Neuromuscular disease genetics in under-represented populations: increasing data diversity

Neuromuscular diseases (NMDs) affect ∼15 million people globally. In high income settings DNA-based diagnosis has transformed care pathways and led to gene-specific therapies. However, most affected families are in low-to-middle income countries (LMICs) with limited access to DNA-based diagnosis. Most (86%) published genetic data is derived from European ancestry. This marked genetic data inequality hampers understanding of genetic diversity and hinders accurate genetic diagnosis in all income settings. We developed a cloud-based transcontinental partnership to build diverse, deeply-phenotyped and genetically characterized cohorts to improve genetic architecture knowledge, and potentially advance diagnosis and clinical management. We connected 18 centres in Brazil, India, South Africa, Turkey, Zambia, Netherlands and the UK. We co-developed a cloud-based data solution and trained 17 international neurology fellows in clinical genomic data interpretation. Single gene and whole exome data were analysed via a bespoke bioinformatics pipeline and reviewed alongside clinical and phenotypic data in global webinars to inform genetic outcome decisions. We recruited 6001 participants in the first 43 months. Initial genetic analyses ‘solved’ or ‘possibly solved’ ∼56% probands overall. In-depth genetic data review of the four commonest clinical categories (limb girdle muscular dystrophy, inherited peripheral neuropathies, congenital myopathy/muscular dystrophies and Duchenne/Becker muscular dystrophy) delivered a ∼59% ‘solved’ and ∼13% ‘possibly solved’ outcome. Almost 29% of disease causing variants were novel, increasing diverse pathogenic variant knowledge. Unsolved participants represent a new discovery cohort. The dataset provides a large resource from under-represented populations for genetic and translational research. In conclusion, we established a remote transcontinental partnership to assess genetic architecture of NMDs across diverse populations. It supported DNA-based diagnosis, potentially enabling genetic counselling, care pathways and eligibility for gene-specific trials. Similar virtual partnerships could be adopted by other areas of global genomic neurological practice to reduce genetic data inequality and benefit patients globally

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Effect of Acorus calamus and Apium graveolens extracts on Egfr and Erbb2 in LNCaP cells

WOS:000437674104027Prostate cancer is one of the most commonly diagnosed cancers in men of developed Western countries. Several treatments are available for treatment of prostate cancer. These include surgery, radiation, radioactive implants and hormonal therapy. However, the treatment often impacts the quality of life due to side‑effects or complications. Thus, numerous investigators have focused on discovering novel drugs or treatments. Among all the agents tested, natural products derived from medicinal plants are among the most favorable. Migration and invasion of cancer cells is regulated by multiple pathways that employ various growth factor and their receptors, integrins and cytoskeletal elements. A key role is played by the EGF receptor (EGFR), which, following interaction with the integrin a6b4, promotes cell migration through activation of PI3K and other downstream pathways. The androgen receptor can be activated indirectly by growth factor receptors, mainly the transmembrane tyrosine kinases EGFR and ERBB2, members of the epidermal growth factor receptor (EGFR) family, which are activated inappropriately in many human cancer types. It has been reported that the EGF receptors EGFR (HER­1) and ERBB2 (HER­2 / neu) are overexpressed in metastatic prostate tumors. In this study, we investigated the effect of A. Calamus and A. Graveolens extracts on Egfr and Erbb2 on the human prostatic carcinoma cell line LNCaP. LNCaP cells were treated with increasing concentrations of an ethanolic extract of A. graveolens ranging from 1000 to 3000 µg/ml, A. Calamus 250 to 750 µg/ml and viability was determined after 24 and 48 h using the XTT cell proliferation assay. The levels of EGFR and ERBB2 were analyzed. Finally, quantitative gene expression analysis of EGFR and ERBB2, was performed using real­time reverse transcription– polymerase chain reaction. As a result, we observed that A. calamus and A. graveolens extracts affected EGFR and ERBB2 levels in LNCaP cell

19 May 2011 Kütahya – Simav earthquake and evaluation of existing sample RC buildings according to the TEC-2007 criteria

This study examines the damage caused to reinforced concrete structures by the 2011 earthquake that occurred in Simav, Turkey. The study briefly reports on post-earthquake field observations, tectonic characteristics of the earthquake area, geotechnical characteristics of the field, and seismic characteristics of the earthquake. The main part of the study comprises a field study, material experiments, and performance analyses of two reinforced concrete buildings that survived the earthquake with medium level damage. The building performance was calculated and assessed according to the Turkish Earthquake Code requirements for existing building stock, and recommendations were made based on the findings