cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5128036
title: Supplementary Material for: Dietary Elimination of Soybean Components Enhances Allergic Immune Response to Peanuts in BALB/c Mice

description: <b><i>Background:</i></b> Food allergy research is hampered by a lack of animal models that consistently mimic human food allergic responses. Laboratory mice are generally fed grain-based chow made with large amounts of soybeans rich in immunomodulatory isoflavones. We tested the role of dietary soy components in the induction of food allergic responses in the BALB/c mouse strain, which is known to be resistant to anaphylaxis when orally challenged by food allergens. <b><i>Methods:</i></b> Mice were fed a soy-free diet for 2 generations. After weaning, mice were maintained on the same diet or fed a diet containing soy isoflavones, i.e. genistein and daidzein, followed by weekly oral sensitizations with crude peanut extract plus cholera toxin and finally challenged at week 7. The anaphylactic symptoms, body temperature, peanut-specific antibodies and mast cell degranulation were assessed. <b><i>Results:</i></b> Soy-free diet mice showed significantly higher anaphylactic symptom scores and mast cell degranulation after challenge and higher peanut-specific antibody levels than mice fed regular chow. Introduction of a regular soy diet or an isoflavone diet to soy-free diet mice significantly suppressed the allergic reactions compared to the soy-free diet. <b><i>Conclusion:</i></b> Rodent diet is an important variable and needs to be taken into consideration when designing experiments involving animal models. Our results indicate that elimination of soy components from the diet enhances peanut sensitization in BALB/c mice. In addition to serving as a valuable tool to mimic human food allergy, the dietary influence on the immune response could have far-reaching consequences in research involving animal models.
DOI: 10.6084/m9.figshare.5128039.v1
title: Supplementary Material for: Group A <b><i>Streptococcus</i></b> Modulates Host Inflammation by Manipulating Polymorphonuclear Leukocyte Cell Death Responses

description: Polymorphonuclear leukocyte (PMN) cell death strongly influences the resolution of inflammatory episodes, and may exacerbate adverse pathologies in response to infection. We investigated PMN cell death mechanisms following infection by virulent group A <i>Streptococcus</i> (GAS). Human PMNs were infected in vitro with a clinical, virulent GAS isolate and an avirulent derivative strain, and compared for phagocytosis, the production of reactive oxygen species (ROS), mitochondrial membrane depolarization and apoptotic markers. C57BL/6J mice were then infected, in order to observe the effects on murine PMNs in vivo. Human PMNs phagocytosed virulent GAS less efficiently, produced less ROS and underwent reduced mitochondrial membrane depolarization compared with phagocytosis of avirulent GAS. Morphological and biochemical analyses revealed that PMNs infected with avirulent GAS exhibited nuclear fragmentation and caspase-3 activation consistent with an anti-inflammatory apoptotic phenotype. Conversely, virulent GAS induced PMN vacuolization and plasma membrane permeabilization, leading to a necrotic form of cell death. Infection of the mice with virulent GAS engendered significantly higher systemic pro-inflammatory cytokine release and localized infiltration of murine PMNs, with cells associated with virulent GAS infection exhibiting reduced apoptotic potential. Avirulent GAS infection was associated with lower levels of proinflammatory cytokines and tissue PMN apoptosis. We propose that the differences in PMN cell death mechanisms influence the inflammatory responses to infection by GAS.
DOI: 10.6084/m9.figshare.5128042.v1
title: Supplementary Material for: Acceptance, Prevalence and Indications for Robot-Assisted Laparoscopy - Results of a Survey Among Urologists in Germany, Austria and Switzerland

description: <b><i>Background:</i></b> Robotic-assisted laparoscopy (RAL) is being widely accepted in the field of urology as a replacement for conventional laparoscopy (CL). Nevertheless, the process of its integration in clinical routines has been rather spontaneous. <b><i>Objective:</i></b> To determine the prevalence of robotic systems (RS) in urological clinics in Germany, Austria and Switzerland, the acceptance of RAL among urologists as a replacement for CL and its current use for 25 different urological indications. <b><i>Materials and Methods:</i></b> To elucidate the practice patterns of RAL, a survey at hospitals in Germany, Austria and Switzerland was conducted. All surgically active urology departments in Germany (303), Austria (37) and Switzerland (84) received a questionnaire with questions related to the one-year period prior to the survey. <b><i>Results:</i></b> The response rate was 63%. Among the participants, 43% were universities, 45% were tertiary care centres, and 8% were secondary care hospitals. A total of 60 RS (Germany 35, Austria 8, Switzerland 17) were available, and the majority (68%) were operated under public ownership. The perception of RAL and the anticipated superiority of RAL significantly differed between robotic and non-robotic surgeons. For only two urologic indications were more than 50% of the procedures performed using RAL: pyeloplasty (58%) and transperitoneal radical prostatectomy (75%). On average, 35% of robotic surgeons and only 14% of non-robotic surgeons anticipated RAL superiority in some of the 25 indications. <b><i>Conclusions:</i></b> This survey provides a detailed insight into RAL implementation in Germany, Austria and Switzerland. RAL is currently limited to a few urological indications with a small number of high-volume robotic centres. These results might suggest that a saturation of clinics using RS has been achieved but that the existing robotic capacities are being utilized ineffectively. The possible reasons for this finding are discussed, and certain strategies to solve these problems are offered.
DOI: 10.6084/m9.figshare.5128030
title: Supplementary Material for: Sequence of Molecular Events during the Maturation of the Developing Mouse Prefrontal Cortex

description: Recent progress in psychiatric research has accumulated many mouse models relevant to developmental neuropsychiatric disorders using numerous genetic and environmental manipulations. Since the prefrontal cortex (PFC) is essential for cognitive functions whose impairments are central symptoms associated with the disorders in humans, it has become crucial to clarify altered developmental processes of PFC circuits in these mice. To that end, we aimed to understand a sequence of molecular events during normal mouse PFC development. Expression profiles for representative genes covering diverse biological processes showed that while there were little changes in genes for neuroreceptors and synaptic molecules during the postnatal period, there were dramatic increases in the expression of myelin-related genes and the parvalbumin gene, peaking at postnatal day (P)21 and P35, respectively. The timing of the peaks is different from that observed in the striatum. Furthermore, the evaluation of the circuitry maturation by measuring extracellular glutamate in the PFC revealed that sensitivity to an NMDA antagonist did not become an adult-like pattern till P56, suggesting that some of the maturation processes continue till P56. The trajectory of molecular events in PFC maturation described here should help us to characterize how the processes are affected in disease model mice, an important first step for translational research.
DOI: 10.6084/m9.figshare.5128033
title: Supplementary Material for: Burden of Common Complex Disease Variants in the Exomes of Two Healthy Centenarian Brothers

description: <b><i>Background:</i></b> It is not understood whether long-term good health is promoted by the absence of disease risk variants, the presence of protective variants, or both. We characterized the exomes of two exceptionally healthy centenarian brothers aged 106 and 109 years who had never been diagnosed with cancer, cardiovascular disease, diabetes, Alzheimer's disease, or major pulmonary disease. <b><i>Objective:</i></b> The aim of this study was to gain insight into whether exceptional health and longevity are a result of carrying fewer disease-associated variants than typical individuals. <b><i>Methods:</i></b> We compared the number of disease-associated alleles, and the proportion of alleles predicted to be functionally damaging, between the centenarian brothers and published population data. Mitochondrial sequence reads were extracted from the exome data in order to analyze mitochondrial variants. <b><i>Results:</i></b> The brothers carry a similar number of common disease-associated variants and predicted damaging variants compared to reference groups. They did not carry any high-penetrance clinically actionable variants. They carry mitochondrial haplogroup T, and one brother has a single heteroplasmic variant. <b><i>Conclusion:</i></b> Although our small sample size does not allow for definitive conclusions, a healthy aging and longevity phenotype is not necessarily due to a decreased burden of common disease-associated variants. Instead, it may be rare ‘positive' variants that play a role in this desirable phenotype.
DOI: 10.6084/m9.figshare.5128021
title: Supplementary Material for: Characteristic <b><i>miR-24</i></b> Expression in Gastric Cancers among Atomic Bomb Survivors

description: <b><i>Objective:</i></b> To elucidate the mechanism of radiation-induced cancers, we analyzed the expression profiles of microRNAs extracted from formalin-fixed paraffin-embedded (FFPE) gastric cancer (GC) tissue samples from atomic bomb survivors. <b><i>Methods:</i></b> The expression levels of <i>miR-21</i>, <i>miR-24</i>, <i>miR-34a</i>, <i>miR-106a</i>, <i>miR-143</i>, and <i>miR-145</i> were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). <b><i>Results:</i></b> The expression of microRNAs was measured by qRT-PCR in a Hiroshima University Hospital cohort comprising 32 patients in the high-dose-exposed group and 18 patients in the low-dose-exposed group who developed GC after the bombing. The GC cases showing high expression of <i>miR-24</i>, <i>miR-143</i>, and <i>miR-145</i> were more frequently found in the high-dose-exposed group than in the low-dose-exposed group. We next performed qRT-PCR of <i>miR-24</i>, <i>miR-143</i>, and <i>miR-145</i> in a cohort from the Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital comprising 122 patients in the high-dose-exposed group and 48 patients in the low-dose-exposed group who developed GC after the bombing. High expressions of <i>miR-24</i> and <i>miR-143</i> were more frequently found in the high-dose-exposed group than in the low-dose-exposed group. Multivariate analysis demonstrated that only high expression of <i>miR-24</i> was an independent predictor for the exposure status. <b><i>Conclusion:</i></b> These results suggest that the measurement of <i>miR-24</i> expression from FFPE samples is useful to identify radiation-associated GC.
DOI: 10.6084/m9.figshare.5128024
title: Supplementary Material for: Assessment of the HNF1B Score as a Tool to Select Patients for <b><i>HNF1B</i></b> Genetic Testing

description: <b><i>Background/Aims:</i></b> Diagnosing hepatocyte nuclear factor 1β (HNF1B)-related disease is a challenging task due to the phenotypic variability and frequent absence of a family history. An HNF1B score has recently been developed to help select appropriate patients for genetic testing with a negative predictive value (NPV) of 99%. We aimed at testing the clinical utility of this score in a large number of referrals for <i>HNF1B</i> genetic testing to the UK diagnostic testing service for the <i>HNF1B</i> gene. <b><i>Methods:</i></b> An HNF1B score was assigned for 686 UK referrals for <i>HNF1B</i> genetic testing using clinical information available at referral. The performance of the score was evaluated by receiver-operating characteristic curve analysis. The relative discriminatory ability of different clinical features for making a genetic diagnosis of HNF1B-related disease were estimated in the UK dataset alone and pooled with French data. <b><i>Results:</i></b> The HNF1B score discriminated between patients with and without a mutation reasonably well with an area under the curve of 0.72. Applying the suggested cut-off score of ≥8 gave a NPV of 85%. In a pooled analysis, antenatal renal abnormalities, renal hyperechogenicity and cysts were discriminatory in children, whereas renal hypoplasia and cysts were discriminatory in adults. Pancreatic abnormalities were discriminatory in both, whereas other extra-renal characteristics had a large effect size only in adults. <b><i>Conclusion:</i></b> The HNF1B score was discriminatory for <i>HNF1B</i> mutations in a large cohort of individuals tested in a single UK centre. The lower NPV (85 vs. 99%) reduces its clinical utility in selecting patients for <i>HNF1B</i> genetic testing, although validation in a prospective cohort is required.
DOI: 10.6084/m9.figshare.5128027
title: Supplementary Material for: Comparison of Stromal/Stem Cells Isolated from Human Omental and Subcutaneous Adipose Depots: Differentiation and Immunophenotypic Characterization

description: The emerging field of regenerative medicine has identified adipose tissue as an abundant source of stromal/stem cells for tissue engineering applications. Therefore, we have compared the differentiation and immunophenotypic features of adipose-derived stromal/stem cells (ASC) isolated from either omental or subcutaneous adipose depots.<b> </b>Human tissue samples were obtained from bariatric and plastic surgical practices at a university-affiliated teaching hospital and a private practice, respectively, with informed patient consent.<b> </b>Primary cultures of human ASC were isolated from adipose specimens within 24 h of surgery and culture expanded in vitro. The passaged ASC were induced to undergo adipogenic or osteogenic differentiation as assessed by histochemical methods or evaluated for surface antigen expression profiles by flow cytometry. ASC yields per unit weight of tissue were comparable between omental and subcutaneous depots. At passage 0, the immunophenotype of omental and subcutaneous ASC were not significantly different with the exception of CD105 and endoglin, a component of the transforming growth factor β receptor. The adipogenic differentiation of omental ASC was less robust than that of subcutaneous ASC based on in vitro histochemical and PCR assays. Although the yield and immunophenotype of ASC from omental adipose depots resembled that of subcutaneous ASC, omental ASC displayed significantly reduced adipogenic differentiation capacity following chemical induction. Further studies are necessary to evaluate and optimize the differentiation function of omental ASC in vitro and in vivo. Pending such analyses, omental ASC should not be used interchangeably with subcutaneous ASC for regenerative medical applications.
DOI: 10.6084/m9.figshare.5128033.v1
title: Supplementary Material for: Burden of Common Complex Disease Variants in the Exomes of Two Healthy Centenarian Brothers

description: <b><i>Background:</i></b> It is not understood whether long-term good health is promoted by the absence of disease risk variants, the presence of protective variants, or both. We characterized the exomes of two exceptionally healthy centenarian brothers aged 106 and 109 years who had never been diagnosed with cancer, cardiovascular disease, diabetes, Alzheimer's disease, or major pulmonary disease. <b><i>Objective:</i></b> The aim of this study was to gain insight into whether exceptional health and longevity are a result of carrying fewer disease-associated variants than typical individuals. <b><i>Methods:</i></b> We compared the number of disease-associated alleles, and the proportion of alleles predicted to be functionally damaging, between the centenarian brothers and published population data. Mitochondrial sequence reads were extracted from the exome data in order to analyze mitochondrial variants. <b><i>Results:</i></b> The brothers carry a similar number of common disease-associated variants and predicted damaging variants compared to reference groups. They did not carry any high-penetrance clinically actionable variants. They carry mitochondrial haplogroup T, and one brother has a single heteroplasmic variant. <b><i>Conclusion:</i></b> Although our small sample size does not allow for definitive conclusions, a healthy aging and longevity phenotype is not necessarily due to a decreased burden of common disease-associated variants. Instead, it may be rare ‘positive' variants that play a role in this desirable phenotype.
DOI: 10.6084/m9.figshare.5128006
title: Supplementary Material for: Influence of Hormonal Profile on Resting Metabolic Rate in Normal, Overweight and Obese Individuals

description: <b><i>Aims:</i></b> To investigate whether blood thyroid stimulating hormone (TSH), cortisol, insulin and glucose concentrations (plus glucose:insulin ratio; GIR) could improve the accuracy of resting metabolic rate (RMR) prediction in normal, overweight and obese persons. <b><i>Methods:</i></b> Predictive equations were developed and compared against indirect calorimetry measures for RMR in 217 weight-control clinic participants (n = 128 males and n = 89 females: ∼24% normal weight, ∼39% overweight and ∼37% obese). <b><i>Results:</i></b> Using the common accuracy criteria of the proportion of predicted RMR within ±10% of measured RMR, our equations (using age, height, weight and gender, plus the blood factors, both independently and in combination) were accurate ∼36-44% of the time, for the whole sample, and when separated by gender and weight class. Specifically, the addition of the blood hormone and glucose concentrations improved the accuracy of predicted RMR by only 1-8% (NS). <b><i>Conclusions:</i></b> Including blood TSH, cortisol, insulin, glucose and GIR into RMR prediction equations did not significantly improve estimation accuracy, which in any case only met a criterion of ±10% of the measured RMR ∼40% of the time. Further work to refine the prediction of RMR is still needed, and at present, direct measurements should be made wherever possible.
DOI: 10.6084/m9.figshare.5128009
title: Supplementary Material for: Evaluation of Angiogenesis in Early Mycosis Fungoides Patients: Dermoscopic and Immunohistochemical Study

description: <b><i>Background:</i></b> Angiogenesis is the production of new blood vessels from an existing vascular network; it plays a critical role in solid tumor development and metastasis. <b><i>Objectives:</i></b> To assess angiogenesis in early cases of mycosis fungoides (MF) and to determine vascular patterns in MF dermoscopically. <b><i>Methods:</i></b> 25 patients with MF and 20 healthy controls were included. The MF lesions were assessed dermoscopically. CD34 immunohistochemistry was performed to count dermal microvessel density (MVD). <b><i>Results:</i></b> The total dermal MVD was significantly higher in MF patients (19.77 ± 5.81) than in controls (4.44 ± 3.16; p = 0.013). Among them, there were 10.8 ± 4.1 sprouts of endothelial buds (clusters of cells per field) in patients and 2.4 ± 2 in controls (p = 0.000). The dotted pattern of blood vessels was the most frequently encountered pattern in the MF lesions by dermoscopy. <b><i>Conclusions:</i></b> Our findings support that neoangiogenesis is significantly increased in early MF lesions and that the main dermoscopic feature of MF is dotted blood vessels.
DOI: 10.6084/m9.figshare.5128015
title: Supplementary Material for: Revisiting Clinical Utility of Chest Radiography and Electrocardiogram to Determine Ischemic Stroke Subtypes: Special Reference on Vascular Pedicle Width and Maximal P-Wave Duration

description: <b><i>Backgrounds:</i></b> It is often difficult to diagnose stroke subtypes at admission, particularly in sinus rhythm cases. Vascular pedicle width (VPW) on chest X-ray (CXR) and maximal P-wave duration (P-max) on electrocardiogram (ECG) are again realized as useful parameters reflecting intravascular volume and atrial conduction status, respectively. We investigated the utility of VPW and P-max as a tool for differentiating ischemic stroke subtypes. <b><i>Methods:</i></b> We studied 343 acute stroke patients showing sinus rhythm on admission. Dividing the patients into cardioembolic (CE) stroke (n = 57) and non-CE (n = 286) groups, we compared clinical backgrounds including VPW on CXR, and P-max in lead II and premature atrial contraction (PAC) on 12-leads ECG. Then, we investigated the independent factors for CE. <b><i>Results:</i></b> Independent factors associated with CE were VPW (≥59.3 mm) (p &lt; 0.001; odds ratio (OR), 10.12; 95% confidence interval (CI), 4.13-24.8), P-max in lead II (≥120 ms) (p &lt; 0.001; OR, 8.61; 95% CI, 3.96-18.7), PAC (p = 0.002; OR, 7.35; 95% CI, 2.14-25.3) and D-dimer level (≥1.11 µg/ml) (p = 0.016; OR, 2.57; 95% CI, 1.20-5.51). <b><i>Conclusions:</i></b> VPW, P-max, PAC and D-dimer are useful parameters for diagnosing CE stroke in patients with sinus rhythm at admission.
DOI: 10.6084/m9.figshare.5128018
title: Supplementary Material for: The Combination of Vascular Endothelial Growth Factor and Stromal Cell-Derived Factor Induces Superior Angiogenic Sprouting by Outgrowth Endothelial Cells

description: Endothelial progenitor cells are being broadly explored for the treatment of ischemic cardiovascular diseases, but their response to molecules commonly used to promote the growth of new blood vessels has not been fully characterized. In this study, angiogenic sprout formation in a 3-dimensional, in vitro model by one type of endothelial progenitor, outgrowth endothelial cells (OECs), was characterized in response to exposure to stromal cell-derived factor (SDF) and vascular endothelial growth factor (VEGF) and then compared to mature endothelial cells. Exposure to SDF alone did not increase angiogenic sprouting in comparison to control media, while a combination of VEGF and SDF demonstrated greater potency than VEGF alone for all cell types. Together, VEGF and SDF reduced the sprout initiation time and maintained sprouting levels over time. In direct competition with mature endothelial cells, OECs preferentially localized to the tip cell position, suggesting an enhanced sprouting potential. Overall, these results reveal the impact of the combination of VEGF and SDF on endothelial cell sprouting, and support the enhanced potential of OECs, as opposed to mature endothelial cells, for treating ischemic diseases.
DOI: 10.6084/m9.figshare.5128009.v1
title: Supplementary Material for: Evaluation of Angiogenesis in Early Mycosis Fungoides Patients: Dermoscopic and Immunohistochemical Study

description: <b><i>Background:</i></b> Angiogenesis is the production of new blood vessels from an existing vascular network; it plays a critical role in solid tumor development and metastasis. <b><i>Objectives:</i></b> To assess angiogenesis in early cases of mycosis fungoides (MF) and to determine vascular patterns in MF dermoscopically. <b><i>Methods:</i></b> 25 patients with MF and 20 healthy controls were included. The MF lesions were assessed dermoscopically. CD34 immunohistochemistry was performed to count dermal microvessel density (MVD). <b><i>Results:</i></b> The total dermal MVD was significantly higher in MF patients (19.77 ± 5.81) than in controls (4.44 ± 3.16; p = 0.013). Among them, there were 10.8 ± 4.1 sprouts of endothelial buds (clusters of cells per field) in patients and 2.4 ± 2 in controls (p = 0.000). The dotted pattern of blood vessels was the most frequently encountered pattern in the MF lesions by dermoscopy. <b><i>Conclusions:</i></b> Our findings support that neoangiogenesis is significantly increased in early MF lesions and that the main dermoscopic feature of MF is dotted blood vessels.