Lundsgaardkramer4630

Bacteria are versatile living systems that enhance our understanding of nature and enable biosynthesis of valuable chemicals. Long fragment editing techniques are of great importance for accelerating bacterial genome engineering to obtain desirable and genetically stable strains. However, the existing genome editing methods cannot meet the needs of engineers. We herein report an efficient long fragment editing method for large-scale and scarless genome engineering in Escherichia coli. The method enabled us to insert DNA fragments up to 12 kb into the genome and to delete DNA fragments up to 186.7 kb from the genome, with positive rates over 95%. We applied this method for E. coli genome simplification, resulting in 12 individual deletion mutants and four cumulative deletion mutants. Menin-MLL Inhibitor manufacturer The simplest genome lost a total of 370.6 kb of DNA sequence containing 364 open reading frames. Additionally, we applied this technique to metabolic engineering and obtained a genetically stable plasmid-independent isobutanol production strain that produced 1.3 g/L isobutanol via shake-flask fermentation. These results suggest that the method is a powerful genome engineering tool, highlighting its potential to be applied in synthetic biology and metabolic engineering. KEY POINTS • This article reports an efficient genome engineering tool for E. coli. • The tool is advantageous for the manipulations of long DNA fragments. • The tool has been successfully applied for genome simplification. • The tool has been successfully applied for metabolic engineering.The burden of osteoporosis in Turkey is not well characterized. Our results indicate that osteoporosis is undertreated in Turkey with 1.35 million fractures predicted to occur from 2019 to 2023 at an associated cost of 2.42 billion USD. Interventions are needed to close the treatment gap and minimize the economic burden.

The number of osteoporotic fractures is expected to increase as populations age, posing a major risk to health systems and patients. We created a scorecard summarizing the burden of disease, policy framework, service provision, and service uptake for osteoporosis in Turkey and estimated the economic burden of osteoporotic fractures in Turkey.

A systematic review of osteoporosis in Turkey was performed. Gaps in the literature were supplemented by surveys with osteoporosis experts. The findings were used to populate a scorecard and burden of illness model focused on adults aged 50 to 89years in Turkey. The scorecard provided a visual representation of osteoporosis burden and management usingy fractures are predicted to occur in Turkey during the next 5 years with costs of 2.42 billion USD. Closing the treatment gap will be imperative for preventing these fractures and minimizing the burden of osteoporosis in Turkey.

Wilms' tumor (WT) represents about 6% of all childhood cancers. The overall survival markedly improved to exceed 90% in developed countries, yet some studies from developing counties still have poorer outcomes. The aim of this study is to assess the clinical outcome and the different prognostic factors that influence the outcome of pediatric loco-regional WT cases treated at National Cancer Institute (NCI), Cairo University, Egypt. This is a retrospective study which included pediatric loco-regional WT patients presented between January 2008 and December 2017. Patients were followed up till June 2019.

Ninety-two eligible patients were included. Median age was 3 years (range 1 month-9 years). Abdominal mass was the commonest presentation (72.8%). The 5-year EFS and OS of the whole group was 83.7% and 94.6% retrospectively. Despite having a similar EFS (84.8 vs. 82.6%), stage III patients had a significantly lower OS than those in stages I and II (89.1% vs. 100%, p value 0.024). Twelve patients had unfavorable histology and had a significantly lower EFS and OS than the patients with favorable histology (50 and 83.3% vs. 88.8 and 96.3%, p value < 0.001 and 0.043, respectively).

Loco-regional Wilms' tumor cases treated in Egypt had OS nearly the same as in developed countries, but had a lower EFS than expected mainly stages I and II. The stage and histological type are the main factors influencing the survival, and further studies are needed to investigate nuclear unrest grades and proper management of such cases.

Loco-regional Wilms' tumor cases treated in Egypt had OS nearly the same as in developed countries, but had a lower EFS than expected mainly stages I and II. The stage and histological type are the main factors influencing the survival, and further studies are needed to investigate nuclear unrest grades and proper management of such cases.Liver and bile duct cancers are leading causes of worldwide cancer death. The most common ones are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Influencing factors and prognosis of HCC and ICC are different. Precise classification of these two liver cancers is essential for treatment and prevention plans. The aim of this study is to develop a machine-based method that differentiates between the two types of liver cancers from multi-phase abdominal computerized tomography (CT) scans. The proposed method consists of two major steps. In the first step, the liver is segmented from the original images using a convolutional neural network model, together with task-specific pre-processing and post-processing techniques. In the second step, by looking at the intensity histograms of the segmented images, we extract features from regions that are discriminating between HCC and ICC, and use them as an input for classification using support vector machine model. By testing on a dataset of labeled multi-phase CT scans provided by Maharaj Nakorn Chiang Mai Hospital, Thailand, we have obtained 88% in classification accuracy. Our proposed method has a great potential in helping radiologists diagnosing liver cancer.Chimeric antigen receptor (CAR) T cells have been indicated effective in treating B cell acute lymphoblastic leukemia and non-Hodgkin lymphoma and have shown encouraging results in preclinical and clinical studies. However, CAR T cells have achieved minimal success against solid malignancies because of the additional obstacles of their insufficient migration into tumors and poor amplification and persistence, in addition to antigen-negative relapse and an immunosuppressive microenvironment. Various preclinical studies are exploring strategies to overcome the above challenges. Mobilization of endogenous immune cells is also necessary for CAR T cells to obtain their optimal therapeutic effect given the importance of the innate immune responses in the elimination of malignant tumors. In this review, we focus on the recent advances in the engineering of CAR T cell therapies to restore the immune response in solid malignancies, especially with CAR T cells acting as cellular carriers to deliver immunomodulators to tumors to mobilize the endogenous immune response.