High incidence of Noonan syndrome features including short stature and pulmonic stenosis in patients carrying NF1 missense mutations affecting p.Arg1809: genotype-phenotype correlation

Neurofibromatosis type 1 (NF1) is one of the most frequent genetic disorders, affecting 1:3,000 worldwide. Identification of genotype-phenotype correlations is challenging because of the wide range clinical variability, the progressive nature of the disorder, and extreme diversity of the mutational spectrum. We report 136 individuals with a distinct phenotype carrying one of five different NF1 missense mutations affecting p.Arg1809. Patients presented with multiple cafe-au-lait macules (CALM) with or without freckling and Lisch nodules, but no externally visible plexiform neurofibromas or clear cutaneous neurofibromas were found. About 25% of the individuals had Noonan-like features. Pulmonic stenosis and short stature were significantly more prevalent compared with classic cohorts (P<0.0001). Developmental delays and/or learning disabilities were reported in over 50% of patients. Melanocytes cultured from a CALM in a segmental NF1-patient showed two different somatic NF1 mutations, p.Arg1809Cys and a multi-exon deletion, providing genetic evidence that p.Arg1809Cys is a loss-of-function mutation in the melanocytes and causes a pigmentary phenotype. Constitutional missense mutations at p.Arg1809 affect 1.23% of unrelated NF1 probands in the UAB cohort, therefore this specific NF1 genotype-phenotype correlation will affect counseling and management of a significant number of patients

BioTIME 2.0 : expanding and improving a database of biodiversity time series

Funding: H2020 European Research Council (Grant Number(s): GA 101044975, GA 101098020).Motivation: Here, we make available a second version of the BioTIME database, which compiles records of abundance estimates for species in sample events of ecological assemblages through time. The updated version expands version 1.0 of the database by doubling the number of studies and includes substantial additional curation to the taxonomic accuracy of the records, as well as the metadata. Moreover, we now provide an R package (BioTIMEr) to facilitate use of the database. Main Types of Variables: Included The database is composed of one main data table containing the abundance records and 11 metadata tables. The data are organised in a hierarchy of scales where 11,989,233 records are nested in 1,603,067 sample events, from 553,253 sampling locations, which are nested in 708 studies. A study is defined as a sampling methodology applied to an assemblage for a minimum of 2 years. Spatial Location and Grain: Sampling locations in BioTIME are distributed across the planet, including marine, terrestrial and freshwater realms. Spatial grain size and extent vary across studies depending on sampling methodology. We recommend gridding of sampling locations into areas of consistent size. Time Period and Grain: The earliest time series in BioTIME start in 1874, and the most recent records are from 2023. Temporal grain and duration vary across studies. We recommend doing sample-level rarefaction to ensure consistent sampling effort through time before calculating any diversity metric. Major Taxa and Level of Measurement: The database includes any eukaryotic taxa, with a combined total of 56,400 taxa. Software Format: csv and. SQL.Peer reviewe

BioTIME 2.0 : expanding and improving a database of biodiversity time series

Motivation. Here, we make available a second version of the BioTIME database, which compiles records of abundance estimates for species in sample events of ecological assemblages through time. The updated version expands version 1.0 of the database by doubling the number of studies and includes substantial additional curation to the taxonomic accuracy of the records, as well as the metadata. Moreover, we now provide an R package (BioTIMEr) to facilitate use of the database. Main Types of Variables Included. The database is composed of one main data table containing the abundance records and 11 metadata tables. The data are organised in a hierarchy of scales where 11,989,233 records are nested in 1,603,067 sample events, from 553,253 sampling locations, which are nested in 708 studies. A study is defined as a sampling methodology applied to an assemblage for a minimum of 2 years. Spatial Location and Grain. Sampling locations in BioTIME are distributed across the planet, including marine, terrestrial and freshwater realms. Spatial grain size and extent vary across studies depending on sampling methodology. We recommend gridding of sampling locations into areas of consistent size. Time Period and Grain. The earliest time series in BioTIME start in 1874, and the most recent records are from 2023. Temporal grain and duration vary across studies. We recommend doing sample-level rarefaction to ensure consistent sampling effort through time before calculating any diversity metric. Major Taxa and Level of Measurement. The database includes any eukaryotic taxa, with a combined total of 56,400 taxa. Software Format. csv and. SQL

Priming of Long-Lived Memory CD8+ T cell Responses in the Spleen During Influenza Virus Infection

Abstract CD8+ T cell responses to influenza virus infection are canonically known to be activated solely in the lung draining, mediastinal lymph node (mLN). Mechanistically, migratory dendritic cells (mDCs) are activated in the lungs and traffic to the mLN where they encounter cognate CD8+ T cells, initiating the heterogeneous response to influenza virus. As such, when mDCs are absent or when migration is inhibited, CD8+ T cell responses are compromised and the viral burden in the lungs increases. In contrast to the current paradigm, local priming of CD8+ T cells has been hypothesized to occur in the spleen, and mDCs are thought to die in the mLN shortly after trafficking. Therefore, how CD8+ T cells could be primed locally in the spleen has remained an unpopular hypothesis. Here we show using a mouse model of influenza infection, that mDCs not only prime CD8+ T cells in the mLN, but can also prime CD8+ T cell responses locally in the spleen. Mechanistically, we show that a portion of the mDCs trafficking to the mLN can egress the mLN, enter the blood via an S1P/S1PR dependent mechanism, and enter the spleen. CD8+ T cell responses initiated in the spleen are longer lived than mLN primed responses. Collectively, our results demonstrate a novel DC trafficking pathway and support a new paradigm for how heterogeneous T cell responses to influenza are initiated.</jats:p

Lung dendritic cells migrate to the spleen to prime long-lived TCF1 ^hi memory CD8 ⁺ T cell precursors after influenza infection

Lung-derived dendritic cells carry influenza antigens to the spleen after egressing the lymph node by an S1P/S1PR-dependent mechanism.</jats:p

Legal authorized representative experience with smartphone-based electronic informed consent in an acute stroke trial

BackgroundThe pilot use of a smartphone platform for electronic informed consent (e-Consent) in large vessel occlusion acute stroke (LVOS) trials has recently been reported. The degree of satisfaction from Legal Authorized Representatives (LARs) with regard to this process remains to be established.MethodsA single-center study evaluating the experience of LARs with the use of e-Consent in a LVOS randomized trial of an investigational drug administered within 12 hours of last known normal was carried out. A structured survey was used to evaluate the experience of the LARs with the e-consenting process.ResultsFrom February to November 2018, 60 consecutive patients were e-Consented. Of these, 53 LARs completed the survey. The median (IQR) age of the patients was 63 (53–70) years, baseline/discharge National Institutes of Health Stroke Scale score was 17 (12–20)/3(1–12), and 45% were independent at discharge. The survey was applied in person in 43% of cases and via telephone in 57%. Median LAR age was 48 (39–59) years, 64% were female, and a multi-ethnic composition was observed. Forty percent of LARs had less than tertiary level of education (high-school or less). Regarding the e-Consent, 98% of LARs reported to be ‘clear’ and 83% felt ‘very comfortable’ in signing. The overall experience was ‘excellent/good’ in 91%. Despite the positive general impression regarding the use of e-Consent, 12 LARs (22%) would have preferred paper consent. Multivariable regression indicated that lower educational status (tertiary education or less: OR 5.09, 95% CI 1.02 to 25.48; p=0.04) and lower baseline ASPECTS score (OR 0.63, 95% CI 0.41 to 0.96; p=0.03) were independently associated with preference for paper consent.Conclusionse-Consent was overall very well perceived by LARs in a randomized clinical trial of LVOS. A minority of proxies, who were more commonly less formally educated, would have preferred paper consenting.</jats:sec