cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5125453.v1
title: Supplementary Material for: Clinical, Dermoscopic and Histopathological Features of Eccrine Poroid Neoplasms

description: <b><i>Background:</i></b> Eccrine poroma (EP) belongs to the group of benign adnexal tumors, but cases of eccrine porocarcinoma (EPC) arising on long-standing and untreated EP suggest a certain risk of malignant transformation. <b><i>Objectives:</i></b> To describe the clinical, dermoscopic and histopathologic features associated with different extremes in the spectrum of eccrine poroid neoplasms and to review the according literature. <b><i>Methods:</i></b> A retrospective analysis of patient characteristics and morphologic features associated with EP, EPC in situ and invasive porocarcinoma patients who attended two skin lesion clinics in Italy and Turkey between 2010 and 2011. <b><i>Results:</i></b> A total of 4 cases including 1 EP, 1 EPC in situ and 2 cases of invasive EPC in 4 patients were analyzed. Recent changes including bleeding, ulceration and sudden enlargement of a pre-existing lesion were associated with malignant transformation. Dermoscopically, polymorphous vessels consisting of coiled, hairpin and linear vessels were seen at all stages of progression. Histopathological findings of EPC in situ were limited to the epidermal component and were evident only at higher magnification. <b><i>Conclusions:</i></b> Clinicians and pathologists should carefully evaluate EPs with a recent history of change and erosion in order to avoid overlooking the potential development of EPC.
DOI: 10.6084/m9.figshare.5125423
title: Supplementary Material for: Culture of Mouse Amniotic Fluid-Derived Cells on Irradiated STO Feeders Results in the Generation of Primitive Endoderm Cell Lines Capable of Self-Renewal in vitro

description: The cells present in amniotic fluid (AF) are currently used for prenatal diagnosis of fetal anomalies but are also a potential source of cells for cell therapy. To better characterize putative progenitor cell populations present in AF, we used culture conditions that support self-renewal to determine if these promoted the generation of stable cell lines from AF-derived cells (AFC). Cells isolated from E11.5 mouse were cultured on irradiated STO fibroblast feeder layers in human embryonic germ cell derivation conditions. The cultures grew multicellular epithelial colonies that could be repropagated from single cells. Reverse transcription semiquantitative polymerase chain reaction of established cell lines revealed that they belonged to the extraembryonic endoderm (ExEn) expressing high levels of <i>Gata6</i>, <i>Gata4</i>, <i>Sox17</i>, <i>Foxa2</i> and <i>Sox7</i> mRNA. Hierarchical clustering based on the whole transcriptome expression profile of the AFC lines (AFCL) shows significant correlation between transcription profiles of AFCL and blastocyst-derived XEN, an ExEn cell line. In vitro differentiation of AFCL results in the generation of cells expressing albumin and α-fetoprotein (AFP), while intramuscular injection of AFCL into immunodeficient mice produced AFP-positive tumors with primitive endodermal appearance. Hence, E11.5 mouse AF contains cells that efficiently produce XEN lines. These AF-derived XEN lines do not spontaneously differentiate into embryonic-type cells but are phenotypically stable and have the capacity for extensive expansion. The lack of requirement for reprogramming factors to turn AF-derived progenitor cells into stable cell lines capable of massive expansion together with the known ability of ExEn to contribute to embryonic tissue suggests that this cell type may be a candidate for banking for cell therapies.
DOI: 10.6084/m9.figshare.5125426
title: Supplementary Material for: Altered T Helper 17 Responses in Children with Food Allergy

description: <b><i>Background:</i></b> While a central role for the T helper (Th) 1/Th2 axis in food allergy has been established, the Th17 response in food-allergic humans has not been addressed. <b><i>Methods:</i></b> Th17 responses in 18 peanut-allergic children, who were also allergic to at least one additional food allergen, were assessed relative to 15 age-matched healthy controls. To account for the atopy background in the allergic children, 7 atopic, but not food-allergic, individuals and their age-matched controls were included in this study. PBMCs were analyzed by flow cytometry ex vivo or were stimulated in vitro with peanut allergens, gliadin, or tetanus toxoid followed by analysis of proliferation and cytokine production in antigen-responsive cells. <b><i>Results:</i></b> We observed a significantly lower interleukin (IL) 17 production in CD4+ T cells of food-allergic individuals ex vivo (p &lt; 0.02). In vitro, we found that IL-17 production in CD4+ T cells in response to all antigens tested was significantly impaired in food-allergic subjects compared to healthy controls (Ara: p &lt; 0.005; gliadin: p &lt; 0.004; TT: p &lt; 0.03). No significant differences were observed between atopic and nonatopic individuals with no food allergy.<b><i> Conclusion:</i></b> Our results thus reveal a systemic, non-allergen-specific defect in Th17 responses to antigen stimulation in food allergic individuals, suggesting a role for Th17 cells in the control of food allergy and implicating IL-17 as a potential biomarker for tolerance to food antigens.
DOI: 10.6084/m9.figshare.5125429
title: Supplementary Material for: Effects of α-Tocopherol Supplementation on Liver of Rats Chronically Exposed to Ethanol

description: <b><i>Background/Aims:</i></b> Chronic alcoholism is characterized by hepatotoxicity associated with antioxidant and redox status imbalance. Continuous ethanol intake induces free radical synthesis, resulting in the depletion of antioxidants, especially α-tocopherol, which has an important role in lipid peroxidation. This study aimed to evaluate if α-tocopherol supplementation can restore liver phenotype in rats chronically exposed to ethanol. <b><i>Methods:</i></b> α-Tocopherol levels were determined and histologic analysis of liver was performed. Hepatic gene expression was analyzed through oligonucleotide microarray and real-time PCR. <b><i>Results:</i></b> Alcohol exposure for 6 weeks did not decrease hepatic α-tocopherol levels; however, both groups exposed to ethanol (supplemented or not with α-tocopherol) displayed fatty liver. The antioxidant supplementation prevented Mallory bodies and inflammatory infiltration, but not apoptosis, in liver of the rats exposed to ethanol. Gene expression analysis showed evidence of adaptive response to chronic alcohol consumption, where antioxidant components were not regulated. Nevertheless, differentially expressed genes reflected the change in cellular homeostasis. <b><i>Conclusion:</i></b> The hepatic α-tocopherol content was coherent with the antioxidant gene expression in this study. Cells are likely to have adapted and restored their antioxidant status after long-term ethanol exposure, which might be the reason for such conflicting reports concerning α-tocopherol status in chronic alcoholism.
DOI: 10.6084/m9.figshare.5125450.v1
title: Supplementary Material for: Numerical Modelling of Tooth Enamel Subsurface Lesion Formation Induced by Dental Plaque

description: Using a one-dimensional mathematical model that couples tooth demineralisation and remineralisation with metabolic processes occurring in the dental plaque, two mechanisms for subsurface lesion formation were evaluated. It was found that a subsurface lesion can develop only as the result of alternating periods of demineralisation (acid attack during sugar consumption) and remineralisation (resting period) in tooth enamel with uniform mineral composition. It was also shown that a minimum plaque thickness that can induce an enamel lesion exists. The subsurface lesion formation can also be explained by assuming the existence of a fluoride-containing layer at the tooth surface that decreases enamel solubility. A nearly constant thickness of the surface layer was obtained with both proposed mechanisms. Sensitivity analysis showed that surface layer formation is strongly dependent on the length of remineralisation and demineralisation cycles. The restoration period is very important and the numerical simulations support the observation that often consumption of sugars is a key factor in caries formation. The calculated profiles of mineral content in enamel are similar to those observed experimentally. Most probably, both studied mechanisms interact in vivo in the process of caries development, but the simplest explanation for subsurface lesion formation remains the alternation between demineralisation and remineralisation cycles without any pre-imposed gradients.
DOI: 10.6084/m9.figshare.5125420
title: Supplementary Material for: Bacterial Lipopolysaccharide Inhibits Influenza Virus Infection of Human Macrophages and the Consequent Induction of CD8+ T Cell Immunity

description: It is well established that infection with influenza A virus (IAV) facilitates secondary bacterial disease. However, there is a growing body of evidence that the microbial context in which IAV infection occurs can affect both innate and adaptive responses to the virus. To date, these studies have been restricted to murine models of disease and the relevance of these findings in primary human cells remains to be elucidated. Here, we show that pre-stimulation of primary human monocyte-derived macrophages (MDMs) with the bacterial ligand lipopolysaccharide (LPS) reduces the ability of IAV to infect these cells. The inhibition of IAV infection was associated with a reduced transcription of viral RNA and the ability of LPS to induce an anti-viral/type I interferon response in human MDMs. We demonstrated that this reduced rate of viral infection is associated with a reduced ability to present a model antigen to autologous CD8+ T cells. Taken together, these data provide the first evidence that exposure to bacterial ligands like LPS can play an important role in modulating the immune response of primary human immune cells towards IAV infection, which may then have important consequences for the development of the host's adaptive immune response.
DOI: 10.6084/m9.figshare.5125423.v1
title: Supplementary Material for: Culture of Mouse Amniotic Fluid-Derived Cells on Irradiated STO Feeders Results in the Generation of Primitive Endoderm Cell Lines Capable of Self-Renewal in vitro

description: The cells present in amniotic fluid (AF) are currently used for prenatal diagnosis of fetal anomalies but are also a potential source of cells for cell therapy. To better characterize putative progenitor cell populations present in AF, we used culture conditions that support self-renewal to determine if these promoted the generation of stable cell lines from AF-derived cells (AFC). Cells isolated from E11.5 mouse were cultured on irradiated STO fibroblast feeder layers in human embryonic germ cell derivation conditions. The cultures grew multicellular epithelial colonies that could be repropagated from single cells. Reverse transcription semiquantitative polymerase chain reaction of established cell lines revealed that they belonged to the extraembryonic endoderm (ExEn) expressing high levels of <i>Gata6</i>, <i>Gata4</i>, <i>Sox17</i>, <i>Foxa2</i> and <i>Sox7</i> mRNA. Hierarchical clustering based on the whole transcriptome expression profile of the AFC lines (AFCL) shows significant correlation between transcription profiles of AFCL and blastocyst-derived XEN, an ExEn cell line. In vitro differentiation of AFCL results in the generation of cells expressing albumin and α-fetoprotein (AFP), while intramuscular injection of AFCL into immunodeficient mice produced AFP-positive tumors with primitive endodermal appearance. Hence, E11.5 mouse AF contains cells that efficiently produce XEN lines. These AF-derived XEN lines do not spontaneously differentiate into embryonic-type cells but are phenotypically stable and have the capacity for extensive expansion. The lack of requirement for reprogramming factors to turn AF-derived progenitor cells into stable cell lines capable of massive expansion together with the known ability of ExEn to contribute to embryonic tissue suggests that this cell type may be a candidate for banking for cell therapies.
DOI: 10.6084/m9.figshare.5125426.v1
title: Supplementary Material for: Altered T Helper 17 Responses in Children with Food Allergy

description: <b><i>Background:</i></b> While a central role for the T helper (Th) 1/Th2 axis in food allergy has been established, the Th17 response in food-allergic humans has not been addressed. <b><i>Methods:</i></b> Th17 responses in 18 peanut-allergic children, who were also allergic to at least one additional food allergen, were assessed relative to 15 age-matched healthy controls. To account for the atopy background in the allergic children, 7 atopic, but not food-allergic, individuals and their age-matched controls were included in this study. PBMCs were analyzed by flow cytometry ex vivo or were stimulated in vitro with peanut allergens, gliadin, or tetanus toxoid followed by analysis of proliferation and cytokine production in antigen-responsive cells. <b><i>Results:</i></b> We observed a significantly lower interleukin (IL) 17 production in CD4+ T cells of food-allergic individuals ex vivo (p &lt; 0.02). In vitro, we found that IL-17 production in CD4+ T cells in response to all antigens tested was significantly impaired in food-allergic subjects compared to healthy controls (Ara: p &lt; 0.005; gliadin: p &lt; 0.004; TT: p &lt; 0.03). No significant differences were observed between atopic and nonatopic individuals with no food allergy.<b><i> Conclusion:</i></b> Our results thus reveal a systemic, non-allergen-specific defect in Th17 responses to antigen stimulation in food allergic individuals, suggesting a role for Th17 cells in the control of food allergy and implicating IL-17 as a potential biomarker for tolerance to food antigens.
DOI: 10.6084/m9.figshare.5125417
title: Supplementary Material for: HIV-1 Induces the First Signal to Activate the NLRP3 Inflammasome in Monocyte-Derived Macrophages

description: <b><i>Background/Aims:</i></b> Inflammasomes are multimolecular complexes that regulate caspase-1. They act as sensors for endogenous and exogenous signals, and mediate the processing of pro-IL-1β into its secreted, biologically active form. The NLRP3 inflammasome and IL-1β are particularly interesting because they are required for efficient control of viral infections. Indeed, HIV-1 induces expression of NLRP3 and IL-1β in healthy controls, but not in HIV-1-infected patients. Here we evaluate whether HIV-1 can induce activation of the NLRP3 inflammasome. <b><i>Methods:</i></b> Human primary monocyte-derived macrophages were infected with HIV-1 in the absence or presence of classical NLRP3 inflammasome activators, and IL-1β release was assessed by ELISA. <b><i>Results:</i></b> HIV-1 initiates the priming signal for NLRP3 inflammasome activation through the NF-κB-associated pathway in human primary monocyte-derived macrophages. Furthermore, priming of NLRP3 activation in response to HIV-1 was independent of the viral envelope, since similar results were observed with HIV-1 and pseudotyped HIV-1 lacking the <i>env</i> gene. <b><i>Conclusion:</i></b> Our findings suggest that HIV-1 infection promotes IL-1β secretion by inducing the first signal for NLRP3 inflammasome activation, a phenomenon that may contribute to AIDS progression.
DOI: 10.6084/m9.figshare.5125420.v1
title: Supplementary Material for: Bacterial Lipopolysaccharide Inhibits Influenza Virus Infection of Human Macrophages and the Consequent Induction of CD8+ T Cell Immunity

description: It is well established that infection with influenza A virus (IAV) facilitates secondary bacterial disease. However, there is a growing body of evidence that the microbial context in which IAV infection occurs can affect both innate and adaptive responses to the virus. To date, these studies have been restricted to murine models of disease and the relevance of these findings in primary human cells remains to be elucidated. Here, we show that pre-stimulation of primary human monocyte-derived macrophages (MDMs) with the bacterial ligand lipopolysaccharide (LPS) reduces the ability of IAV to infect these cells. The inhibition of IAV infection was associated with a reduced transcription of viral RNA and the ability of LPS to induce an anti-viral/type I interferon response in human MDMs. We demonstrated that this reduced rate of viral infection is associated with a reduced ability to present a model antigen to autologous CD8+ T cells. Taken together, these data provide the first evidence that exposure to bacterial ligands like LPS can play an important role in modulating the immune response of primary human immune cells towards IAV infection, which may then have important consequences for the development of the host's adaptive immune response.
DOI: 10.6084/m9.figshare.5125429.v1
title: Supplementary Material for: Effects of α-Tocopherol Supplementation on Liver of Rats Chronically Exposed to Ethanol

description: <b><i>Background/Aims:</i></b> Chronic alcoholism is characterized by hepatotoxicity associated with antioxidant and redox status imbalance. Continuous ethanol intake induces free radical synthesis, resulting in the depletion of antioxidants, especially α-tocopherol, which has an important role in lipid peroxidation. This study aimed to evaluate if α-tocopherol supplementation can restore liver phenotype in rats chronically exposed to ethanol. <b><i>Methods:</i></b> α-Tocopherol levels were determined and histologic analysis of liver was performed. Hepatic gene expression was analyzed through oligonucleotide microarray and real-time PCR. <b><i>Results:</i></b> Alcohol exposure for 6 weeks did not decrease hepatic α-tocopherol levels; however, both groups exposed to ethanol (supplemented or not with α-tocopherol) displayed fatty liver. The antioxidant supplementation prevented Mallory bodies and inflammatory infiltration, but not apoptosis, in liver of the rats exposed to ethanol. Gene expression analysis showed evidence of adaptive response to chronic alcohol consumption, where antioxidant components were not regulated. Nevertheless, differentially expressed genes reflected the change in cellular homeostasis. <b><i>Conclusion:</i></b> The hepatic α-tocopherol content was coherent with the antioxidant gene expression in this study. Cells are likely to have adapted and restored their antioxidant status after long-term ethanol exposure, which might be the reason for such conflicting reports concerning α-tocopherol status in chronic alcoholism.
DOI: 10.6084/m9.figshare.5125405
title: Supplementary Material for: Presenting Neuropsychological Testing Profile of Autopsy-Confirmed Frontotemporal Lobar Degeneration

description: <b><i>Aims:</i></b> We aimed to investigate how neuropsychological test measures at presentation might differentiate frontotemporal lobar degeneration (FTLD) from Alzheimer's disease (AD). <b><i>Methods:</i></b> We compared autopsy-confirmed FTLD and definite AD with Clinical Dementia Rating ≤1. Factor scores and t values of each neuropsychological test measure were compared between FTLD and AD patients. Logistic regression analyses were applied to identify independent predictors within test measures for the differentiation of FTLD from AD. <b><i>Results:</i></b> Factor analyses showed that the memory domain was more severely impaired in AD than in FTLD, whereas the language and attention domains were more severely impaired in FTLD than in AD. Multiple logistic regression analysis showed that Letter Fluency, Boston Naming Test and delayed memory recall remained independent predictors of FTLD compared to AD. However, test measures did not discriminate between FTLD-tau and FTLD-ubiquitin.<b><i> Conclusion:</i></b> We confirm that memory and language function tests discriminate between FTLD and AD.
DOI: 10.6084/m9.figshare.5125408
title: Supplementary Material for: Individual Genetic Variations Related to Satiety and Appetite Control Increase Risk of Obesity in Preschool-Age Children in the STRONG Kids Program

description: <b><i>Background/Aims:</i></b> The burden of the childhood obesity epidemic is well recognized; nevertheless, the genetic markers and gene-environment interactions associated with the development of common obesity are still unknown. In this study, candidate genes associated to satiety and appetite control pathways with obesity-related traits were tested in Caucasian preschoolers from the STRONG Kids project. <b><i>Methods:</i></b> Eight genetic variants in genes related to obesity (BDNF, LEPR, FTO, PCSK1, POMC, TUB, LEP, and MC4R) were genotyped in 128 children from the STRONG Kids project (mean age 39.7 months). Data were analyzed for individual associations and to test for genetic predisposition scores (GPSs) with body mass index (BMI) and anthropometric traits (Z-scores, e.g. height-for-age Z-score, HAZ). Covariates included age, sex, and breastfeeding (BF) duration. <b><i>Results:</i></b> Obesity and overweight prevalence was 6.3 and 19.5%, respectively, according to age- and sex-specific BMI percentiles. Individual genetic associations of MC4R and LEPR markers with HAZ were strengthened when BF duration was included as a covariate. Our GPSs show that, as the number of risk alleles increased, the risk of higher BMI and HAZ also increased. Overall, the GPSs assembled were able to explain 2-3% of the variability in BMI and HAZ phenotypes. <b><i>Conclusion:</i></b> Genetic associations with common obesity-related phenotypes were found in the STRONG Kids project. GPSs assembled for specific candidate genes were associated with BMI and HAZ phenotypes.
DOI: 10.6084/m9.figshare.5125414
title: Supplementary Material for: Low Birthweight and Premature Birth Are Risk Factors for Podocytopenia and Focal Segmental Glomerulosclerosis

description: <b><i>Background:</i></b> Recent reports suggest that low birthweight (LBW) is a risk factor for kidney diseases, including focal segmental glomerulosclerosis (FSGS), although the underlying pathological mechanism remains unknown. Podocyte loss triggers glomerulosclerosis; however, whether FSGS in LBW children is associated with podocytopenia is unclear. <b><i>Methods:</i></b> We reviewed the birthweights and gestational age of all patients who underwent renal biopsies from 1995 to 2011 at our Institute. Sixteen patients had FSGS, of which 6 (37.5%) had LBW; this LBW rate was significantly higher than the overall LBW rate in Japan (9.7%). The incidence of LBW was also high in patients with minimal change nephrotic syndrome (MCNS; 12.5%). The glomerular cell numbers in biopsy sections were calculated using computer image analysis and compared with FSGS of normal birthweight (NBW-FSGS). Biopsy specimens from age-matched patients with MCNS were also compared. Wilms' tumor-1 (WT1) immunohistochemistry was performed to enumerate the podocytes. <b><i>Results:</i></b> All patients in the LBW-FSGS group were also preterm, with an average gestational age of 25.8 weeks. The number of podocytes per glomerulus in the LBW-FSGS patients was 34 and 24% lower as compared to that in the MCNS patients (p &lt; 0.01) and the NBW-FSGS patients (p &lt; 0.05), respectively. Similar results were observed for the WT1-positive glomerular cell number. <b><i>Conclusion:</i></b> LBW and premature birth were associated with FSGS development. The possibility that LBW and premature birth may be predisposing factors for severe podocytopenia in children with FSGS warrants further investigation.