Lactate Dehydrogenase A is a potential prognostic marker in clear cell renal cell carcinoma

BACKGROUND: Over 90% of cancer-related deaths in clear cell renal cell carcinoma (RCC) are caused by tumor relapse and metastasis. Thus, there is an urgent need for new molecular markers that can potentiate the efficacy of the current clinical-based models of prognosis assessment. The objective of this study is to evaluate the potential significance of lactate dehydrogenase A (LDHA), assessed by immunohistochemical staining, as a prognostic marker in clear cell renal cell carcinoma in relation to clinicopathological features and clinical outcome. METHODS: We assessed the expression of LDHA at the protein level, by immunohistochemistry, and correlated its expression with multiple clinicopathological features including tumor size, clinical stage, histological grade, disease-free and overall survival in 385 patients with primary clear cell renal cell carcinoma. We also correlated the LDHA expression with overall survival, at mRNA level, in an independent data set of 170 clear cell renal cell carcinoma cases from The Cancer Genome Atlas databases. Cox proportional hazards models adjusted for the potential clinicopathological factors were used to test for associations between the LDHA expression and both disease-free survival and overall survival. RESULTS: There is statistically significant positive correlation between LDHA level of expression and tumor size, clinical stage and histological grade. Moreover, LDHA expression shows significantly inverse correlation with both disease-free survival and overall survival in patients with clear cell renal cell carcinoma. Our results are validated by examining LDHA expression, at the mRNA level, in the independent data set of clear cell renal cell carcinoma cases from The Cancer Genome Atlas databases which also shows that higher lactate dehydrogenase A expression is associated with significantly shorter overall survival. CONCLUSION: Our results indicate that LDHA up-regulation can be a predictor of poor prognosis in clear cell renal cell carcinoma. Thus, it represents a potential prognostic biomarker that can boost the accuracy of other prognostic models in patients with clear cell renal cell carcinoma

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance.

Investment in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing in Africa over the past year has led to a major increase in the number of sequences that have been generated and used to track the pandemic on the continent, a number that now exceeds 100,000 genomes. Our results show an increase in the number of African countries that are able to sequence domestically and highlight that local sequencing enables faster turnaround times and more-regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and illuminate the distinct dispersal dynamics of variants of concern-particularly Alpha, Beta, Delta, and Omicron-on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve while the continent faces many emerging and reemerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Mathematical modeling of point kinetic equations with temperature feedback for reactivity transient analysis in MTR

Abstract The behavior of the nuclear reactor in response to any sudden change in reactivity is very important for reactor control. Positive reactivity insertions causes power excursion and could have a destructive impact on the reactor core. The aim of the study is to investigate the safety features of a material test reactor (MTR) during reactivity transient with emphasis on the capability of the mathematical modeling using programming language. Therefore a mathematical model using Python3.6; high-level programming language is developed to solve the point kinetic equations taking into account Doppler and moderator feedback effects. The model is validated with AIREKMOD_RR; point kinetic computer code for reactivity transient analysis in nuclear research reactors. The results of the Python model demonstrate the inherent safety features of the MTR reactor. Also, there is good agreement between the results of the Python model and AIREKMOD_RR code, illustrating the efficiency of the Python model in simulating the behavior of the reactor core under reactivity transient.</jats:p

Neurological Sequelae Following Pediatric Cardiac Interventions

AIM: The aim of the present study was to assess neurological sequelae within 30 days of surgical or cardiac catheter interventions in infants and children.&#x0D; METHOD: In this cross-sectional study, we evaluated all patients who developed neurological problems after cardiac interventions either by surgery or by catheter by clinical evaluation, brain imaging, and electrophysiological studies.&#x0D; RESULTS: Among 1200 procedures were performed; 895 (74.6%) were cardiac catheterizations either diagnostic or intervention, 167 (13.9%) were open-heart surgery, and 138 (11.5%) were closed heart surgery. The overall incidence of post-procedure neurological dysfunction in the studied population was 3.4%. The differences between the three groups were statistically significant (p &lt; 0.0001(. In our series, the neurological complications were in the form of disturbed conscious level in 2/41 (4.9%), impaired motor function in 11/41 (26.8%), impaired mental functions in 6/41(14.6%), hyperreflexia in 27/41 (65.9%), and seizures in 38/41 (92.7%). The most common presentation of seizures was in the form of focal fits 21/41 (51.2%), followed by generalized fits in 15/41(36.6%) and then myoclonic fits 2/41 (4.9%).&#x0D; CONCLUSION: Seizures are the most common complication following cardiac interventions in pediatric age and the highest percentage following open heart surgery.</jats:p