cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.20326501.v1
title: Natural course and determinants of short-term kidney function decline in hereditary transthyretin amyloidosis: a French observational study

description: Data regarding renal involvement in patients with hereditary transthyretin (ATTRv) amyloidosis are scarce and the natural course of chronic kidney disease (CKD) in this population remains unclear. This observational study, including adult patients diagnosed with ATTRv amyloidosis at the French Reference Centre for Cardiac Amyloidosis, investigated renal function outcome and its determinants. Multivariable logistic regression models identified factors associated with CKD at baseline. Determinants of the change in estimated glomerular filtration rate (eGFR) over 24 months of follow-up were assessed with a multivariable linear mixed-effects model. In total, 232 patients (78 women [34%], mean age: 64 years) with ATTRv amyloidosis were classified on the basis of their <i>TTR</i> variants: ATTRV122I (37%), ATTRV30M (29%), and other variants (34%). Median baseline eGFR was 78 ml/min/1.73 m<sup>2</sup>. Seventy-two patients (31%) had an eGFR below 60 ml/min/1.73m<sup>2</sup> and 27/137 patients (20%) had significant proteinuria (urine protein/creatinine ratio ≥30 mg/mmol). Renal biopsy, performed in four cases, found typical Congo red-positive and TTR-labelled amyloid deposits in all cases. Older age (OR 1.07, <i>p</i> &lt; .001) and a prior history of hypertension (OR 2.09, <i>p</i> = .04) were associated with a higher prevalence of CKD at baseline, whereas higher left ventricular global longitudinal strain (LVGLS) (OR 0.83, <i>p</i> &lt; .001) was associated with a lower prevalence. The estimated change in eGFR was −7.12 [−9.61, −4.63] and −8.21 [−10.81, −5.60] ml/min/1.73 m<sup>2</sup> after 12 and 24 months of follow-up, respectively. eGFR decline was independently associated with older age ((67–74], coefficient= −14.35 mL/min/1.73 m<sup>2</sup>, <i>p</i> &lt; .01, &gt;74, coefficient = −22.93 mL/min/1.73 m<sup>2</sup>, <i>p</i> &lt; .001, versus &lt;56), ATTRV122I (coefficient = −17.17 mL/min/1.73m<sup>2</sup>, <i>p</i> &lt; .01, versus ATTRV30M) and LVGLS (coefficient = 1.22, <i>p</i> &lt; .01). These data suggest that CKD is a common finding in patients with ATTRv amyloidosis, and that eGFR decline is rapid during the first year of evaluation. Older age, lower LVGLS and ATTRV122I were associated with a worse renal outcome. Further studies are now needed to evaluate effects of new targeted therapies on long term renal function.
DOI: 10.6084/m9.figshare.21252731
title: Distribution and progression of cerebral amyloid angiopathy in early-onset V30M (p.V50M) hereditary ATTR amyloidosis

description: Cerebral amyloid angiopathy (CAA) is becoming the most common and serious complications in long-lived hereditary ATTR amyloidosis patients. It is therefore imperative to elucidate the characteristics of ATTR-type CAA and develop useful biomarkers. We enrolled 34 ATTRv amyloidosis patients with the V30M (p.V50M) variant for analysis with three-dimensional stereotactic surface projection <i>z</i> score imaging of Pittsburgh compound B (PiB)-PET. Eight patients exhibited central nervous system (CNS) symptoms. Seven patients suffered transient focal neurologic episodes, and 2 patients each experienced cerebellar haemorrhages or cognitive decline. The amount of <sup>11</sup>C-PiB accumulation increased as a function of disease duration. <sup>11</sup>C-PiB-PET abnormalities were seen at 8 years from onset and were associated with CNS manifestations from 12 years. The annual increase rate of the standardised uptake value ratio (SUVR) in female patients was significantly higher than in male patients. CNS amyloid deposition started in the upper middle surface of the cerebellar cortex, and then spread out over the entire surface of the cerebellum, Sylvian fissure, and anterior part of the longitudinal fissure of the cerebrum. PiB-PET is a useful biomarker for the early detection and treatment evaluation of ATTR-type CAA. Female gender is associated with more rapid progression of ATTR-type CAA.
DOI: 10.6084/m9.figshare.21252731.v1
title: Distribution and progression of cerebral amyloid angiopathy in early-onset V30M (p.V50M) hereditary ATTR amyloidosis

description: Cerebral amyloid angiopathy (CAA) is becoming the most common and serious complications in long-lived hereditary ATTR amyloidosis patients. It is therefore imperative to elucidate the characteristics of ATTR-type CAA and develop useful biomarkers. We enrolled 34 ATTRv amyloidosis patients with the V30M (p.V50M) variant for analysis with three-dimensional stereotactic surface projection <i>z</i> score imaging of Pittsburgh compound B (PiB)-PET. Eight patients exhibited central nervous system (CNS) symptoms. Seven patients suffered transient focal neurologic episodes, and 2 patients each experienced cerebellar haemorrhages or cognitive decline. The amount of <sup>11</sup>C-PiB accumulation increased as a function of disease duration. <sup>11</sup>C-PiB-PET abnormalities were seen at 8 years from onset and were associated with CNS manifestations from 12 years. The annual increase rate of the standardised uptake value ratio (SUVR) in female patients was significantly higher than in male patients. CNS amyloid deposition started in the upper middle surface of the cerebellar cortex, and then spread out over the entire surface of the cerebellum, Sylvian fissure, and anterior part of the longitudinal fissure of the cerebrum. PiB-PET is a useful biomarker for the early detection and treatment evaluation of ATTR-type CAA. Female gender is associated with more rapid progression of ATTR-type CAA.
DOI: 10.6084/m9.figshare.21252728
title: Tafamidis polyneuropathy amelioration requires modest increases in transthyretin stability even though increases in plasma native TTR and decreases in non-native TTR do not predict response

description: TTR aggregation causes hereditary transthyretin (TTR) polyneuropathy (ATTRv-PN) in individuals with destabilised TTR variants. ATTRv-PN can be treated with ligands that bind TTR and prevent aggregation. One such ligand, tafamidis, is widely approved to treat ATTRv-PN. We explore how TTR stabilisation markers relate to clinical efficacy in 210 ATTRv-PN patients taking tafamidis. TTR concentration in patient plasma was measured before and after tafamidis treatment using assays for native or combined native + non-native TTR. TTR tetramer dissociation kinetics, which are slowed by tafamidis binding, were also measured. Native TTR levels increased by 56.8% while combined native + non-native TTR levels increased by 3.1% after 24 months of tafamidis treatment, implying that non-native TTR decreased. Accordingly, the fraction of native TTR increased from 0.54 to 0.71 with tafamidis administration. Changes in native and non-native TTR levels were uncorrelated with clinical response to tafamidis. TTR tetramer dissociation generally slowed to an extent consistent with ∼40% of TTR being tafamidis-bound. Male non-responders had a lower extent of binding. Native and non-native TTR concentration changes cannot be used as surrogate measures for therapeutic efficacy. Also, successful tafamidis therapy requires only moderate TTR stabilisation. Male patients may benefit from higher tafamidis doses.
DOI: 10.6084/m9.figshare.21252728.v1
title: Tafamidis polyneuropathy amelioration requires modest increases in transthyretin stability even though increases in plasma native TTR and decreases in non-native TTR do not predict response

description: TTR aggregation causes hereditary transthyretin (TTR) polyneuropathy (ATTRv-PN) in individuals with destabilised TTR variants. ATTRv-PN can be treated with ligands that bind TTR and prevent aggregation. One such ligand, tafamidis, is widely approved to treat ATTRv-PN. We explore how TTR stabilisation markers relate to clinical efficacy in 210 ATTRv-PN patients taking tafamidis. TTR concentration in patient plasma was measured before and after tafamidis treatment using assays for native or combined native + non-native TTR. TTR tetramer dissociation kinetics, which are slowed by tafamidis binding, were also measured. Native TTR levels increased by 56.8% while combined native + non-native TTR levels increased by 3.1% after 24 months of tafamidis treatment, implying that non-native TTR decreased. Accordingly, the fraction of native TTR increased from 0.54 to 0.71 with tafamidis administration. Changes in native and non-native TTR levels were uncorrelated with clinical response to tafamidis. TTR tetramer dissociation generally slowed to an extent consistent with ∼40% of TTR being tafamidis-bound. Male non-responders had a lower extent of binding. Native and non-native TTR concentration changes cannot be used as surrogate measures for therapeutic efficacy. Also, successful tafamidis therapy requires only moderate TTR stabilisation. Male patients may benefit from higher tafamidis doses.
DOI: 10.6084/m9.figshare.21130099
title: Selective recognition of human small transthyretin aggregates by a novel monoclonal antibody

description: Biochemical characterisation of transthyretin variant TTR Y78F showed that this variant adopts a tetrameric conformation as normal TTR but exhibits some of the characteristics of an intermediate structure in the fibrillogenesis pathway. It was hypothesised that native Y78F might represent an early event in TTR amyloidogenesis. We immunised TTR knock out mice with recombinant variant TTR Y78F. One stable hybridoma named CE11, of the IgM isotype, was tested for reactivity towards several soluble recombinant TTR variants both amyloidogenic and non-amyloidogenic. CE11 only recognises the highly amyloidogenic TTR variants L55P, S52P, A97S, Y78F or acidified TTR wt preparations. At the same time, this clone was negative for TTR V30M, soluble wild type protein or TTR T119M. The reactivity increased with oligomer formation and decreased as mature fibrils grow. After size exclusion chromatography (SEC) followed by sandwich ELISA and native immunoblotting, the mAb recognised two peaks (i) peak 1 present in acidified and in soluble variant proteins preparations with material above 146 KDa (ii) peak 2 only present in soluble L55P and S52P TTR preparations with material between 66 and 146 KDa. mAb CE11 may be a potential tool to survey therapeutical agents against TTR aggregation.
DOI: 10.6084/m9.figshare.21130099.v2
title: Selective recognition of human small transthyretin aggregates by a novel monoclonal antibody

description: Biochemical characterisation of transthyretin variant TTR Y78F showed that this variant adopts a tetrameric conformation as normal TTR but exhibits some of the characteristics of an intermediate structure in the fibrillogenesis pathway. It was hypothesised that native Y78F might represent an early event in TTR amyloidogenesis. We immunised TTR knock out mice with recombinant variant TTR Y78F. One stable hybridoma named CE11, of the IgM isotype, was tested for reactivity towards several soluble recombinant TTR variants both amyloidogenic and non-amyloidogenic. CE11 only recognises the highly amyloidogenic TTR variants L55P, S52P, A97S, Y78F or acidified TTR wt preparations. At the same time, this clone was negative for TTR V30M, soluble wild type protein or TTR T119M. The reactivity increased with oligomer formation and decreased as mature fibrils grow. After size exclusion chromatography (SEC) followed by sandwich ELISA and native immunoblotting, the mAb recognised two peaks (i) peak 1 present in acidified and in soluble variant proteins preparations with material above 146 KDa (ii) peak 2 only present in soluble L55P and S52P TTR preparations with material between 66 and 146 KDa. mAb CE11 may be a potential tool to survey therapeutical agents against TTR aggregation.
DOI: 10.6084/m9.figshare.21130099.v1
title: Selective recognition of human small transthyretin aggregates by a novel monoclonal antibody

description: Biochemical characterisation of transthyretin variant TTR Y78F showed that this variant adopts a tetrameric conformation as normal TTR but exhibits some of the characteristics of an intermediate structure in the fibrillogenesis pathway. It was hypothesised that native Y78F might represent an early event in TTR amyloidogenesis. We immunised TTR knock out mice with recombinant variant TTR Y78F. One stable hybridoma named CE11, of the IgM isotype, was tested for reactivity towards several soluble recombinant TTR variants both amyloidogenic and non-amyloidogenic. CE11 only recognises the highly amyloidogenic TTR variants L55P, S52P, A97S, Y78F or acidified TTR wt preparations. At the same time, this clone was negative for TTR V30M, soluble wild type protein or TTR T119M. The reactivity increased with oligomer formation and decreased as mature fibrils grow. After size exclusion chromatography (SEC) followed by sandwich ELISA and native immunoblotting, the mAb recognised two peaks (i) peak 1 present in acidified and in soluble variant proteins preparations with material above 146 KDa (ii) peak 2 only present in soluble L55P and S52P TTR preparations with material between 66 and 146 KDa. mAb CE11 may be a potential tool to survey therapeutical agents against TTR aggregation.
DOI: 10.6084/m9.figshare.20363197.v6
title: Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial

description: The study objective was to assess the effect of vutrisiran, an RNA interference therapeutic that reduces transthyretin (TTR) production, in patients with hereditary transthyretin (ATTRv) amyloidosis with polyneuropathy. HELIOS-A was a phase 3, global, open-label study comparing the efficacy and safety of vutrisiran with an external placebo group (APOLLO study). Patients were randomized 3:1 to subcutaneous vutrisiran 25 mg every 3 months (Q3M) or intravenous patisiran 0.3 mg/kg every 3 weeks (Q3W) for 18 months. HELIOS-A enrolled 164 patients (vutrisiran, <i>n</i> = 122; patisiran reference group, <i>n</i> = 42); external placebo, <i>n</i> = 77. Vutrisiran met the primary endpoint of change from baseline in modified Neuropathy Impairment Score +7 (mNIS+7) at 9 months (<i>p</i> = 3.54 × 10<sup>−12</sup>), and all secondary efficacy endpoints; significant improvements versus external placebo were observed in Norfolk Quality of Life-Diabetic Neuropathy, 10-meter walk test (both at 9 and 18 months), mNIS+7, modified body-mass index, and Rasch-built Overall Disability Scale (all at 18 months). TTR reduction with vutrisiran Q3M was non-inferior to within-study patisiran Q3W. Most adverse events were mild or moderate in severity, and consistent with ATTRv amyloidosis natural history. There were no drug-related discontinuations or deaths. Vutrisiran significantly improved multiple disease-relevant outcomes for ATTRv amyloidosis versus external placebo, with an acceptable safety profile. NCT03759379
DOI: 10.5281/zenodo.7429722
title: Dataset for Bayesian parametric models for survival prediction in medical applications

description: <strong>Data Source</strong> The data for these experiments were derived from these sources: * Hosmer Jr DW, Lemeshow S, May S. Applied Survival Analysis: Regression Modeling of Time-to-Event Data. 2nd ed: John Wiley & Sons; 2008. * Jd K, Prentice R. The statistical analysis of failure time data. New York: John Wiley and Sons; 1980. * Fleming T, Harrington D. Counting Processes and Survival Analysis: John Wiley & Sons; 1991. The raw data was downloaded from web archive. https://web.archive.org/web/20170114043458/http://www.umass.edu/statdata/statdata/data/ <strong>Contents</strong> Each folder contains the original data, a textfile with a description of the data, and the pre-processed version with one-hot encoded variables. An additional YAML file is included with the list of included variables, name of the time and censor variable, name of continuous variables and splitting and partitioning information.
description: {"references": ["Hosmer Jr DW, Lemeshow S, May S. Applied Survival Analysis: Regression Modeling of Time-to-Event Data. 2nd ed: John Wiley & Sons; 2008.", "Jd K, Prentice R. The statistical analysis of failure time data. New York: John Wiley and Sons; 1980.", "Fleming T, Harrington D. Counting Processes and Survival Analysis: John Wiley & Sons; 1991."]}
DOI: 10.5281/zenodo.7429721
title: Dataset for Bayesian parametric models for survival prediction in medical applications

description: <strong>Data Source</strong> The data for these experiments were derived from these sources: * Hosmer Jr DW, Lemeshow S, May S. Applied Survival Analysis: Regression Modeling of Time-to-Event Data. 2nd ed: John Wiley & Sons; 2008. * Jd K, Prentice R. The statistical analysis of failure time data. New York: John Wiley and Sons; 1980. * Fleming T, Harrington D. Counting Processes and Survival Analysis: John Wiley & Sons; 1991. The raw data was downloaded from web archive. https://web.archive.org/web/20170114043458/http://www.umass.edu/statdata/statdata/data/ <strong>Contents</strong> Each folder contains the original data, a textfile with a description of the data, and the pre-processed version with one-hot encoded variables. An additional YAML file is included with the list of included variables, name of the time and censor variable, name of continuous variables and splitting and partitioning information.
description: {"references": ["Hosmer Jr DW, Lemeshow S, May S. Applied Survival Analysis: Regression Modeling of Time-to-Event Data. 2nd ed: John Wiley & Sons; 2008.", "Jd K, Prentice R. The statistical analysis of failure time data. New York: John Wiley and Sons; 1980.", "Fleming T, Harrington D. Counting Processes and Survival Analysis: John Wiley & Sons; 1991."]}
DOI: 10.6084/m9.figshare.19100047
title: Randomized Spectral Clustering in Large-Scale Stochastic Block Models

description: Spectral clustering has been one of the widely used methods for community detection in networks. However, large-scale networks bring computational challenges to the eigenvalue decomposition therein. In this paper, we study the spectral clustering using randomized sketching algorithms from a statistical perspective, where we typically assume the network data are generated from a stochastic block model that is <i>not</i> necessarily of full rank. To do this, we first use the recently developed sketching algorithms to obtain two randomized spectral clustering algorithms, namely, the random projection-based and the random sampling-based spectral clustering. Then we study the theoretical bounds of the resulting algorithms in terms of the approximation error for the population adjacency matrix, the misclassification error, and the estimation error for the link probability matrix. It turns out that, under mild conditions, the randomized spectral clustering algorithms lead to the same theoretical bounds as those of the original spectral clustering algorithm. We also extend the results to degree-corrected stochastic block models. Numerical experiments support our theoretical findings and show the efficiency of randomized methods. A new R package called Rclust is developed and made available to the public. Supplementary materials for this article are available online.
DOI: 10.6084/m9.figshare.19100047.v1
title: Randomized Spectral Clustering in Large-Scale Stochastic Block Models

description: Spectral clustering has been one of the widely used methods for community detection in networks. However, large-scale networks bring computational challenges to the eigenvalue decomposition therein. In this paper, we study the spectral clustering using randomized sketching algorithms from a statistical perspective, where we typically assume the network data are generated from a stochastic block model that is <i>not</i> necessarily of full rank. To do this, we first use the recently developed sketching algorithms to obtain two randomized spectral clustering algorithms, namely, the random projection-based and the random sampling-based spectral clustering. Then we study the theoretical bounds of the resulting algorithms in terms of the approximation error for the population adjacency matrix, the misclassification error, and the estimation error for the link probability matrix. It turns out that, under mild conditions, the randomized spectral clustering algorithms lead to the same theoretical bounds as those of the original spectral clustering algorithm. We also extend the results to degree-corrected stochastic block models. Numerical experiments support our theoretical findings and show the efficiency of randomized methods. A new R package called Rclust is developed and made available to the public. Supplementary materials for this article are available online.
DOI: 10.6084/m9.figshare.19100092
title: Sequential Learning of Regression Models by Penalized Estimation

description: When data arrive in a sequence of two or more datasets, modeling on the most recent dataset should take previous datasets into account. We specifically investigate a strategy for regression modeling when parameter estimates from previous data can be used as anchoring points, yet may not be available for all parameters, thus, covariance information cannot be reused. A procedure that updates through targeted penalized estimation, which shrinks the estimator toward a nonzero value, is presented. The parameter estimate from the previous data serves as this nonzero value when an update is sought from novel data. This naturally extends to a sequence of datasets with the same response, but potentially only partial overlap in covariates. The iteratively updated regression parameter estimator is shown to be asymptotically unbiased and consistent. The penalty parameter is chosen through constrained cross-validated log-likelihood optimization. The constraint bounds the amount of shrinkage of the updated estimator toward the current one from below. The bound aims to preserve the (updated) estimator’s goodness of fit on all-but-the-novel data. The proposed approach is compared to other regression modeling procedures. Finally, it is illustrated on an epidemiological study where the data arrive in batches with different covariate-availability and the model is refitted with the availability of a novel batch. Supplementary materials for this article are available online.
DOI: 10.6084/m9.figshare.19100092.v2
title: Sequential Learning of Regression Models by Penalized Estimation

description: When data arrive in a sequence of two or more datasets, modeling on the most recent dataset should take previous datasets into account. We specifically investigate a strategy for regression modeling when parameter estimates from previous data can be used as anchoring points, yet may not be available for all parameters, thus, covariance information cannot be reused. A procedure that updates through targeted penalized estimation, which shrinks the estimator toward a nonzero value, is presented. The parameter estimate from the previous data serves as this nonzero value when an update is sought from novel data. This naturally extends to a sequence of datasets with the same response, but potentially only partial overlap in covariates. The iteratively updated regression parameter estimator is shown to be asymptotically unbiased and consistent. The penalty parameter is chosen through constrained cross-validated log-likelihood optimization. The constraint bounds the amount of shrinkage of the updated estimator toward the current one from below. The bound aims to preserve the (updated) estimator’s goodness of fit on all-but-the-novel data. The proposed approach is compared to other regression modeling procedures. Finally, it is illustrated on an epidemiological study where the data arrive in batches with different covariate-availability and the model is refitted with the availability of a novel batch. Supplementary materials for this article are available online.