cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5128144.v1
title: Supplementary Material for: Multiple Sclerosis Epidemiology in Middle East and North Africa: A Systematic Review and Meta-Analysis

description: <b><i>Background:</i></b> Multiple sclerosis (MS) is one of the most common neurological disorders and a leading cause of nontraumatic disability in young adults in many countries. Recent reports from the Middle East and North Africa have suggested a moderate to high risk of MS in these countries. <b><i>Methods:</i></b> A literature search was performed in August 2014 in MEDLINE, EMBASE, and IMEMR to retrieve original population-based studies on MS epidemiology in the Middle East and North African countries published between 1st January 1985 and 1st August 2014. We designed search strategies using the key words: MS, prevalence, incidence, and epidemiology. According to the inclusion criteria, 52 studies were included in this systematic review. <b><i>Results:</i></b> McDonald's criteria were the most widely used diagnostic criteria in the studies. Most studies were conducted in single hospital-based centers with a defined catchment area. The female/male ratio ranged from 0.8 in Oman to 4.3 in Saudi Arabia. MS prevalence ranged from 14.77/100,000 population in Kuwait (2000) to 101.4/100,000 in Turkey (2006). The overall MS prevalence in the region was 51.52/100,000. The mean age at disease onset ranged from 25.2 years in Kuwait to 32.5 years in Northeastern Iran, with an overall estimate of 28.54 years. <b><i>Conclusions:</i></b> Recent advances in MS registries will allow nation-wide studies and temporal comparisons between countries, provided that age- and sex-standardized estimates are available.
DOI: 10.6084/m9.figshare.5128132
title: Supplementary Material for: The Effectiveness of a Patient-Centred Assessment with a Solution-Focused Approach (DIALOG+) for Patients with Psychosis: A Pragmatic Cluster-Randomised Controlled Trial in Community Care

description: <b><i>Background:</i></b> DIALOG+ was developed as a computer-mediated intervention, consisting of a structured assessment of patients' concerns combined with a solution-focused approach to initiate change. This study tested the effectiveness of DIALOG+ in the community treatment of patients with psychosis. <b><i>Method:</i></b> This was a pragmatic, exploratory, parallel-group, cluster-randomised controlled trial. Clinicians within community teams - along with patients with psychosis under their care - were randomised to use DIALOG+ once per month for 6 months or an active control. The primary outcome (subjective quality of life, SQOL) and secondary outcomes were assessed after 3, 6 and 12 months by blinded assessors and analysed using mixed-effect models. <b><i>Results:</i></b> A total of 49 clinicians and 179 patients were randomised. Implementation of DIALOG+ was variable, with an average of 1.8 sessions (SD = 1.6) in the first 3 months and 1.1 (SD = 1.2) in the following 3 months. Patients in the DIALOG+ arm had better SQOL at 3, 6 and 12 months (p = 0.035, 0.058 and 0.014, respectively; Cohen's d = 0.29-0.34). They also had significantly fewer unmet needs at 3 and 6 months, fewer general psychopathological symptoms at all time points and better objective social outcomes at 12 months, with no significant differences in other outcomes. Overall care costs were lower in the intervention group. <b><i>Conclusion:</i></b> Despite variable implementation, DIALOG+ is a beneficial intervention for community patients with psychosis. As a non-expensive and potentially cost-saving, generic intervention, DIALOG+ may be widely used and may improve the effectiveness of community treatment. Further trials should test DIALOG+ in different patient groups and contexts.
DOI: 10.6084/m9.figshare.5128135
title: Supplementary Material for: The RoPE Score and Right-to-Left Shunt Severity by Transcranial Doppler in the CODICIA Study

description: <b><i>Background:</i></b> For patients with cryptogenic stroke (CS) and patent foramen ovale (PFO), it is unknown whether the magnitude of right-to-left shunt (RLSh) measured by contrast transcranial Doppler (c-TCD) is correlated with the likelihood an identified PFO is related to CS as determined by the Risk of Paradoxical Embolism (RoPE) score. Additionally, for patients with CS, it is unknown whether PFO assessment by c-TCD is more sensitive for identifying RLSh compared with transesophageal echocardiography (TEE). Our aim was to determine the significance of RLSh grade by c-TCD in patients with PFO and CS. <b><i>Methods:</i></b> We evaluated patients with CS who had RLSh quantified by c-TCD in the Multicenter Study into RLSh in Cryptogenic Stroke (CODICIA) to determine whether there is an association between c-TCD shunt grade and the RoPE Score. For patients who underwent c-TCD and TEE, we determined whether there is agreement in identifying and grading RLSh between these two modalities. <b><i>Results:</i></b> The RoPE score predicted the presence versus the absence of RLSh documented by c-TCD (c-statistic = 0.66). For patients with documented RLSh by c-TCD, shunt severity was correlated with increasing RoPE score (rank correlation (r) = 0.15, p = 0.01). Among 293 patients who had both c-TCD and TEE performed, c-TCD was more sensitive (98.7%) for detecting RLSh. Of the 97 patients with no PFO identified on TEE, 28 (29%) had a large amount of RLSh seen on c-TCD. <b><i>Conclusions:</i></b> For patients with CS, severity of RLSh by c-TCD is positively correlated with the RoPE score, indicating that this technique for shunt grading identifies patients more likely to have pathogenic rather than incidental PFOs. c-TCD is also more sensitive in detecting RLSh than TEE. These findings suggest an important role for c-TCD in the evaluation of PFO in the setting of CS.
DOI: 10.6084/m9.figshare.5128138.v1
title: Supplementary Material for: Sex and Hemisphere - A Neglected, Nature-Determined Relationship in Acute Ischemic Stroke

description: <b><i>Background:</i></b> Sex differences in the structural connectome of the brain are clinically highly relevant, but they have mostly been neglected in stroke trials. We investigated the impact of the interaction sex-by-hemisphere on outcome in stroke patients after intravenous thrombolysis (IVT). <b><i>Methods:</i></b> This is an observational study based on consecutively collected supratentorial stroke patients treated with IVT (n = 1,231). The 3-month modified Rankin scale (mRS) was estimated by adjusted binary (mRS 0-2 for good outcome) and ordinal regression analysis. As baseline characteristics differ substantially between the sexes, we aimed for better covariate balance by employing coarsened exact matching. <b><i>Results:</i></b> Sex-by-hemisphere predicted good outcome in the entire cohort (726 left, 505 right hemispheric strokes, p value<sub>interaction</sub> 0.032) and in the matched cohort (338 left, 273 right, p value<sub>interaction</sub> 0.003). Ordinal regression suggested a comparable estimate in the matched cohort (p value<sub>interaction</sub> 0.006). Further investigation revealed relevant between-sex and within-sex risk: right hemispheric strokes in men were 1.54 times (95% confidence intervals (CIs) 1.15-2.01) more likely than in women to achieve mRS 0-2. Women with right hemispheric strokes were 0.72 times (95% CI 0.54-0.92) less likely to reach mRS 0-2 than women with left hemispheric strokes. Conversely, men with right hemispheric strokes were 1.35 times (95% CI 1.06-1.70) more likely to achieve mRS 0-2 than men with left hemispheric strokes. <b><i>Conclusion:</i></b> This study suggests that outcomes are different in both sexes after IVT when different hemispheres are affected. Further consideration of this hypothesis in clinical trials might help in guiding individualized, injury-specific treatment approaches for acute ischemic stroke.
DOI: 10.6084/m9.figshare.5128141
title: Supplementary Material for: A Comprehensive Atlas of the Adult Mouse Penis

description: Mice are routinely used to study the development of the external genitalia and, in particular, the process of male urethral closure. This is because misplacement of the male penile urethra, or hypospadias, is amongst the most common birth defects reported in humans. While mice present a tractable model to study penile development, several structures differ between mice and humans, and there is a lack of consensus in the literature on their annotation and developmental origins. Defining the ontology of the mouse prepuce is especially important for the relevance and interpretation of mouse models of hypospadias to human conditions. We have developed a detailed annotation of the adult mouse penis that addresses these differences and enables an accurate comparison of murine and human hypospadias phenotypes. Through MRI data, gross morphology and section histology, we define the origin of the mouse external and internal prepuces, their relationship to the single human foreskin as well as provide a comprehensive view of the various structures of the mouse penis and their associated muscle attachments within the body. These data are combined to annotate structures in a novel 3D adult penis atlas that can be downloaded, viewed at any angle, and manipulated to examine the relationship of various structures.
DOI: 10.6084/m9.figshare.5128129
title: Supplementary Material for: Pioglitazone Identifies a New Target for Aneurysm Treatment: Role of Egr1 in an Experimental Murine Model of Aortic Aneurysm

description: Peroxisome proliferator-activated receptor γ agonists have been shown to inhibit angiotensin II (AngII)-induced experimental abdominal aortic aneurysms. Macrophage infiltration to the vascular wall is an early event in this pathology, and therefore we explored the effects of the peroxisome proliferator-activated receptor γ agonist pioglitazone on AngII-treated macrophages. Using microarray-based expression profiling of phorbol ester-stimulated THP-1 cells, we found that a number of aneurysm-related gene changes effected by AngII were modulated following the addition of pioglitazone. Among those genes, polycystic kidney disease 1 <i>(PKD1)</i> was significantly up-regulated (multiple testing corrected p &lt; 0.05). The analysis of the <i>PKD1</i> proximal promoter revealed a putative early growth response 1 (EGR1) binding site, which was confirmed by chromatin immunoprecipitation (ChIP) and quantitative PCR. Further analysis of publicly available ChIP-sequencing data revealed that this putative binding site overlapped with a conserved EGR1 binding peak present in 5 other cell lines. Quantitative real-time PCR showed that EGR1 suppressed <i>PKD1</i>, while AngII significantly up-regulated <i>PKD1</i>, an effect counteracted by pioglitazone. Conversely, in EGR1 short hairpin RNA lentivirally transduced THP-1 cells, reduced EGR1 led to a significant up-regulation of <i>PKD1</i>, especially after treatment with pioglitazone. In vivo, deficiency of <i>Egr1</i> in the haematopoietic compartment of mice completely abolished the incidence of CaCl<sub>2</sub>-induced aneurysm formation.
DOI: 10.6084/m9.figshare.5128117
title: Supplementary Material for: Influence of Lentiviral β-Synuclein Overexpression in the Hippocampus of a Transgenic Mouse Model of Alzheimer's Disease on Amyloid Precursor Protein Metabolism and Pathology

description: <b><i>Background:</i></b> β-Synuclein (β-Syn) is a member of the highly homologous synuclein protein family. The most prominent family member, α-synuclein (α-Syn), abnormally accumulates in so-called Lewy bodies, one of the major pathological hallmarks of α-synucleinopathies. Notably, parts of the peptide backbone, called the nonamyloid component, are also found in amyloid plaques. However, β-Syn seems to have beneficial effects by reducing α-Syn aggregation, and amyloid antiaggregatory activity has been described. <b><i>Objective:</i></b> The aim of the study was to analyze if wild-type β-Syn can counteract functional and pathological changes in a murine Alzheimer model over different time periods. <b><i>Methods:</i></b> At the onset of pathology, lentiviral particles expressing human β-Syn were injected into the hippocampus of transgenic mice overexpressing human amyloid precursor protein with Swedish and London mutations (APP<sub>SL</sub>). An empty vector served as the control. Behavioral analyses were performed 1, 3 and 6 months after injection followed by biochemical and histological examinations of brain samples. <b><i>Results:</i></b> β-Syn expression was locally concentrated and rather modest, but nevertheless changed its effect on APP expression and plaque load in a time- and concentration-dependent manner. Interestingly, the phosphorylation of glycogen synthase kinase 3 beta was enhanced in APP<sub>SL</sub> mice expressing human β-Syn, but an inverse trend was observed in wild-type animals. <b><i>Conclusion:</i></b> The initially reported beneficial effects of β-Syn could be partially reproduced, but locally elevated levels of β-Syn might also cause neurodegeneration. To enlighten the controversial pathological mechanism of β-Syn, further examinations considering the relationship between concentration and exposure time of β-Syn are needed.
DOI: 10.6084/m9.figshare.5128120
title: Supplementary Material for: Cognitive Impairment and Its Structural Correlates in the Parkinsonian Subtype of Multiple System Atrophy

description: <b><i>Background/Aims:</i></b> Previous studies indicate that patients with the parkinsonian subtype of multiple system atrophy (MSA-P) experience cognitive impairment. This study aimed to identify the existence of cognitive impairments and the different topographic patterns of morphological changes in MSA-P by means of imaging analysis, and also whether these morphological changes could be associated with cognitive dysfunctions in MSA-P. <b><i>Methods:</i></b> We recruited 15 nondemented probable MSA-P patients and 32 normal controls (NC) for neuropsychological testing and MRI. We analyzed morphological changes using cortical thickness analysis, voxel-based morphometry (VBM) and cerebellar volumetry. Multiple linear regression analysis was performed to evaluate the correlation of each cognitive score with the mean thickness of significant cortical-thinning clusters, mean gray-matter density of VBM clusters and cerebellar volume. <b><i>Results:</i></b> The scores on the Digit Span Test, the Seoul Verbal Learning Test (immediate and delayed), the phonemic Controlled Oral Word Association Test and the Stroop color test were significantly lower in the MSA-P group than in the NC group. We found two clusters exhibiting significant cortical thinning in the right paracentral lobule and parahippocampal gyrus. VBM analysis revealed significant gray-matter atrophy in the MSA-P group in the bilateral basal ganglia, cerebellum and temporal and frontal cortical areas. Multiple linear regression analysis demonstrated that cognitive dysfunction correlated significantly with thinning in the neocortex, cerebellum and striatum. <b><i>Conclusions:</i></b> Our data demonstrate that cortical and cerebellar atrophy and striatal degeneration are associated with cognitive impairment in patients with MSA-P.
DOI: 10.6084/m9.figshare.5128123
title: Supplementary Material for: New Reference Values for Energy Intake

description: The reference values for energy intake of the German, Austrian and Swiss nutrition societies for children, adolescents and adults are derived using the factorial method. For adults, a mean BMI of 22 kg/m<sup>2</sup> is taken as a basis given the current mean body size for adults residing in Germany (taken from the German Health Interview and Examination Survey for Adults, DEGS1). The determination of the energy expenditure for infants is based on data obtained using the doubly labelled water (DLW) method. The energy storage in growing tissue will be added for the purpose of deriving reference values for this age group. For pregnant women, given an increase in body weight of 12 kg during pregnancy, guiding values for additional energy intake in the second trimester of 250 kcal/day and in the third trimester of 500 kcal/day are indicated using DLW data sets and taking energy storage in growing tissue into account. In case of overweight prior to pregnancy as well as in the case of reduced physical activity during pregnancy, the additional requirement is lower. For women exclusively breastfeeding during the first 4-6 months, the guiding value for additional energy intake is quoted as 500 kcal/day.
DOI: 10.6084/m9.figshare.5128126
title: Supplementary Material for: Novel Mutation and Structural RNA Analysis of the Noncoding RNase <b><i>MRP</i></b> Gene in Cartilage-Hair Hypoplasia

description: Cartilage-hair hypoplasia (CHH) is an autosomal recessive disorder which is characterized by bone metaphysis anomalies with manifestations that include short stature, defective cellular immunity, and predisposition to several cancers. It is caused by mutations in <i>RMRP</i>, which is transcribed as an RNA component of the mitochondrial RNA-processing ribonuclease. We report the clinical and molecular data of a Moroccan patient with CHH. Sequencing of <i>RMRP</i> identified 2 mutations in the patient: the known mutation g.97G&gt;A and the variation g.27G&gt;C, which has not been reported previously. Given the high mutational heterogeneity, the high frequency of variations in the region, and the fact that <i>RMRP</i> is a non-coding gene, assigning the pathogenicity to <i>RMRP</i> mutations remains a difficult task. Therefore, we compared the characteristics of the primary and secondary structures of mutated RMRP sequences. The location of our mutations within the secondary structure of the RMRP molecule revealed that the novel g.27G&gt;C mutation causes a disruption in the Watson-Crick base pairing, which results in an impairment of a highly conserved P3 domain. Our work prompts considering the consequences of novel <i>RMRP</i> nucleotide variations on conserved RNA structures to gain insights into the pathogenicity of mutations.
DOI: 10.6084/m9.figshare.5128114
title: Supplementary Material for: Intracranial Cerebral Artery Dissection of Anterior Circulation as a Cause of Convexity Subarachnoid Hemorrhage

description: <b><i>Background:</i></b> Convexity subarachnoid hemorrhage (cSAH), defined as intrasulcal bleeding restricted to hemispheric convexities, has several etiologies: reversible cerebral vasoconstriction syndrome, cerebral amyloid angiopathy, and internal carotid artery (ICA) stenosis or occlusion. However, it remains unknown whether cerebral artery dissection causes cSAH. <b><i>Methods:</i></b> We retrospectively investigated patients admitted to our hospital between 2005 and 2013 with ischemic stroke or transient ischemic attack caused by cerebral artery dissection. Cerebral artery dissection was diagnosed by cervical or cerebral magnetic resonance imaging (MRI) or computed tomography (CT) showing a wall hematoma. CT angiography, ultrasonography, or intra-arterial digital-subtraction angiography detected cerebral artery dissection if a double lumen, string sign, intimal flap, or dissecting aneurysm was observed at a nonbifurcation site. We used CT or MRI to detect cSAH, which was defined as blood collection restricted to one or few cerebral sulci without extending to the basal cisterns, ventricles, or Sylvian and interhemispheric fissures. Demographic, neuroimaging, treatment, and prognostic data were collected. <b><i>Results:</i></b> In total, 82 patients were diagnosed with ischemic stroke caused by cerebral artery dissection. The following arteries were affected: the ICA (9 patients), anterior cerebral artery (ACA; 12 patients), middle cerebral artery (MCA; 12 patients), vertebral artery (37 patients), basilar artery (5 patients), posterior cerebral artery (2 patients), and posterior inferior cerebellar artery (4 patients). In addition, 1 patient presented with simultaneous dissection in both the vertebral and internal carotid arteries, and 6 patients (7%) presented with cSAH (3 men and 3 women, age 39-67 years). The MCA was dissected in four cases and the ACA in two cases, with cSAH frequencies of 33 (4 of 12) and 17% (2 of 12), respectively, in those vessels. Artery dissection in the vertebrobasilar artery system was not responsible for cSAH (0 of 48). In all the MCA dissection cases, cSAH occurred in the arterial border zone between the ACA and MCA territories. Although 2 patients showed early reperfusion with temporary cSAH enlargement, cSAH was self-limiting. Antithrombotic treatment did not complicate the clinical course when used in 4 patients during acute or subacute phases. All patients achieved a 3-month poststroke modified Rankin Scale of 0-2. <b><i>Conclusion:</i></b> Our data suggest that cSAH caused by intracranial cerebral artery dissection is not rare. Further investigations are needed to elucidate the precise mechanism underlying cSAH in cerebral artery dissection.
DOI: 10.6084/m9.figshare.5128114.v1
title: Supplementary Material for: Intracranial Cerebral Artery Dissection of Anterior Circulation as a Cause of Convexity Subarachnoid Hemorrhage

description: <b><i>Background:</i></b> Convexity subarachnoid hemorrhage (cSAH), defined as intrasulcal bleeding restricted to hemispheric convexities, has several etiologies: reversible cerebral vasoconstriction syndrome, cerebral amyloid angiopathy, and internal carotid artery (ICA) stenosis or occlusion. However, it remains unknown whether cerebral artery dissection causes cSAH. <b><i>Methods:</i></b> We retrospectively investigated patients admitted to our hospital between 2005 and 2013 with ischemic stroke or transient ischemic attack caused by cerebral artery dissection. Cerebral artery dissection was diagnosed by cervical or cerebral magnetic resonance imaging (MRI) or computed tomography (CT) showing a wall hematoma. CT angiography, ultrasonography, or intra-arterial digital-subtraction angiography detected cerebral artery dissection if a double lumen, string sign, intimal flap, or dissecting aneurysm was observed at a nonbifurcation site. We used CT or MRI to detect cSAH, which was defined as blood collection restricted to one or few cerebral sulci without extending to the basal cisterns, ventricles, or Sylvian and interhemispheric fissures. Demographic, neuroimaging, treatment, and prognostic data were collected. <b><i>Results:</i></b> In total, 82 patients were diagnosed with ischemic stroke caused by cerebral artery dissection. The following arteries were affected: the ICA (9 patients), anterior cerebral artery (ACA; 12 patients), middle cerebral artery (MCA; 12 patients), vertebral artery (37 patients), basilar artery (5 patients), posterior cerebral artery (2 patients), and posterior inferior cerebellar artery (4 patients). In addition, 1 patient presented with simultaneous dissection in both the vertebral and internal carotid arteries, and 6 patients (7%) presented with cSAH (3 men and 3 women, age 39-67 years). The MCA was dissected in four cases and the ACA in two cases, with cSAH frequencies of 33 (4 of 12) and 17% (2 of 12), respectively, in those vessels. Artery dissection in the vertebrobasilar artery system was not responsible for cSAH (0 of 48). In all the MCA dissection cases, cSAH occurred in the arterial border zone between the ACA and MCA territories. Although 2 patients showed early reperfusion with temporary cSAH enlargement, cSAH was self-limiting. Antithrombotic treatment did not complicate the clinical course when used in 4 patients during acute or subacute phases. All patients achieved a 3-month poststroke modified Rankin Scale of 0-2. <b><i>Conclusion:</i></b> Our data suggest that cSAH caused by intracranial cerebral artery dissection is not rare. Further investigations are needed to elucidate the precise mechanism underlying cSAH in cerebral artery dissection.