cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5124406
title: Supplementary Material for: Long-Term Survival of Ischemic Cerebrovascular Disease in the Acute Inflammatory Stroke Study, a Hospital-Based Cohort Described by TOAST and ASCO

description: <b><i>Background:</i></b> Ischemic cerebrovascular disease (ICVD) comprises multiple etiological phenotypes that share common clinical characteristics. Etiological classification of patients with ICVD is of major clinical interest to achieve optimal medical treatment and predict prognosis. The TOAST classification system has been widely used to describe stroke etiology but provides restricted phenotypic homogeneity within groups. The ASCO classification system has introduced a new approach in phenotypic classification, and aims to describe clinical characteristics without merging concurrent comorbidities. Inflammatory processes have been suggested to mediate stroke etiology and pathology. The Acute Inflammatory Stroke Study (AISS), a hospital-based cohort, is here introduced and described by TOAST and ASCO classification systems. The aim of this first analysis of AISS was to investigate long-term mortality in relation to ischemic stroke subtypes, and clinical and biochemical markers. <b><i>Methods:</i></b> AISS consecutively follows patients on 6 occasions up to 1 year after stroke onset. Complete workup according to ASCO comprised CT or MRI of the head, ECG, duplex of the extracranial arteries or CT/MR angiography and ultrasound of the heart. Level 2 evidence was required in each domain to obtain a comparable system to TOAST (ASCO2). Clinical and biochemical characteristics and mortality rates were documented and compared by the two classification systems. <b><i>Results:</i></b> Of 142 patients consecutively evaluated and recruited in the study, a total of 101 ICVD patients (ischemic stroke, n = 84; transient ischemic attack, n = 17) were included in the final analysis. Agreement between ASCO2 and TOAST was very good. During the mean observation period of 28 months, 26 patients died. The 1- and 4-year mortality rates were 0 and 4% for large artery atherosclerosis (LAA); 23 and 36% for cardioembolism (CE); 0% for small artery occlusion (SAO); 63 and 100% for the subtype with unknown etiology due to incomplete workup (Unknown), and 12 and 29% for the cryptogenic subtype. As for the ASCO2 groups, the 1- and 4-year mortality rates were 0 and 6% in LAA, 25 and 36% in CE, 0% in SAO, 0 and 14% in LAA + CE, 0% in SAO + CE, 16 and 36% in the subgroup with undetermined etiology despite complete workup, and 56 and 100% in Unknown. Regression analysis showed that age, white blood cell count, fibrinogen and bilirubin, but not etiological subgroup, were independent predictors of mortality. <b><i>Conclusion:</i></b> Our findings indicate that clinical and biochemical markers may differentiate phenotypically homogeneous etiological subtypes and predict long-term mortality. Further studies with larger patient numbers are needed to investigate possible causative mechanisms.
DOI: 10.6084/m9.figshare.5124409.v1
title: Supplementary Material for: Systematic Review of Blinding Assessment in Randomized Controlled Trials in Schizophrenia and Affective Disorders 2000-2010

description: <b><i>Background:</i></b> Blinding is an integral part of many randomized controlled trials (RCTs). However, both blinding and blinding assessment seem to be rarely documented in trial reports. <b><i>Method:</i></b> Systematic review of articles on RCTs in schizophrenia and affective disorders research during 2000-2010. <b><i>Results:</i></b> Among 2,467 publications, 61 (2.5%; 95% confidence interval: 1.9-3.1%) reported assessing participant, rater, or clinician blinding: 5/672 reports on schizophrenia (0.7%; 0.3-1.6%) and 33/1,079 (3.1%; 2.1-4.2%) on affective disorders, without significant trends across the decade. Rarely was blinding assessed at the beginning, in most studies assessment was at the end. Proportion of patients' and raters' correct guesses of study arm averaged 54.4 and 62.0% per study, with slightly more correct guesses in treatment arms than in placebo arms. Three fourths of responders correctly guessed that they received the active agent. Blinding assessment was more frequently reported in papers on psychotherapy and brain stimulation than on drug trials (5.1%, 1.7-11.9%, vs. 8.3%, 4.3-14.4%, vs. 2.1%, 1.5-2.8%). Lack of assessment of blinding was associated with: (a) positive findings, (b) full industrial sponsorship, and (c) diagnosis of schizophrenia. There was a moderate association of treatment success and blinding status of both trial participants (r = 0.51, p = 0.002) and raters (r = 0.55, p = 0.067). Many RCT reports did not meet CONSORT standards regarding documentation of persons blinded (60%) or of efforts to match interventions (50%). <b><i>Conclusions:</i></b> Recent treatment trials in major psychiatric disorders rarely reported on or evaluated blinding. We recommend routine documentation of blinding strategies in reports.
DOI: 10.6084/m9.figshare.5124394
title: Supplementary Material for: Incorporating Prior Biologic Information for High-Dimensional Rare Variant Association Studies

description: <b><i>Background:</i></b> Given the increasing scale of rare variant association studies, we introduce a method for high-dimensional studies that integrates multiple sources of data as well as allows for multiple region-specific risk indices. <b><i>Methods:</i></b> Our method builds upon the previous Bayesian risk index by integrating external biological variant-specific covariates to help guide the selection of associated variants and regions. Our extension also incorporates a second level of uncertainty as to which regions are associated with the outcome of interest. <b><i>Results:</i></b> Using a set of study-based simulations, we show that our approach leads to an increase in power to detect true associations in comparison to several commonly used alternatives. Additionally, the method provides multi-level inference at the pathway, region and variant levels. <b><i>Conclusion:</i></b> To demonstrate the flexibility of the method to incorporate various types of information and the applicability to high-dimensional data, we apply our method to a single region within a candidate gene study of second primary breast cancer and to multiple regions within a candidate pathway study of colon cancer.
DOI: 10.6084/m9.figshare.5124397
title: Supplementary Material for: Breathing Pattern and Chest Wall Kinematics during Phonation in Chronic Obstructive Pulmonary Disease Patients

description: <b><i>Background:</i></b> Breathing pattern description and chest wall kinematics during phonation have not been studied in male and female patients with chronic obstructive pulmonary disease. <b><i>Objectives:</i></b> We used optoelectronic plethysmography to provide a quantitative description of breathing pattern and chest wall kinematics. <b><i>Methods:</i></b> Volumes of chest wall compartments (rib cage and abdomen) were assessed in 15 patients while reading aloud (R), singing (SI) and during high-effort whispering (HW). <b><i>Results:</i></b> Relative to quiet breathing, tidal volume and expiratory time increased while inspiratory time decreased. The expiratory flow decreased during R and SI, but was unchanged during HW. In males, the end-expiratory volume decreased as a result of a decreased volume of rib cage during R, SI and HW and due to a decreased volume of abdomen during HW. In females, a decrease in end-expiratory volume was accomplished by a decrease in abdominal volume during R and HW. During R, the chest wall end-expiratory volume of the last expiration in females was to the left of the maximal expiratory flow volume curve (MEFV), with still substantial expiratory reserve volume available. In contrast, during SI and HW in females and during all types of phonation in males, chest wall end-expiratory volume of the last expiration was well to the right of the MEFV curve and associated with respiratory discomfort. Gender had a greater importance than physical characteristics in determining more costal breathing in females than in males under all conditions studied. <b><i>Conclusions:</i></b> Phonation imposes more abdominal breathing pattern changes in males and costal changes in females. Expiratory flow encroaches upon the MEFV curve with higher phonatory efforts and respiratory discomfort.
DOI: 10.6084/m9.figshare.5124403.v1
title: Supplementary Material for: Longitudinal Measurements of Oxygen Consumption in Growing Infants during the First Weeks after Birth: Old Data Revisited

description: <b><i>Background:</i></b> In a study conducted in 1966–1969, longitudinal measurements were made of the metabolic rate in growing infants. Statistical methods for analyzing longitudinal data weren’t readily accessible at that time. <b><i>Objectives:</i></b> To measure minimal rates of oxygen consumption (V·O<sub>2</sub>, ml/min) in growing infants during the first postnatal weeks and to determine the relationships between postnatal increases in V·O<sub>2</sub>, body size and postnatal age. <b><i>Methods:</i></b> We studied 61 infants of any birth weight or gestational age, including 19 of very low birth weight. The infants, nursed in incubators, were clinically well and without need of oxygen supplementation or respiratory assistance. Serial measures of V·O<sub>2</sub> using a closed-circuit method were obtained at approximately weekly intervals. V·O<sub>2</sub> was measured under thermoneutral conditions with the infant asleep or resting quietly. Data were analyzed using mixed-effects models. <b><i>Results:</i></b> During early postnatal growth, V·O<sub>2</sub> rises as surface area (m<sup>2</sup>)<sup>1.94</sup> (standard error, SE 0.054) or body weight (kg)<sup>1.24</sup> (SE 0.033). Multivariate analyses show statistically significant effects of both size and age. Reference intervals (RIs) for V·O<sub>2</sub> for fixed values of body weight and postnatal age are presented. As V·O<sub>2</sub> rises with increasing size and age, there is an increase in the skin-operative environmental temperature gradient (T skin-op) required for heat loss. Required T skin-op can be predicted from surface area and heat loss (heat production minus heat storage). <b><i>Conclusions:</i></b> Generation of RIs for minimal rates of V·O<sub>2</sub> in growing infants from the 1960s was enabled by application of mixed-effects statistical models for analyses of longitudinal data. Results apply to the precaffeine era of neonatal care.
DOI: 10.6084/m9.figshare.5124415.v1
title: Supplementary Material for: Differences in the Receptor Status between Primary and Recurrent Breast Cancer - The Frequency of and the Reasons for Discordance

description: <b><i>Objective:</i></b> Receptor discordances between primary and recurrent breast cancer have been described for years, but only a few analyses have elucidated the factors that influence receptor changes. <b><i>Methods:</i></b> Explorative analyses of prospective data from a breast cancer database of a tertiary breast cancer unit. <b><i>Results:</i></b> Recurrent tumours that had expressed oestrogen (ER) and progesterone receptors (PR) and human epidermal growth factor receptor 2 (HER2) as primary tumours were negative for the respective receptor in 22.8, 41.4 and 40.8% of cases. ER, PR and HER2 expression was found in 19.8, 16.7 and 11.5% of recurrent tumours, although no expression had been observed in primary tumours. Receptor discordances in recurrent disease leading to different therapeutic approaches were noted in 126 of 411 patients (30.7%). In patients with tumours expressing primary ER and HER2, independent factors associated with discordance were endocrine therapy and treatment with trastuzumab. <b><i>Conclusion:</i></b> High rates of receptor discordance were found. The impact of factors that influence receptor changes is small so that no subgroup of patients with recurrent breast cancer should be excluded from biopsy. Whenever possible, a biopsy should be taken to confirm the diagnosis of a possible relapse as well as the receptor status of patients with breast cancer.
DOI: 10.6084/m9.figshare.5124394.v1
title: Supplementary Material for: Incorporating Prior Biologic Information for High-Dimensional Rare Variant Association Studies

description: <b><i>Background:</i></b> Given the increasing scale of rare variant association studies, we introduce a method for high-dimensional studies that integrates multiple sources of data as well as allows for multiple region-specific risk indices. <b><i>Methods:</i></b> Our method builds upon the previous Bayesian risk index by integrating external biological variant-specific covariates to help guide the selection of associated variants and regions. Our extension also incorporates a second level of uncertainty as to which regions are associated with the outcome of interest. <b><i>Results:</i></b> Using a set of study-based simulations, we show that our approach leads to an increase in power to detect true associations in comparison to several commonly used alternatives. Additionally, the method provides multi-level inference at the pathway, region and variant levels. <b><i>Conclusion:</i></b> To demonstrate the flexibility of the method to incorporate various types of information and the applicability to high-dimensional data, we apply our method to a single region within a candidate gene study of second primary breast cancer and to multiple regions within a candidate pathway study of colon cancer.
DOI: 10.6084/m9.figshare.5124397.v1
title: Supplementary Material for: Breathing Pattern and Chest Wall Kinematics during Phonation in Chronic Obstructive Pulmonary Disease Patients

description: <b><i>Background:</i></b> Breathing pattern description and chest wall kinematics during phonation have not been studied in male and female patients with chronic obstructive pulmonary disease. <b><i>Objectives:</i></b> We used optoelectronic plethysmography to provide a quantitative description of breathing pattern and chest wall kinematics. <b><i>Methods:</i></b> Volumes of chest wall compartments (rib cage and abdomen) were assessed in 15 patients while reading aloud (R), singing (SI) and during high-effort whispering (HW). <b><i>Results:</i></b> Relative to quiet breathing, tidal volume and expiratory time increased while inspiratory time decreased. The expiratory flow decreased during R and SI, but was unchanged during HW. In males, the end-expiratory volume decreased as a result of a decreased volume of rib cage during R, SI and HW and due to a decreased volume of abdomen during HW. In females, a decrease in end-expiratory volume was accomplished by a decrease in abdominal volume during R and HW. During R, the chest wall end-expiratory volume of the last expiration in females was to the left of the maximal expiratory flow volume curve (MEFV), with still substantial expiratory reserve volume available. In contrast, during SI and HW in females and during all types of phonation in males, chest wall end-expiratory volume of the last expiration was well to the right of the MEFV curve and associated with respiratory discomfort. Gender had a greater importance than physical characteristics in determining more costal breathing in females than in males under all conditions studied. <b><i>Conclusions:</i></b> Phonation imposes more abdominal breathing pattern changes in males and costal changes in females. Expiratory flow encroaches upon the MEFV curve with higher phonatory efforts and respiratory discomfort.
DOI: 10.6084/m9.figshare.5124406.v1
title: Supplementary Material for: Long-Term Survival of Ischemic Cerebrovascular Disease in the Acute Inflammatory Stroke Study, a Hospital-Based Cohort Described by TOAST and ASCO

description: <b><i>Background:</i></b> Ischemic cerebrovascular disease (ICVD) comprises multiple etiological phenotypes that share common clinical characteristics. Etiological classification of patients with ICVD is of major clinical interest to achieve optimal medical treatment and predict prognosis. The TOAST classification system has been widely used to describe stroke etiology but provides restricted phenotypic homogeneity within groups. The ASCO classification system has introduced a new approach in phenotypic classification, and aims to describe clinical characteristics without merging concurrent comorbidities. Inflammatory processes have been suggested to mediate stroke etiology and pathology. The Acute Inflammatory Stroke Study (AISS), a hospital-based cohort, is here introduced and described by TOAST and ASCO classification systems. The aim of this first analysis of AISS was to investigate long-term mortality in relation to ischemic stroke subtypes, and clinical and biochemical markers. <b><i>Methods:</i></b> AISS consecutively follows patients on 6 occasions up to 1 year after stroke onset. Complete workup according to ASCO comprised CT or MRI of the head, ECG, duplex of the extracranial arteries or CT/MR angiography and ultrasound of the heart. Level 2 evidence was required in each domain to obtain a comparable system to TOAST (ASCO2). Clinical and biochemical characteristics and mortality rates were documented and compared by the two classification systems. <b><i>Results:</i></b> Of 142 patients consecutively evaluated and recruited in the study, a total of 101 ICVD patients (ischemic stroke, n = 84; transient ischemic attack, n = 17) were included in the final analysis. Agreement between ASCO2 and TOAST was very good. During the mean observation period of 28 months, 26 patients died. The 1- and 4-year mortality rates were 0 and 4% for large artery atherosclerosis (LAA); 23 and 36% for cardioembolism (CE); 0% for small artery occlusion (SAO); 63 and 100% for the subtype with unknown etiology due to incomplete workup (Unknown), and 12 and 29% for the cryptogenic subtype. As for the ASCO2 groups, the 1- and 4-year mortality rates were 0 and 6% in LAA, 25 and 36% in CE, 0% in SAO, 0 and 14% in LAA + CE, 0% in SAO + CE, 16 and 36% in the subgroup with undetermined etiology despite complete workup, and 56 and 100% in Unknown. Regression analysis showed that age, white blood cell count, fibrinogen and bilirubin, but not etiological subgroup, were independent predictors of mortality. <b><i>Conclusion:</i></b> Our findings indicate that clinical and biochemical markers may differentiate phenotypically homogeneous etiological subtypes and predict long-term mortality. Further studies with larger patient numbers are needed to investigate possible causative mechanisms.
DOI: 10.6084/m9.figshare.5124382
title: Supplementary Material for: Postmortem Biopsy to Obtain Lung Tissue in Congenital Diaphragmatic Hernia

description: <b><i>Background:</i></b> The accrual of human tissues from autopsies for diagnostic and translational research has decreased significantly over the last decades. <b><i>Objectives:</i></b> The objective of this study was to evaluate our experience with lung biopsy through a minithoracotomy as an alternative for obtaining postmortem tissue when full autopsy is refused in congenital diaphragmatic hernia (CDH) patients. <b><i>Methods:</i></b> Within 2 h of death we routinely asked parents for permission to perform an autopsy. Starting in 2001, parents who refused autopsy were asked permission for a postmortem lung biopsy. Pathology autopsy and biopsy reports were compared to clinical records. <b><i>Results:</i></b> Between 2001 and 2009, 46 patients died from CDH. Permission for autopsy was granted in 5 patients (11%). Of the remaining 41 patients, the parents of 15 (33%) agreed to postmortem lung biopsy. In all cases, additional findings were reported from the autopsy or biopsy, without changing the originally reported cause of death<i>.</i> In 1 case, we isolated fibroblasts from the lung biopsy using standardized cell culture techniques. Parents were able to take their child home with a minimal delay following biopsy. <b><i>Conclusions:</i></b> Parents refusing a full autopsy frequently agree to postmortem organ biopsy. This approach should therefore be considered as a valuable alternative, when permission for full autopsy is declined, for obtaining human tissues for both diagnostic and research purposes and is potentially applicable to other anomalies.
DOI: 10.6084/m9.figshare.5124385
title: Supplementary Material for: Automated Spectral EEG Analyses of Premature Infants during the First Three Days of Life Correlated with Developmental Outcomes at 24 Months

description: <b><i>Background:</i></b> Spectral EEG analysis using automated quantification of total absolute band power (tABP) for long-term brain monitoring is reliable. We hypothesised that tABP during the first critical days of life could be a useful tool for predicting later developmental outcomes. <b><i>Objective:</i></b> To determine whether measuring EEG background activity in premature infants with automated tABP quantification during the first 3 days of life correlated with their developmental outcomes at 24 months. <b><i>Methods:</i></b> Preterm infants (group 1, gestational age, GA 24–28 weeks and group 2, GA 28–31 weeks) were continuously monitored by EEG for 3 days after birth. Their developmental outcomes were assessed using the Bayley-II and Peabody-2 developmental tests at 24 months. Their respective indices were calculated. Normal (index ≥85) and abnormal (index &lt;85) outcomes were correlated with the tABP. <b><i>Results:</i></b> In group 1, the tABP was significantly lower in the abnormal infants than in the normal infants. The specificity and negative predictive value were also high for all of the tests that were applied in this group. In group 2, there was no correlation between the tABP and developmental outcome. <b><i>Conclusion:</i></b> This study found that extremely premature infants with poor developmental outcomes had significantly lower tABP values in their first days of life compared to infants from the same group with normal outcomes. This method may be useful in predicting later outcomes in extremely premature infants and has the advantage of being automated.
DOI: 10.6084/m9.figshare.5124388
title: Supplementary Material for: Variation in Human Brains May Facilitate Evolutionary Change toward a Limited Range of Phenotypes

description: Individual variation is the foundation for evolutionary change, but little is known about the nature of normal variation between brains. Phylogenetic variation across mammalian brains is characterized by high intercorrelations in brain region volumes, distinct allometric scaling for each brain region and the relative independence of olfactory and limbic structure volumes from the rest of the brain. Previous work examining brain variation in individuals of some domesticated species showed that these three features of phylogenetic variation were mirrored in individual variation. We extend this analysis to the human brain and 10 of its subdivisions (e.g., isocortex and hippocampus) by using magnetic resonance imaging scans of 90 human brains ranging between 16 and 25 years of age. Human brain variation resembles both the individual variation seen in other species and variation observed across mammalian species, i.e., the relative differences in the slopes of each brain region compared to medulla size within humans and between mammals are concordant, and limbic structures scale with relative independence from other brain regions. This nonrandom pattern of variation suggests that developmental programs channel the variation available for selection.