cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5129146
title: Supplementary Material for: Intraventricular Extension of Supratentorial Intracerebral Hemorrhage: The Modified Graeb Scale Improves Outcome Prediction in Lund Stroke Register

description: <b><i>Background/Aims:</i></b> The modified Graeb Scale (mGS) is a semi-quantitative method to assess the extension of intraventricular hemorrhage (IVH) in patients with intracerebral hemorrhage (ICH). The mGS has been shown to prognosticate outcome after ICH in cohorts derived from convenience samples. We evaluated the external validity of mGS in supratentorial ICH-patients from an unselected cohort. <b><i>Methods:</i></b> ICH-patients were included prospectively and consecutively in Lund Stroke Register. Follow-up survival status was obtained from the National Census Office; functional outcome was obtained from the Swedish Stroke Register or medical records. Using multivariate analyses, we examined if mGS was related to 30-day survival or poor functional outcome (modified Rankin Scale ≥4) at 90 days. <b><i>Results:</i></b> Of 198 supratentorial ICH-patients, 86 (43%) had IVH (median mGS 12, range 1-28). In multivariate regression analyses, the mGS independently predicted 30-day mortality (per point; OR 1.16; 95% CI 1.06-1.27; p = 0.002) and poor functional outcome (OR 1.11; 95% CI 1.02-1.20; p = 0.011) after ICH. In receiver-operator characteristic analysis, the addition of mGS tended to be associated with a higher prognostic accuracy for survival (area under curve 0.886 vs. not including mGS 0.812; p = 0.053). <b><i>Conclusions:</i></b> The mGS improves outcome prediction after supratentorial ICH beyond other previously established factors in an unselected population.
DOI: 10.6084/m9.figshare.5129149
title: Supplementary Material for: Branch Atheromatous Disease: A Clinically Meaningful, Yet Unproven Concept

description: <b><i>Background:</i></b> In 1989, Louis Caplan first used the term branch atheromatous disease (BAD) to describe an occlusion or stenosis at the origin of a deep penetrating artery of the brain, associated with a microatheroma or a junctional plaque, and leading to an internal capsule or pontine small infarct. BAD remained an understudied concept for decades. In recent years, the increasing diffusion of high-resolution magnetic resonance imaging (HRMRI) techniques brought new attention to the BAD debate. We have reviewed clinical studies dealing with BAD-related stroke checking whether a univocal definition of BAD existed, as well as to what extent were consistently associated clinical and imaging features reported. <b><i>Summary:</i></b> We conducted a search of the available literature published up to October 20, 2015 via PubMed using the following search terms: ‘branch atheromatous disease,' ‘intracranial branch atheromatous disease,' ‘cerebral branch atheromatous disease,' combined with ‘stroke.' Forty-six articles were included. We found discrepant definitions and a large variation among clinical features reported in BAD-related stroke patients: among others, a consistent association between BAD and any specific vascular risk factor profile was not detected. Despite this, early neurological deterioration (END) was consistently reported to occur frequently in such patients, although no clear-cut rate range or specific predictor or mechanism of progression was established. In a majority of the studies reporting imaging data, BAD diagnosis was not based on the selective site or type of arterial walls changes, but was inferred based on the vascular territory, size and/or shape of the ischemic lesion. Following the concept that these changes are seated proximally along the perforator artery, differently from to lipohyalinosis changes located distally, the consequent ischemic lesion was hypothesized to be larger in BAD than in lacunar infarcts. However, across reviewed studies, there was little consistency on the dimensional cutoff used to define BAD-related infarcts. In the last few years, a still limited number of studies using HRMRI techniques is providing preliminary proofs that atheromatous changes causing selective remodeling in the parent vessel and extending through the proximal segment of perforating vessel may subtend BAD. <b><i>Key Messages:</i></b> Our literature search showed the lack of a clear-cut definition of BAD, although BAD-related strokes were consistently considered a high risk of END. The use of high-resolution imaging techniques in the assessment of small subcortical strokes may represent the cornerstone in the perspective to better delimiting the boundaries of BAD as a nosological entity.
DOI: 10.6084/m9.figshare.5129161.v1
title: Supplementary Material for: Clinical and Emergent Biomarkers and Their Relationship to the Prognosis of Ovarian Cancer

description: <b><i>Objective:</i></b> Ovarian cancer is the most lethal gynecological malignancy, but information relevant to prognosis and outcomes remain unknown. Here, we used statistical methods to focus specifically on interactions between candidate prognostic variables. <b><i>Methods and Results:</i></b> Univariate, multivariate, and elastic net modeling of 42 variables were applied to a cohort of 542 ovarian cancer patients with 393 episodes of cancer recurrence/death. In univariate analyses, overexpression of TFF3, MDM2, and p53 were associated with improved recurrence-free survival. In multivariate analyses adjusted for age, histology, stage, grade, ascites, and residual disease, overexpression of PR appeared to provide a protective effect [hazard ratio for &gt;50% of cells positive, 0.64 (95% confidence interval 0.44-0.94) compared to &lt;1%], and TFF3 showed a nonlinear association. Importantly, we observed no interactions among variables. However, patients with tumors with moderate TFF3 expression were at a marginally increased risk of recurrence, and patients with tumors with high expression were at a similar to slightly lower risk, compared to those with tumors with no TFF3 expression. <b><i>Conclusions:</i></b> Although no interactions among variables were observed, this study provides important precedent for seeking interactions between clinical and tumor variables in future studies.
DOI: 10.6084/m9.figshare.5129140
title: Supplementary Material for: Collagen Matrix Remodeling in Stented Pulmonary Arteries after Transapical Heart Valve Replacement

description: The use of valved stents for minimally invasive replacement of semilunar heart valves is expected to change the extracellular matrix and mechanical function of the native artery and may thus impair long-term functionality of the implant. Here we investigate the impact of the stent on matrix remodeling of the pulmonary artery in a sheep model, focusing on matrix composition and collagen (re)orientation of the host tissue. Ovine native pulmonary arteries were harvested 8 (n = 2), 16 (n = 4) and 24 (n = 2) weeks after transapical implantation of self-expandable stented heart valves. Second harmonic generation (SHG) microscopy was used to assess the collagen (re)orientation of fresh tissue samples. The collagen and elastin content was quantified using biochemical assays. SHG microscopy revealed regional differences in collagen organization in all explants. In the adventitial layer of the arterial wall far distal to the stent (considered as the control tissue), we observed wavy collagen fibers oriented in the circumferential direction. These circumferential fibers were more straightened in the adventitial layer located behind the stent. On the luminal side of the wall behind the stent, collagen fibers were aligned along the stent struts and randomly oriented between the struts. Immediately distal to the stent, however, fibers on both the luminal and the adventitial side of the wall were oriented in the axial direction, demonstrating the stent impact on the collagen structure of surrounding arterial tissues. Collagen orientation patterns did not change with implantation time, and biochemical analyses showed no changes in the trend of collagen and elastin content with implantation time or location of the vascular wall. We hypothesize that the collagen fibers on the adventitial side of the arterial wall and behind the stent straighten in response to the arterial stretch caused by oversizing of the stent. However, the collagen organization on the luminal side suggests that stent-induced remodeling is dominated by contact guidance.
DOI: 10.6084/m9.figshare.5129146.v1
title: Supplementary Material for: Intraventricular Extension of Supratentorial Intracerebral Hemorrhage: The Modified Graeb Scale Improves Outcome Prediction in Lund Stroke Register

description: <b><i>Background/Aims:</i></b> The modified Graeb Scale (mGS) is a semi-quantitative method to assess the extension of intraventricular hemorrhage (IVH) in patients with intracerebral hemorrhage (ICH). The mGS has been shown to prognosticate outcome after ICH in cohorts derived from convenience samples. We evaluated the external validity of mGS in supratentorial ICH-patients from an unselected cohort. <b><i>Methods:</i></b> ICH-patients were included prospectively and consecutively in Lund Stroke Register. Follow-up survival status was obtained from the National Census Office; functional outcome was obtained from the Swedish Stroke Register or medical records. Using multivariate analyses, we examined if mGS was related to 30-day survival or poor functional outcome (modified Rankin Scale ≥4) at 90 days. <b><i>Results:</i></b> Of 198 supratentorial ICH-patients, 86 (43%) had IVH (median mGS 12, range 1-28). In multivariate regression analyses, the mGS independently predicted 30-day mortality (per point; OR 1.16; 95% CI 1.06-1.27; p = 0.002) and poor functional outcome (OR 1.11; 95% CI 1.02-1.20; p = 0.011) after ICH. In receiver-operator characteristic analysis, the addition of mGS tended to be associated with a higher prognostic accuracy for survival (area under curve 0.886 vs. not including mGS 0.812; p = 0.053). <b><i>Conclusions:</i></b> The mGS improves outcome prediction after supratentorial ICH beyond other previously established factors in an unselected population.
DOI: 10.6084/m9.figshare.5129152.v1
title: Supplementary Material for: ApoE Polymorphisms and the Risk of Different Subtypes of Stroke in the Chinese Population: A Comprehensive Meta-Analysis

description: <b><i>Background and Purpose:</i></b> Numerous studies have evaluated the association between apolipoprotein E (ApoE) gene polymorphisms and the risk of different subtypes of stroke. However, the results remain uncertain, and few sources of data specific to the Chinese ethnic population contribute to these outstanding questions. Therefore, we performed a meta-analysis to derive a more comprehensive estimate of the association between ApoE polymorphisms and stroke risk in the Chinese population. <b><i>Methods:</i></b> Case-control studies in Chinese and English publications were identified by searching the PubMed, EMBASE, Web of Science, China Nation Knowledge Infrastructure Platform, Wanfang, and VIP databases and by hand-searching relevant journals and the reference lists of the retrieved articles. ORs and 95% CIs were applied to assess the strength of the associations. Subgroup and sensitivity analyses were performed to explore between-study heterogeneity. <b><i>Results:</i></b> Evidence of a significant association was found between the ApoE ε4 allele and different subtypes of stroke (for ischemic stroke (IS): OR 2.19, 95% CI 1.90-2.52, p &lt; 0.001; for intracerebral hemorrhage (ICH): OR 2.08, 95% CI 1.57-2.75, p &lt; 0.001; and for subarachnoid hemorrhage (SAH): OR 2.03, 95% CI 1.28-3.23, p = 0.003) among the Chinese population. In addition, a significant difference in the risk for different subtypes of stroke between ε4 carriers and ε3ε3 genotype carriers was found (for IS: OR 2.41, 95% CI 2.00-2.89, p &lt; 0.001; for ICH: OR 2.41, 95% CI 1.68-3.47, p &lt; 0.001; and for SAH: OR 2.04, 95% CI 1.21-3.45, p = 0.008). <b><i>Conclusion:</i></b> The ApoE ε4 allele may predict an increased risk for different subtypes of stroke, including IS, ICH and SAH, in the Chinese population, and the results of this genotypic analysis may help to identify populations at an increased risk for stroke. Further studies with larger sample sizes are needed to confirm our findings.
DOI: 10.6084/m9.figshare.5129137
title: Supplementary Material for: Inhibition of Notch Signaling Ameliorates Acute Kidney Failure and Downregulates Platelet-Derived Growth Factor Receptor β in the Mouse Model

description: Ischemic acute kidney injury (AKI) is associated with high morbidity and frequent complications. Repeated episodes of AKI may lead to end-stage renal failure. The pathobiology of regeneration in AKI is not well understood and there is no effective clinical therapy that improves regeneration. The Notch signaling pathway plays an essential role in kidney development and has been implicated in tissue repair in the adult kidney. Here, we found that kidneys after experimental AKI in mice showed increased expression of Notch receptors, specifically Notch1-3, of the Notch ligands Jagged-1 (Jag1), Jag2 and Delta-like-4 (Dll4) and of the Notch target genes <i>Hes1</i>, <i>Hey2</i>, <i>HeyL</i>, <i>Sox9</i> and <i>platelet-derived growth factor receptor β (Pdgfrb)</i>. Treatment of ischemic mice with the γ-secretase inhibitor DBZ blocked Notch signaling and specifically downregulated the expression of Notch3 and the Notch target genes <i>Hes1</i>, <i>Hey2</i>, <i>HeyL</i> and <i>Pdgfrb</i>. After DBZ treatment, the mice developed less interstitial edema and displayed altered interstitial inflammation patterns. Furthermore, serum urea and creatinine levels were significantly decreased from 6 h onwards when compared to control mice treated with DMSO only. Our data are consistent with an amelioration of the severity of kidney injury by blocking Notch activation following AKI, and suggest an involvement of Notch-regulated Pdgfrb in AKI pathogenesis.
DOI: 10.6084/m9.figshare.5129143
title: Supplementary Material for: Management of Bilateral Carotid Occlusive Disease

description: <b><i>Background:</i></b> Symptomatic bilateral internal carotid occlusive disease is a rare but potentially devastating entity. Medical therapy alone is associated with high rates of mortality and recurrent stroke. The optimal management of this disease remains poorly understood. <b><i>Methods:</i></b> A retrospective review of a prospectively maintained database was conducted for patients who presented with an acute stroke in the setting of bilateral carotid occlusive disease between May and October 2013. <b><i>Results:</i></b> We identified 3 patients. The admission National Institutes of Health Stroke Scale score ranged from 4 to 7. All patients had small- to moderate-sized infarcts in the anterior circulation on presentation. Angiography confirmed bilateral internal carotid occlusions with collateral filling via the posterior communicating artery and retrograde filling via external carotid artery supply to the ophthalmic artery. All patients were initially managed with permissive hypertension and anticoagulation followed by carotid angioplasty and stenting. At 1-year follow-up, all patients demonstrated a modified Rankin scale score of 0-1. <b><i>Conclusions:</i></b> Carotid stenting may be a safe and effective therapy for patients presenting with symptomatic bilateral carotid occlusions.
DOI: 10.6084/m9.figshare.5129134
title: Supplementary Material for: Atrial and Ventricular Arrhythmia-Associated Factors in Stable Patients with Chronic Obstructive Pulmonary Disease

description: <b><i>Background:</i></b> Supraventricular and ventricular premature complexes (SVPC and VPC, respectively) are associated with chronic obstructive pulmonary disease (COPD) and with increased mortality in COPD patients. However, there are few reports on the causes of arrhythmia in COPD patients. <b><i>Objectives:</i></b> This study explores the associations between cardiopulmonary dysfunction and COPD by comparing patients with defined arrhythmias (&gt;100 beats per 24 h) and those without, based on 24-hour electrocardiogram (ECG) recordings. <b><i>Methods:</i></b> Patients with arrhythmia underwent a 24-hour ECG and subsequent pulmonary function tests, computed tomography, ECG, 6-min walk test (6MWT), and BODE (body mass index, airflow obstruction, modified Medical Research Council Dyspnoea Scale, exercise capacity) index calculation. <b><i>Results:</i></b> Of 103 study patients (71 COPD patients and 32 at-risk patients), 36 had VPC, 45 had SVPC, 20 had both, and 42 had neither. The predicted post-bronchodilator forced expiratory volume in 1 s, the proportion of low-attenuation area on computed tomography, and BODE index values were significantly worse in the SVPC and VPC groups compared with the corresponding reference groups. Patients in the VPC group showed significantly increased right ventricular pressure and increased desaturation in the 6MWT compared with the reference group. In the multivariate analyses, bronchodilator use was a significant risk factor in the SVPC group, whereas in the VPC group, all parameters of the BODE index except for the dyspnoea score were identified as risk factors. <b><i>Conclusions:</i></b> Increased SVPC might be caused by bronchodilator use, whereas increased VPC is likely related to the peculiar pathophysiology of COPD.
DOI: 10.6084/m9.figshare.5129128
title: Supplementary Material for: Unusual Dermoscopic Patterns of Seborrheic Keratosis

description: <b><i>Background:</i></b> Seborrheic keratoses (SKs) may sometimes mimic benign and malignant skin tumors, and a biopsy can be necessary in order to rule out malignancy. <b><i>Methods:</i></b> From the database of our pigmented lesion clinic, we evaluated the dermoscopic features of difficult-to-diagnose SKs that were biopsied between January 2010 and December 2014. <b><i>Results:</i></b> SKs represented 3.8% of all excised lesions (161/ 4,182). Specifically, 91 (56.5%) were excised to rule out melanoma, 63 (39.1%) to rule out squamous cell carcinoma and 7 (4.4%) to rule out basal cell carcinoma. The following 10 global dermoscopic patterns were identified: multicomponent (32; 19.9%); reticular (24; 14.9%), characterized by an irregular pigment network; bowenoid (21; 13.0%); hairpin (19; 11.8%); keratoacanthoma-like (16; 9.9%); blue-nevus-like (15; 9.3%); lichenoid (6; 3.7%); hyperkeratotic (6; 3.7%); clonal (5; 3.1%); spitzoid (5; 3.1%). Furthermore, 12 SKs (7.5%) were not included in any of such patterns (not classified). <b><i>Conclusion:</i></b> Our results are in line with previous studies highlighting the dermoscopic variability of SKs. Although excised SKs may be classified into 1 of 10 repetitive dermoscopic patterns, a biopsy remains mandatory for those that cannot be clearly differentiated from common skin malignancies.
DOI: 10.6084/m9.figshare.5129131
title: Supplementary Material for: Measuring Global Brain Atrophy with the Brain Volume/Cerebrospinal Fluid Index: Normative Values, Cut-Offs and Clinical Associations

description: <b><i>Background:</i></b> Global brain atrophy is present in normal aging and different neurodegenerative disorders such as Alzheimer's disease (AD) and is becoming widely used to monitor disease progression. <b><i>Summary:</i></b> The brain volume/cerebrospinal fluid index (BV/CSF index) is validated in this study as a measurement of global brain atrophy. We tested the ability of the BV/CSF index to detect global brain atrophy, investigated the influence of confounders, provided normative values and cut-offs for mild, moderate and severe brain atrophy, and studied associations with different outcome variables. A total of 1,009 individuals were included [324 healthy controls, 408 patients with mild cognitive impairment (MCI) and 277 patients with AD]. Magnetic resonance images were segmented using FreeSurfer, and the BV/CSF index was calculated and studied both cross-sectionally and longitudinally (1-year follow-up). Both AD patients and MCI patients who progressed to AD showed greater global brain atrophy compared to stable MCI patients and controls. Atrophy was associated with older age, larger intracranial volume, less education and presence of the ApoE ε4 allele. Significant correlations were found with clinical variables, CSF biomarkers and several cognitive tests. <b><i>Key Messages:</i></b> The BV/CSF index may be useful for staging individuals according to the degree of global brain atrophy, and for monitoring disease progression. It also shows potential for predicting clinical changes and for being used in the clinical routine.
DOI: 10.6084/m9.figshare.5129137.v1
title: Supplementary Material for: Inhibition of Notch Signaling Ameliorates Acute Kidney Failure and Downregulates Platelet-Derived Growth Factor Receptor β in the Mouse Model

description: Ischemic acute kidney injury (AKI) is associated with high morbidity and frequent complications. Repeated episodes of AKI may lead to end-stage renal failure. The pathobiology of regeneration in AKI is not well understood and there is no effective clinical therapy that improves regeneration. The Notch signaling pathway plays an essential role in kidney development and has been implicated in tissue repair in the adult kidney. Here, we found that kidneys after experimental AKI in mice showed increased expression of Notch receptors, specifically Notch1-3, of the Notch ligands Jagged-1 (Jag1), Jag2 and Delta-like-4 (Dll4) and of the Notch target genes <i>Hes1</i>, <i>Hey2</i>, <i>HeyL</i>, <i>Sox9</i> and <i>platelet-derived growth factor receptor β (Pdgfrb)</i>. Treatment of ischemic mice with the γ-secretase inhibitor DBZ blocked Notch signaling and specifically downregulated the expression of Notch3 and the Notch target genes <i>Hes1</i>, <i>Hey2</i>, <i>HeyL</i> and <i>Pdgfrb</i>. After DBZ treatment, the mice developed less interstitial edema and displayed altered interstitial inflammation patterns. Furthermore, serum urea and creatinine levels were significantly decreased from 6 h onwards when compared to control mice treated with DMSO only. Our data are consistent with an amelioration of the severity of kidney injury by blocking Notch activation following AKI, and suggest an involvement of Notch-regulated Pdgfrb in AKI pathogenesis.
DOI: 10.6084/m9.figshare.5129128.v1
title: Supplementary Material for: Unusual Dermoscopic Patterns of Seborrheic Keratosis

description: <b><i>Background:</i></b> Seborrheic keratoses (SKs) may sometimes mimic benign and malignant skin tumors, and a biopsy can be necessary in order to rule out malignancy. <b><i>Methods:</i></b> From the database of our pigmented lesion clinic, we evaluated the dermoscopic features of difficult-to-diagnose SKs that were biopsied between January 2010 and December 2014. <b><i>Results:</i></b> SKs represented 3.8% of all excised lesions (161/ 4,182). Specifically, 91 (56.5%) were excised to rule out melanoma, 63 (39.1%) to rule out squamous cell carcinoma and 7 (4.4%) to rule out basal cell carcinoma. The following 10 global dermoscopic patterns were identified: multicomponent (32; 19.9%); reticular (24; 14.9%), characterized by an irregular pigment network; bowenoid (21; 13.0%); hairpin (19; 11.8%); keratoacanthoma-like (16; 9.9%); blue-nevus-like (15; 9.3%); lichenoid (6; 3.7%); hyperkeratotic (6; 3.7%); clonal (5; 3.1%); spitzoid (5; 3.1%). Furthermore, 12 SKs (7.5%) were not included in any of such patterns (not classified). <b><i>Conclusion:</i></b> Our results are in line with previous studies highlighting the dermoscopic variability of SKs. Although excised SKs may be classified into 1 of 10 repetitive dermoscopic patterns, a biopsy remains mandatory for those that cannot be clearly differentiated from common skin malignancies.