Protecting Astronaut Medical Privacy: Review of Presentations and Publications for Attributability

Retrospective research and medical data collected on astronauts can be a valuable resource for researchers. This data can be requested from two separate NASA Archives. The Lifetime Surveillance of Astronaut Health (LSAH) holds astronaut medical data, and the Life Sciences Data Archive (LSDA) holds research data. One condition of use of astronaut research and medical data is the requirement that all abstracts, publications and presentations using this data must be reviewed for attributability. All final versions of abstracts, presentations, posters, and manuscripts must be reviewed by LSDA/LSAH prior to submission to a conference, journal, or other entities outside the Principal Investigator (PI) laboratory [including the NASA Export Control Document Availability Authorization (DAA) system]. If material undergoes multiple revisions (e.g., journal editor comments), the new versions must also be reviewed by LSDA/LSAH prior to re-submission to the journal. The purpose of this review is to ensure that no personally identifiable information (PII) is included in materials that are presented in a public venue or posted to the public domain. The procedures for submitting materials for review will be outlined. The process that LSAH/LSDA follows for assessing attributability will be presented. Characteristics and parameter combinations that often prompt attributability concerns will be identified. A published case report for a National Football League (NFL) player will be used to demonstrate how, in a population of public interest, a combination of information can result in inadvertent release of private or sensitive information

Formate induces a metabolic switch in nucleotide and energy metabolism

Formate is a precursor for the de novo synthesis of purine and deoxythymidine nucleotides. Formate also interacts with energy metabolism by promoting the synthesis of adenine nucleotides. Here we use theoretical modelling together with metabolomics analysis to investigate the link between formate, nucleotide and energy metabolism. We uncover that endogenous or exogenous formate induces a metabolic switch from low to high adenine nucleotide levels, increasing the rate of glycolysis and repressing the AMPK activity. Formate also induces an increase in the pyrimidine precursor orotate and the urea cycle intermediate argininosuccinate, in agreement with the ATP-dependent activities of carbamoyl-phosphate and argininosuccinate synthetase. In vivo data for mouse and human cancers confirms the association between increased formate production, nucleotide and energy metabolism. Finally, the in vitro observations are recapitulated in mice following and intraperitoneal injection of formate. We conclude that formate is a potent regulator of purine, pyrimidine and energy metabolism

Two fish in a pod. Mislabelling on board threatens sustainability in mixed fisheries

Accuracy in reporting captures is a key element to achieve fisheries sustainability. However, identification of the catches might be a challenge when two or more species are morphologically similar and caught jointly, like the mixed fisheries of black hakes in East Atlantic African waters. Black hakes (Merluccius senegalensis and M. polli) are tough to differentiate without previous training due to their high morphological resemblance. The two species are managed as a single stock, although the biological differences between them suggest the need of a separate management. In this study, a total of 806 black hakes were visually identified by fishers on deck of fishing vessels operating in Mauritania and Senegal waters, then assigned to a species by sequencing 450bp of the Mitochondrial Control Region. Comparing the results with visual identification we found 31.4% of the total catch were incorrectly labelled on board by the fishermen. The accuracy of the fishers' identification depended on the depth of capture and on fish size, larger individuals caught from deeper waters being more correctly assigned to M. polli. Mislabelling biased to M. polli suggests that M. senegalensis, already catalogued as endangered, is being underreported, which could endanger the conservation of this species and threaten the sustainability of black hake fisheries. Our results highlight the need for separate evaluation of the stocks in mixed fisheries for morphologically similar fish. Thus, monitoring through DNA barcoding in the very first step of the seafood chain surveys would improve accurate species delimitation and reduce its impact on the correct assessment of the stocks.info:eu-repo/semantics/publishedVersio

Assessment of the clinical utility of four NGS panels in myeloid malignancies. Suggestions for NGS panel choice or design

The diagnosis of myeloid neoplasms (MN) has significantly evolved through the last few decades. Next Generation Sequencing (NGS) is gradually becoming an essential tool to help clinicians with disease management. To this end, most specialized genetic laboratories have implemented NGS panels targeting a number of different genes relevant to MN. The aim of the present study is to evaluate the performance of four different targeted NGS gene panels based on their technical features and clinical utility. A total of 32 patient bone marrow samples were accrued and sequenced with 3 commercially available panels and 1 custom panel. Variants were classified by two geneticists based on their clinical relevance in MN. There was a difference in panel¿s depth of coverage. We found 11 discordant clinically relevant variants between panels, with a trend to miss long insertions. Our data show that there is a high risk of finding different mutations depending on the panel of choice, due both to the panel design and the data analysis method. Of note, CEBPA, CALR and FLT3 genes, remains challenging the use of NGS for diagnosis of MN in compliance with current guidelines. Therefore, conventional molecular testing might need to be kept in place for the correct diagnosis of MN for now

Smoking and age-related macular degeneration: review and update

Age-related macular degeneration (AMD) is one of the main socioeconomical health issues worldwide. AMD has a multifactorial etiology with a variety of risk factors. Smoking is the most important modifiable risk factor for AMD development and progression. The present review summarizes the epidemiological studies evaluating the association between smoking and AMD, the mechanisms through which smoking induces damage to the chorioretinal tissues, and the relevance of advising patients to quit smoking for their visual health

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected

Spanish guidelines for the use of targeted deep sequencing in myelodysplastic syndromes and chronic myelomonocytic leukaemia

The landscape of medical sequencing has rapidly changed with the evolution of next generation sequencing (NGS). These technologies have contributed to the molecular characterization of the myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML), through the identification of recurrent gene mutations, which are present in >80% of patients. These mutations contribute to a better classification and risk stratification of the patients. Currently, clinical laboratories include NGS genomic analyses in their routine clinical practice, in an effort to personalize the diagnosis, prognosis and treatment of MDS and CMML. NGS technologies have reduced the cost of large-scale sequencing, but there are additional challenges involving the clinical validation of these technologies, as continuous advances are constantly being made. In this context, it is of major importance to standardize the generation, analysis, clinical interpretation and reporting of NGS data. To that end, the Spanish MDS Group (GESMD) has expanded the present set of guidelines, aiming to establish common quality standards for the adequate implementation of NGS and clinical interpretation of the results, hoping that this effort will ultimately contribute to the benefit of patients with myeloid malignancies

Type I interferon autoantibodies are associated with systemic immune alterations in patients with COVID-19

Neutralizing autoantibodies against type I interferons (IFNs) have been found in some patients with critical coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the prevalence of these antibodies, their longitudinal dynamics across the disease severity scale, and their functional effects on circulating leukocytes remain unknown. Here, in 284 patients with COVID-19, we found type I IFN–specific autoantibodies in peripheral blood samples from 19% of patients with critical disease and 6% of patients with severe disease. We found no type I IFN autoantibodies in individuals with moderate disease. Longitudinal profiling of over 600,000 peripheral blood mononuclear cells using multiplexed single-cell epitope and transcriptome sequencing from 54 patients with COVID-19 and 26 non–COVID-19 controls revealed a lack of type I IFN–stimulated gene (ISG-I) responses in myeloid cells from patients with critical disease. This was especially evident in dendritic cell populations isolated from patients with critical disease producing type I IFN–specific autoantibodies. Moreover, we found elevated expression of the inhibitory receptor leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) on the surface of monocytes isolated from patients with critical disease early in the disease course. LAIR1 expression is inversely correlated with ISG-I expression response in patients with COVID-19 but is not expressed in healthy controls. The deficient ISG-I response observed in patients with critical COVID-19 with and without type I IFN–specific autoantibodies supports a unifying model for disease pathogenesis involving ISG-I suppression through convergent mechanisms

Measuring and forecasting progress in education: what about early childhood?

A recent Nature article modelled within-country inequalities in primary, secondary, and tertiary education and forecast progress towards Sustainable Development Goal (SDG) targets related to education (SDG 4). However, their paper entirely overlooks inequalities in achieving Target 4.2, which aims to achieve universal access to quality early childhood development, care and preschool education by 2030. This is an important omission because of the substantial brain, cognitive and socioemotional developments that occur in early life and because of increasing evidence of early-life learning's large impacts on subsequent education and lifetime wellbeing. We provide an overview of this evidence and use new analyses to illustrate medium- and longterm implications of early learning, first by presenting associations between pre-primary programme participation and adolescent mathematics and science test scores in 73 countries and secondly, by estimating the costs of inaction (not making pre-primary programmes universal) in terms of forgone lifetime earnings in 134 countries. We find considerable losses, comparable to or greater than current governmental expenditures on all education (as percentages of GDP), particularly in low- and lower-middle-income countries. In addition to improving primary, secondary and tertiary schooling, we conclude that to attain SDG 4 and reduce inequalities in a post-COVID era, it is essential to prioritize quality early childhood care and education, including adopting policies that support families to promote early learning and their children's education

AMP-Activated Kinase Restricts Rift Valley Fever Virus Infection by Inhibiting Fatty Acid Synthesis

The cell intrinsic innate immune responses provide a first line of defense against viral infection, and often function by targeting cellular pathways usurped by the virus during infection. In particular, many viruses manipulate cellular lipids to form complex structures required for viral replication, many of which are dependent on de novo fatty acid synthesis. We found that the energy regulator AMPK, which potently inhibits fatty acid synthesis, restricts infection of the Bunyavirus, Rift Valley Fever Virus (RVFV), an important re-emerging arthropod-borne human pathogen for which there are no effective vaccines or therapeutics. We show restriction of RVFV both by AMPK and its upstream activator LKB1, indicating an antiviral role for this signaling pathway. Furthermore, we found that AMPK is activated during RVFV infection, leading to the phosphorylation and inhibition of acetyl-CoA carboxylase, the first rate-limiting enzyme in fatty acid synthesis. Activating AMPK pharmacologically both restricted infection and reduced lipid levels. This restriction could be bypassed by treatment with the fatty acid palmitate, demonstrating that AMPK restricts RVFV infection through its inhibition of fatty acid biosynthesis. Lastly, we found that this pathway plays a broad role in antiviral defense since additional viruses from disparate families were also restricted by AMPK and LKB1. Therefore, AMPK is an important component of the cell intrinsic immune response that restricts infection through a novel mechanism involving the inhibition of fatty acid metabolism