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

Data from: An atlas of polygenic risk score associations to highlight putative causal relationships across the human phenome

The age of large-scale genome-wide association studies (GWAS) has provided us with an unprecedented opportunity to evaluate the genetic liability of complex disease using polygenic risk scores (PRS). In this study, we have analysed 162 PRS (p<5×10−05) derived from GWAS and 551 heritable traits from the UK Biobank study (N = 334,398). Findings can be investigated using a web application (http://mrcieu.mrsoftware.org/PRS_atlas/), which we envisage will help uncover both known and novel mechanisms which contribute towards disease susceptibility. To demonstrate this, we have investigated the results from a phenome-wide evaluation of schizophrenia genetic liability. Amongst findings were inverse associations with measures of cognitive function which extensive follow-up analyses using Mendelian randomization (MR) provided evidence of a causal relationship. We have also investigated the effect of multiple risk factors on disease using mediation and multivariable MR frameworks. Our atlas provides a resource for future endeavours seeking to unravel the causal determinants of complex disease.,5e05.txtPRS results using P<5e05 threshold. These data are derived from the UK Biobank Resource as part of projects 8786 and 15825.5e08.txtPRS results using P<5e08 threshold. These data are derived from the UK Biobank Resource as part of projects 8786 and 15825.

Genetic instruments for Mendelian Randomization analyses of childhood and adult BMI

This file lists variants used as instrumental variables for the manuscript "Separating the effects of childhood and adult body size on inflammatory arthritis: a Mendelian randomisation study". We selected independent (linkage disequilibrium threshold of r

Additional file 1 of Role of circulating polyunsaturated fatty acids on cardiovascular diseases risk: analysis using Mendelian randomization and fatty acid genetic association data from over 114,000 UK Biobank participants

Additional file 1: Supplementary Tables S1–S11

The FRANK friends study: Data

This is data from The FRANK friends study. The protocol for the study can be found here: https://njl-admin.nihr.ac.uk/document/download/2031358 The dataset is saved and uploaded as a stata dta file. The associated metadata is uploaded as an excel workbook (FF_Metadata v1.0.xlsv). It has the column headings of: variable name, variable label (containing the question), data type, value, value labels, variable length, missing code, display format, validation type, information on anonymisation and source questions. Any uses of this dataset must acknowlegde the funder using the text: "This work was supported by the National Institute of Health Research (NIHR) Public Health Research programme, grant number NIHR PHR 17/97/02.

The FRANK friends study: Data

This is data from The FRANK friends study. The protocol for the study can be found here: https://njl-admin.nihr.ac.uk/document/download/2031358 The dataset is saved and uploaded as a stata dta file. The associated metadata is uploaded as an excel workbook (FF_Metadata v1.0.xlsv). It has the column headings of: variable name, variable label (containing the question), data type, value, value labels, variable length, missing code, display format, validation type, information on anonymisation and source questions. Any uses of this dataset must acknowlegde the funder using the text: "This work was supported by the National Institute of Health Research (NIHR) Public Health Research programme, grant number NIHR PHR 17/97/02.

Multivariate Genome-wide association summary statistics for shared aging factor

This dataset contains genome-wide summary statistics (autosomal variants) computed from a multivariate genome-wide association study of five aging-related phenotypes using Genomic Structural Equation Modeling (https://github.com/GenomicSEM/GenomicSEM). The effective sample size is calculated to be 1,958,774. Column descriptions are included in the accompanying README file. The summary statistics are provided on an "AS-IS" basis, without any type of warranty, expressed or implied, including but not limited to any warranty as to their performance, merchantability, or fitness for any particular purpose. If investigators use these data, any and all consequences are entirely their responsibility. The user agrees that to cite the appropriate publication in any communications or publications arising directly or indirectly from these data by downloading and and using these data,. The user also agrees to respect the requested responsibilities of resource users under 2003 Fort Lauderdale principles and also agree that they will never attempt to identify any participant

Assessing causal links between age at menarche and adolescent mental health: a Mendelian randomisation study [Registered Report Stage 1 Protocol]

ABSTRACT: The timing of puberty may have a substantial impact on adolescent mental health. In particular, earlier age at menarche has been associated with elevated rates of depression in adolescents. Some preliminary evidence suggests that this relationship is causal, but replication and an investigation of the broader generalisability of this finding is warranted. In this Registered Report, we will triangulate different causal inference methods using a new wave of data from the Norwegian Mother, Father and Child Cohort Study (MoBa). We will investigate: (1) to what extent age at menarche is associated with adolescent depression; (2) if associations extend to other domains of mental health; and (3) whether links between age at menarche and mental health are likely to be causal. The findings will elucidate the impact of pubertal timing on mental health and may help inform early detection and prevention. ITEMS: Additional file 1: design table.pdf; Additional file 2: supplementary methods.pdf; Additional file 3: psychometric properties of sympton scales.pdf; Additional file 4: variable overview.pdf; Additional file 5: overview of ALSPAC and MoBa variables for replication; Additional file 6: summary of arrays and batching in genotyping.pdf; Additional file 7: Stage 1 RR Supplementary code.pdf; Additional file 8: results of power analyses.pdf; Letter from data controller.pdf; Stage 1 RR age at menarche.pd

Data from: Heterogeneity of t-tubules in pig hearts

Background: T-tubules are invaginations of the sarcolemma that play a key role in excitation-contraction coupling in mammalian cardiac myocytes. Although t-tubules were generally considered to be effectively absent in atrial myocytes, recent studies on atrial cells from larger mammals suggest that t-tubules may be more numerous than previously supposed. However, the degree of heterogeneity between cardiomyocytes in the extent of the t-tubule network remains unclear. The aim of the present study was to investigate the t-tubule network of pig atrial myocytes in comparison with ventricular tissue. Methods: Cardiac tissue was obtained from young female Landrace White pigs (45–75 kg, 5–6 months old). Cardiomyocytes were isolated by arterial perfusion with a collagenase-containing solution. Ca2+ transients were examined in field-stimulated isolated cells loaded with fluo-4-AM. Membranes of isolated cells were visualized using di-8-ANEPPS. T-tubules were visualized in fixed-frozen tissue sections stained with Alexa-Fluor 488-conjugated WGA. Binary images were obtained by application of a threshold and t-tubule density (TTD) calculated. A distance mapping approach was used to calculate half-distance to nearest t-tubule (HDTT). Results & Conclusion: The spatio-temporal properties of the Ca2+ transient appeared to be consistent with the absence of functional t-tubules in isolated atrial myocytes. However, t-tubules could be identified in a sub-population of atrial cells in frozen sections. While all ventricular myocytes had TTD >3% (mean TTD = 6.94±0.395%, n = 24), this was true of just 5/22 atrial cells. Mean atrial TTD (2.35±0.457%, n = 22) was lower than ventricular TTD (P<0.0001). TTD correlated with cell-width (r = 0.7756, n = 46, P<0.0001). HDTT was significantly greater in the atrial cells with TTD ≤3% (2.29±0.16 μm, n = 17) than in either ventricular cells (1.33±0.05 μm, n = 24, P<0.0001) or in atrial cells with TTD >3% (1.65±0.06 μm, n = 5, P<0.05). These data demonstrate considerable heterogeneity between pig cardiomyocytes in the extent of t-tubule network, which correlated with cell size.,Folder 1 - linescansFolder contains linescans in TIF format of the four atrial cells referred to in Figure 1 of the manuscript.Folder 2 - di-8-ANEPPSA folder containing two further folders ('atrial' and 'ventricular'), which contain, respectively, TIF images of the 10 atrial and 4 ventricular di-8-ANEPPS-stained cells referred to in Figure 2.Folder 2 - di-8.7zSham v control TTDA spreadsheet containing t-tubule densities (TTD) of atrial and ventricular cells from Sham and Control animals to establish that there was no difference the t-tubule network in either atrial or ventricular cells between these two groups of animals.Pig TTD A V Sham vs control.xlsxControl atrial 1Original images of sections from atrial tissue from control animals used for analysis presented in Figures 4 - 6. Folder 1 of 5.Control atrial 2Original images of sections of atrial tissue from control animals used for analysis shown in Figures 4 - 6. Folder 2 of 5.Sham atrialOriginal images of atrial sections from Sham animals used for analysis presented in Figures 4 - 6. Folder 3 of 5.Control ventricularOriginal images of ventricular sections from control animals used for analysis presented in Figures 4 - 6. Folder 4 of 5.Sham ventricularOriginal images of sections from ventricular cells from Sham animals used for analysis presented in Figures 4 - 6. Folder 5 of 5.

Data from: Heterogeneity of t-tubules in pig hearts

Background: T-tubules are invaginations of the sarcolemma that play a key role in excitation-contraction coupling in mammalian cardiac myocytes. Although t-tubules were generally considered to be effectively absent in atrial myocytes, recent studies on atrial cells from larger mammals suggest that t-tubules may be more numerous than previously supposed. However, the degree of heterogeneity between cardiomyocytes in the extent of the t-tubule network remains unclear. The aim of the present study was to investigate the t-tubule network of pig atrial myocytes in comparison with ventricular tissue. Methods: Cardiac tissue was obtained from young female Landrace White pigs (45–75 kg, 5–6 months old). Cardiomyocytes were isolated by arterial perfusion with a collagenase-containing solution. Ca2+ transients were examined in field-stimulated isolated cells loaded with fluo-4-AM. Membranes of isolated cells were visualized using di-8-ANEPPS. T-tubules were visualized in fixed-frozen tissue sections stained with Alexa-Fluor 488-conjugated WGA. Binary images were obtained by application of a threshold and t-tubule density (TTD) calculated. A distance mapping approach was used to calculate half-distance to nearest t-tubule (HDTT). Results & Conclusion: The spatio-temporal properties of the Ca2+ transient appeared to be consistent with the absence of functional t-tubules in isolated atrial myocytes. However, t-tubules could be identified in a sub-population of atrial cells in frozen sections. While all ventricular myocytes had TTD >3% (mean TTD = 6.94±0.395%, n = 24), this was true of just 5/22 atrial cells. Mean atrial TTD (2.35±0.457%, n = 22) was lower than ventricular TTD (P<0.0001). TTD correlated with cell-width (r = 0.7756, n = 46, P<0.0001). HDTT was significantly greater in the atrial cells with TTD ≤3% (2.29±0.16 μm, n = 17) than in either ventricular cells (1.33±0.05 μm, n = 24, P<0.0001) or in atrial cells with TTD >3% (1.65±0.06 μm, n = 5, P<0.05). These data demonstrate considerable heterogeneity between pig cardiomyocytes in the extent of t-tubule network, which correlated with cell size.,Folder 1 - linescansFolder contains linescans in TIF format of the four atrial cells referred to in Figure 1 of the manuscript.Folder 2 - di-8-ANEPPSA folder containing two further folders ('atrial' and 'ventricular'), which contain, respectively, TIF images of the 10 atrial and 4 ventricular di-8-ANEPPS-stained cells referred to in Figure 2.Folder 2 - di-8.7zSham v control TTDA spreadsheet containing t-tubule densities (TTD) of atrial and ventricular cells from Sham and Control animals to establish that there was no difference the t-tubule network in either atrial or ventricular cells between these two groups of animals.Pig TTD A V Sham vs control.xlsxControl atrial 1Original images of sections from atrial tissue from control animals used for analysis presented in Figures 4 - 6. Folder 1 of 5.Control atrial 2Original images of sections of atrial tissue from control animals used for analysis shown in Figures 4 - 6. Folder 2 of 5.Sham atrialOriginal images of atrial sections from Sham animals used for analysis presented in Figures 4 - 6. Folder 3 of 5.Control ventricularOriginal images of ventricular sections from control animals used for analysis presented in Figures 4 - 6. Folder 4 of 5.Sham ventricularOriginal images of sections from ventricular cells from Sham animals used for analysis presented in Figures 4 - 6. Folder 5 of 5.