cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5122711
title: Supplementary Material for: Profiling of Sputum Inflammatory Mediators in Asthma and Chronic Obstructive Pulmonary Disease

description: <i>Background:</i> Asthma and chronic obstructive pulmonary disease (COPD) display features of overlap in airway physiology and airway inflammation. Whether inflammatory phenotypes in airway disease describe similar mediator expression is unknown. <i>Objectives:</i> To explore the relationship of airway inflammation and cytokine and chemokine expression in asthma and COPD. <i>Methods:</i> Subjects with asthma and COPD (n = 54 and n = 49) were studied. Clinical characteristics and sputum were collected at entry into the study. A 2-step sputum processing method was performed for supernatant and cytospin preparation. Meso Scale Discovery and Luminex platforms were used to measure cytokines, chemokines and matrix metalloproteinase levels. <i>Results:</i> Analytes sensitive to dithiothreitol (DTT) that had increased recovery in the 2-step sputum process were IL-1β, 4, 5, 10, 13, IFN-γ, TNFRI, GM-CSF, CCL2, 3, 4, 5, 13 and 17. There was a differential expression in IL-8, TNFRI and TNFRII between asthma and COPD [mean fold difference (95% CI): IL-8, 2.6 (1.3–5.4), p = 0.01; TNFRI, 2.1 (1.3–5.4), p = 0.03; TNFRII, 2.6 (1.2–5.6), p = 0.02]. In neutrophilic and eosinophilic airway inflammation, TNFα, TNFRI, TNFRII, IL-6, IL-8 and IL-5 could differentiate between these phenotypes. However, these phenotypes were unrelated to the diagnosis of asthma or COPD. <i>Conclusion:</i> Recovery of sputum mediators sensitive to DTT can be improved using the described sputum processing technique. Within airway inflammatory sub-phenotypes there is a differential pattern of mediator expression that is independent of disease. Whether these inflammatory phenotypes in asthma and COPD confer distinct pathogeneses, therapeutic responses and clinical phenotypes needs to be further evaluated.
DOI: 10.6084/m9.figshare.5122714
title: Supplementary Material for: Chronic Kidney Disease and Risk of Death from Infection

description: <i>Background:</i> Infection, bacteremia and sepsis are major sources of morbidity and mortality in patients with end-stage renal disease. This study sought to determine the association between predialysis chronic kidney disease (CKD) and infection-related mortality. <i>Methods:</i> We analyzed participants in the Third National Health and Nutrition Examination Survey (NHANES III). The study included adults ≧45- years-old without end-stage renal disease. Estimated glomerular filtration rate (eGFR) was categorized as ≧60, 45–59.9 and &lt;45 ml/min per 1.73 m<sup>2</sup>, and urinary albumin-to-creatinine ratio (ACR) as &lt;30, 30–299.9 and ≧300 mg/g. The study identified infection-related mortality, including septicemia, respiratory, abdominal and gastrointestinal, cardiac, kidney and genitourinary, neurologic, and other infections over a median of 13 years using the National Death Index. <i>Results:</i> Of 7,400 participants included in the study, 206 died from infections. Compared to individuals with eGFR ≧60 ml/min per 1.73 m<sup>2</sup>, infection-related mortality was higher for those with lower eGFR [adjusted HR = 1.36 (95% CI: 0.81, 2.30) and 2.36 (1.04, 5.38) for eGFR of 45–59.9 and &lt;45 ml/min per 1.73 m<sup>2</sup>, respectively; p trend = 0.06]. Compared to individuals with ACR &lt;30 mg/g, infection-related mortality was higher for ACR levels of 30–299 and ≧300 mg/g [adjusted HR = 1.68 (95% CI: 0.97, 2.92) and 2.84 (0.92, 8.74), p trend = 0.02]. <i>Conclusions:</i> Reduced eGFR and albuminuria are associated with increased risk for infection-related mortality. Efforts are needed to reduce its incidence and mitigate the effects of infections among individuals with CKD.
DOI: 10.6084/m9.figshare.5122726.v1
title: Supplementary Material for: Beta-Arrestin2 as a Competitor for GRK2 Interaction with the GLP-1 Receptor upon Receptor Activation

description: The signaling of seven transmembrane receptors/G-protein- coupled receptors (GPCRs) is regulated by a number of receptor interacting proteins, including βarrestins (βarrs) and GPCR kinases (GRKs). In the present report, we have analyzed the interaction pattern between the glucagon-like peptide-1 (GLP-1) receptor (GLP-1R), βarr2, and GRK2 using bioluminescence resonance energy transfer assays. We found that βarr2 interacts with the GLP-1R in a biphasic manner with a phosphorylation-independent and a phosphorylation-dependent component. In competition experiments, we observed βarr2 competing with GRK2 for interaction with GLP-1R. We propose a model were βarr2 competes with GRK2 for interaction with the activated and GRK phosphorylated GLP-1R, suggesting a new role of βarr2 in regulating the orchestration of GRK2 functionality.
DOI: 10.6084/m9.figshare.5122708
title: Supplementary Material for: Susceptibility to Vaccinia Virus Infection and Spread in Mice Is Determined by Age at Infection, Allergen Sensitization and Mast Cell Status

description: <i>Background:</i> Patients, especially young children, with atopic dermatitis are at an increased risk of developing eczema vaccinatum, a severe reaction to the smallpox vaccine, either through direct vaccination or indirect contact with a person recently vaccinated. <i>Methods:</i> Using a mouse model of infection, the severity of vaccinia-induced lesions was assessed from their appearance and viral DNA content. The response to vaccinia inoculation was assessed in young and adult mice, allergen-sensitized mice, and in mast cell-deficient mice. <i>Results:</i> Young age, sensitization to an allergen prior to infection, and a mast cell deficit, accomplished by using mast cell-deficient mice, resulted in more severe viral lesions at the site of inoculation, according to lesion appearance and viral DNA content. All three factors combined demonstrated maximal susceptibility, characterized by the severity of primary lesions and the development of secondary (satellite) lesions, as occurs in eczema vaccinatum in humans. Resistance to the appearance of satellite lesions could be restored by adoptive transfer of bone marrow-derived mast cells from either wild-type or cathelicidin-related antimicrobial peptide-deficient mice. Primary lesions were more severe following the latter transfer, indicating that cathelicidin-related antimicrobial peptide does contribute to the protective activity of mast cells against infection. <i>Conclusions:</i> The combination of young age, allergen sensitization and a mast cell deficit resulted in the most severe lesions, including satellite lesions. Understanding the factors determining the relative resistance/sensitivity to vaccinia virus will aid in the development of strategies for preventing and treating adverse reactions which can occur after smallpox vaccination.
DOI: 10.6084/m9.figshare.5122714.v1
title: Supplementary Material for: Chronic Kidney Disease and Risk of Death from Infection

description: <i>Background:</i> Infection, bacteremia and sepsis are major sources of morbidity and mortality in patients with end-stage renal disease. This study sought to determine the association between predialysis chronic kidney disease (CKD) and infection-related mortality. <i>Methods:</i> We analyzed participants in the Third National Health and Nutrition Examination Survey (NHANES III). The study included adults ≧45- years-old without end-stage renal disease. Estimated glomerular filtration rate (eGFR) was categorized as ≧60, 45–59.9 and &lt;45 ml/min per 1.73 m<sup>2</sup>, and urinary albumin-to-creatinine ratio (ACR) as &lt;30, 30–299.9 and ≧300 mg/g. The study identified infection-related mortality, including septicemia, respiratory, abdominal and gastrointestinal, cardiac, kidney and genitourinary, neurologic, and other infections over a median of 13 years using the National Death Index. <i>Results:</i> Of 7,400 participants included in the study, 206 died from infections. Compared to individuals with eGFR ≧60 ml/min per 1.73 m<sup>2</sup>, infection-related mortality was higher for those with lower eGFR [adjusted HR = 1.36 (95% CI: 0.81, 2.30) and 2.36 (1.04, 5.38) for eGFR of 45–59.9 and &lt;45 ml/min per 1.73 m<sup>2</sup>, respectively; p trend = 0.06]. Compared to individuals with ACR &lt;30 mg/g, infection-related mortality was higher for ACR levels of 30–299 and ≧300 mg/g [adjusted HR = 1.68 (95% CI: 0.97, 2.92) and 2.84 (0.92, 8.74), p trend = 0.02]. <i>Conclusions:</i> Reduced eGFR and albuminuria are associated with increased risk for infection-related mortality. Efforts are needed to reduce its incidence and mitigate the effects of infections among individuals with CKD.
DOI: 10.6084/m9.figshare.5122699
title: Supplementary Material for: Power of Data Mining Methods to Detect Genetic Associations and Interactions

description: <i>Background:</i> Genetic association studies, thus far, have focused on the analysis of individual main effects of SNP markers. Nonetheless, there is a clear need for modeling epistasis or gene-gene interactions to better understand the biologic basis of existing associations. Tree-based methods have been widely studied as tools for building prediction models based on complex variable interactions. An understanding of the power of such methods for the discovery of genetic associations in the presence of complex interactions is of great importance. Here, we systematically evaluate the power of three leading algorithms: random forests (RF), Monte Carlo logic regression (MCLR), and multifactor dimensionality reduction (MDR). <i>Methods:</i> We use the algorithm-specific variable importance measures (VIMs) as statistics and employ permutation-based resampling to generate the null distribution and associated p values. The power of the three is assessed via simulation studies. Additionally, in a data analysis, we evaluate the associations between individual SNPs in pro-inflammatory and immunoregulatory genes and the risk of non-Hodgkin lymphoma. <i>Results:</i> The power of RF is highest in all simulation models, that of MCLR is similar to RF in half, and that of MDR is consistently the lowest. <i>Conclusions:</i> Our study indicates that the power of RF VIMs is most reliable. However, in addition to tuning parameters, the power of RF is notably influenced by the type of variable (continuous vs. categorical) and the chosen VIM.
DOI: 10.6084/m9.figshare.5122702
title: Supplementary Material for: Monoclonal Antibodies against the Human Somatostatin Receptor Subtypes 1–5: Development and Immunohistochemical Application in Neuroendocrine Tumors

description: <b><i>Background:</i></b> Activation of somatostatin receptors (sstr1–5) by somatostatin and its analogues exerts an inhibitory effect on hormone secretion and provides the basis for the treatment of a range of endocrine diseases such as acromegaly, Cushing’s disease and neuroendocrine tumors (NET). The lack of well-characterized commercially available sstr subtype-specific antibodies prevents routine identification of the sstr expression profile in patients. <b><i>Methods:</i></b> We generated and characterized new mouse monoclonal antibodies (mAbs) targeting the five human sstr subtypes using ELISA and immunohistochemistry, and tested their suitability in formalin-fixed and paraffin-embedded (FFPE) human tissues and archival samples of normal pancreatic tissue and NET. <b><i>Results:</i></b> All mAbs were highly specific with no cross-reactivity. The sstr1–5 immunoreactivity in gastrointestinal NET (n = 67) was correlated with clinicopathologic data. With the exception of sstr3, NET were highly positive for all receptor subtypes (42, 63, 6, 32 and 65% of tumors were positive for sstr1, sstr2a, sstr3, sstr4 and sstr5, respectively). sstr1, sstr2a and sstr5 were present at the plasma membrane and in the cytoplasm of tumor cells, whereas sstr3 and sstr4 were almost exclusively cytoplasmic. Immunoreactivity of sstr1, sstr2a and sstr4 tended to decrease as tumor aggressiveness increased. sstr5 showed an opposite pattern, with higher staining in well-differentiated carcinomas compared with well-differentiated tumors. sstr5 immunoreactivity was correlated with the presence of metastases and angioinvasion, suggesting a possible association with more aggressive behavior. <b><i>Conclusion:</i></b> Determination of the sstr1–5 by immunohistochemistry using subtype-specific mAbs is feasible in FFPE tissue and may provide a tool for routine clinical practice.
DOI: 10.6084/m9.figshare.5122705
title: Supplementary Material for: The FUS3/KSS1-Type MAP KinaseGene FPK1 Is Involved in Hyphal Growth, Conidiation and Plant Infection of Fusarium proliferatum

description: <i>Fusarium proliferatum</i> is an important pathogen of maize that is responsible for ear rots, stalk rots and seeding blight worldwide. During the past decade, <i>F. proliferatum</i> has caused several severe epidemics of maize seedling blight in many areas of China, which led to significant losses in maize. To understand the molecular mechanisms in the fungal developmental regulation and pathogenicity, we isolated and characterized the <i>FPK1 </i>gene (GenBank accession No. HQ844224) encoding a MAP kinase homolog of <i>FUS3</i>/<i>KSS1</i> in yeast. The gene includes a 1,242-bp DNA sequence from ATG to TAA, with a coding region of 1,068 bp, 3 introns (58 bp, 56 bp and 60 bp) and a predicted protein of 355 aa.The mutant Δ<i>FPK1</i>, which has a disruption of the <i>FPK1</i> gene, showed reduced vegetative growth, fewer and shorter aerial mycelia, strongly impaired conidiation and spore germination, as well as deviant germ tube outgrowth. When the strain was inoculated in susceptible maize varieties, the infection of the mutant Δ<i>FPK1 </i>was delayed, and the infection efficiency was reduced compared to the wild-type strain. Complementation of the disruptions within the<i> FPK1 </i>open reading frame restored wild-type levels of conidiation, growth rate and virulence to maize seedlings. Our results indicated that the <i>FPK1</i> gene functioned in hyphal growth, conidiation, spore germination and virulence in <i>F. proliferatum</i>.
DOI: 10.6084/m9.figshare.5122708.v1
title: Supplementary Material for: Susceptibility to Vaccinia Virus Infection and Spread in Mice Is Determined by Age at Infection, Allergen Sensitization and Mast Cell Status

description: <i>Background:</i> Patients, especially young children, with atopic dermatitis are at an increased risk of developing eczema vaccinatum, a severe reaction to the smallpox vaccine, either through direct vaccination or indirect contact with a person recently vaccinated. <i>Methods:</i> Using a mouse model of infection, the severity of vaccinia-induced lesions was assessed from their appearance and viral DNA content. The response to vaccinia inoculation was assessed in young and adult mice, allergen-sensitized mice, and in mast cell-deficient mice. <i>Results:</i> Young age, sensitization to an allergen prior to infection, and a mast cell deficit, accomplished by using mast cell-deficient mice, resulted in more severe viral lesions at the site of inoculation, according to lesion appearance and viral DNA content. All three factors combined demonstrated maximal susceptibility, characterized by the severity of primary lesions and the development of secondary (satellite) lesions, as occurs in eczema vaccinatum in humans. Resistance to the appearance of satellite lesions could be restored by adoptive transfer of bone marrow-derived mast cells from either wild-type or cathelicidin-related antimicrobial peptide-deficient mice. Primary lesions were more severe following the latter transfer, indicating that cathelicidin-related antimicrobial peptide does contribute to the protective activity of mast cells against infection. <i>Conclusions:</i> The combination of young age, allergen sensitization and a mast cell deficit resulted in the most severe lesions, including satellite lesions. Understanding the factors determining the relative resistance/sensitivity to vaccinia virus will aid in the development of strategies for preventing and treating adverse reactions which can occur after smallpox vaccination.
DOI: 10.6084/m9.figshare.5122711.v1
title: Supplementary Material for: Profiling of Sputum Inflammatory Mediators in Asthma and Chronic Obstructive Pulmonary Disease

description: <i>Background:</i> Asthma and chronic obstructive pulmonary disease (COPD) display features of overlap in airway physiology and airway inflammation. Whether inflammatory phenotypes in airway disease describe similar mediator expression is unknown. <i>Objectives:</i> To explore the relationship of airway inflammation and cytokine and chemokine expression in asthma and COPD. <i>Methods:</i> Subjects with asthma and COPD (n = 54 and n = 49) were studied. Clinical characteristics and sputum were collected at entry into the study. A 2-step sputum processing method was performed for supernatant and cytospin preparation. Meso Scale Discovery and Luminex platforms were used to measure cytokines, chemokines and matrix metalloproteinase levels. <i>Results:</i> Analytes sensitive to dithiothreitol (DTT) that had increased recovery in the 2-step sputum process were IL-1β, 4, 5, 10, 13, IFN-γ, TNFRI, GM-CSF, CCL2, 3, 4, 5, 13 and 17. There was a differential expression in IL-8, TNFRI and TNFRII between asthma and COPD [mean fold difference (95% CI): IL-8, 2.6 (1.3–5.4), p = 0.01; TNFRI, 2.1 (1.3–5.4), p = 0.03; TNFRII, 2.6 (1.2–5.6), p = 0.02]. In neutrophilic and eosinophilic airway inflammation, TNFα, TNFRI, TNFRII, IL-6, IL-8 and IL-5 could differentiate between these phenotypes. However, these phenotypes were unrelated to the diagnosis of asthma or COPD. <i>Conclusion:</i> Recovery of sputum mediators sensitive to DTT can be improved using the described sputum processing technique. Within airway inflammatory sub-phenotypes there is a differential pattern of mediator expression that is independent of disease. Whether these inflammatory phenotypes in asthma and COPD confer distinct pathogeneses, therapeutic responses and clinical phenotypes needs to be further evaluated.
DOI: 10.6084/m9.figshare.5122693
title: Supplementary Material for: The Use of S100B and Tau Protein Concentrations in the Cerebrospinal Fluid for the Differential Diagnosis of Bacterial Meningitis: A Retrospective Analysis

description: <i>Background:</i> Patients with meningitis are often difficult to classify into bacterial (BM) or benign viral (VM) meningitis. To facilitate the differential diagnosis, S100B and Tau protein in the cerebrospinal fluid (CSF) were measured and compared with standard laboratory parameters. <i>Methods:</i> S100B<sub>CSF</sub>, Tau<sub>CSF</sub>, and routine parameters (CSF leukocyte count, protein<sub>CSF</sub>, lactate<sub>CSF</sub>, serum C-reactive protein, blood leukocyte count and body temperature) were analyzed in 33 patients with microbiologically confirmed BM and in 19 with VM. Their classification accuracy, sensitivity and specificity were studied by receiver operating characteristic (ROC) curves. <i>Results:</i> S100B<sub>CSF</sub> concentrations were higher in BM than in VM patients (p = 0.03) and showed a promising accuracy (90%) for the differential diagnosis of BM versus VM. Its discriminative properties were comparable to routine parameters. Of all parameters, S100B<sub>CSF</sub> showed the highest specificity (100%) with an optimal cut-off of 3.1 ng/ml. Tau<sub>CSF</sub> concentrations were useless for the discrimination (p = 0.64). <i>Conclusions:</i> In contrast to Tau<sub>CSF</sub>, S100B<sub>CSF</sub> concentrations ≧3.1 ng/ml are promising to discriminate bacterial from viral meningitis.
DOI: 10.6084/m9.figshare.5122696
title: Supplementary Material for: Karyotype Evolution of Eulipotyphla (Insectivora): The Genome Homology of Seven Sorex Species Revealed by Comparative Chromosome Painting and Banding Data

description: The genus <i>Sorex</i> is one of the most successful genera of Eulipotyphla. Species of this genus are characterized by a striking chromosome variability including XY1Y2 sex chromosome systems and exceptional chromosomal polymorphisms within and between populations. To study chromosomal evolution of the genus in detail, we performed cross-species chromosome painting of 7 <i>Sorex </i>species with <i>S. granarius</i> and <i>S. araneus</i> whole-chromosome probes and found that the tundra shrew <i>S. tundrensis</i> has the most rearranged karyotype among these. We reconstructed robust phylogeny of the genus <i>Sorex</i> based on revealed conserved chromosomal segments and syntenic associations. About 16 rearrangements led to formation of 2 major Palearctic groups after their divergence from the common ancestor: the<i> S. araneus</i> group (10 fusions and 1 fission) and the <i>S. minutus</i> group (5 fusions). Further chromosomal evolution of the 12 species inside the groups, including 5 previously investigated species, was accompanied by multiple reshuffling events: 39 fusions, 20 centromere shifts and 10 fissions. The rate of chromosomal exchanges upon formation of the genus was close to the average rate for eutherians, but increased during recent (about 6–3 million years ago) speciation within <i>Sorex</i>. We propose that a plausible ancestral <i>Sorex</i> karyotype consists of 56 elements. It underwent 20 chromosome rearrangements from the boreoeutherian ancestor, with 14 chromosomes retaining the conserved state. The set of genus-specific chromosome signatures was drawn from the human (HSA)-shrew comparative map (HSA3/12/22, 8/19/3/21, 2/13, 3/18, 11/17, 12/15 and 1/12/22). The syntenic association HSA4/20, that was previously proposed as a common trait of all Eulipotyphla species, is shown here to be an apomorphic trait of <i>S. araneus</i>.
DOI: 10.6084/m9.figshare.5122702.v1
title: Supplementary Material for: Monoclonal Antibodies against the Human Somatostatin Receptor Subtypes 1–5: Development and Immunohistochemical Application in Neuroendocrine Tumors

description: <b><i>Background:</i></b> Activation of somatostatin receptors (sstr1–5) by somatostatin and its analogues exerts an inhibitory effect on hormone secretion and provides the basis for the treatment of a range of endocrine diseases such as acromegaly, Cushing’s disease and neuroendocrine tumors (NET). The lack of well-characterized commercially available sstr subtype-specific antibodies prevents routine identification of the sstr expression profile in patients. <b><i>Methods:</i></b> We generated and characterized new mouse monoclonal antibodies (mAbs) targeting the five human sstr subtypes using ELISA and immunohistochemistry, and tested their suitability in formalin-fixed and paraffin-embedded (FFPE) human tissues and archival samples of normal pancreatic tissue and NET. <b><i>Results:</i></b> All mAbs were highly specific with no cross-reactivity. The sstr1–5 immunoreactivity in gastrointestinal NET (n = 67) was correlated with clinicopathologic data. With the exception of sstr3, NET were highly positive for all receptor subtypes (42, 63, 6, 32 and 65% of tumors were positive for sstr1, sstr2a, sstr3, sstr4 and sstr5, respectively). sstr1, sstr2a and sstr5 were present at the plasma membrane and in the cytoplasm of tumor cells, whereas sstr3 and sstr4 were almost exclusively cytoplasmic. Immunoreactivity of sstr1, sstr2a and sstr4 tended to decrease as tumor aggressiveness increased. sstr5 showed an opposite pattern, with higher staining in well-differentiated carcinomas compared with well-differentiated tumors. sstr5 immunoreactivity was correlated with the presence of metastases and angioinvasion, suggesting a possible association with more aggressive behavior. <b><i>Conclusion:</i></b> Determination of the sstr1–5 by immunohistochemistry using subtype-specific mAbs is feasible in FFPE tissue and may provide a tool for routine clinical practice.