell Lines are Mediated by Down-Regulation of GSS and XDH and Correlated to Poor Prognosis.

Background: Tamoxifen is commonly used in the treatment of hormonal-positive breast cancer. However, 30%-40% of tumors treated with tamoxifen develop resistance; therefore, an important step to overcome this resistance is to understand the underlying molecular and metabolic mechanisms. In the present work, we used metabolic profiling to determine potential biomarkers of tamoxifen resistance, and gene expression levels of enzymes important to these metabolites and then correlated the expression to the survival of patients receiving tamoxifen. Methods: Tamoxifen-resistant cell lines previously developed and characterized in our laboratory were metabolically profiled with nuclear magnetic resonance spectroscopy (NMR) using cryogenic probe, and the findings were correlated with the expression of genes that encode the key enzymes of the significant metabolites. Moreover, the effect of significantly altered genes on the overall survival of patients was assessed using the Kaplan-Meier plotter web tool. Results: We observed a significant increase in the levels of glutamine, taurine, glutathione, and xanthine, and a significant decrease in the branched-chain amino acids, valine, and isoleucine, as well as glutamate and cysteine in the tamoxifen-resistant cells compared to tamoxifen sensitive cells. Moreover, xanthine dehydrogenase and glutathione synthase gene expression were downregulated, whereas glucose-6-phosphate dehydrogenase was upregulated compared to control. Additionally, increased expression of xanthine dehydrogenase was associated with a better outcome for breast cancer patients. Conclusion: Overall, this study sheds light on metabolic pathways that are dysregulated in tamoxifen-resistant cell lines and the potential role of each of these pathways in the development of resistance.

Myelodysplastic Syndromes and Myelodysplastic Syndromes/Myeloproliferative Neoplasms: A Real-World Experience From a Developing Country.

PURPOSE: Myelodysplastic syndromes (MDS) include a heterogeneous group of clonal bone marrow disorders characterized by ineffective hematopoiesis. They manifest as dysplasia in bone marrow hemopoietic elements associated with peripheral cytopenias with variable risk of AML transformation. PATIENTS AND METHODS: We analyzed retrospectively registry data collected prospectively from patients with primary MDS and patients with MDS/myeloproliferative neoplasm (MPN) in the Jordan University Hospital between January 2007 and September 2021. The registry captured epidemiologic information such as date of diagnosis, age, gender, date of AML transformation, cytogenetics, MDS subtype, risk group according to Revised International Prognostic Scoring System, and survival. The registry also captured baseline ferritin, B12, and lactate dehydrogenase levels. RESULTS: A total of 112 patients with MDS and MDS/MPN were included in the registry. Median age at diagnosis was 59 years. The male-to-female ratio was about 1.2. In a multivariate cox regression model, baseline serum ferritin significantly affected survival as patients with levels exceeding 1,000 µg/L had a risk of death three times higher compared with those with <1,000 µg/L levels (P < .05). CONCLUSION: To our knowledge, our study is the first comprehensive study examining the epidemiology and prognostic factors in patients with MDS and patients with MDS/MPN in Jordan. Our results show that MDS and MDS/MPN epidemiology in Jordan is different compared with Western countries. Our results also show that baseline serum ferritin levels can be used as a prognostic marker for patients with MDS.

Characteristics of post hoc subgroup analyses of oncology clinical trials: a systematic review.

BACKGROUND: Subgroup analyses in clinical trials assess intervention effects on specific patient subgroups, ensuring generalizability. However, they are usually only able to generate hypotheses rather than definitive conclusions. This study examined the prevalence and characteristics of post hoc subgroup analysis in oncology. METHODS: We systematically reviewed published subgroup analyses from 2000 to 2022. We included articles presenting secondary, post hoc, or subgroup analyses of interventional clinical trials in oncology, cancer survivorship, or cancer screening, published separately from the original clinical trial publication. We collected cancer type, year of publication, where and how subgroup analyses were reported, and funding. RESULTS: Out of 16 487 screened publications, 1612 studies were included, primarily subgroup analyses of treatment trials for solid tumors (82%). Medical writers contributed to 31% of articles, and 58% of articles reported conflicts of interest. Subgroup analyses increased significantly over time, with 695 published between 2019 and 2022, compared to 384 from 2000 to 2014. Gastrointestinal tumors (25%) and lymphoid lineage tumors (39%) were the most frequently studied solid and hematological malignancies, respectively. Industry funding and reporting of conflicts of interest increased over time. Subgroup analyses often neglected to indicate their secondary nature in the title. Most authors were from high-income countries, most commonly North America (45%). CONCLUSIONS: This study demonstrates the rapidly growing use of post hoc subgroup analysis of oncology clinical trials, revealing that the majority are supported by pharmaceutical companies, and they frequently fail to indicate their secondary nature in the title. Given the known methodological limitations of subgroup analyses, caution is recommended among authors, readers, and reviewers when conducting and interpreting these studies.

Defining an optimal cut-off point for reticulocyte hemoglobin as a marker for iron deficiency anemia: An ROC analysis.

Reticulocyte hemoglobin (CHr) is a measure of the amount of hemoglobin in reticulocytes and a marker of cell hemoglobinization. In this study, we aimed to find the optimal cut-off point for reticulocyte hemoglobin to diagnose iron deficiency anemia using multiple methods. A total of 309 patients were included. The median age at diagnosis was 54 years. Most were females (71.2%). 68% had iron deficiency anemia. Patients with IDA had significantly lower levels of CHr compared to those who had non-IDA (p < 0.0001). The optimal cut-off value of CHr for detecting IDA, determined using various methods, was 30.15 pg. This cut-off point had a sensitivity of 87.8% and a specificity of 77.7%. CHr showed a significant positive correlation with hemoglobin, mean corpuscular volume, serum iron, serum ferritin, and transferrin saturation and a significant negative correlation with total iron-binding capacity. CHr levels correlate with most established laboratory tests for IDA. It reliably detects IDA. Our results indicate the importance of CHr in diagnosing IDA, and that CHr should be used more widely in suspected cases of IDA since it is a cheap, fast, and reliable test.

The Osteogenic Role of Biomaterials Combined with Human-Derived Dental Stem Cells in Bone Tissue Regeneration.

The use of stem cells in regenerative medicine had great potential for clinical applications. However, cell delivery strategies have critical importance in stimulating the differentiation of stem cells and enhancing their potential to regenerate damaged tissues. Different strategies have been used to investigate the osteogenic potential of dental stem cells in conjunction with biomaterials through in vitro and in vivo studies. Osteogenesis has a broad implication in regenerative medicine, particularly for maxillofacial defects. This review summarizes some of the most recent developments in the field of tissue engineering using dental stem cells.

Knowledge, attitudes, and practices toward tuberculosis among Jordanian university students.

Background: Tuberculosis (TB) is one of the leading causes of death from infectious diseases worldwide with numerous undiagnosed and untreated cases, emphasizing the need for TB awareness to minimize transmission and initiate early treatment. Data regarding the knowledge, attitudes, and practices (KAP) toward TB among Jordanians is lacking but requires attention given the massive migration spells to Jordan from neighboring countries in the past decade. Methods: A descriptive cross-sectional study was conducted from May to June 2022. An online questionnaire was developed following World Health Organization (WHO) recommendations for TB KAP surveys and was distributed to Jordanian university students. The questionnaire documented sociodemographic data and measured participants' KAP toward TB. Descriptive and analytic statistics were used to report KAP levels and highlight relevant sociodemographic factors associated with better KAP. Results: 602 participants completed the survey; most were females (60.8%), in their first 3 years of school (84.4%), and from a healthcare field of study (57.0%). The knowledge section median score was 27 out of 51. Knowledge gaps in TB treatment, and to a lesser extent, TB transmission routes were identified. The attitudes section median score was 6 out of 9, attitudes were generally positive toward TB patients with no indication of a social stigma. The practice section median score was 6 out of 8, most participants would take the correct measures if they suspected being infected, yet around 41.0% were not confident that masks are important in preventing airborne diseases. Students in healthcare specialties had significantly better KAP scores and identifying as a smoker was associated with a lower practice score. Conclusion: Although university students displayed satisfactory KAP scores, the focus should be aimed at informing students from non-healthcare fields on TB transmission routes, treatment options, and the role of masks in preventing disease transmission.

Evaluating Knowledge of Human Microbiota among University Students in Jordan, an Online Cross-Sectional Survey.

Human microbiota have a significant impact on the health of individuals, and reciprocally, lifestyle choices of individuals have an important effect on the diversity and composition of microbiota. Studies assessing microbiota knowledge among the public are lacking, although it is hypothesized that this knowledge can motivate healthier behavior. Hence, this study aimed to measure microbiota knowledge among university students, and the effect of this knowledge on behavioral beliefs. A descriptive cross-sectional study was conducted among students from various fields of study enrolled at the University of Jordan, using an online questionnaire. The questionnaire consisted of 3 parts: demographics, general knowledge of microbiota, and behavioral beliefs related to microbiota. Four hundred and two responses were collected from verified university students. Participants were divided into two groups depending on whether they took a formal microbiology course (45 h) or not. Results from those two groups were compared using appropriate statistical methods. Results showed that most participants, even those who did not take a formal microbiology course, displayed good knowledge of what microbiota is and how they can be influenced by personal and environmental factors. Participants who took a microbiology course had significantly higher microbiota knowledge scores and were more aware of the effect of antibiotics on microbiota. Participants' behavioral beliefs regarding their antibiotic use, but not their diet and lifestyle choices, were affected by their knowledge of microbiota. The study indicates that disseminating knowledge regarding microbiota and microbiology in general, can improve behaviors related to antibiotic use.