cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5122855.v1
title: Supplementary Material for: Contribution of Cystatin C Gene Polymorphisms to Cerebral White Matter Lesions

description: <i>Background:</i> Vascular remodeling plays an important role in the development of arteriosclerosis and any of the resulting white matter lesions in the brain. An imbalance between cysteine proteases and the cysteine protease inhibitor cystatin C (CST3) may exacerbate vascular remodeling through degradation of extracellular matrix proteins. Therefore, we evaluated the association between functional polymorphisms in the <i>CST3</i> gene and the development of cerebral white matter lesions. <i>Methods:</i> In a total of 2,676 participants, 3<i> CST3</i> genepolymorphisms were genotyped in 92 cases with severe deep white matter hyperintensity (DWMH), and 184 subjects were randomly selected age- and sex-matched controls without any signs of DWMH. The genetic effects of these polymorphisms on DWMH and plasma CST3 levels were examined. CST3 expression vectors were transfected into an astrocytoma cell line and the expression level of CST3 mRNA was analyzed by quantitative RT-PCR. Intracellular and secreted levels of CST3 in the cell culture were quantified by Western blot and ELISA, respectively. <i>Results:</i> A significant association was found between one <i>CST3</i> gene haplotype and DWMH (p = 0.002). This haplotype was also associated with lower plasma CST3 levels (p = 0.01). An in vitro transfection study revealed that the +148A allele, which is included in the risk haplotype, significantly reduced the secretion and increased the intracellular accumulation of CST3; however, it had no effect on the mRNA expression. <i>Conclusions:</i> Our study shows that polymorphisms in the <i>CST3</i> gene are significantly associated with the likelihood of DWMH. Substitution of A for G at +148 of the<i> CST3</i> gene decreased the extracellular availability of CST3 in vitro, which might result in the activation of protease activity.
DOI: 10.6084/m9.figshare.5122846.v1
title: Supplementary Material for: Klinische Forschung zur Anthroposophischen Medizin – Update eines «Health Technology Assessment»-Berichts und Status Quo

description: <i>Hintergrund und Fragestellung:</i> 2005 wurde ein «Health Technology Assessment»(HTA)-Bericht zu Wirksamkeit, Sicherheit, Wirtschaftlichkeit und Bedarf der Anthroposophischen Medizin (AM) erstellt. Im Kontext des «Schweizer Volksvotums pro Komplementärmedizin» (Mai 2009) erfolgte ein Update des HTA-Berichts. <i>Design:</i> Update des HTA-Berichts durch eine systematische Übersichtsarbeit. <i>Methoden:</i> Das Update wurde in Anlehnung an den bereits vorhandenen HTA-Bericht sowie entsprechend den Vorgaben des Schweizer Bundesamtes für Gesundheit durchgeführt. Nach klinischen Studien wurde systematisch in vier Datenbanken, in einer spezialisierten Zeitschrift und mit Hilfe umfassender Expertenkontakte gesucht. Studien wurden nach vorab definierten Kriterien ausgewählt, die Daten extrahiert und die Qualität individuell überprüft. <i>Ergebnisse:</i> 70 neue klinische Studien zur Wirksamkeit wurden gefunden. Damit liegen derzeit insgesamt 265 klinische Studien zur AM vor: 38 randomisierte Studien, 36 prospektive und 49 retrospektive, nichtrandomisierte, vergleichende Studien sowie 90 prospektive und 52 retrospektive Studien ohne Kontrollgruppe. Die Studien untersuchten ein weites Spektrum an AM-Therapien bei einer Vielzahl von Erkrankungen; das Gesamtsystem der AM untersuchten 38 Studien, in 10 Studien ging es um nichtpharmakologische Therapien, 133 befassten sich mit Misteltherapie bei Krebs und 84 untersuchten sonstige AM-Arzneitherapien. Die Studien zeigten in der Mehrzahl ein positives Ergebnis für AM. Die methodische Qualität der Studien variierte sehr; einige wiesen erhebliche Schwächen auf, andere waren sorgfältig durchgeführt. Die Praxisrelevanz war überwiegend hoch. Bei Beschränkung auf die qualitativ besseren Studien ergab sich ein positives Ergebnis für die AM. Nebenwirkungen und Risiken waren selten und im Schweregrad meist mild oder mäßig. Studien zur Sicherheit zeigten eine insgesamt gute Verträglichkeit. <i>Schlussfolgerung:</i> Studien unterschiedlichen Designs und unterschiedlicher Qualität beschreiben bei einer Vielzahl von Erkrankungen ein für die AM medizinisch gutes und für die Patienten zufriedenstellendes, sicheres und vermutlich auch kostengünstiges Behandlungsergebnis. Weiterführende qualitativ hochwertige Evaluationen sind wünschenswert.
DOI: 10.6084/m9.figshare.5122849
title: Supplementary Material for: Interactions of Lymphocytes, Thyrocytes and Fibroblasts in Hashimoto’s Thyroiditis: An Immunohistochemical and Ultrastructural Study

description: <i>Background:</i> The mechanism of autoimmune reaction, a diffuse process consisting of a combination of epithelial cell destruction, lymphoid cellular infiltration, and fibrosis in Hashimoto’s thyroiditis, is not well known. The aim of this study was to analyse the cell subsets in thyroid tissue of patients with Hashimoto’s thyroiditis. <i>Methods:</i> We studied paraffin-embedded thyroid specimens obtained from children with Hashimoto’s thyroiditis and children without an autoimmune thyroid disease. Mononuclear T cells were detected by means of CD3+, CD4+, CD8+ antibodies, B cells by CD79 alpha+ antibodies, and antigen-presenting cells by CD1a+ antibodies, and they were counted in every 1,000 cells. The specimens from each patient were routinely estimated and investigated under the electron microscope. <i>Results:</i> In Hashimoto’s thyroiditis, we observed a statistically significant increase in T suppressor/cytotoxic cells CD8+ (20.54 ± 0.68%) in comparison to the control group (0.65 ± 0.30%), simple goitre (4.01 ± 5.54%) and nodular goitre (8.53 ± 2.37%), and a statistically significant increase in plasma CD79 alpha+ cells (31.65 ± 9.11%) in comparison to the control group (4.11 ± 1.94%), simple goitre (1.83 ± 0.64%) and nodular goitre (5.22 ± 1.63%). Simultaneously, we observed a low number of CD4+ T helper cells in the thyroid gland (0.93 ± 0.99%) in Hashimoto’s thyroiditis (0.19 ± 0.05% in the control group, 1.05 ± 2.71% in simple goitre, 2.03 ± 1.06% in nodular goitre). The ultrastructural investigations showed interactions between T cells, plasmocytes, fibrocytes and thyrocytes leading to apoptosis of thyrocytes. An immunological synapse between T cells, plasmocytes and thyrocytes in the thyroid gland was noticed. <i>Conclusions:</i> In Hashimoto’s thyroiditis, autoantigen presentation in combination with a low number of CD4+ T helper cells and a high number of CD8+ cells and plasmocytes caused the development of a cytotoxic reaction against thyrocytes, leading to apoptosis of the thyrocytes.
DOI: 10.6084/m9.figshare.5122852
title: Supplementary Material for: Hospital and Community Validation of a Screening Instrument for Detection of Neurodisability in Indian Children Aged 6 Months to 2 Years

description: <i>Objective:</i> To develop and validate a screening instrument for neurological disorders in children aged 6 months to 2 years in the community. <i>Methods:</i> A comprehensive parent-administered instrument was developed to screen for hearing, vision, seizures, motor deficits and development in Indian children aged 6–24 months. This was tested for reliability and validated in the hospital setting by comparing with pre-decided gold standards. It was then used in a community survey in a two-phase design in which all screen positives and a random sample of screen negatives were validated. <i>Result:</i> The screening instrument had overall sensitivity, specificity and positive predictive values of 95.8, 68.1 and 76.1%, respectively, in the hospital setting. In the field setting, these figures changed to 95.4, 51.8 and 20.6%, respectively. The reasons for this are discussed. <i>Conclusion:</i> Community surveys must use a two-phase design to get the true prevalence. A falsely high prevalence will be computed if only a single-phase design or hospital validation is used.
DOI: 10.6084/m9.figshare.5122840
title: Supplementary Material for: Upregulation of Nestin Protects Podocytes from Apoptosis Induced by Puromycin Aminonucleoside

description: <i>Background:</i> Nestin is an intermediate filament protein widely used as a marker of stem cells or progenitor cells. Nestin is also highly expressed in the glomerular podocyte, a type of terminally differentiated epithelial cell. Little is known about the significance of nestin in podocytes. <i>Methods:</i> Puromycin aminonucleoside (PAN) was injected into the rats to produce a PAN nephrosis model. Transmission electronic microscopy and terminal dUTP nick end-labeling assay were used to examine the podocyte foot process (FP) effacement and apoptosis, respectively. A mouse podocyte cell line was cultured and incubated with PAN. Immunoblot was used to examine the level of nestin expression both in vivo and in vitro. Enhanced green fluorescence protein-tagged plasmids containing nestin shRNA were transfected into the cultured podocytes to silence nestin expression. F-actin arrangement within cultured podocytes was investigated by immunofluorescence, while the apoptosis rate was examined by both Hoechst stain and flow cytometry. <i>Results:</i> In the PAN-induced rat nephrosis model, podocyte nestin expression was increased in the absence of apparent podocyte apoptosis, even though the FP was significantly effaced. In the cultured mouse podocytes, PAN upregulated nestin expression in a time-dependent manner within 24 h of treatment. Notably, no significant apoptosis occurred, however knocking down nestin expression resulted in a remarkable derangement of actin cytoskeleton and an increase in apoptosis in the cultured podocytes 24 h after being incubated with PAN. <i>Conclusions:</i> Upregulation of nestin expression during PAN nephrosis could protect podocytes from apoptosis and that this process is mediated by maintaining the regular arrangement of actin cytoskeleton.
DOI: 10.6084/m9.figshare.5122843
title: Supplementary Material for: Type D Personality as a Cardiovascular Risk Marker in the General Population: Results from the Gutenberg Health Study

description: <i>Background:</i> Type D personality is considered as an independent risk factor for morbidity and mortality in cardiovascular patients and a vulnerability factor for distress in the general population. Because representative community studies are rare, we sought to determine the prevalence of type D personality and its relationship with demographic characteristics, different features of mental disorders, cardiovascular risk factors, health behavior, endothelial function and cardiovascular biomarkers in the general population. <i>Methods:</i> The prevalence of type D personality and its correlates were analyzed cross-sectionally in a population-based sample of 5,000 Mid-Europeans aged 35–74 years from the Gutenberg Health Study. <i>Results:</i> The prevalence of type D personality was 22.2% without remarkable differences in sex distribution. Type D subjects were characterized by lower socioeconomic status, lack of a partnership, increased depression, anxiety, depersonalization and health care utilization. Despite its strong association with mental disorders, type D personality emerged as psychometrically distinct. Although type D personality was independently associated with coronary heart disease (OR = 1.54, p = 0.044), no associations with traditional cardiovascular risk factors were found independently from depression or anxiety. <i>Conclusions:</i> Although type D personality is strongly associated with depression, anxiety, impaired mental and somatic health status, and increased health care utilization, the type D construct seems to comprise dysfunctional personality patterns not covered by depression and anxiety scales. Beyond these associations, the pathways of the cardiotoxic impact of type D personality remain to be elucidated. There is a need for prospective population studies on potential links between type D personality and cardiac disease.
DOI: 10.6084/m9.figshare.5122849.v1
title: Supplementary Material for: Interactions of Lymphocytes, Thyrocytes and Fibroblasts in Hashimoto’s Thyroiditis: An Immunohistochemical and Ultrastructural Study

description: <i>Background:</i> The mechanism of autoimmune reaction, a diffuse process consisting of a combination of epithelial cell destruction, lymphoid cellular infiltration, and fibrosis in Hashimoto’s thyroiditis, is not well known. The aim of this study was to analyse the cell subsets in thyroid tissue of patients with Hashimoto’s thyroiditis. <i>Methods:</i> We studied paraffin-embedded thyroid specimens obtained from children with Hashimoto’s thyroiditis and children without an autoimmune thyroid disease. Mononuclear T cells were detected by means of CD3+, CD4+, CD8+ antibodies, B cells by CD79 alpha+ antibodies, and antigen-presenting cells by CD1a+ antibodies, and they were counted in every 1,000 cells. The specimens from each patient were routinely estimated and investigated under the electron microscope. <i>Results:</i> In Hashimoto’s thyroiditis, we observed a statistically significant increase in T suppressor/cytotoxic cells CD8+ (20.54 ± 0.68%) in comparison to the control group (0.65 ± 0.30%), simple goitre (4.01 ± 5.54%) and nodular goitre (8.53 ± 2.37%), and a statistically significant increase in plasma CD79 alpha+ cells (31.65 ± 9.11%) in comparison to the control group (4.11 ± 1.94%), simple goitre (1.83 ± 0.64%) and nodular goitre (5.22 ± 1.63%). Simultaneously, we observed a low number of CD4+ T helper cells in the thyroid gland (0.93 ± 0.99%) in Hashimoto’s thyroiditis (0.19 ± 0.05% in the control group, 1.05 ± 2.71% in simple goitre, 2.03 ± 1.06% in nodular goitre). The ultrastructural investigations showed interactions between T cells, plasmocytes, fibrocytes and thyrocytes leading to apoptosis of thyrocytes. An immunological synapse between T cells, plasmocytes and thyrocytes in the thyroid gland was noticed. <i>Conclusions:</i> In Hashimoto’s thyroiditis, autoantigen presentation in combination with a low number of CD4+ T helper cells and a high number of CD8+ cells and plasmocytes caused the development of a cytotoxic reaction against thyrocytes, leading to apoptosis of the thyrocytes.
DOI: 10.6084/m9.figshare.5122834
title: Supplementary Material for: Arl6ip1 Plays a Role in Proliferation during Zebrafish Retinogenesis

description: <b><i>Objective:</i></b> Arl6ip1 has been reported to play a role in ocular development, but its regulatory function as it relates to proliferation is unclear. Therefore, this study aimed to evaluate how Arl6ip1 may regulate the proliferative behavior of retinal progenitor cells during zebrafish embryogenesis. <b><i>Method:</i></b> Arl6ip1 was specifically knocked down by introducing morpholino nucleic acid oligomers. The DNA content of cells dissociated from morphant eyes was analyzed by fluorescence-activated cell sorting (FACS). Retinal cells in the S- and late G2/M-phase were detected by labeling with BrdU and then immunostaining with anti-BrdU antibody and by immunostaining with phospho-histone H3 antibody, respectively. We also examined the expressions of <i>shh,</i><i>p57kip2,</i> and <i>cyclin D1</i> in retinas of experimental animals. The bidirectional plasmid pGFP:HSE:p57kip2 was used to rescue the defect in cell cycle exit. <b><i>Results:</i></b> FACS analysis showed that the &gt;2C DNA content per cell in the eyes of <i>arl6ip1</i> morphants was 2-fold greater than that of the wild type. Following functional Arl6ip1 knockdown, anti-BrdU- and anti-phospho-histone H3-positive signals were higher and the retinal progenitors kept expressing <i>cyclin D1</i> but not <i>shh</i> or <i>p57kip2,</i> suggesting that eye progenitor cells remained in an early progenitor state and could not exit the cell cycle to progress to differentiation. Interestingly, overexpression of p57kip2, which enables exit from the cell cycle, led to a reduction of anti-BrdU-positive signals in the retinas of <i>arl6ip1</i> morphants. <b><i>Conclusion:</i></b> Arl6ip1 not only affects signals controlling eye development but also plays an important role in the proliferation of retinal progenitor cells.
DOI: 10.6084/m9.figshare.5122837
title: Supplementary Material for: Risk of Falling in Parkinson’s Disease at the Hoehn-Yahr Stage III

description: <i>Background:</i> It is difficult to predict the risk of falling, especially in patients with good motor ability, and the mechanisms underlying the relation between gait patterns and falling in Parkinson’s disease (PD) remain unclear. We investigated factors related to falling, including walking speed and time, in patients with Hoehn-Yahr stage III PD. <i>Methods:</i> We performed clinical assessments and evaluated balance in 30 patients with PD. Information on falling was obtained from questionnaires and personal interviews. Gait patterns were analyzed with the use of an originally designed, suddenly narrowed path. <i>Results:</i> Gait velocity was slower in fallers than in non-fallers (p = 0.047). Unified Parkinson’s Disease Rating Scale part II (UPDRS part II) score, fear of falling, and gait velocity were significantly related to falling on analysis with a single logistic model. When a multiple logistic model was used, the UPDRS part II score was significantly related to falling (OR: 1.48, p = 0.037, 95% CI: 1.02–2.16). <i>Conclusions:</i> Patients with Hoehn-Yahr stage III PD showed slow gait velocity attributed to fear of falling before arrival at a narrowed entrance or while walking on a narrowed path. The UPDRS part II score is significantly related to the risk of future falls.
DOI: 10.6084/m9.figshare.5122843.v1
title: Supplementary Material for: Type D Personality as a Cardiovascular Risk Marker in the General Population: Results from the Gutenberg Health Study

description: <i>Background:</i> Type D personality is considered as an independent risk factor for morbidity and mortality in cardiovascular patients and a vulnerability factor for distress in the general population. Because representative community studies are rare, we sought to determine the prevalence of type D personality and its relationship with demographic characteristics, different features of mental disorders, cardiovascular risk factors, health behavior, endothelial function and cardiovascular biomarkers in the general population. <i>Methods:</i> The prevalence of type D personality and its correlates were analyzed cross-sectionally in a population-based sample of 5,000 Mid-Europeans aged 35–74 years from the Gutenberg Health Study. <i>Results:</i> The prevalence of type D personality was 22.2% without remarkable differences in sex distribution. Type D subjects were characterized by lower socioeconomic status, lack of a partnership, increased depression, anxiety, depersonalization and health care utilization. Despite its strong association with mental disorders, type D personality emerged as psychometrically distinct. Although type D personality was independently associated with coronary heart disease (OR = 1.54, p = 0.044), no associations with traditional cardiovascular risk factors were found independently from depression or anxiety. <i>Conclusions:</i> Although type D personality is strongly associated with depression, anxiety, impaired mental and somatic health status, and increased health care utilization, the type D construct seems to comprise dysfunctional personality patterns not covered by depression and anxiety scales. Beyond these associations, the pathways of the cardiotoxic impact of type D personality remain to be elucidated. There is a need for prospective population studies on potential links between type D personality and cardiac disease.
DOI: 10.6084/m9.figshare.5122831
title: Supplementary Material for: Immune Dysregulation in Chronic Stress: A Quantitative and Functional Assessment of Regulatory T Cells

description: <i>Objective:</i> Chronic stress is closely related to immune dysfunction. Immune parameters have been analyzed in many ways in humans and animals under chronic stress. Recently, it has been proved that FoxP3+ regulatory T cells (Tregs) play a key role in immune regulation in vivo. However, it has not yet been elucidated how Tregs respond to chronic stress in vivo. Therefore, in the present study, we investigated the frequency of and functional changes in Tregs from mice under chronic stress. <i>Methods:</i> Spleen cells were separated from C57/BL6 mice that had been exposed to immobilization stress for 3 weeks. The frequencies of FoxP3+ and CD4+ CD25+ cells were analyzed by flow cytometry. CD4+CD25– cells (effector T cells, Teffs), CD4+CD25+ cells (Tregs) and CD4– cells (antigen-presenting cells, APCs) were separated for the functional assessment of the proliferative activity of Teffs, the suppressive activity of Tregs and the feeder activity of APCs. <i>Results:</i> The results showed that chronic immobilization stress significantly increased the frequencies of CD4+CD25+ and CD4+FoxP3+ cells. Chronic immobilization stress also enhanced the suppressive function of CD4+ CD25+ Tregs. On the other hand, the proliferative activity of Teffs and the feeder activity of APCs were decreased in the mice under chronic immobilization stress. <i>Conclusion:</i> Taken together, it is suggested that increased number and function of Tregs may actively contribute to the immune dysfunction in chronic immobilization stress, synergizing with the decreased function of Teffs and APCs.
DOI: 10.6084/m9.figshare.5122825
title: Supplementary Material for: Concerns for the Reliability and Validity of the National Stroke Project Stroke Severity Scale

description: <i>Background:</i> The National Stroke Project (NSP) was a retrospective cohort study of US Medicare beneficiaries hospitalized with stroke or transient ischemic attack (TIA). The NSP included a simple assessment of stroke severity (NSP-Stroke Scale, NSP-SS). Used for risk adjustment in outcome studies, the reliability and validity of the NSP-SS have not been assessed. We determined the reliability, concurrent and construct validity of theNSP-SS. <i>Methods:</i> The initial neurologic examinations of 100 consecutive patients hospitalized with ischemic stroke/TIA in a single academic medical center were reviewed. The NSP-SS was retrospectively scored twice by the same rater and independently by a second rater to assess reliability. The National Institutes of Health Stroke Scale (NIH-SS) was also scored retrospectively and used as the criterion standard for concurrent validity. Construct validity was based on discharge status. <i>Results:</i> The NSP-SS had moderate-substantial inter-rater (weighted kappa, ĸ<sub>w</sub> = 0.66, 95% CI 0.55–0.77) and intra-rater (ĸ<sub>w</sub> = 0.63, 95% CI 0.52–0.75) reliability. Correlation between NSP-SS and NIH-SS scores was moderate (Spearman r = 0.65, 95% CI 0.52–0.75, p &lt; 0.0001) but some categorizations in the NSP-SS seemed inappropriate reflecting poor content validity. Each NSP-SS point was associated with a greater likelihood of poor outcome (OR = 2.1, 95% CI 1.1–3.7, p = 0.016). Based on dichotomized scores (NSP 0–2 and NIH-SS &lt;6; mild deficits), the NSP-SS sensitivity was 70.9% (95% CI 57.9–81.2%), specificity 82.2% (95% CI 68.7–90.7%), likelihood ratio for severe stroke 4.0 (95% CI 2.1–7.6) and likelihood ratio for mild stroke 0.3 (95% CI 0.20–0.5). The dichotomized NSP-SS and NIH-SS similarly predicted poor outcome (NSP-SS &gt;2, OR = 4.7, 95% CI 1.7–13.0, p = 0.003 vs. NIH-SS ≧6, OR = 4.4, 95% CI 1.5–13.0, p = 0.006) with excellent discrimination (C = 0.827 and 0.826, respectively). <i>Conclusion:</i> The NSP-SS has moderate-substantial reliability but poor content validity and poor to moderate concurrent validity as compared with the NIH-SS. In addition, it is not clear that the NSP-SS is easier to extract from medical records than the NIH-SS. Given this, and its other limitations, the utility of this scale for risk adjustment in future stroke outcome studies is questionable.