cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.28435275.v2
title: Model Selection for Mixed-Effects Location-Scale Models with Confidence Interval for LOO or WAIC Difference

description: LOO (Leave-One-Out cross-validation) and WAIC (Widely Applicable Information Criterion) are widely used for model selection in Bayesian statistics. Most studies select the model with the smallest value based on point estimates, often without considering the differences in fit indices or the uncertainty of the estimates. To address this gap, we propose a sequential method for comparing models based on confidence intervals for ΔLOO or ΔWAIC. A simulation study was conducted to evaluate this method in selecting mixed-effects location-scale models (MELSMs). Our study revealed that the sequential methods, especially when using a 90% confidence interval, achieved a higher accuracy rate of model selection compared to the point method when the true model was simple, had a large magnitude of random intercept in the scale model, or had a large sample size. Models selected by the sequential methods demonstrated higher power, narrower credible interval width, smaller standard errors for the fixed effect in the location model, and lower bias for the random effect of the intercept in the location model. Differences between LOO and WAIC were significant only when the level-1 sample size was small, with LOO performing better when the true model had homogeneous or severe heterogeneity in residual variances.
DOI: 10.6084/m9.figshare.28944673
title: Tissue engineering with targeted delivery of nanotized S-nitrosyl mutant of NEMO ameliorates myocardial infarction

description: Myocardial infarction (MI) is characterized by an elevated nitrosative and hypoxic microenvironment due to reduced coronary blood flow. NEMO (IKKγ) regulates the formation of the IKK holo-complex to activate NFκB-p65 signaling. This study reports successful restoration of MI through cardiomyocyte-targeted nanotized S-nitrosyl mutant of NEMO under elevated nitrosative stress. The MI model was generated in male Wistar rats. S-nitrosyl mutant of NEMO (R- NEMO) was selectively delivered to the cardiomyocytes via targeted chitosan nano-vehicle. Nano-conjugated R- NEMO delivery to diseased cardiomyocytes resulted in downregulation of nitrosative stress and cellular apoptosis leading to regressed infarct area with improved cardiac pathophysiology. Mechanistically, NEMO-p300 binding in R- NEMO expressed cells destabilized p65-p300 complex leading to regressed nitrosative stress and cellular apoptosis. The NEMO mutant inhibits the PGC1α-p65 complex-mediated degradation of PGC1α, leading to upregulation of VEGF. A shift in the binding preference of p65 from PGC1α/p300 to HDAC1 results in the downregulation of the cell-cycle inhibitor and the induction of cell-cycle re-entry markers during MI. Tissue-targeted R- NEMO nanoconjugates show potential to ameliorate MI insult by downregulating apoptosis and promoting the proliferative prowess of the resident cardiomyocytes with potential revascularization at infarct sites; thus, repairing the damaged myocardium.
DOI: 10.6084/m9.figshare.28944673.v1
title: Tissue engineering with targeted delivery of nanotized S-nitrosyl mutant of NEMO ameliorates myocardial infarction

description: Myocardial infarction (MI) is characterized by an elevated nitrosative and hypoxic microenvironment due to reduced coronary blood flow. NEMO (IKKγ) regulates the formation of the IKK holo-complex to activate NFκB-p65 signaling. This study reports successful restoration of MI through cardiomyocyte-targeted nanotized S-nitrosyl mutant of NEMO under elevated nitrosative stress. The MI model was generated in male Wistar rats. S-nitrosyl mutant of NEMO (R- NEMO) was selectively delivered to the cardiomyocytes via targeted chitosan nano-vehicle. Nano-conjugated R- NEMO delivery to diseased cardiomyocytes resulted in downregulation of nitrosative stress and cellular apoptosis leading to regressed infarct area with improved cardiac pathophysiology. Mechanistically, NEMO-p300 binding in R- NEMO expressed cells destabilized p65-p300 complex leading to regressed nitrosative stress and cellular apoptosis. The NEMO mutant inhibits the PGC1α-p65 complex-mediated degradation of PGC1α, leading to upregulation of VEGF. A shift in the binding preference of p65 from PGC1α/p300 to HDAC1 results in the downregulation of the cell-cycle inhibitor and the induction of cell-cycle re-entry markers during MI. Tissue-targeted R- NEMO nanoconjugates show potential to ameliorate MI insult by downregulating apoptosis and promoting the proliferative prowess of the resident cardiomyocytes with potential revascularization at infarct sites; thus, repairing the damaged myocardium.
DOI: 10.6084/m9.figshare.28497412
title: European general practitioners’ attitudes towards person-centred care and factors that influence its implementation in everyday practice: The protocol of the cross-sectional PACE GP/FP study in 24 European countries

description: Person-centred care (PCC) is a fundamental principle in general practice, emphasising practices tailored to individual patient preferences, needs, and values. Despite the importance of PCC, general practitioners (GPs) face obstacles in effectively implementing it, with associated factors remaining unclear. The PACE GP/FP study aims to explore GPs’ attitudes towards PCC and the factors facilitating or hindering its implementation in daily practice across European countries. This paper outlines the PACE GP/FP study protocol. The cross-sectional design with data collection <i>via</i> an online survey distribution to GPs in 24 European countries. Study instruments include two validated questionnaires (Perceived Stress Scale (PSS) and Patient Physician Orientation Scale (PPOS)) and additional items covering general information about the doctor and their practice, as well as facilitators and barriers to PCC. These additional items were specifically developed for the study, translated using the forward-backward method, evaluated through cognitive debriefing, and integrated into the REDCap platform to create language and country-specific survey links. The STROBE checklist guides the reporting of the manuscript. The PACE GP/FP study will provide a comprehensive exploration of GPs’ attitudes towards PCC and the factors shaping its practice in Europe. The findings from the PACE GP/FP study will provide evidence for designing future implementation strategies and guide targeted interventions to promote PCC in primary care across Europe.
DOI: 10.6084/m9.figshare.28497412.v1
title: European general practitioners’ attitudes towards person-centred care and factors that influence its implementation in everyday practice: The protocol of the cross-sectional PACE GP/FP study in 24 European countries

description: Person-centred care (PCC) is a fundamental principle in general practice, emphasising practices tailored to individual patient preferences, needs, and values. Despite the importance of PCC, general practitioners (GPs) face obstacles in effectively implementing it, with associated factors remaining unclear. The PACE GP/FP study aims to explore GPs’ attitudes towards PCC and the factors facilitating or hindering its implementation in daily practice across European countries. This paper outlines the PACE GP/FP study protocol. The cross-sectional design with data collection <i>via</i> an online survey distribution to GPs in 24 European countries. Study instruments include two validated questionnaires (Perceived Stress Scale (PSS) and Patient Physician Orientation Scale (PPOS)) and additional items covering general information about the doctor and their practice, as well as facilitators and barriers to PCC. These additional items were specifically developed for the study, translated using the forward-backward method, evaluated through cognitive debriefing, and integrated into the REDCap platform to create language and country-specific survey links. The STROBE checklist guides the reporting of the manuscript. The PACE GP/FP study will provide a comprehensive exploration of GPs’ attitudes towards PCC and the factors shaping its practice in Europe. The findings from the PACE GP/FP study will provide evidence for designing future implementation strategies and guide targeted interventions to promote PCC in primary care across Europe.
DOI: 10.34622/datarepositorium/vvcf9m
title: RARAA Properties and Classes Vocabulary for Rock Art

description: RDFS file containing the definition of the new RARAA properties and classes.
DOI: 10.6084/m9.figshare.28254932
title: Maximizing the translational potential of neurophysiology in amyotrophic lateral sclerosis: a study on compound muscle action potentials

description: Mouse models of amyotrophic lateral sclerosis (ALS) enable testing of novel therapeutic interventions. However, treatments that have extended survival in mice have often failed to translate into human benefit in clinical trials. Compound muscle action potentials (CMAPs) are a simple neurophysiological test that measures the summation of muscle fiber depolarization in response to maximal stimulation of the innervating nerve. CMAPs can be measured in both mice and humans and decline with motor axon loss in ALS, making them a potential translational read-out of disease progression. We assessed the translational potential of CMAPs and ascertained time points when human and mouse data aligned most closely. We extracted data from 18 human studies and compared with results generated from SOD1<sup>G93A</sup> and control mice at different ages across different muscles. The relative CMAP amplitude difference between SOD1<sup>G93A</sup> and control mice in tibialis anterior (TA) and gastrocnemius muscles at 70 days of age was most similar to the relative difference between baseline ALS patient CMAP measurements and healthy controls in the abductor pollicis brevis (APB) muscle. We also found that the relative decline in SOD1<sup>G93A</sup> TA CMAP amplitude between 70 and 140 days was similar to that observed in 12 month human longitudinal studies in APB. Our findings suggest CMAP amplitudes can provide a “translational window”, from which to make comparisons between the SOD1<sup>G93A</sup> model and human ALS patients. CMAPs are easy to perform and can help determine the most clinically relevant starting/end points for preclinical studies and provide a basis for predicting potential clinical effect sizes.
DOI: 10.6084/m9.figshare.28254932.v1
title: Maximizing the translational potential of neurophysiology in amyotrophic lateral sclerosis: a study on compound muscle action potentials

description: Mouse models of amyotrophic lateral sclerosis (ALS) enable testing of novel therapeutic interventions. However, treatments that have extended survival in mice have often failed to translate into human benefit in clinical trials. Compound muscle action potentials (CMAPs) are a simple neurophysiological test that measures the summation of muscle fiber depolarization in response to maximal stimulation of the innervating nerve. CMAPs can be measured in both mice and humans and decline with motor axon loss in ALS, making them a potential translational read-out of disease progression. We assessed the translational potential of CMAPs and ascertained time points when human and mouse data aligned most closely. We extracted data from 18 human studies and compared with results generated from SOD1<sup>G93A</sup> and control mice at different ages across different muscles. The relative CMAP amplitude difference between SOD1<sup>G93A</sup> and control mice in tibialis anterior (TA) and gastrocnemius muscles at 70 days of age was most similar to the relative difference between baseline ALS patient CMAP measurements and healthy controls in the abductor pollicis brevis (APB) muscle. We also found that the relative decline in SOD1<sup>G93A</sup> TA CMAP amplitude between 70 and 140 days was similar to that observed in 12 month human longitudinal studies in APB. Our findings suggest CMAP amplitudes can provide a “translational window”, from which to make comparisons between the SOD1<sup>G93A</sup> model and human ALS patients. CMAPs are easy to perform and can help determine the most clinically relevant starting/end points for preclinical studies and provide a basis for predicting potential clinical effect sizes.
DOI: 10.15468/dl.bemdut
title: Occurrence Download

description: A dataset containing 0 species occurrences available in GBIF matching the query:
{"type":"and","predicates":[{"type":"within","geometry":"POLYGON ((101.257 1.574182, 101.186711 1.568614, 101.118153 1.552047, 101.053017 1.524889, 100.992905 1.48781, 100.939299 1.441722, 100.893519 1.387762, 100.856692 1.327257, 100.829723 1.261699, 100.813277 1.192702, 100.807757 1.121965, 100.813298 1.05123, 100.829764 0.9822380000000001, 100.856748 0.916687, 100.893585 0.856192, 100.939368 0.802242, 100.992971 0.756165, 101.053072 0.719095, 101.118194 0.691945, 101.186732 0.675383, 101.257 0.669816, 101.327268 0.675383, 101.395806 0.691945, 101.460928 0.719095, 101.521029 0.756165, 101.574632 0.802242, 101.620415 0.856192, 101.657252 0.916687, 101.684236 0.9822380000000001, 101.700702 1.05123, 101.706243 1.121965, 101.700723 1.192702, 101.684277 1.261699, 101.657308 1.327257, 101.620481 1.387762, 101.574701 1.441722, 101.521095 1.48781, 101.460983 1.524889, 101.395847 1.552047, 101.327289 1.568614, 101.257 1.574182))"},{"type":"equals","key":"CLASS_KEY","value":"212","matchCase":false},{"type":"greaterThanOrEquals","key":"YEAR","value":"2015","matchCase":false},{"type":"not","predicate":{"type":"in","key":"BASIS_OF_RECORD","values":["MATERIAL_CITATION","MATERIAL_SAMPLE","PRESERVED_SPECIMEN"],"matchCase":false}},{"type":"lessThanOrEquals","key":"COORDINATE_UNCERTAINTY_IN_METERS","value":"10000","matchCase":false},{"type":"equals","key":"LICENSE","value":"CC BY 4.0","matchCase":false}]}

 The dataset includes 0 records from 0 constituent datasets; see https://api.gbif.org/v1/occurrence/download/0002373-260120142942310/datasets/export for details.
DOI: 10.6084/m9.figshare.27930771
title: Gut metabolomic and microbiota analyses in ALS mice reveal specific metabolites despite the absence of significant gut dysbiosis

description: Over the past years, interest in the role of gut microbiota in neurodegenerative diseases has emerged. Despite numerous publications over the past decade, both in human and pre-clinical studies, there is no clear consensus on the microbiota’s role or involvement in ALS. Few studies on mouse models of ALS highlighted a correlation between specific bacteria species and the prognostic or severity of the disease. Still these results lack reproducibility and remain controverted. In this article we present a study of fecal microbiota in the SOD1<sup>G93A</sup> mouse model associated with a metabolomic analysis of cecum content, compared to controls. Intestinal metabolomic profile and fecal microbiota were assessed in two cohorts of SOD<sup>G93A</sup> mice compared to wildtype controls at the terminal stage of the ALS disease. Results showed a significant difference in metabolomic profile in SOD1<sup>G93A</sup> mice compared to controls but without a marked change in composition and diversity of fecal microbiota. Nevertheless, we observed an increase of <i>Lachnospiraceae</i> family, which are butyrate-producer bacteria, in SOD1<sup>G93A</sup> mice. Moreover, some metabolites with significantly different intestinal concentrations are partially produced and linked with intestinal bacteria, such as riboflavin, hippurate, and N-acetylputrescine, leaving us convinced of the interest in looking further into the role of the microbiota in ALS. Despite an alteration of the intestinal metabolome in SOD1<sup>G93A</sup> mice, microbiota data did not show significant changes, underlying the need for further research.
DOI: 10.6084/m9.figshare.27999444
title: Contributions of neurologists to diagnostic timelines of ALS and thinkALS as an early referral instrument for clinicians

description: <i>Objectives:</i> To evaluate neurologists and other clinicians’ contributions to U.S. ALS diagnostic timelines. <i>Background</i>: Over the past two decades, the average time to ALS diagnosis in the U.S. has remained unchanged at 12 months. ALS patients see 3-4 clinicians prior to referral to an ALS specialist for diagnosis confirmation and/or treatment initiation. There is an urgent need to identify where delays occur, so that targeted clinician awareness may be raised about early suspicion and referrals. <i>Methods</i>: Review of Medicare claims database for health care utilization patterns by ALS beneficiaries during diagnostic journey. Survey of typical clinic wait times for new consultations reported by 75-78 ALS Certified Treatment Centers of Excellence (2019-2021). <i>Results</i>: During 2011-2021, 78,520 Medicare beneficiaries were diagnosed with ALS (T0). The mean (median) timelines between first neurologist ambulatory visit and T0, is 16.5 (11.0) months; mean ± SD for ALS/neuromuscular providers being 9.6 ± 12.6 months versus 16.7 ± 17.5 months for non-neuromuscular neurologists. During the 12-months preceding T0, an ALS patient undergoes median(max) 1.5(4.0) brain-MRIs, 1.6(6.0) spine-MRIs, and 1.3(4.0) electromyography studies. Greater than 75% of ALS centers consistently report ≤ 4 week wait times for new ALS consults. This study introduces “thinkALS,” an easy-to-use clinical diagnostic and referral guide for non-ALS neurologists to tackle this challenge. <i>Conclusions:</i> This study is the first to provide metrics on how non-neuromuscular/ALS specialists contribute to ALS diagnostic timelines in the U.S.
DOI: 10.6084/m9.figshare.27999444.v1
title: Contributions of neurologists to diagnostic timelines of ALS and thinkALS as an early referral instrument for clinicians

description: <i>Objectives:</i> To evaluate neurologists and other clinicians’ contributions to U.S. ALS diagnostic timelines. <i>Background</i>: Over the past two decades, the average time to ALS diagnosis in the U.S. has remained unchanged at 12 months. ALS patients see 3-4 clinicians prior to referral to an ALS specialist for diagnosis confirmation and/or treatment initiation. There is an urgent need to identify where delays occur, so that targeted clinician awareness may be raised about early suspicion and referrals. <i>Methods</i>: Review of Medicare claims database for health care utilization patterns by ALS beneficiaries during diagnostic journey. Survey of typical clinic wait times for new consultations reported by 75-78 ALS Certified Treatment Centers of Excellence (2019-2021). <i>Results</i>: During 2011-2021, 78,520 Medicare beneficiaries were diagnosed with ALS (T0). The mean (median) timelines between first neurologist ambulatory visit and T0, is 16.5 (11.0) months; mean ± SD for ALS/neuromuscular providers being 9.6 ± 12.6 months versus 16.7 ± 17.5 months for non-neuromuscular neurologists. During the 12-months preceding T0, an ALS patient undergoes median(max) 1.5(4.0) brain-MRIs, 1.6(6.0) spine-MRIs, and 1.3(4.0) electromyography studies. Greater than 75% of ALS centers consistently report ≤ 4 week wait times for new ALS consults. This study introduces “thinkALS,” an easy-to-use clinical diagnostic and referral guide for non-ALS neurologists to tackle this challenge. <i>Conclusions:</i> This study is the first to provide metrics on how non-neuromuscular/ALS specialists contribute to ALS diagnostic timelines in the U.S.
DOI: 10.6084/m9.figshare.27930771.v1
title: Gut metabolomic and microbiota analyses in ALS mice reveal specific metabolites despite the absence of significant gut dysbiosis

description: Over the past years, interest in the role of gut microbiota in neurodegenerative diseases has emerged. Despite numerous publications over the past decade, both in human and pre-clinical studies, there is no clear consensus on the microbiota’s role or involvement in ALS. Few studies on mouse models of ALS highlighted a correlation between specific bacteria species and the prognostic or severity of the disease. Still these results lack reproducibility and remain controverted. In this article we present a study of fecal microbiota in the SOD1<sup>G93A</sup> mouse model associated with a metabolomic analysis of cecum content, compared to controls. Intestinal metabolomic profile and fecal microbiota were assessed in two cohorts of SOD<sup>G93A</sup> mice compared to wildtype controls at the terminal stage of the ALS disease. Results showed a significant difference in metabolomic profile in SOD1<sup>G93A</sup> mice compared to controls but without a marked change in composition and diversity of fecal microbiota. Nevertheless, we observed an increase of <i>Lachnospiraceae</i> family, which are butyrate-producer bacteria, in SOD1<sup>G93A</sup> mice. Moreover, some metabolites with significantly different intestinal concentrations are partially produced and linked with intestinal bacteria, such as riboflavin, hippurate, and N-acetylputrescine, leaving us convinced of the interest in looking further into the role of the microbiota in ALS. Despite an alteration of the intestinal metabolome in SOD1<sup>G93A</sup> mice, microbiota data did not show significant changes, underlying the need for further research.
DOI: 10.15468/dl.8ngyct
title: Occurrence Download

description: A dataset containing 753 species occurrences available in GBIF matching the query:
{
 "and" : [
 "Country is Brazil",
 "TaxonKey is Laterallus flaviventer"
 ]
}

 The dataset includes 753 records from 5 constituent datasets; see https://api.gbif.org/v1/occurrence/download/0002375-260120142942310/datasets/export for details.
 
Data from some individual datasets included in this download may be licensed under less restrictive terms.
DOI: 10.6084/m9.figshare.27969566
title: Routine blood biochemical biomarkers in amyotrophic lateral sclerosis: Systematic review and cohort analysis

description: <i>Introduction</i>: Blood biochemical biomarkers, including urate, creatinine, albumin, and creatine kinase, have been shown to be useful in ALS. To provide further information about the roles of these four biomarkers roles we performed a systematic review. In addition, we also performed a new study of the role of these biomarkers in predicting survival, using data from our local ALS cohort. <i>Methods</i>: (1) Using established databases and other sources, we searched for papers about the use of urate, creatinine, albumin, and creatine kinase as biomarkers in ALS. Included articles were reviewed for information about biomarker levels in ALS and controls, association with markers of functional decline, and survival. (2) For our local ALS cohort, we performed survival analysis, Cox-proportionate-hazard ratio and ROC curves to investigate the use of these biomarkers in predicting survival. <i>Results</i>: (1) For systematic review, 104 papers were included. There was some variability in the findings. For urate, there was evidence of decreased levels in ALS, with higher levels associated ith longer survival. For creatinine, there was evidence of decreased levels in ALS, and higher levels correlated with longer survival. For albumin, some reports of reduced levels in ALS, but no consistent association with survival. For creatine kinase, some reports of increased levels in ALS, with inconsistent association with survival. (2) For the local ALS cohort there was evidence that urate and creatinine were associated with survival, but no significant association with survival. There was less evidence for albumin and CK. <i>Discussion</i>: This study provides support for further studies of these readily available biochemical measurement as bioamerkers in ALS.