cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5120680
title: Supplementary Material for: Digital Probabilistic Atlas of the Border Region between the Middle and Posterior Cerebral Arteries

description: <i>Background and Purpose:</i> The diagnosis of external borderzone infarction is made when the stroke is located at the border between the arterial territories. Recent studies have raised questions regarding the location of this borderzone given the variability in the arterial territories. We examined the location of this region using a digital approach and its correspondence with the ‘traditional’ template. <i>Methods:</i> Infarcts resulting from occlusion of the middle cerebral artery (MCA) or posterior cerebral artery (PCA) trunk or branches were segmented from T<sub>2</sub>-weighted MR images and linearly registered into a common stereotaxic coordinate space. For MCA infarcts and PCA infarcts, maps of voxels in a rim surrounding the infarct were created. The maps of individual rims were averaged to create images of the probability of each voxel lying in the MCA and PCA rims. The MCA and PCA rims were used to create a digital atlas of the probability of each voxel lying concurrently in both rims. <i>Results:</i> The MCA group consisted of 36 patients (16 males) with a median age of 73 (range 25–87) years. The PCA territory group consisted of 30 patients (24 males) with a median age of 61 (range 22–86) years. The probability of involvement in the digital atlas was higher in the posterior putamen (probability 0.12–0.29) and optic tract (probability 0.13–0.0.20) than in the angular gyrus (probability 0.01). <i>Conclusion:</i> We have created a digital model of the border region between the MCA and PCA territories. This approach may be useful for evaluating the likelihood of a stroke mechanism from topography.
DOI: 10.6084/m9.figshare.5120683.v1
title: Supplementary Material for: Influence of Cyclooxygenase-1 Genotype on ex vivo Aspirin Response in Patients at Risk for Stroke

description: <i>Background:</i> We sought to determine whether cyclooxygenase-1 <i>(PTGS1)</i> genotype is associated with the ability of aspirin to inhibit platelet aggregation in patients at risk for stroke. <i>Methods:</i> Blood and urine samples were collected from 60 subjects, including 28 African Americans, who were taking aspirin for primary or secondary stroke prevention. Samples were analyzed for the <i>PTGS1 </i>A–707G, <i>PTGS1</i> P17L, and glycoprotein IIIa (<i>ITGB3</i>)P1<sup>A1/A2</sup> genotypes, ex-vivo platelet aggregation, serum cholesterol, plasma salicylate levels, and urinary 11-dehydrothromboxane B<sub>2</sub> (11-dhTxB<sub>2</sub>) concentrations. The association between <i>PTGS1 </i>A–707G and P17L genotypes and aspirin response, as assessed by ex vivo studies and 11-dhTxB<sub>2</sub> concentrations, was evaluated by statistical testing and nonlinear mapping. <i>Results:</i> Salicylate concentrations, <i>ITGB3</i> genotype distribution and 11-dhTxB<sub>2</sub> concentrations were similar among <i>PTGS1</i> genotype groups. More subjects with the <i>PTGS1 </i>17PP versus PL genotype had incomplete ex-vivo inhibition of platelet aggregation by aspirin (57 vs. 20%; p = 0.04). Fifty-nine percent of subjects homozygous for both the <i>PTGS</i> –707A and 17P alleles, but none with both the <i>PTGS1</i> –707G and 17L alleles had incomplete inhibition with aspirin; p = 0.04. Similarly, nonlinear mapping showed a direct relationship between the <i>PTGS1</i> 17P allele and decreased aspirin response. When analyzed separately by ethnicity, the association with the P17L genotype and aspirin response persisted in African Americans, but not Caucasians. <i>Conclusions:</i> Our data suggest that the <i>PTGS1</i> P17L genotype contributes to response to aspirin as assessed by ex-vivo platelet aggregation. Our data further suggest that the association between <i>PTGS1</i> genotype and aspirin response might vary by ethnicity.
DOI: 10.6084/m9.figshare.5120674
title: Supplementary Material for: Endothelial Dysfunction in Lacunar Stroke: A Systematic Review

description: <i>Background:</i> Endothelial dysfunction is thought to play an important role in the pathogenesis and progression of cerebral small-vessel disease in lacunar stroke patients. <i>Methods:</i> We systematically searched the literature (MEDLINE, EMBASE) for evidence of endothelial activation and dysfunction in lacunar stroke. The selected papers were assessed by a predefined checklist to estimate methodological and informative quality. The papers were categorized into subheadings concerning the different physiologic functions of the endothelium and a subheading concerning toxins for the endothelium. <i>Results:</i> 29 articles were eligible for further analysis. We found 16 publications on regulation of vascular tone by the endothelium, which showed an impaired function at several time points after the stroke by means of different clinical methods (e.g. flow-mediated vasodilatation and CO<sub>2</sub> reactivity). Nine references showed elevated levels of markers of hemostatic function of the vascular endothelium (e.g. von Willebrand factor, thrombomodulin) in acute and subsequent phases. In 4 papers, adhesion molecules (e.g. E- and P-selectin) were elevated only during the acute phase. Homocysteine, a toxin for the endothelium, was elevated in patients in 3 papers. <i>Conclusions:</i> The current literature suggests that endothelial dysfunction might be involved in the pathogenesis of lacunar stroke, especially in those patients with concomitant silent lacunar infarcts and ischemic white matter lesions. Future research on endothelial function in lacunar stroke should concentrate on long-term clinical as well as radiological follow-up in well-defined cases and combine multiple methods to evaluate endothelial function.
DOI: 10.6084/m9.figshare.5120668
title: Supplementary Material for: Skin Biopsies Demonstrate Site-Specific Endothelial Activation in Mouse Models of Sepsis

description: <i>Background/Aims:</i> Skin biopsies allow for direct phenotyping of the endothelium in clinical settings. <i>Objectives:</i> We hypothesize that in murine sepsis endothelial activation is manifested by changes in protein and mRNA expression in skin biopsies, and that such alterations differ from other organs. <i>Methods:</i> In two mouse models of sepsis [endotoxemia and cecal ligation puncture (CLP)], we measured circulating levels of endothelial biomarkers, quantitated mRNA expression of activation markers and assayed for protein expression using immunohistochemistry. <i>Results:</i> Endotoxemic mice demonstrated increased circulating levels of sE-selectin, sICAM-1, sVCAM-1 and sP-selectin at 24 h, while CLP was associated with increased levels of sE-selectin alone. In real-time PCR, mRNA levels for P-selectin, ICAM-1 and PAI-1 were increased in skin from endotoxemic mice. In CLP, mRNA levels for P-selectin, ICAM-1, E-selectin and PAI-1 were elevated, while VCAM-1 expression was reduced in skin. Most, but not all of these changes correlated with alterations in immunohistochemical staining. Expression patterns in skin differed from those in brain, heart, and lung. <i>Conclusions:</i> Skin biopsies demonstrated endothelial cell activation during sepsis. The expression patterns differed by type of sepsis model and between vascular beds of skin, brain, heart, and lung, providing a foundation for identifying skin microvascular-bed-specific molecule signatures.
DOI: 10.6084/m9.figshare.5120671
title: Supplementary Material for: Comparison of Methods for Combining Case-Control and Family-Based Association Studies

description: <i>Objectives:</i> Combining the analysis of family-based samples with unrelated individuals can enhance the power of genetic association studies. Various combined analysis techniques have been recently developed; as yet, there have been no comparisons of their power, or robustness to confounding factors. We investigated empirically the power of up to six combined methods using simulated samples of trios and unrelated cases/controls (TDTCC), trios and unrelated controls (TDTC), and affected sibpairs with parents and unrelated cases/controls (ASPFCC). <i>Methods:</i> We simulated multiplicative, dominant and recessive models with varying risk parameters in single samples. Additionally, we studied false-positive rates and investigated, if possible, the coverage of the true genetic effect (TDTCC). <i>Results/Conclusions:</i> Under the TDTCC design, we identified four approaches with equivalent power and false-positive rates. Combined statistics were more powerful than single-sample statistics or a pooled χ<sup>2</sup>-statistic when risk parameters were similar in single samples. Adding parental information to the CC part of the joint likelihood increased the power of generalised logistic regression under the TDTC but not the TDTCC scenario. Formal testing of differences between risk parameters in subsamples was the most sensitive approach to avoid confounding in combined analysis. Non-parametric analysis based on Monte-Carlo testing showed the highest power for ASPFCC samples.
DOI: 10.6084/m9.figshare.5120677.v1
title: Supplementary Material for: Infections Related to Airway Stenting: A Systematic Review

description: <i>Background:</i> Airway stenting is nowadays an established method for the palliative and/or curative treatment of central airways obstruction. However, complications related to the use of airway stents have been reported. <i>Objective:</i> We endeavored to systematically evaluate the currently available evidence regarding the infections associated with airway stenting. <i>Methods:</i> We independently searched in PubMed for relevant reports. We considered articles which reported on clinical infections related to airway stenting. A case was identified as stent-associated respiratory tract infection (SARTI) according to the authors of the individual papers, based on clinical findings with or without radiological or microbiological confirmation. <i>Results:</i> Twenty-three articles (19 cohorts/case series and 4 case reports), involving 501 patients with airway stents, were included. The indication for airway stenting was malignancy and benign disease in 45 and 55% of the included patients, respectively. Ninety-three (19%) out of the 501 stented patients experienced SARTI. Pneumonia was the most common type of SARTI (47%), followed by bronchial infection (24%), cavitary pneumonia/lung abscess and intraluminal fungus ball. <i>Staphylococcus aureus</i> (39%) and <i>Pseudomonas aeruginosa</i> (28%) were the most commonly identified pathogens. Twenty-six (68%) out of the 38 patients with SARTI, for whom outcome data were available, died. <i>Conclusion:</i> The accumulated and evaluated evidence suggests that SARTI probably involves 1 in 5 patients with airway stent. Although the possibility of SARTI should not discourage the interventional pneumologists from inserting airway stents, the data seem to underline the urgent need for establishing a consensus definition and diagnostic criteria for SARTI.
DOI: 10.6084/m9.figshare.5120665
title: Supplementary Material for: Local Population Structure in Arabian Peninsula Revealed by Y-STR Diversity

description: Genetic studies have been underway on Arabian Peninsula populations because of their pivotal geographic location for population migration and times of occurrence. To assist in better understanding population dynamics in this region, evidence is presented herein on local population structure in the Arabian Peninsula, based on Y-STR characterisation in four Arabian samples and its comparison in a broad geographical scale. Our results demonstrate that geography played an important role in shaping the genetic structure of the region around the Near-East. Populations are grouped regionally but none of these groups is significantly differentiated from others and all groups merge in the Near-East, in keeping with this important migration corridor for the human species. Focusing on the Arabian Peninsula, we show that Dubai and Oman share genetic affinities with other Near-Eastern populations, while Saudi Arabia and Yemen show a relative distinctive isolated background. Those two populations may have been kept relatively separated from migration routes, maybe due to their location in a desert area.
DOI: 10.6084/m9.figshare.5120671.v1
title: Supplementary Material for: Comparison of Methods for Combining Case-Control and Family-Based Association Studies

description: <i>Objectives:</i> Combining the analysis of family-based samples with unrelated individuals can enhance the power of genetic association studies. Various combined analysis techniques have been recently developed; as yet, there have been no comparisons of their power, or robustness to confounding factors. We investigated empirically the power of up to six combined methods using simulated samples of trios and unrelated cases/controls (TDTCC), trios and unrelated controls (TDTC), and affected sibpairs with parents and unrelated cases/controls (ASPFCC). <i>Methods:</i> We simulated multiplicative, dominant and recessive models with varying risk parameters in single samples. Additionally, we studied false-positive rates and investigated, if possible, the coverage of the true genetic effect (TDTCC). <i>Results/Conclusions:</i> Under the TDTCC design, we identified four approaches with equivalent power and false-positive rates. Combined statistics were more powerful than single-sample statistics or a pooled χ<sup>2</sup>-statistic when risk parameters were similar in single samples. Adding parental information to the CC part of the joint likelihood increased the power of generalised logistic regression under the TDTC but not the TDTCC scenario. Formal testing of differences between risk parameters in subsamples was the most sensitive approach to avoid confounding in combined analysis. Non-parametric analysis based on Monte-Carlo testing showed the highest power for ASPFCC samples.
DOI: 10.6084/m9.figshare.5120674.v1
title: Supplementary Material for: Endothelial Dysfunction in Lacunar Stroke: A Systematic Review

description: <i>Background:</i> Endothelial dysfunction is thought to play an important role in the pathogenesis and progression of cerebral small-vessel disease in lacunar stroke patients. <i>Methods:</i> We systematically searched the literature (MEDLINE, EMBASE) for evidence of endothelial activation and dysfunction in lacunar stroke. The selected papers were assessed by a predefined checklist to estimate methodological and informative quality. The papers were categorized into subheadings concerning the different physiologic functions of the endothelium and a subheading concerning toxins for the endothelium. <i>Results:</i> 29 articles were eligible for further analysis. We found 16 publications on regulation of vascular tone by the endothelium, which showed an impaired function at several time points after the stroke by means of different clinical methods (e.g. flow-mediated vasodilatation and CO<sub>2</sub> reactivity). Nine references showed elevated levels of markers of hemostatic function of the vascular endothelium (e.g. von Willebrand factor, thrombomodulin) in acute and subsequent phases. In 4 papers, adhesion molecules (e.g. E- and P-selectin) were elevated only during the acute phase. Homocysteine, a toxin for the endothelium, was elevated in patients in 3 papers. <i>Conclusions:</i> The current literature suggests that endothelial dysfunction might be involved in the pathogenesis of lacunar stroke, especially in those patients with concomitant silent lacunar infarcts and ischemic white matter lesions. Future research on endothelial function in lacunar stroke should concentrate on long-term clinical as well as radiological follow-up in well-defined cases and combine multiple methods to evaluate endothelial function.
DOI: 10.6084/m9.figshare.5120656
title: Supplementary Material for: ADAR1 and ADAR2 Expression and Editing Activity during Forebrain Development

description: The conversion of adenosine to inosine within RNA transcripts is regulated by a family of double-stranded RNA-specific adenosine deaminases referred to as adenosine deaminases that act on RNA (ADARs). Little is known regarding the developmental expression of ADAR family members or the mechanisms responsible for the specific patterns of editing observed for ADAR substrates. We have examined the spatiotemporal expression patterns for ADAR1 and ADAR2 in mouse forebrain. ADAR1 and ADAR2 are broadly distributed in most regions of the mouse forebrain by P0, including the cerebral cortex, hippocampus, and diencephalon. High expression levels were maintained into adulthood. Colocalization studies demonstrated ADAR1 and ADAR2 expression in neurons but not astrocytes. Editing for specific ADAR mRNA targets precedes high expression of ADAR proteins, suggesting that region-specific differences in editing patterns may not be mediated solely by ADAR expression levels.
DOI: 10.6084/m9.figshare.5120659
title: Supplementary Material for: Increased Expression of Cyclooxygenase-2 and Increased Infiltration of Regulatory T Cells in Tumors of Patients with Hepatocellular Carcinoma

description: <i>Background:</i> Studies on Cox-2 and Foxp3+ regulatory T cells (Treg) in hepatocellular carcinoma (HCC) showed that Treg suppress local immune response in a Cox-2-dependent fashion. <i>Aims:</i> To investigate Cox-2 expression, Foxp3+ Treg infiltration and CD4+ T cell frequency in HCC tumors. <i>Methods:</i> Tumors and the corresponding nontumor hepatitis B virus-related liver tissues from 40 HCC patients with hepatitis B virus infection, plus 10 liver samples from patients with hemangioma as controls, were assessed for Cox-2 expression, Foxp3+ Treg and total CD4+ T cell numbers using immunohistochemistry. Serum TGF-β1 was assessed by ELISA. <i>Results:</i> Reduced Cox-2 expression, increased Treg and increased CD4+ T cells were shown in tumor as compared with nontumor tissues. Moreover, of 40 tumor tissues, 23 that expressed Cox-2 showed increased Foxp3+ Treg and reduced CD4+ T cells compared with the remaining 17 that did not express Cox-2. Correlation analyses showed that within tumors Treg infiltration correlated positively with Cox-2 expression, and that Treg infiltration or Cox-2 expression correlated negatively with CD4+ T cells. Additionally, serum TGF-β1 was higher in HCC patients than in controls. <i>Conclusion:</i> Within tumors, Cox-2 expression, Treg infiltration and CD4+ T cell frequency were increased, and the Cox-2 expression correlated positively with Treg infiltration and negatively with CD4+ T cell frequency.
DOI: 10.6084/m9.figshare.5120662
title: Supplementary Material for: Analysis of Allele and Haplotype Diversity Across 25 Genomic Regions in Three Eastern European Populations

description: <i>Objective:</i> Individual population history is the main reason for the variability of linkage disequilibrium (LD) patterns and haplotype frequencies among populations. Such diversity may influence the transferability of tag SNPs from one population to another. Our goal was to compare patterns of pairwise LD and allele and haplotype frequencies in Estonian and Russian populations, to estimate the genetic variation between populations and assess the potential transferability of tag SNPs. <i>Methods:</i> 452 SNPs from 25 unlinked genomic regions on 12 chromosomes were genotyped in 140 Estonians and 207 Russians from Northern and Western regions of the European area of Russia. <i>Results:</i> The allele frequency distributions were highly consistent between populations (<i>R</i> &gt; 0.90 for all pairwise comparisons). The overall frequency variation among populations was low (F<sub>ST</sub> = 0.0054). The number of SNPs with high-range F<sub>ST</sub> values (0.02–0.09) was most prominent for the <i>MC5R</i> genomic region. Haplotype heterogeneity among populations was low (F<sub>ST</sub> values ranged within 0.00–0.01, with the exception of haploblocks in the <i>ADIPOR2</i> and <i>MC5R</i> regions). The interpopulation proximity was also evaluated using haplotype diversity. <i>Conclusion:</i> Our data showed a high concordance between the populations studied, which may be considered as the result of their historical formation on a cognate genetic basis.
DOI: 10.6084/m9.figshare.5120650
title: Supplementary Material for: Safety of Acupuncture: Results of a Prospective Observational Study with 229,230 Patients and Introduction of a Medical Information and Consent Form

description: <i>Background: </i>To evaluate the safety of acupuncture in a large number of patients receiving conventional health care and, based on these results, to develop a new medical consent form for acupuncture. <i>Methods: </i>The prospective observational study included patients who received acupuncture treatment for chronic osteoarthritis pain of the knee or hip, low back pain, neck pain or headache, allergic rhinitis, asthma, or dysmenorrhoea. After treatment, all patients documented adverse events associated with acupuncture (defined as adverse effects). Patients who reported a need for treatment due to an adverse effect completed an additional standardised questionnaire on the most important adverse effect. Based on this data and considering ethical and legal aspects a new consent form was developed. <i>Results: </i>A total of 229,230 patients received on average 10.2 ± 3.0 acupuncture treatments. Altogether, 19,726 patients (8.6%) reported experiencing at least one adverse effect and 4,963 (2.2%) reported one which required treatment. Common adverse effects were bleedings or haematoma (6.1% of patients, 58% of all adverse effects), pain (1.7%) and vegetative symptoms (0.7%). Two patients experienced a pneumothorax (one needed hospital treatment, the other observation only). The longest duration of a side effect was 180 days (nerve lesion of the lower limb). The resulting medical consent form consists of five modules: Introduction to acupuncture and moxibustion, Risks of acupuncture treatment, Conditions which can increase the risk, Doctor’s statement, and Consent. <i>Conclusion: </i>Acupuncture provided by physicians is a relatively safe treatment and the proposed consent form could support both patients and professionals in the process of obtaining informed consent.
DOI: 10.6084/m9.figshare.5120653
title: Supplementary Material for: Prenatal Diagnosis of a Spontaneous Monochorionic Five-Amniotic Quintuplet Pregnancy

description: <i>Objectives:</i> It is the aim of this study to report on the prenatal diagnosis and course of a spontaneous monochorionic (MC) 5-amniotic (5A) quintuplet pregnancy which is such a rare event that it has up to now never been described antenatally. <i>Case Report:</i> A spontaneous MC 5A quintuplet pregnancy was diagnosed at 12 weeks by 2D ultrasound. Video tapes (2D and 4D) were made showing that 2D ultrasound still better documented simultaneous visualization of all quintuplets including their activities compared with 4D ultrasound, which, however, adds the information of space location. Variances of crown-rump length, nuchal translucency and nasal bone were evaluated. After informed consent and a second opinion of 2 centers performing invasive laser coagulation or occlusion of the umbilical cord, the parents decided to interrupt pregnancy. Pathologic evaluation confirmed MC 5A quintuplet pregnancy. <i>Conclusion:</i> The case demonstrates that splitting of 1 zygote into 5 embryos might even occur spontaneously. In view of the poor outcome and limited success of fetal reduction, pregnancy termination was finally part of the counseling.