cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5120860.v1
title: Supplementary Material for: Cytokines Involved in Interferon-γ Production by Human Macrophages

description: Interferon (IFN)-γ is important to the immune defense against intracellular pathogens and specifically the ability of macrophages to control <i>Mycobacterium tuberculosis</i> (MTB). Increasing evidence has accumulated to support the idea that macrophages produce IFN-γ. We describe here the cytokine interactions that determine IFN-γ expression and secretion during MTB infection of human macrophages. Detection of biologically important IFN-γ levels in culture supernatants of MTB-infected human macrophages requires the addition of interleukin (IL)-12. IL-18 augmented IFN-γ production from human macrophages in response to the combination of MTB and supplemental IL-12. Although IL-18 gene expression was generally unchanged, IL-18 protein secretion was enhanced by the combination of MTB and IL-12, and functioned primarily to stimulate IFN-γ release. Importantly, IL-27 induced by MTB infection opposed IFN-γ production by antagonizing IL-18 activity in human macrophages. Neutralization of IL-27 increased the expression of the IL-18 receptor β-chain. Additionally, IL-27 blocked NF-ĸB activation in response to IL-18. These results define the signals required for IFN-γ production by human macrophages and highlight the interactions between cytokines produced during MTB infection. Together, they identify a novel role for IL-27 in regulating macrophage function by disrupting IL-18 activity.
DOI: 10.6084/m9.figshare.5120842
title: Supplementary Material for: Management of Obstructive Uropathy Patients with Advanced Prostate Cancer – A Systematic Review

description: <i>Background: </i>The optimal management of malignant ureteral obstruction in prostate cancer patients remains under debate and there exist no evidence-based recommendations to assist clinicians in advising patients. <i>Material and Methods: </i>Four databases were searched for the best available evidence for the treatment of ureteral obstruction and subsequent obstructive uropathy in prostate cancer regarding efficacy, overall survival and side effects. Treatment options considered were percutaneous nephrostomy (PCN), retrograde stenting and androgen deprivation (AD). The retrieved publications were screened for inclusion and exclusion criteria and assessed for methodological quality. <i>Results: </i>Of 987 identified publications, 13 were included in the review. The identified evidence consists of 3 cohort studies and 10 case series. More data and higher rates of successful decompression are published for PCN than for internal stenting. The results show inferior overall survival in patients pretreated with AD and high response rates for hormone-naive patients when treated with AD. There are no consistent results regarding the influence of unilateral or bilateral obstruction on overall survival. <i>Conclusions: </i>Various methodological flaws reduce the validity and generalisability of these results. There is currently no scientific evidence allowing for a reliable answer to the optimal management of malignant ureteral obstruction in prostate cancer patients.
DOI: 10.6084/m9.figshare.5120839
title: Supplementary Material for: Performance of FDG PET for Detection of Alzheimer’s Disease in Two Independent Multicentre Samples (NEST-DD and ADNI)

description: <i>Aim:</i> We investigated the performance of FDG PET using an automated procedure for discrimination between Alzheimer’s disease (AD) and controls, and studied the influence of demographic and technical factors. <i>Methods:</i> FDG PET data were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) [102 controls (76.0 ± 4.9 years) and 89 AD patients (75.7 ± 7.6 years, MMSE 23.5 ± 2.1) and the Network for Standardisation of Dementia Diagnosis (NEST-DD) [36 controls (62.2 ± 5.0 years) and 237 AD patients (70.8 ± 8.3 years, MMSE 20.9 ± 4.4). The procedure created t-maps of abnormal voxels. The sum of t-values in predefined areas that are typically affected by AD (AD t-sum) provided a measure of scan abnormality associated with a preset threshold for discrimination between patients and controls. <i>Results:</i> AD patients had much higher AD t-sum scores compared to controls (p &lt; 0.01), which were significantly related to dementia severity (ADNI: r = –0.62, p &lt; 0.01; NEST-DD: r = –0.59, p &lt; 0.01). Early-onset AD patients had significantly higher AD t-sum scores than late-onset AD patients (p &lt; 0.01). Differences between databases were mainly due to different age distributions. The predefined AD t-sum threshold yielded a sensitivity and specificity of 83 and 78% in ADNI and 78 and 94% in NEST-DD, respectively. <i>Conclusion:</i> The automated FDG PET analysis procedure provided good discrimination power, and was most accurate for early-onset AD.
DOI: 10.6084/m9.figshare.5120833
title: Supplementary Material for: Chromatin Flow Cytometry Identifies Changes in Epigenetic Cell States

description: We report flow cytometric protocols that quantitatively display the levels of different histone modifications on the single cell level. This method allows the rapid and simultaneous analysis of the global levels of chromatin marks in combination with other flow cytometric features. We show that chromatin flow cytometry identifies changes in epigenetic marks, such as histone acetylation and methylation, in drug-treated and differentiated mouse embryonic stem cell populations.
DOI: 10.6084/m9.figshare.5120836
title: Supplementary Material for: Mini-Mental State Examination Is Sensitive to Brain Atrophy in Alzheimer’s Disease

description: <i>Background/Aims:</i> Screening instruments such as the Mini-Mental State Examination (MMSE) are useful for the early identification of Alzheimer’s disease (AD). We tested whether macrostructural differences in brain volume are related to the MMSE. <i>Methods:</i> The MMSE was related to cortical thickness and the volume of 19 brain structures in 96 patients with mild to moderate AD. In addition, the patients were compared to 93 healthy elderly controls. <i>Results:</i> The MMSE was related to the volume of the total brain, cerebral cortex, accumbens, cerebral white matter, inferior lateral ventricles and hippocampus. Positive correlations with cortical thickness were found for 41% of the brain surface, and 58% of this area was significantly thinner in AD. <i>Conclusion:</i> The MMSE is sensitive to macrostructural brain atrophy in AD, but also to morphometric variation not specifically related to AD.
DOI: 10.6084/m9.figshare.5120842.v1
title: Supplementary Material for: Management of Obstructive Uropathy Patients with Advanced Prostate Cancer – A Systematic Review

description: <i>Background: </i>The optimal management of malignant ureteral obstruction in prostate cancer patients remains under debate and there exist no evidence-based recommendations to assist clinicians in advising patients. <i>Material and Methods: </i>Four databases were searched for the best available evidence for the treatment of ureteral obstruction and subsequent obstructive uropathy in prostate cancer regarding efficacy, overall survival and side effects. Treatment options considered were percutaneous nephrostomy (PCN), retrograde stenting and androgen deprivation (AD). The retrieved publications were screened for inclusion and exclusion criteria and assessed for methodological quality. <i>Results: </i>Of 987 identified publications, 13 were included in the review. The identified evidence consists of 3 cohort studies and 10 case series. More data and higher rates of successful decompression are published for PCN than for internal stenting. The results show inferior overall survival in patients pretreated with AD and high response rates for hormone-naive patients when treated with AD. There are no consistent results regarding the influence of unilateral or bilateral obstruction on overall survival. <i>Conclusions: </i>Various methodological flaws reduce the validity and generalisability of these results. There is currently no scientific evidence allowing for a reliable answer to the optimal management of malignant ureteral obstruction in prostate cancer patients.
DOI: 10.6084/m9.figshare.5120827
title: Supplementary Material for: Considerations for Designing a Prototype Genetic Test for Use in Translational Research

description: <i>Background:</i> Translational research is needed to explore how people will respond to personal genetic susceptibility information related to common health conditions. Maximizing the rigor of this research will require that genetic test results be returned to study participants. Currently, there is no established method that guides the selection of genetic variants to be used in research with these objectives. <i>Methods and Results:</i> To address this question, we designed a process to identify gene variants and health conditions to be included in a prototype genetic test for use in a larger research effort, the Multiplex Initiative. The intention of this exploration was to facilitate research that generates individual genetic test results that are returned to study participants. Inclusion criteria were developed as part of a transdisciplinary and iterative process that considered the weight of evidential support for genetic association with common health conditions, the appropriateness of use in human subjects research, and the recommendations of expert peer reviewers. <i>Conclusions:</i> The selection process was designed to identify gene variants for the limited purpose of translational research and, therefore, should not be seen as producing a valid clinical test. However, this example of an applied selection process may provide guidance for researchers who are designing studies to evaluate the implications of genetic susceptibility testing through the return of personalized genetic information. As the rate of genomic discoveries increases, such research will be essential in steering the translation of this information towards the greatest public health benefit.
DOI: 10.6084/m9.figshare.5120830
title: Supplementary Material for: A Critical Period in Cortical Interneuron Neurogenesis in Down Syndrome Revealed by Human Neural Progenitor Cells

description: Down syndrome (DS) is a developmental disorder whose mental impairment is due to defective cortical development. Human neural progenitor cells (hNPCs) derived from fetal DS cortex initially produce normal numbers of neurons, but generate fewer neurons with time in culture, similar to the pattern of neurogenesis that occurs in DS in vivo. Microarray analysis of DS hNPCs at this critical time reveals gene changes indicative of defects in interneuron progenitor development. In addition, dysregulated expression of many genes involved in neural progenitor cell biology points to changes in the progenitor population and subsequent reduction in interneuron neurogenesis. Delineation of a critical period in interneuron development in DS provides a foundation for investigation of the basis of reduced neurogenesis in DS and defines a time when these progenitor cells may be amenable to therapeutic treatment.
DOI: 10.6084/m9.figshare.5120836.v1
title: Supplementary Material for: Mini-Mental State Examination Is Sensitive to Brain Atrophy in Alzheimer’s Disease

description: <i>Background/Aims:</i> Screening instruments such as the Mini-Mental State Examination (MMSE) are useful for the early identification of Alzheimer’s disease (AD). We tested whether macrostructural differences in brain volume are related to the MMSE. <i>Methods:</i> The MMSE was related to cortical thickness and the volume of 19 brain structures in 96 patients with mild to moderate AD. In addition, the patients were compared to 93 healthy elderly controls. <i>Results:</i> The MMSE was related to the volume of the total brain, cerebral cortex, accumbens, cerebral white matter, inferior lateral ventricles and hippocampus. Positive correlations with cortical thickness were found for 41% of the brain surface, and 58% of this area was significantly thinner in AD. <i>Conclusion:</i> The MMSE is sensitive to macrostructural brain atrophy in AD, but also to morphometric variation not specifically related to AD.
DOI: 10.6084/m9.figshare.5120821
title: Supplementary Material for: Validation of Endogenous Internal Real-Time PCR Controls in Renal Tissues

description: <i>Background:</i> Endogenous internal controls (‘reference’ or ‘housekeeping’ genes) are widely used in real-time PCR (RT-PCR) analyses. Their use relies on the premise of consistently stable expression across studied experimental conditions. Unfortunately, none of these controls fulfills this premise across a wide range of experimental conditions; consequently, none of them can be recommended for universal use. <i>Methods:</i> To determine which endogenous RT-PCR controls are suitable for analyses of renal tissues altered by kidney disease, we studied the expression of 16 commonly used ‘reference genes’ in 7 mildly and 7 severely affected whole kidney tissues from a well-characterized cystic kidney disease model. Expression levels of these 16 genes, determined by TaqMan® RT-PCR analyses and Affymetrix GeneChip® arrays, were normalized and tested for overall variance and equivalence of the means. <i>Results:</i> Both statistical approaches and both TaqMan- and GeneChip-based methods converged on 3 out of the 4 top-ranked genes (<i>Ppia</i>, <i>Gapdh</i> and <i>Pgk1</i>) that had the most constant expression levels across the studied phenotypes. <i>Conclusion:</i> A combination of the top-ranked genes will provide a suitable endogenous internal control for similar studies of kidney tissues across a wide range of disease severity.
DOI: 10.6084/m9.figshare.5120824
title: Supplementary Material for: Activation of Sonic Hedgehog Signaling Pathway in Olfactory Neuroblastoma

description: <i>Objectives:</i> Sonic hedgehog (Shh) signaling pathway is associated with tumor development; however, the role of Shh signaling in the development of olfactory neuroblastoma (ONB) is unknown. This study aimed to investigate the relationship between the regulation of Shh signaling and the pathogenesis of ONB. <i>Methods:</i> The expression of Shh signaling components was characterized by immunohistochemistry in human non-tumor olfactory epithelium and ONB specimens, and by RT-PCR and immunoblotting in human ONB cell lines. The impact of the treatment with cyclopamine (a selective inhibitor of the Shh pathway) and/or exogenous Shh on ONB cell proliferation, cycle and apoptosis was examined by MTT, soft agar colony formation and flow cytometry assays, respectively. The influence of Shh signaling on the expression of Shh signaling components and cell cycle-related regulators was determined by immunoblotting and quantitative RT-PCR, respectively. <i>Results:</i> The expression of Pacthed1, Gli1 and Gli2 was detected in 70, 70, and 65% of human ONB specimens, respectively, and in proportion of ONB cell lines, but not in non-tumor olfactory epithelium. Treatment with cyclopamine inhibited the proliferation and colony formation of ONB cells, induced ONB cell cycle arrest and apoptosis, and down-regulated the expression of Pacthed1, Gli1 and cyclin D1, but up-regulated p21 expression in vitro. These regulatory effects of cyclopamine were partially or completely erased by exogenous Shh. <i>Conclusion:</i> These data suggest that the Shh signaling pathway is crucial for the growth of ONB.
DOI: 10.6084/m9.figshare.5120815
title: Supplementary Material for: CNGA2 Contributes to ATP-Induced Noncapacitative Ca<sup>2+</sup> Influx in Vascular Endothelial Cells

description: <i>Background/Aims:</i> ATP can activate several Ca<sup>2+</sup> influx channels in vascular endothelial cells. For example, it stimulates TRPC channels via capacitative and noncapacitative Ca<sup>2+</sup> entry (CCE and non-CCE, respectively) mechanisms; it also directly acts on P2X purinoceptors, resulting in Ca<sup>2+</sup> influx. In the present study, we tested the hypothesis that cyclic nucleotide-gated (CNG) channels also contribute to ATP-induced non-CCE. <i>Methods:</i> Two selective inhibitors of CNG channels, <i>L</i>-<i>cis</i>-diltiazem and LY-83583, and CNGA2-specific siRNA were used to study the involvement of CNGA2 in ATP-induced non-CCE in endothelial cells. Ca<sup>2+</sup> influx was studied using Ca<sup>2+</sup>-sensitive fluorescence dyes Fluo-3 and Fluo-4. <i>Results/Conclusion:</i><i>L</i>-<i>cis</i>-diltiazem and LY-83583 markedly reduced ATP-induced non-CCE in 3 types of endothelial cells including the H5V endothelial cell line, the primary cultured bovine aortic endothelial cells and the endothelial cells within isolated mouse aortic strips. The CNGA2-specific siRNA also reduced the ATP-induced non-CCE in H5V endothelial cells. The Ca<sup>2+</sup> influx was inhibited by Rp-8-CPT-cAMPS, MDL-12330A, SQ-22536 and MRS-2179, but not by ODQ or NF-157. Taken together, the present study demonstrated that CNGA2 channels contribute to ATP-induced non-CCE in vascular endothelial cells. It is likely that ATP acts through P2Y<sub>1 </sub>receptors and adenylyl cyclases to stimulate CNGA2.
DOI: 10.6084/m9.figshare.5120818
title: Supplementary Material for: Is There a Decline in the Vascular Event Rate after Transient Ischemic Attack or Stroke in Antiplatelet Trials?

description: <i>Background:</i> We examined the baseline characteristics and the rates of serious vascular events in randomized clinical trials after cerebral ischemia of presumed arterial origin to identify study features that predict vascular event incidence and to identify whether event rates have declined over time. <i>Methods:</i> We performed a systematic review to identify all published randomized controlled trials of patients with stroke or transient ischemic attack of presumed arterial origin that included an aspirin arm. We performed metaregression to analyze whether baseline features of included patients, design features and the year of study start and publication influenced vascular event rates under aspirin treatment. <i>Results:</i> Included studies comprised 23,247 patients who had 3,615 serious vascular events. Baseline characteristics of patients included in the different trials varied substantially over time. In multivariate metaregression analysis a shorter maximum allowed delay from symptom onset to randomization (p = 0.012) and a double-blind design were associated with higher annual event rates (p = 0.014). Event rates did not significantly decrease over time (p = 0.242). <i>Conclusion:</i> The baseline characteristics of patients included in trials that study antiplatelet agents have changed over time. The strongest predictors for higher event rates are a double-blind design and a short delay between symptom onset and randomization. An important reduction in event rates over time could not be demonstrated.
DOI: 10.6084/m9.figshare.5120809
title: Supplementary Material for: The 450-Band Resolution G- and R-Banded Standard Karyotype of the Donkey (<i>Equus asinus</i>, 2n = 62)

description: Donkey chromosomes were earlier characterized separately by C-, G- and R-banding techniques. However, direct comparisons between G- and R-banding patterns have still not been carried out in this species. The present study reports this comparison at the 450-band level by using replication G- and R-banding patterns. Two sets of synchronized lymphocyte cultures were set up to obtain early (GBA+CBA-banding) and late (RBA-banding) BrdU incorporation. Slides were stained with acridine orange and observed under a fluorescence microscope. Reverse GBA+CBA- and RBA-banded karyotypes at the 450-band level were constructed. To verify G- and R-banding patterns in some acrocentric chromosomes, sequential GBA+CBA/Ag-NORs and RBA/Ag-NORs were also performed. The results of CBA-banding patterns obtained in 12 animals from 2 breeds showed a pronounced polymorphism of heterochromatin, especially in EAS1q-prox. Ideogrammatic representations of G- and R-banded karyotypes were constructed using only one common G- and R-banding nomenclature. In the present study both G- and R-banding patterns and relative ideograms are presented as standard karyotype for this species at the 450-band level.
DOI: 10.6084/m9.figshare.5120821.v1
title: Supplementary Material for: Validation of Endogenous Internal Real-Time PCR Controls in Renal Tissues

description: <i>Background:</i> Endogenous internal controls (‘reference’ or ‘housekeeping’ genes) are widely used in real-time PCR (RT-PCR) analyses. Their use relies on the premise of consistently stable expression across studied experimental conditions. Unfortunately, none of these controls fulfills this premise across a wide range of experimental conditions; consequently, none of them can be recommended for universal use. <i>Methods:</i> To determine which endogenous RT-PCR controls are suitable for analyses of renal tissues altered by kidney disease, we studied the expression of 16 commonly used ‘reference genes’ in 7 mildly and 7 severely affected whole kidney tissues from a well-characterized cystic kidney disease model. Expression levels of these 16 genes, determined by TaqMan® RT-PCR analyses and Affymetrix GeneChip® arrays, were normalized and tested for overall variance and equivalence of the means. <i>Results:</i> Both statistical approaches and both TaqMan- and GeneChip-based methods converged on 3 out of the 4 top-ranked genes (<i>Ppia</i>, <i>Gapdh</i> and <i>Pgk1</i>) that had the most constant expression levels across the studied phenotypes. <i>Conclusion:</i> A combination of the top-ranked genes will provide a suitable endogenous internal control for similar studies of kidney tissues across a wide range of disease severity.
DOI: 10.6084/m9.figshare.5120812
title: Supplementary Material for: Nitric Oxide Suppresses Cerebral Vasomotion by sGC-Independent Effects on Ryanodine Receptors and Voltage-Gated Calcium Channels

description: <i>Background/Aims:</i> In cerebral arteries, nitric oxide (NO) release plays a key role in suppressing vasomotion. Our aim was to establish the pathways affected by NO in rat middle cerebral arteries. <i>Methods:</i> In isolated segments of artery, isometric tension and simultaneous measurements of either smooth muscle membrane potential or intracellular [Ca<sup>2+</sup>] ([Ca<sup>2+</sup>]<sub>SMC</sub>) changes were recorded. <i>Results:</i> In the absence of <i>L</i>-NAME, asynchronous propagating Ca<sup>2+</sup> waves were recorded that were sensitive to block with ryanodine, but not nifedipine. <i>L</i>-NAME stimulated pronounced vasomotion and synchronous Ca<sup>2+</sup> oscillations with close temporal coupling between membrane potential, tone and [Ca<sup>2+</sup>]<sub>SMC</sub>. If nifedipine was applied together with <i>L</i>-NAME, [Ca<sup>2+</sup>]<sub>SMC</sub> decreased and synchronous Ca<sup>2+</sup> oscillations were lost, but asynchronous propagating Ca<sup>2+</sup> waves persisted. Vasomotion was similarly evoked by either iberiotoxin, or by ryanodine, and to a lesser extent by ODQ. Exogenous application of NONOate stimulated endothelium-independent hyperpolarization and relaxation of either <i>L</i>-NAME-induced or spontaneous arterial tone. NO-evoked hyperpolarization involved activation of BK<sub>Ca</sub> channels via ryanodine receptors (RYRs), with little involvement of sGC. Further, in whole cell mode, NO inhibited current through L-type voltage-gated Ca<sup>2+</sup> channels (VGCC), which was independent of both voltage and sGC. <i>Conclusion:</i> NO exerts sGC-independent actions at RYRs and at VGCC, both of which normally suppress cerebral artery myogenic tone.