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From patient-specific induced pluripotent stem cells to clinical translation in long QT syndrome Type 2
<p><strong>Aims</strong>: Having shown that Lumacaftor rescued the hERG trafficking defect in the induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) of two LQT2 patients, we tested whether the commercial association Lumacaftor+Ivacaftor (LUM+IVA) could shorten the QTc in the same two patients.</p> <p><strong>Methods and Results</strong>: After hospital admission and one day of baseline recordings, half dose LUM+IVA was administered on day 1, followed by full dose (LUM 800 mg + IVA 500 mg) for 7 days. A continuous 12-lead Holter ECG allowed a large number of blind QTc measurements. LUM+IVA shortened QTc significantly in both patients: in V6 from 551±22 to 523±35 ms in Patient1, and from 472±21 to 449±20 ms in Patient2; in DII from 562±25 to 549±35 ms in Patient1, and from 485±32 to 452±18 ms in Patient2. In both patients the percentage of QTc values in the lower tertile increased strikingly: in V6 from 33% to 68% and from 33% to 76%; in DII from 33% to 50% and from 33% to 87%. In the wash-out period a rebound in QTc was observed. Patient1 more than Patient2 developed diarrhoea during the study.</p> <p><strong>Conclusion</strong>: This represents the first attempt to validate in patients the <em>in vitro</em> results of a drug repurposing strategy for cardiovascular disorders. LUM+IVA shortened significantly the QTc in the two LQT2 patients with a trafficking defect, largely confirming the findings in their iPSC-CMs but with smaller quantitative changes. The findings are encouraging but immediate translation into clinical practice, without validation in more patients, would be premature.</p>
Data set and 3d model from Emendi M, Sturla F, Ghosh RP, Bianchi M, Piatti F, Pluchinotta FR, Giese D, Lombardi M, Redaelli A, Bluestein D. Patient-Specific Bicuspid Aortic Valve Biomechanics: A Magnetic Resonance Imaging Integrated Fluid-Structure Interaction Approach. Ann Biomed Eng. 2020 Aug 17. doi: 10.1007/s10439-020-02571-4. Epub ahead of print. PMID: 32804291.
<p>Data set and 3d model from Emendi M, Sturla F, Ghosh RP, Bianchi M, Piatti F, Pluchinotta FR, Giese D, Lombardi M, Redaelli A, Bluestein D. Patient-Specific Bicuspid Aortic Valve Biomechanics: A Magnetic Resonance Imaging Integrated Fluid-Structure Interaction Approach. Ann Biomed Eng. 2020 Aug 17. doi: 10.1007/s10439-020-02571-4. Epub ahead of print. PMID: 32804291.</p> <p> </p> <p>This is the abstract:</p> <p>Congenital bicuspid aortic valve (BAV) consists of two fused cusps and represents a major risk factor for calcific valvular stenosis. Herein, a fully coupled fluid-structure interaction (FSI) BAV model was developed from patient-specific magnetic resonance imaging (MRI) and compared against in vivo 4-dimensional flow MRI (4D Flow). FSI simulation compared well with 4D Flow, confirming direction and magnitude of the flow jet impinging onto the aortic wall as well as location and extension of secondary flows and vortices developing at systole: the systolic flow jet originating from an elliptical 1.6 cm<sup>2</sup> orifice reached a peak velocity of 252.2 cm/s, 0.6% lower than 4D Flow, progressively impinging on the ascending aorta convexity. The FSI model predicted a peak flow rate of 22.4 L/min, 6.7% higher than 4D Flow, and provided BAV leaflets mechanical and flow-induced shear stresses, not directly attainable from MRI. At systole, the ventricular side of the non-fused leaflet revealed the highest wall shear stress (WSS) average magnitude, up to 14.6 Pa along the free margin, with WSS progressively decreasing towards the belly. During diastole, the aortic side of the fused leaflet exhibited the highest diastolic maximum principal stress, up to 322 kPa within the attachment region. Systematic comparison with ground-truth non-invasive MRI can improve the computational model ability to reproduce native BAV hemodynamics and biomechanical response more realistically, and shed light on their role in BAV patients' risk for developing complications; this approach may further contribute to the validation of advanced FSI simulations designed to assess BAV biomechanics.</p> <p> </p>
Non-occupational and occupational factors associated with specific SARS-CoV-2 antibodies among Hospital Workers – a multicentre cross-sectional study
<p>Variables and baseline data from this cross-sectional study. Manuscript currently available as preprint: https://medrxiv.org/cgi/content/short/2020.11.10.20229005v1.</p>
Interactome analysis of the human Cap-specific mRNA (nucleoside-2'-O-)-methyltransferase 1 (hMTr1) protein
<p>This is a raw mass spectrometry dataset related to the publication: Simabuco FM, Pavan ICB, Pestana NF, Carvalho PC, Basei FL, Campos Granato D, Paes Leme AF, Zanchin NIT. Interactome analysis of the human Cap-specific mRNA (nucleoside-2'-O-)-methyltransferase 1 (hMTr1) protein. J Cell Biochem. 2019 Apr;120(4):5597-5611. doi: 10.1002/jcb.27843. Epub 2018 Oct 15. PMID: 30320910.</p> <p>Here we determined the composition of complexes isolated by hMTr1 immunoprecipitation from HEK293 cellular extracts. Consistently, a large set of proteins that function in pre-mRNA maturation was identified, including splicing factors, spliceosome-associated proteins, RNA helicases, heterogeneous nuclear ribonucleoproteins (HNRNPs), RNA-binding proteins and proteins involved in mRNA 5'- and 3'-end processing, forming an extensive interaction network. In total, 137 proteins were identified in two independent experiments.</p>
Cell type-specific predictive model
<p>The analyzed single-nucleus gene expression data of ASD and controls in the paper of "Prioritization of Genes and Gene Sets Associated with Autism Based on Cell Type-specific Predictive Models".</p>
The Differential Impacts of Domain-Specific Anxiety on L2 Writing Performance Across Different Levels of Topic Familiarity
Open the record for dataset details and reuse information.
Adoptive Transfer of JC Virus-Specific T Lymphocytes for the Treatment of Progressive Multifocal Leukoencephalopathy
<p>The dataset reports the clinical and paraclinical characteristics of the 9 patients treated with T cell therapy included in the final article, including gender, age at diagnosis, underlying hematological conditions, neurological symptoms at diagnosis, JCV viral load in the cerebrospinal fluid, number of T cell infusions, and neurological outcome following treatment. Nuclear magnetic resonance data are not reported.</p> <p>The aim of this study was to analyze the safety and carry out preliminary evaluation of the efficacy of polyomavirus JC (JCPyV) -specific T cell therapy in a cohort of hematological patients with PML.</p> <p>9 patients with a diagnosis of "definite PML" who were showing progressive clinical deterioration received JCPyV-specific T cells. Cell lines were expanded from autologous or allogenic peripheral blood mononuclear cells by stimulation with JCPyV antigen-derived peptides.</p> <p>In the evaluable patients, an increase in the frequency of circulating JCPyV-specific lymphocytes was observed, with a decrease or clearance of JCPyV viral load in cerebrospinal fluid. In responsive patients, transient appearance of punctate areas of contrast enhancement within, or close to, PML lesions was observed, which was interpreted as a sign of immune control and which regressed spontaneously without the need for steroid treatment. Six of 9 patients achieved PML control, with 5 alive and in good clinical condition at their last follow-up. None of the patients experienced treatment-related adverse events.</p>
Dataset to submitted manuscript "Imaging Fluorescence Blinking of a Mitochondrial Localization Probe – a Strategy Combining Site-Specificity with Multi-Parametric Sensing of Cellular Microenvironments"
<p><strong>This folder contains all raw data underlying the results presented in a manuscript, submitted to <em>Small</em></strong><strong>, and entitled:</strong></p> <p> </p> <p><strong><em>Imaging Fluorescence Blinking of a Mitochondrial Localization Probe – a Strategy Combining Site-Specificity with Multi-Parametric Sensing of Cellular Microenvironments</em></strong></p> <p> </p> <p><strong>Authored by:</strong></p> <p>Zhixue Du<sup>a</sup><em>, </em>Joachim Piguet<sup>a,+</sup>, Gleb Baryshnikov<sup>b,+</sup>, Johan Tornmalm<sup>a</sup>, Baris Demirbay<sup>a</sup>, Hans Ågren<sup>b</sup>, Jerker Widengren<sup>a,*</sup></p> <p> </p> <p><sup>a</sup> Royal Institute of Technology (KTH), Experimental Biomolecular Physics, Dept. Applied Physics, Albanova Univ Center 106 91 Stockholm, Sweden</p> <p><sup>b</sup> Royal Institute of Technology (KTH), Dept Theroretical Chemistry and Biology, Albanova Univ Center 106 91 Stockholm, Sweden</p> <p><sup>+</sup> Contributed equally</p> <p>* Corresponding author: Email: <a href="mailto:jwideng@kth.se">jwideng@kth.se</a>, Phone: +46-8-7907813</p> <p> </p> <p><strong>The data files are grouped into the different techniques used to generate them, and refer to the figures/tables in the manuscript where the extracted results are presented. </strong></p> <p> </p> <p><strong>ABSTRACT</strong></p> <p>The local microenvironment of mitochondrial membranes directly influences cellular metabolic states but are difficult to follow locally. Here, we demonstrate a robust and straightforward strategy, transforming the widely used mitochondrial membrane localization fluorophore 10-Nonyl Acridine Orange (NAO) into a multi-functional probe of membrane microenvironments. By monitoring the blinking kinetics of NAO in small unilamellar vesicles, and by computational simulations, we found that NAO exhibits prominent reversible singlet-triplet state transitions and can act as a light-induced Lewis acid forming a red-emissive doublet radical. The resulting blinking kinetics are highly environment sensitive, specifically reflecting local membrane oxygen concentrations, redox conditions, membrane charge, fluidity and lipid compositions, and can also be imaged in live cells, in a spatially resolved manner. They also reflect hydroxyl ion dependent transitions to and from the fluorophore doublet radical, closely coupled to proton transfer events in the membranes, local pH, and two- and three-dimensional buffering properties on and above the membranes. Generally, by the demonstrated blinking imaging strategy existing fluorophore markers can be transformed into multi-parametric microenvironmental sensors. The strategy makes it possible to image local cellular conditions highly relevant to cancer, metabolic and infectious diseases, thereby providing a basis for cellular diagnostics and for fundamental membrane studies.</p>
Dataset: Which Specific Golf Skills are Related to Performance in Skilled Junior Golfers?
<p>Dataset: Which Specific Golf Skills are Related to Performance in Skilled Junior Golfers?</p>
data set from the article De Marco F, Casenghi M, Spagnolo P, Popolo Rubbio A, Brambilla N, Testa L, Bedogni F. A patient-specific algorithm to achieve commissural alignment with Acurate Neo: The sextant technique. Catheter Cardiovasc Interv. 2021 Nov 15;98(6):E847-E854. doi: 10.1002/ccd.29737. Epub 2021 May 7. PMID: 33960624.
<p>data set from the article De Marco F, Casenghi M, Spagnolo P, Popolo Rubbio A, Brambilla N, Testa L, Bedogni F. A patient-specific algorithm to achieve commissural alignment with Acurate Neo: The sextant technique. Catheter Cardiovasc Interv. 2021 Nov 15;98(6):E847-E854. doi: 10.1002/ccd.29737. Epub 2021 May 7. PMID: 33960624</p> <p>abstract:</p> <p><strong>Aims: </strong>The aim of this proof-of-concept study was to investigate safety and efficacy of a CT-scan based patient-specific algorithm to maximize coronary clearance and secondarily to achieve anatomically correct commissural alignment with the Acurate Neo device.</p> <p><strong>Method and results: </strong>A total of 45 consecutive patients undergoing TAVR with the Acurate Neo THV were prospectively enrolled in the study. Mean age was 81.6 ± 5.5 years, mean STS score was 6.1 ± 3.7. Device success rate was 100%. Aim of the technique was to rotationally deploy the TAVR device with a commissure lying on the bisector between the coronary ostia as calculated on the pre-procedural CT-scan. At post-TAVR CT-scan, coronary clearance was achieved in 98% of patients with no cases of severe coronary artery overlap. In 42 out of 45 patients, THV was aligned or, at most, mildly misaligned; there were 2 cases of moderate misalignment without any case of severe misalignment. Post-TAVR selective coronary artery engagement was attempted and succeeded in all patients (100%).</p> <p><strong>Conclusion: </strong>Our CT-scan based patient-specific algorithm is safe and proven to be effective in avoiding coronary artery overlap and providing commissural alignment with Acurate Neo in all treated patients.</p>
Design Principles of PI(4,5)P2 Clustering Under Protein-Free Conditions: Specific Cation Effects and Calcium-Potassium Synergy
<p>Last 60ns trajectories of all systems (S1-S3 and five replicas (R1-5) of S4).</p> <p>Each *.dcd file contains 2.4ns trajectory and CHARMM *.psf files are also provided. </p>
Evolution and modulation of antigen-specific T cell responses in melanoma patients
<p>* Unpublished TCRseq repertoire data (Helsinki cohort)<br> * Unpublished epitope-specific (MART1 AAGIGILTV) TCRseq data <br> * Unpublished TCRGP models for predicting anti-MAA T cells with TCRGP (please see https://github.com/emmijokinen/TCRGP)<br> * Published TCRseq reperotire data</p>
Subject-specific features of excitation/inhibition profiles in neurodegenerative diseases
<p>Brain pathologies are based on microscopic changes in neurons and synapses that reverberate into large scale networks altering brain dynamics and functional states. An important yet unresolved issue concerns the impact of patients excitation/inhibition (E/I) profiles on neurodegenerative diseases including Alzheimer’s disease (AD), Frontotemporal Dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS). In this work we used a simulation platform, The Virtual Brain (TVB), to simulate brain dynamics in healthy controls (HC) and in AD, FTD and ALS patients. The brain connectome and functional connectivity were extracted from 3T-MRI scans and the TVB nodes were represented by a Wong-Wang neural mass model endowing an explicit representation of the E/I balance. The integration of cerebro-cerebellar loops improved the correlation between experimental and simulated functional connectivity, and hence TVB predictive power, in all pathological conditions. The TVB biophysical parameters differed between clinical phenotypes, predicting higher global coupling and inhibition in AD and stronger NMDA receptor-dependent excitation in ALS. These physio-pathological parameters allowed an advanced analysis of patients’ state.</p> <p>This database includes structural and functional connectivity matrices estimated from tractography and rs-fMRI time-series of each subject analyzed (15 HC, 15 AD, 15 FTD, 15 ALS). An ad-hoc grey matter (GM) parcellation atlas has been created combining 93 cerebral (including cortical/subcortical structures) and 31 cerebellar labels. Each GM parcellation is reported as a node in the connectivity matrices. Two types of SC matrices are reported: a distance matrix containing the length of tracts connecting each pair of nodes and a weight matrix in which connections strengths (number of streamlines) are normalized by the maximum value per each subject. The time-course of BOLD signals has been extracted for each node and the experimental FC matrix (expFC) is computed as the Pearson’s correlation coefficient (PCC) of the time-courses between each pair of brain regions. </p> <p> </p>
Subjects who have developed SARS-CoV-2 specific IgM-S after vaccination show a longer humoral immunity and a lower frequency of infection
<p>We analysed anti-SARS-CoV-2 spike (S) protein (IgG-S), anti-nucleocapsid IgG (IgG-N) and anti-Spike IgM (IgM-S) in 1872 vaccinees at the first dose (D1; w0), after three weeks at the second dose (D2; w3) at three (w6) and 23 weeks (w29) after D2; 109 subjects where further tested at the booster dose (D3, w44), at three weeks (w47) and six months (w70) after D3. Two-level linear regression models were used to evaluate the differences in IgG-S levels.</p>
Inference of tumor cell-specific transcription factor binding from cell-free DNA enables tumor subtype prediction and early detection of cancer
<p>Deregulation of transcription factors (TFs) is an important driver of tumorigenesis. We developed and validated a minimally invasive method for assessing TF activity based on cell-free DNA sequencing and nucleosome footprint analysis. We analyzed whole genome sequencing data for >1,000 cell-free DNA samples from cancer patients and healthy controls using a newly developed bioinformatics pipeline that infers accessibility of TF binding sites from cell-free DNA fragmentation patterns. We observed patient-specific as well as tumor-specific patterns, including accurate prediction of tumor subtypes in prostate cancer, with important clinical implications for the management of patients. Furthermore, we show that cell-free DNA TF profiling is capable of early detection of colorectal carcinomas. Our approach for mapping tumor-specific transcription factor binding <em>in vivo</em> based on blood samples makes a key part of the noncoding genome amenable to clinical analysis</p> <p>This dataset comprises genome-wide midpoint coverages across the early stage colon cancer cohort and non-cancer controls. For every TF and every sample, coverage values relative to the transcription factor binding site are specified ni tab-separated values (one file per sample, one line per TF)</p>
Scleroderma-specific autoantibodies embedded in immune complexes mediate endothelial damage: an early event in the pathogenesis of systemic sclerosis
<p><strong>Background: </strong>Consistently with their diagnostic and prognostic value, autoantibodies specific for systemic sclerosis (SSc) embedded in immune complexes (ICs) elicited a pro-inflammatory and pro-fibrotic cascade in healthy skin fibroblasts, engaging Toll-like Receptors (TLRs) via their nucleic acid components. The objective of this study was to investigate the pathogenicity of SSc-ICs in endothelial cells.</p> <p><strong>Methods: </strong>ICs were purified from sera of SSc patients bearing different autoantibody specificities (antibodies against DNA topoisomerase I, centromeric proteins, RNA polymerase and Th/To), patients with systemic lupus erythematosus (SLE), primary anti-phospholipid syndrome (PAPS) or healthy controls (NHS) using polyethylen glycol precipitation. Human umbilical vein endothelial cells (HUVECs) were incubated with ICs, positive and negative controls. mRNA levels of <em>endothelin-1 (et-1)</em>, <em>collagenIα1 (colI</em><em>a</em><em>1)</em>, <em>interferon (IFN)-α</em> and <em>IFN-β</em> were investigated by Real-Time PCR; <em>et-1</em> and <em>il-6</em> mRNA levels were assessed after pre-treatment with bafilomycin. ICAM-1 expression was evaluated by cell-ELISA; secretion of IL-6, IL-8 and transforming growth factor (TGF)-β1 in culture supernatants was measured by ELISA. The expression of Fcg receptors (CD64, CD32 and CD16) was assessed in endothelial cells at FACS analysis. Intracellular signalling pathways culminating with NFkB, p38MAPK, SAPK-JNK and Akt were assessed by Western Blotting. Healthy skin fibroblasts were stimulated with supernatants from HUVEC incubated with ICs, and TGF-b1 secretion, mRNA levels of <em>colIα1</em> and <em>matrix metalloproteinase (mmp)-1</em>, protein expression of a smooth muscle actin (a-SMA) and IL-6 were evaluated by Western Blotting<em>; et-1</em> mRNA levels were assessed in fibroblasts pre-treated with IL-6 and TGF-b inhibitors and stimulated with ATA-ICs.</p> <p><strong>Results: </strong>All SSc stimulated IL-6 secretion; ACA-ICs and anti-Th/To-ICs increased ICAM-1 expression; all SSc-ICs but anti-Th/To-ICs augmented IL-8 levels; all SSc-ICs but ACA and ARA-ICs up-regulated <em>et-1 </em>and all SSc-ICs but ARA-ICs affected TGF-b1 secretion. c<em>olI</em><em>a</em><em>1</em>, <em>IFN-</em><em>a</em> and <em>IFN-</em><em>b </em>mRNA levels were not affected by any SSc-IC. FcgRII (CD32) and FcgRIII (CD16) were not detectable on HUVECs, while FcgRI (CD64) was minimally expressed. A differential modulation of<em> tlr</em> expression was observed: <em>tlr2</em>, <em>tlr3</em> and <em>tlr4</em> were up-regulated by ATA-ICs and ACA-ICs, while anti-Th/To-ICs resulted in <em>tlr9</em> up-regulation. Pre-treatment with bafilomycin did not affect the up-regulation of <em>et-1</em> and <em>il-6</em> induced by ATA-ICs, ACA-ICs and anti-Th/To-ICs; a 23% reduction in both genes was reported for ARA-ICs. All SSc-ICs activated p38MAPK and AKT, all SSc-ICs but ARA-ICs yielded the activation of NFkB; ATA-ICs and ACA-ICs increased the activation rate of both subunits of SAPK-JNK. When healthy skin fibroblasts were stimulated with supernatants from HUVECs incubated with SSc-ICs, TGF-b1 secretion, <em>colI</em><em>a</em><em>1, </em>a-SMA and IL-6 expression levels were significantly modulated. Pre-treatment with IL-6 and TGF-b inhibitors prevented <em>et-1</em> up-regulation induced by ATA-ICs by 85% and 77% respectively.</p> <p><strong>Conclusions: </strong>These data provide the first demonstration of the pathogenicity of ICs from scleroderma patients with different autoantibodies on the endothelium. Endothelial activation induced by SSc-ICs ultimately led to a pro-fibrotic phenotype in healthy skin fibroblasts.</p>
Global crop-specific nitrogen fertilization dataset in 1961-2020
<p>This is a dataset for crop-specific N fertilization with 5-arc-min resolution during 1961 to 2020, including N fertilizer inputs, types and placements. The N fertilization data was classified into 21 crop types, 13 fertilizer types and 2 fertilization placements.The datasets extend from 180°E to 180°W longtitude and 90°S to 90°N latitude with a resolution of 5 arc-min for the temporal period 1961–2020 in standard WGS84 coordinate system, with a temporal resolution. The data are provided in Hierarchical Data Format (HDF5) format.</p>
This record contains raw data related to the article "Sex-Specific Cell Types and Molecular Pathways Indicate Fibro-Calcific Aortic Valve Stenosis"
<p>This record contains raw data related to the article "Sex-Specific Cell Types and Molecular Pathways Indicate Fibro-Calcific Aortic Valve Stenosis"</p> <p><strong>Background:</strong> Aortic stenosis (AS) is the most common valve disorder characterized by fibro-calcific remodeling of leaflets. Recent evidence indicated that there is a sex-related difference in AS development and progression. Fibrotic remodeling is peculiar in women’s aortic valves, while men’s leaflets are more calcified. Our study aimed to assess aortic valve fibrosis (AVF) in a severe AS cohort using non-invasive diagnostic tools and determine whether sex-specific pathological pathways and cell types are associated with severe AS.</p> <p><strong>Materials and Methods:</strong> We have included 28 men and 28 women matched for age with severe AS who underwent echocardiography and cardiac contrast-enhanced computed tomography (CT) before intervention. The calcium and fibrosis volumes were assessed and quantified using the ImageJ thresholding method, indexed calcium and fibrosis volume were calculated by dividing the volume by the aortic annular area. For a deeper understanding of molecular mechanisms characterizing AS disorder, differentially expressed genes and functional inferences between women and men’s aortic valves were carried out on a publicly available microarray-based gene expression dataset (GSE102249). Cell types enrichment analysis in stenotic aortic valve tissues was used to reconstruct the sex-specific cellular composition of stenotic aortic valves.</p> <p><strong>Results:</strong> In agreement with the literature, our CT quantifications showed that women had significantly lower aortic valve calcium content compared to men, while fibrotic tissue composition was significantly higher in women than men. The expression profiles of human stenotic aortic valves confirm sex-dependent processes. Pro-fibrotic processes were prevalent in women, while pro-inflammatory ones, linked to the immune response system, were enhanced in men. Cell-type enrichment analysis showed that mesenchymal cells were over-represented in AS valves of women, whereas signatures for monocytes, macrophages, T and B cells were enriched men ones.</p> <p><strong>Conclusions:</strong> Our data provide the basis that the fibro-calcific process of the aortic valve is sex-specific, both at gene expression and cell type level. The quantification of aortic valve fibrosis by CT could make it possible to perform population-based studies and non-invasive assessment of novel therapies to reduce or halt sex-related calcific aortic valve stenosis (CAVS) progression, acting in an optimal window of opportunity early in the course of the disease.</p>
Adults with tetralogy of Fallot show specific features of cerebral small vessel disease: the BACH San Donato study
<p>Melazzini L, Savoldi F, Chessa M, Vitali P, Zanardo M, Bertoldo EG, Fiolo V, Griffanti L, Carminati M, Frigiola A, Giamberti A, Secchi F, Callus E, Codari M, Sardanelli F. Adults with tetralogy of Fallot show specific features of cerebral small vessel disease: the BACH San Donato study. Brain Imaging Behav. 2022 Aug;16(4):1721-1731. doi: 10.1007/s11682-022-00629-6. Epub 2022 Mar 9. PMID: 35266099; PMCID: PMC8906830.</p> <p>Abstract</p> <p>Life expectancy in adults with congenital heart disease (ACHD) has increased. As these patients grow older, they experience aging-related diseases more than their healthy peers. To better characterize this field, we launched the multi-disciplinary BACH (Brain Aging in Congenital Heart disease) San Donato study, that aimed at investigating signs of brain injury in ACHD. Twenty-three adults with repaired tetralogy of Fallot and 23 age- and sex-matched healthy controls were prospectively recruited and underwent brain magnetic resonance imaging. White matter hyperintensities (WMHs) were segmented using a machine-learning approach and automatically split into periventricular and deep. Cerebral microbleeds were manually counted. A subset of 14 patients were also assessed with an extensive neuropsychological battery. Age was 41.78 ± 10.33 years (mean ± standard deviation) for patients and 41.48 ± 10.28 years for controls (p = 0.921). Albeit not significantly, total brain (p = 0.282) and brain tissue volumes (p = 0.539 for cerebrospinal fluid, p = 0.661 for grey matter, p = 0.793 for white matter) were lower in ACHD, while total volume (p = 0.283) and sub-classes of WMHs (p = 0.386 for periventricular WMHs and p = 0.138 for deep WMHs) were higher in ACHD than in controls. Deep WMHs were associated with poorer performance at the frontal assessment battery (r = -0.650, p = 0.012). Also, patients had a much larger number of microbleeds than controls (median and interquartile range 5 [3-11] and 0 [0-0] respectively; p < 0.001). In this study, adults with tetralogy of Fallot showed specific signs of brain injury, with some clinical implications. Eventually, accurate characterization of brain health using neuroimaging and neuropsychological data would aid in the identification of ACHD patients at risk of cognitive deterioration.</p>
Dataset related to article "Multicentric evaluation of a machine learning model to streamline the radiotherapy patient specific quality assurance process"
<p> This record contains raw data related to article “Multicentric evaluation of a machine learning model to streamline the radiotherapy patient specific quality assurance process"</p> <p><em>Purpose:</em> Patient-specific quality assurance (PSQA) is performed to ensure that modulated treatment plans can be delivered as intended, but constitutes a substantial workload that could slow down the radiotherapy process and delay the start of clinical treatments. In this study, we investigated a machine learning (ML) tree-based ensemble model to predict the gamma passing rate (GPR) for volumetric modulated arc therapy (VMAT) plans.</p> <p><em>Materials and Methods:</em> 5622 VMAT plans from multiple treatment sites were selected from a database of Institution 1 and the ML model trained using 19 metrics. PSQA analyses were performed automatically using criteria 3%/1 mm (global normalization, absolute dose, 10% threshold) and 95% action limit. Model’s performance was evaluated on an out-of-sample test set of Institution 1 and on two independent sets of measurements collected at Institution 2 and Institution 3. Mean absolute error (MAE), as well as the model’s sensitivity and specificity, were computed.</p> <p><em>Results:</em> The model obtained a MAE of 2.33%, 2.54% and 3.91% for the three Institutions, with a specificity of 0.90, 0.90 and 0.68, and a sensitivity of 0.61, 0.25, and 0.55, respectively. Small positive median values of the residuals (i.e., the difference between measurements and predictions) were observed for each Institution (0.95%, 1.66%, and 3.42%). Thus, the model’s predictions were, on average, close to the real values and provided a conservative estimation of the GPR.</p> <p><em>Conclusions</em>: ML models can be integrated into clinical practice to streamline the radiotherapy workflow, but they should be center-specific or thoroughly verified within centers before clinical use.</p> <p> </p>
ScienceDex guides
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These curated guides explain access requirements, typical timelines, costs, and reuse considerations for widely used research datasets.
Allen Brain Atlas
Allen Brain Atlas is an Allen Institute collection of brain map atlases, datasets, APIs, and analysis tools covering mouse, human, and non-human primate brain resources.
Annotated Behaviour and Observability Dataset (ABODe)
ABODe is a University of Edinburgh DataShare dataset for behavior classification in group-housed mice using home-cage video, identities, bounding boxes, ground-plate positions, and annotator labels.
DANDI Archive for NWB datasets
DANDI is a BRAIN Initiative archive for publishing and sharing neurophysiology data, including electrophysiology, optophysiology, and behavioral data packaged as NWB and related standards.
International Brain Laboratory public data
The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.