cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5126125
title: Supplementary Material for: Cerebral Microbleeds Are Not Associated with Long-Term Cognitive Outcome in Patients with Transient Ischemic Attack or Minor Stroke

description: <b><i>Background:</i></b> Cerebral microbleeds have been related to cerebrovascular disease and dementia. They occur more frequently in patients with ischemic stroke than in the general population, but their relation to cognition in these patients is uncertain, particularly in the long run. We examined the relationship between microbleeds in patients with a transient ischemic attack (TIA) or minor ischemic stroke, and cognitive performance 4 years later. <b><i>Methods:</i></b> Participants were recruited from a prospective multicenter cohort of patients with a TIA or minor ischemic stroke (n = 397). They underwent magnetic resonance imaging (MRI), including a T2*-weighted sequence, within 3 months after their ischemic event. Microbleeds, atrophy, lacunae and white matter hyperintensities (WMH) were rated visually. Cognitive status was examined in 94% of all patients who were still alive after a mean interval of 3.8 years by the Dutch version of the Telephone Interview for Cognitive Status (TICS; n = 280) or by an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) obtained from a close relative if a TICS could not be obtained (n = 48). The relationship between presence of microbleeds and TICS or IQCODE score was assessed with linear regression analyses adjusted for age, sex, educational level and time interval between MRI and cognitive evaluation. <b><i>Results:</i></b> The mean age was 65 ± 12 years at inclusion. The vascular event at inclusion was a TIA in 170 patients (52%) and a minor ischemic stroke in 155 patients (47%). Microbleeds were present in 11.6% of the patients. Patients with microbleeds were significantly older than patients without microbleeds (70 ± 9 vs. 64 ± 12 years), more often had hypertension, and had more cerebral atrophy, WMH and lacunae on MRI (all p &lt; 0.05). The mean TICS score was 35.3 ± 5.9 for patients with microbleeds (n = 29) and 34.6 ± 5.2 for patients without microbleeds (n = 251); the adjusted mean difference (95% CI) was 1.69 (-0.01 to 3.38). The total IQCODE score was 66.0 ± 10.8 for patients with microbleeds (n = 9) and 63.1 ± 12.9 for patients without microbleeds (n = 39); the adjusted mean difference was 2.43 (-7.55 to 12.41). The relative risk (adjusted for age) for abnormal cognitive performance when having microbleeds was 1.19 (95% CI: 0.63-2.26). Subcortical atrophy was associated with lower TICS score [standardized regression coefficient β: -0.12 (-0.23 to 0.00); p = 0.04] and with lower IQCODE score [0.51 (0.19-0.83); p = 0.00]. The adjusted mean difference of IQCODE scores between patients with and those without a lacunar infarct was 0.39 (0.12-0.65; p = 0.01). <b><i>Conclusions:</i></b> In this sample of patients with a recent TIA or minor ischemic stroke, microbleeds were not associated with cognitive performance 4 years later. Apparently, this association is different from other markers of small vessel disease.
DOI: 10.6084/m9.figshare.5126116
title: Supplementary Material for: AxonQuant: A Microfluidic Chamber Culture-Coupled Algorithm That Allows High-Throughput Quantification of Axonal Damage

description: Published methods for imaging and quantitatively analyzing morphological changes in neuronal axons have serious limitations because of their small sample sizes, and their time-consuming and nonobjective nature. Here we present an improved microfluidic chamber design suitable for fast and high-throughput imaging of neuronal axons. We developed the AxonQuant algorithm, which is suitable for automatic processing of axonal imaging data. This microfluidic chamber-coupled algorithm allows calculation of an ‘axonal continuity index' that quantitatively measures axonal health status in a manner independent of neuronal or axonal density. This method allows quantitative analysis of axonal morphology in an automatic and nonbiased manner. Our method will facilitate large-scale high-throughput screening for genes or therapeutic compounds for neurodegenerative diseases involving axonal damage. When combined with imaging technologies utilizing different gene markers, this method will provide new insights into the mechanistic basis for axon degeneration. Our microfluidic chamber culture-coupled AxonQuant algorithm will be widely useful for studying axonal biology and neurodegenerative disorders. © 2014 S. Karger AG, Basel
DOI: 10.6084/m9.figshare.5126119
title: Supplementary Material for: Sputum Eicosanoid Profiling in Exacerbations of Chronic Obstructive Pulmonary Disease

description: <b><i>Background:</i></b> Eicosanoids are small lipid molecules with diverse biological functions in the airways. <b><i>Objectives:</i></b> The aim of this study was to investigate changes in leukotriene B<sub>4</sub> (LTB<sub>4</sub>), 8-isoprostane, prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) and cysteinyl-leukotriene (cys-LT) levels in the sputum of patients with chronic obstructive pulmonary disease (COPD) at the onset of a severe exacerbation and during the course of recovery. <b><i>Methods:</i></b> Thirty-seven ex-smoker COPD patients suffering an episode of acute exacerbation were enrolled. Samples were taken (i) on hospital admission and (ii) after regular treatment. Twenty-five stable ex-smoker COPD patients served as controls. Eicosanoids were determined by enzyme immunoassay. <b><i>Results:</i></b> Sputum PGE<sub>2</sub> [39.8 (13.3-103.3) vs. 5.05 (2.3-12.1) pg/ml, p &lt; 0.001], 8-isoprostane [89.5 (36.9-184.7) vs. 29.7 (13.8-68.8) pg/ml, p &lt; 0.01] and LTB<sub>4</sub> [587.7 (252.9-774.8) vs. 276.1 (105.4-594.7) pg/ml, p &lt; 0.05] levels were increased in patients with exacerbation compared to stable subjects. After treatment only PGE<sub>2</sub> levels decreased significantly [at discharge: 19.6 (4.6-52.5) pg/ml, p &lt; 0.01], the levels of other eicosanoids remained elevated (p = NS). Sputum cys-LT levels were similar in stable patients and in those with exacerbation and treatment did not influence cys-LTs either. There was a significant correlation between PGE<sub>2</sub> and sputum neutrophil and lymphocyte cell counts in patients with exacerbation. <b><i>Conclusions:</i></b> Our results suggest that 8-isoprostane, LTB<sub>4</sub> and PGE<sub>2</sub> but not cys-LTs may be involved in exacerbation-associated inflammatory processes in the airways of patients with COPD. Validation of PGE<sub>2</sub> for use as a biomarker of recovery from an exacerbation requires further studies.
DOI: 10.6084/m9.figshare.5126122
title: Supplementary Material for: Dysphagia Risk Assessment in Acute Left-Hemispheric Middle Cerebral Artery Stroke

description: <b><i>Background and Purpose:</i></b> Bedside evaluation of dysphagia may be challenging in left middle cerebral artery (MCA) stroke due to frequently existing aphasia. Here we analyse the predictive value of common bedside screening tests and of two items of cortical dysfunction, aphasia and buccofacial apraxia (BFA), for the detection of dysphagia. <b><i>Methods:</i></b> We prospectively examined 67 consecutive patients with clinical and imaging evidence of acute (&lt;72 h) left MCA stroke. Dysphonia, dysarthria, abnormal volitional cough and abnormal gag reflex were assessed followed by a standardized 50-ml water-swallowing test determining the symptoms cough and voice change after swallow. Aphasia and BFA were assessed according to defined criteria. Fibre-optic endoscopic evaluation of swallowing (FEES) was performed for validation of dysphagia. <b><i>Results:</i></b> 41 (61%) patients had FEES-proven dysphagia. Abnormal gag reflex, abnormal volitional cough, cough after swallow, aphasia and BFA were significantly more frequent in dysphagic as compared to non-dysphagic patients, while dysphonia, dysarthria and voice change after swallow were not. Aphasia and BFA had the highest sensitivity (97 and 78%, respectively) and high negative predictive values (89 and 68%, respectively) for dysphagia. Multivariate regression analysis did not identify an independent predictor of dysphagia. <b><i>Conclusions:</i></b> In left MCA stroke, the sensitivity and specificity of common bedside dysphagia screening methods are low. In contrast, aphasia and BFA have a high sensitivity and high negative predictive power, presumably due to the neuro-anatomical overlap between cortical regions involved in swallowing, speech production, imitation and voluntary movement control.
DOI: 10.6084/m9.figshare.5126125.v1
title: Supplementary Material for: Cerebral Microbleeds Are Not Associated with Long-Term Cognitive Outcome in Patients with Transient Ischemic Attack or Minor Stroke

description: <b><i>Background:</i></b> Cerebral microbleeds have been related to cerebrovascular disease and dementia. They occur more frequently in patients with ischemic stroke than in the general population, but their relation to cognition in these patients is uncertain, particularly in the long run. We examined the relationship between microbleeds in patients with a transient ischemic attack (TIA) or minor ischemic stroke, and cognitive performance 4 years later. <b><i>Methods:</i></b> Participants were recruited from a prospective multicenter cohort of patients with a TIA or minor ischemic stroke (n = 397). They underwent magnetic resonance imaging (MRI), including a T2*-weighted sequence, within 3 months after their ischemic event. Microbleeds, atrophy, lacunae and white matter hyperintensities (WMH) were rated visually. Cognitive status was examined in 94% of all patients who were still alive after a mean interval of 3.8 years by the Dutch version of the Telephone Interview for Cognitive Status (TICS; n = 280) or by an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) obtained from a close relative if a TICS could not be obtained (n = 48). The relationship between presence of microbleeds and TICS or IQCODE score was assessed with linear regression analyses adjusted for age, sex, educational level and time interval between MRI and cognitive evaluation. <b><i>Results:</i></b> The mean age was 65 ± 12 years at inclusion. The vascular event at inclusion was a TIA in 170 patients (52%) and a minor ischemic stroke in 155 patients (47%). Microbleeds were present in 11.6% of the patients. Patients with microbleeds were significantly older than patients without microbleeds (70 ± 9 vs. 64 ± 12 years), more often had hypertension, and had more cerebral atrophy, WMH and lacunae on MRI (all p &lt; 0.05). The mean TICS score was 35.3 ± 5.9 for patients with microbleeds (n = 29) and 34.6 ± 5.2 for patients without microbleeds (n = 251); the adjusted mean difference (95% CI) was 1.69 (-0.01 to 3.38). The total IQCODE score was 66.0 ± 10.8 for patients with microbleeds (n = 9) and 63.1 ± 12.9 for patients without microbleeds (n = 39); the adjusted mean difference was 2.43 (-7.55 to 12.41). The relative risk (adjusted for age) for abnormal cognitive performance when having microbleeds was 1.19 (95% CI: 0.63-2.26). Subcortical atrophy was associated with lower TICS score [standardized regression coefficient β: -0.12 (-0.23 to 0.00); p = 0.04] and with lower IQCODE score [0.51 (0.19-0.83); p = 0.00]. The adjusted mean difference of IQCODE scores between patients with and those without a lacunar infarct was 0.39 (0.12-0.65; p = 0.01). <b><i>Conclusions:</i></b> In this sample of patients with a recent TIA or minor ischemic stroke, microbleeds were not associated with cognitive performance 4 years later. Apparently, this association is different from other markers of small vessel disease.
DOI: 10.6084/m9.figshare.5126113
title: Supplementary Material for: The M1 Protein of <b><i>Streptococcus pyogenes</i></b> Triggers an Innate Uptake Mechanism into Polarized Human Endothelial Cells

description: Serotype M1 <i>Streptococcus pyogenes</i> is a major human pathogen associated with severe invasive diseases causing high morbidity and mortality. In a substantial number of cases, invasive disease develops in previously healthy individuals with no obvious port of entry. This has led to the hypothesis that the source of streptococci in these cases is a transient bacteraemia. This study focuses on the analysis of interaction of tissue-invasive serotype M1 <i>S. pyogenes</i> with human endothelial cells (EC) of the vascular system. We identify the M1 surface protein of <i>S. pyogenes</i> as the EC invasin which is recognised by polarized human blood EC, thereby triggering rapid, phagocytosis-like uptake of streptococci into polarized EC layers. Upon internalization, the M1 <i>S. pyogenes</i> serotype is incorporated into phagosomes which traffic via the endosomal/lysosomal pathway. However, some of the streptococci successfully evade this innate killing process and hereby mediate their escape into the cytoplasm of the host cell. The results of this study demonstrate that blood EC possess an efficient uptake mechanism for serotype M1 <i>S. pyogenes</i>. Despite efficient phagocytosis, streptococcal survival within EC constitutes one potential mechanism which favours intracellular persistence and thus facilitates continuous infection and dissemination from the primary side of infection into deep tissue.
DOI: 10.6084/m9.figshare.5126119.v1
title: Supplementary Material for: Sputum Eicosanoid Profiling in Exacerbations of Chronic Obstructive Pulmonary Disease

description: <b><i>Background:</i></b> Eicosanoids are small lipid molecules with diverse biological functions in the airways. <b><i>Objectives:</i></b> The aim of this study was to investigate changes in leukotriene B<sub>4</sub> (LTB<sub>4</sub>), 8-isoprostane, prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) and cysteinyl-leukotriene (cys-LT) levels in the sputum of patients with chronic obstructive pulmonary disease (COPD) at the onset of a severe exacerbation and during the course of recovery. <b><i>Methods:</i></b> Thirty-seven ex-smoker COPD patients suffering an episode of acute exacerbation were enrolled. Samples were taken (i) on hospital admission and (ii) after regular treatment. Twenty-five stable ex-smoker COPD patients served as controls. Eicosanoids were determined by enzyme immunoassay. <b><i>Results:</i></b> Sputum PGE<sub>2</sub> [39.8 (13.3-103.3) vs. 5.05 (2.3-12.1) pg/ml, p &lt; 0.001], 8-isoprostane [89.5 (36.9-184.7) vs. 29.7 (13.8-68.8) pg/ml, p &lt; 0.01] and LTB<sub>4</sub> [587.7 (252.9-774.8) vs. 276.1 (105.4-594.7) pg/ml, p &lt; 0.05] levels were increased in patients with exacerbation compared to stable subjects. After treatment only PGE<sub>2</sub> levels decreased significantly [at discharge: 19.6 (4.6-52.5) pg/ml, p &lt; 0.01], the levels of other eicosanoids remained elevated (p = NS). Sputum cys-LT levels were similar in stable patients and in those with exacerbation and treatment did not influence cys-LTs either. There was a significant correlation between PGE<sub>2</sub> and sputum neutrophil and lymphocyte cell counts in patients with exacerbation. <b><i>Conclusions:</i></b> Our results suggest that 8-isoprostane, LTB<sub>4</sub> and PGE<sub>2</sub> but not cys-LTs may be involved in exacerbation-associated inflammatory processes in the airways of patients with COPD. Validation of PGE<sub>2</sub> for use as a biomarker of recovery from an exacerbation requires further studies.
DOI: 10.6084/m9.figshare.5126107
title: Supplementary Material for: Low Expression of Transforming Growth Factor Beta-1 in Cancer Tissue Predicts a Poor Prognosis for Patients with Stage III Rectal Cancers

description: <b><i>Objective:</i></b> Transforming growth factor beta (TGF-β) plays an important role in tumorigenesis and metastasis. It works as a tumor suppressor in the normal colon, but acts as a cancer promoter during the late stages of colorectal carcinogenesis. High expression of TGF-β is known to be associated with advanced stages, tumor recurrence and decreased survival of patients. We investigated the expression of TGF-β and its signaling axis molecules and evaluated their prognostic significance in patients with stage III rectal cancers. <b><i>Methods:</i></b> Tissues from 201 cases of stage III rectal cancer were subjected to immunohistochemistry for TGF-β1, type II TGF-β receptor, Smad3, Smad4 and Smad7 proteins. The immunoactivities of these molecules were evaluated and the results were compared with clinicopathological variables including patient survival. <b><i>Results:</i></b> Low expression of TGF-β1 protein was correlated with a decreased disease-free survival in univariate Kaplan-Meier (p = 0.003) and multivariate Cox regression (HR 9.188 and 95% CI 1.256-67.198, p = 0.029) analyses. The loss of Smad4 protein expression was associated with a reduction in disease-free survival in the univariate analysis, but this finding was not significant after the multivariate analysis. <b><i>Conclusion:</i></b> Low expression of TGF-β1 protein is associated with a poor prognosis for patients with stage III rectal cancers.
DOI: 10.6084/m9.figshare.5126110
title: Supplementary Material for: Pre-End-Stage Renal Disease Care Not Associated with Dialysis Facility Neighborhood Poverty in the United States

description: <b><i>Background:</i></b> Receipt of nephrology care prior to end-stage renal disease (ESRD) is a strong predictor of decreased mortality and morbidity, and neighborhood poverty may influence access to care. Our objective was to examine whether neighborhood poverty is associated with lack of pre-ESRD care at dialysis facilities. <b><i>Methods:</i></b> In a multi-level ecological study using geospatially linked 2007-2010 Dialysis Facility Report and 2006-2010 American Community Survey data, we examined whether<b> </b>high<b> </b>neighborhood poverty (≥20% of households in census tract living below poverty) was associated with dialysis facility-level lack of pre-ESRD care (percentage of patients with no nephrology care prior to dialysis start) in mixed-effects models, adjusting for facility and neighborhood confounders and allowing for neighborhood and regional random effects. <b><i>Results:</i></b> Among the 5,184 facilities examined, 1,778 (34.3%) were located in a high-poverty area. Lack of pre-ESRD care was similar in poverty areas (30.8%) and other neighborhoods (29.6%). With adjustment, the absolute increase in percentage of patients at a facility with no pre-ESRD care associated with facility location in a poverty area versus other neighborhood was only 0.08% (95% CI -1.32, 1.47; p = 0.9). Potential effect modification by race and income inequality was detected. <b><i>Conclusion:</i></b> Despite previously reported detrimental effects of neighborhood poverty on health, facility neighborhood poverty was not associated with receipt of pre-ESRD care, suggesting no need to target interventions to increase access to pre-ESRD care at facilities in poorer geographic areas.
DOI: 10.6084/m9.figshare.5126113.v1
title: Supplementary Material for: The M1 Protein of <b><i>Streptococcus pyogenes</i></b> Triggers an Innate Uptake Mechanism into Polarized Human Endothelial Cells

description: Serotype M1 <i>Streptococcus pyogenes</i> is a major human pathogen associated with severe invasive diseases causing high morbidity and mortality. In a substantial number of cases, invasive disease develops in previously healthy individuals with no obvious port of entry. This has led to the hypothesis that the source of streptococci in these cases is a transient bacteraemia. This study focuses on the analysis of interaction of tissue-invasive serotype M1 <i>S. pyogenes</i> with human endothelial cells (EC) of the vascular system. We identify the M1 surface protein of <i>S. pyogenes</i> as the EC invasin which is recognised by polarized human blood EC, thereby triggering rapid, phagocytosis-like uptake of streptococci into polarized EC layers. Upon internalization, the M1 <i>S. pyogenes</i> serotype is incorporated into phagosomes which traffic via the endosomal/lysosomal pathway. However, some of the streptococci successfully evade this innate killing process and hereby mediate their escape into the cytoplasm of the host cell. The results of this study demonstrate that blood EC possess an efficient uptake mechanism for serotype M1 <i>S. pyogenes</i>. Despite efficient phagocytosis, streptococcal survival within EC constitutes one potential mechanism which favours intracellular persistence and thus facilitates continuous infection and dissemination from the primary side of infection into deep tissue.
DOI: 10.6084/m9.figshare.5126101
title: Supplementary Material for: Functional Closure of the Ductus Arteriosus at Birth: Evidence against an Intermediary Role of Angiotensin II

description: The fetal ductus arteriosus (DA) closes postnatally first functionally and then structurally. Normal rise in blood oxygenation is regarded as a prime trigger, but closure may occur more slowly without this stimulus. Here, our aim was<b> </b>to assess the role of angiotensin II (Ang II) in functional closure of DA since its action may not be conditioned by oxygen. Experiments were performed with wild-type fetal and neonatal mice, using whole-body freezing technique to assess DA caliber in vivo. Transcripts for Ang II type 1 (AT<sub>1</sub>R) and type 2 (AT<sub>2</sub>R) receptors were also examined. We found that<b> </b>the AT<sub>1</sub>R antagonist olmesartan had no effect in the fetus, but delayed ductus closure in the neonate. However, this response was short-lived and disappeared upon concomitant treatment with the AT<sub>2</sub>R antagonist PD123319. Coincidentally, olmesartan promoted the <i>Agtr2 </i>transcript. We conclude that AT<sub>1</sub>R-based Ang II has no role in the functional closure of DA. Conversely, the compound may modulate this process through AT<sub>2</sub>R-mediated vasodilatation.
DOI: 10.6084/m9.figshare.5126104
title: Supplementary Material for: Cross-Reactivity between <b><i>Anisakis</i></b> spp. and Wasp Venom Allergens

description: <b><i>Background:</i></b> Anisakiasis is caused by the consumption of raw or undercooked fish or cephalopods parasitized by live L3 larvae of nematode <i>Anisakis </i>spp. Larvae anchor to stomach mucosa releasing excretion/secretion products which contain the main allergens. It has been described that nematode larvae release venom allergen-like proteins among their excretion/secretion products. We investigated potential cross-reactivity between <i>Anisakis </i>and wasp venom allergens. <b><i>Methods:</i></b> Two groups of 25 patients each were studied: wasp venom- and <i>Anisakis-</i>allergic patients. Sera from patients were tested by ImmunoCAP, dot-blotting with recombinant <i>Anisakis</i> allergens and ADVIA-Centaur system with Hymenoptera allergens. Cross-reactivity was assessed by IgE immunoblotting inhibition assays. Role of cross-reactive carbohydrate determinants (CCDs) was studied by inhibition with bromelain and periodate treatment. <b><i>Results:</i></b> A total of 40% of wasp venom-allergic patients had specific IgE to <i>Anisakis simplex </i>and 20% detected at least one of the <i>Anisakis</i> recombinant allergens tested. Likewise, 44% of <i>Anisakis-</i>allergic patients had specific IgE to <i>Vespula </i>spp<i>.</i> venom and 16% detected at least one of the Hymenoptera allergens tested. Wasp venom-allergic patients detected CCDs in <i>Anisakis</i> extract and peptide epitopes on <i>Anisakis </i>allergens rAni s 1 and rAni s 9, whereas <i>Anisakis-</i>allergic patients only detected CCDs on nVes v 1 allergen from <i>Vespula </i>spp. venom. The only <i>Anisakis</i> allergen inhibited by <i>Vespula </i>venom was rAni s 9. <b><i>Conclusions:</i></b> This is the first time that cross-sensitization between wasp venom and <i>Anisakis </i>is described. CCDs are involved in both cases; however, peptide epitopes are only recognized by wasp venom-allergic patients.