Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascade Inhibitors: How Mutations Can Result in Therapy Resistance and How to Overcome Resistance

The Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades are often activated by genetic alterations in upstream signaling molecules such as receptor tyrosine kinases (RTK). Integral components of these pathways, Ras, B-Raf, PI3K, and PTEN are also activated/inactivated by mutations. These pathways have profound effects on proliferative, apoptotic and differentiation pathways. Dysregulation of these pathways can contribute to chemotherapeutic drug resistance, proliferation of cancer initiating cells (CICs) and premature aging. This review will evaluate more recently described potential uses of MEK, PI3K, Akt and mTOR inhibitors in the proliferation of malignant cells, suppression of CICs, cellular senescence and prevention of aging. Ras/Raf/MEK/ERK and Ras/PI3K/PTEN/Akt/mTOR pathways play key roles in the regulation of normal and malignant cell growth. Inhibitors targeting these pathways have many potential uses from suppression of cancer, proliferative diseases as well as aging

The Past, Present, and Future of the Brain Imaging Data Structure (BIDS)

The Brain Imaging Data Structure (BIDS) is a community-driven standard for the organization of data and metadata from a growing range of neuroscience modalities. This paper is meant as a history of how the standard has developed and grown over time. We outline the principles behind the project, the mechanisms by which it has been extended, and some of the challenges being addressed as it evolves. We also discuss the lessons learned through the project, with the aim of enabling researchers in other domains to learn from the success of BIDS.Development of the BIDS Standard has been supported by the International Neuroinformatics Coordinating Facility, Laura and John Arnold Foundation, National Institutes of Health (R24MH114705, R24MH117179, R01MH126699, R24MH117295, P41EB019936, ZIAMH002977, R01MH109682, RF1MH126700, R01EB020740), National Science Foundation (OAC-1760950, BCS-1734853, CRCNS-1429999, CRCNS-1912266), Novo Nordisk Fonden (NNF20OC0063277), French National Research Agency (ANR-19-DATA-0023, ANR 19-DATA-0021), Digital Europe TEF-Health (101100700), EU H2020 Virtual Brain Cloud (826421), Human Brain Project (SGA2 785907, SGA3 945539), European Research Council (Consolidator 683049), German Research Foundation (SFB 1436/425899996), SFB 1315/327654276, SFB 936/178316478, SFB-TRR 295/424778381), SPP Computational Connectomics (RI 2073/6-1, RI 2073/10-2, RI 2073/9-1), European Innovation Council PHRASE Horizon (101058240), Berlin Institute of Health & Foundation Charité, Johanna Quandt Excellence Initiative, ERAPerMed Pattern-Cog, and the Virtual Research Environment at the Charité Berlin – a node of EBRAINS Health Data Cloud.N

The past, present, and future of the Brain Imaging Data Structure (BIDS)

The Brain Imaging Data Structure (BIDS) is a community-driven standard for the organization of data and metadata from a growing range of neuroscience modalities. This paper is meant as a history of how the standard has developed and grown over time. We outline the principles behind the project, the mechanisms by which it has been extended, and some of the challenges being addressed as it evolves. We also discuss the lessons learned through the project, with the aim of enabling researchers in other domains to learn from the success of BIDS

The benefits of hepatitis C virus cure: Every rose has thorns

To examine mid-term benefits on hepatic complications, extrahepatic clinical syndromes and quality of life associated with HCV cure; to review the few safety issues linked to oral direct-acting antivirals (DAAs); and to discuss the potential population benefits of reducing the burden of HCV infection. DAAs cure HCV infection in more than 95% of patients. The halting of liver inflammation and fibrosis progression translates into both hepatic and extrahepatic benefits and reduces the need for liver transplantation. A reduction in the frequency of extrahepatic manifestations such as mixed cryoglobulinaemia and vasculitis and improvements in quality of life and fatigue have also been described. A few safety issues linked to DAAs such as the potential recurrence of aggressive HCC, the flares of hepatitis B virus in patients with overt or occult HBV infection are been discussed. Curing HCV infection also has a high potential to reduce the burden of HCV infection at the population level. With widespread scaling up of HCV treatment, several modeling studies suggest that major reductions in HCV prevalence and incidence are possible, and that elimination of viral hepatitis is an achievable target by 2030