cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5125186.v1
title: Supplementary Material for: Clinicians' Attitudes toward General Screening of the Ashkenazi-Jewish Population for Prevalent Founder <b><i>BRCA1/2</i></b> and <b><i>LRRK2</i></b> Mutations

description: <b><i>Aims:</i></b> Advances in genomics may eventually lead to genetic susceptibility screening of the general population, regardless of a personal or familial history of the disease in question. Yet, little is known about clinicians' attitudes toward such programs. We explored attitudes of family practitioners, medical geneticists and genetic counselors toward genetic screening of the general Ashkenazi-Jewish population for the common founder mutations in <i>BRCA1/2</i> and <i>LRRK2</i> genes (which increase the risk of hereditary breast/ovarian cancers and Parkinson's disease, respectively). <b><i>Methods:</i></b> Participants (n = 204) completed a specially designed questionnaire, distributed by e-mail, regular mail or in-person. <b><i>Results:</i></b> Slightly more than half (52%) were in favor of <i>BRCA</i> screening, while the vast majority (86%) opposed to <i>LRRK2</i> screening. About two-thirds (68%) of the respondents supported pre-test genetic counseling. Attitudes were largely independent of professional background and sociodemographic characteristics, though a correlation was found with personal interest in genetic self-testing for the above genes. Adverse psychological impact and discrimination in insurance and employment were the major concerns cited by respondents with regard to screening programs. <b><i>Conclusion:</i></b> Our findings suggest that the availability of measures for prevention and/or treatment is a major factor in the attitudes of healthcare providers toward population screening for late-onset conditions.
DOI: 10.6084/m9.figshare.5125171
title: Supplementary Material for: Environmental and Genomic Factors as well as Interventions Influencing Smoking Cessation: A Systematic Review of Reviews and a Proposed Working Model

description: <b><i>Background:</i></b> Smoking behaviour is a major public health problem worldwide. Several sources have confirmed the implication of genomic factors in smoking behaviour. These factors interact both with environmental factors and interventions to develop a certain behaviour. <b><i>Objectives:</i></b> Describing the environmental and genomic factors as well as the interventions influencing smoking cessation (SC) and developing a working model incorporating the different factors influencing SC were our main objectives. <b><i>Methods:</i></b> Two systematic reviews were conducted using articles in English from the Cochrane library, PubMed and HuGENet from January 2000 to September 2012: (1) a systematic review of systematic reviews and meta-analyses and (2) a systematic review of original research for genomic factors. The proposed working model was developed by making use of previous models of SC and applying an iterative process of discussion and re-examination by the authors. <b><i>Results:</i></b> We confirmed the importance of the 4 main factors influencing SC: (1) environmental factors, (2) genomic factors, (3) gene-environment interactions, and (4) evidence-based interventions. The model demonstrates the complex network of factors influencing SC. <b><i>Conclusion:</i></b> The working model of SC proposed a global view of factors influencing SC, warranting future research in this area. Future testing of the model will consolidate the understanding of the different factors affecting SC and will help to improve interventions in this field.
DOI: 10.6084/m9.figshare.5125174
title: Supplementary Material for: Flagellins of <b><i>Salmonella</i></b> Typhi and Nonpathogenic <b><i>Escherichia coli</i></b> Are Differentially Recognized through the NLRC4 Pathway in Macrophages

description: Flagellin is recognized by both Toll-like receptor (TLR)5 and NAIP5/NLRC4 inflammasome receptors. We hypothesized that the flagellins derived from different bacteria might differentially activate TLR5 and/or NAIP5/NLRC4 signal pathways. To test this, the immune recognition of recombinant flagellins derived from pathogenic <i>Salmonella</i> Typhi (SF) and the nonpathogenic <i>Escherichia coli</i> K12 strain MG1655 (KF) were examined by the activation of TLR5 and NLRC4 pathways in various cell types. While flagellins SF and KF were not distinguishable in activating the TLR5 pathway, KF induced significantly less interleukin-1β production and pyroptotic cell death in peritoneal macrophages than SF, and showed markedly lower efficiency in activating caspase-1 through the NLRC4 pathway than SF. Macrophages may differentially recognize flagellins by intracellular sensors and thereby initiate the immune response to invading pathogenic bacteria. Our findings suggest an active role of flagellin as an important determinant in host differential immune recognition and for the control of bacteria infection.
DOI: 10.6084/m9.figshare.5125177.v1
title: Supplementary Material for: Impact of Age on the Management of Primary Melanoma Patients

description: <b><i>Objectives:</i></b> Age is an understudied factor when considering treatment options for melanoma. Here, we examine the impact of age on primary melanoma treatment in a prospective cohort of patients. <b><i>Methods:</i></b> We used logistic regression models to examine the associations between age and initial treatment, using recurrence and melanoma-specific survival as endpoints. <b><i>Results:</i></b> 444 primary melanoma patients were categorized into three groups by age at diagnosis: 19-45 years (24.3%), 46-70 (50.2%), and 71-95 (25.5%). In multivariate models, older patients experienced a higher risk of recurrence (hazard ratio 3.34, 95% confidence interval, CI, 1.53-7.25; p &lt; 0.01). No significant differences were observed in positive biopsy margin rates or extent of surgical margins across age groups. Patients in the middle age group were more likely to receive adjuvant therapy than those in the older group (odds ratio 2.78, 95% CI 1.19-6.45; p = 0.02) and showed a trend to longer disease-free survival when receiving adjuvant therapy (p = 0.09). <b><i>Conclusion:</i></b> Our data support age as an independent negative prognostic factor in melanoma. Our data suggest that age does not affect primary surgical treatment but may affect decisions of whether or not patients receive postoperative treatment(s). Further work is needed to better understand the biological variables affecting treatment decisions and efficacy in older patients.
DOI: 10.6084/m9.figshare.5125168
title: Supplementary Material for: ‘Born in Michigan? You're in the Biobank': Engaging Population Biobank Participants through Facebook Advertisements

description: <b><i>Background/Aims:</i></b> Despite a broad call for biobanks to use social media, data is lacking regarding the capacity of social media tools, especially advertising, to engage large populations on this topic. <b><i>Methods:</i></b> We used Facebook advertising to engage Michigan residents about the BioTrust for Health. We conducted a low-budget (<i>Results:</i> The Facebook page was viewed 1,249 times during the month of the advertising campaign, versus once in the month prior. 779,004 Michigan residents saw ads an average of 25.8 times; 4,275 clicked ads; the average click-through-ratio was 0.021%. Interactions included 516 ‘likes' and 30 photo contest entries. Cost per outcome ranged from <i>Conclusion:</i> A social media strategy to build public awareness about biobanking is not likely to be effective without a promotional ‘push' to distribute content. Social media advertisements have the capacity to scale-up engagement on biobanking while keeping costs manageable. Facebook advertisements provide necessary access points for unaware participants, with implications for public trust.
DOI: 10.6084/m9.figshare.5125174.v1
title: Supplementary Material for: Flagellins of <b><i>Salmonella</i></b> Typhi and Nonpathogenic <b><i>Escherichia coli</i></b> Are Differentially Recognized through the NLRC4 Pathway in Macrophages

description: Flagellin is recognized by both Toll-like receptor (TLR)5 and NAIP5/NLRC4 inflammasome receptors. We hypothesized that the flagellins derived from different bacteria might differentially activate TLR5 and/or NAIP5/NLRC4 signal pathways. To test this, the immune recognition of recombinant flagellins derived from pathogenic <i>Salmonella</i> Typhi (SF) and the nonpathogenic <i>Escherichia coli</i> K12 strain MG1655 (KF) were examined by the activation of TLR5 and NLRC4 pathways in various cell types. While flagellins SF and KF were not distinguishable in activating the TLR5 pathway, KF induced significantly less interleukin-1β production and pyroptotic cell death in peritoneal macrophages than SF, and showed markedly lower efficiency in activating caspase-1 through the NLRC4 pathway than SF. Macrophages may differentially recognize flagellins by intracellular sensors and thereby initiate the immune response to invading pathogenic bacteria. Our findings suggest an active role of flagellin as an important determinant in host differential immune recognition and for the control of bacteria infection.
DOI: 10.6084/m9.figshare.5125159
title: Supplementary Material for: The Influence of Aspirin on Release of Eoxin C4, Leukotriene C4 and 15-HETE, in Eosinophilic Granulocytes Isolated from Patients with Asthma

description: <b><i>Background:</i></b> The effect of aspirin on the release of key arachidonic acid metabolites in activated eosinophils from subjects with aspirin-intolerant asthma (AIA) has not been investigated previously, despite the characteristic eosinophilia in AIA. <b><i>Methods:</i></b> Peripheral blood eosinophils were isolated from four groups of subjects: healthy volunteers (HV; n = 8), mild asthma (MA; n = 8), severe asthma (SA; n = 9) and AIA (n = 7). In the absence or presence of lysine-aspirin, eosinophils were stimulated with arachidonic acid or calcium ionophore to trigger the 15-lipoxygenase-1 (15-LO) and 5-lipoxygenase (5-LO) pathways, respectively. 15(S)-hydroxy-eicosatetraenoic acid (15-HETE) and eoxin C<sub>4</sub> (EXC<sub>4</sub>) were measured as 15-LO products and leukotriene (LT)C<sub>4</sub> as a product of the 5-LO pathway. <b><i>Results:</i></b> Activated eosinophils from patients with SA and AIA produced approximately five times more 15-HETE than eosinophils from HV or MA patients. In the presence of lysine-aspirin, eosinophils from AIA, MA and SA patients generated higher levels of 15-HETE than in the absence of lysine-aspirin. Furthermore, in the presence of lysine-aspirin, formation of EXC<sub>4</sub> was also significantly increased in eosinophils from AIA patients, and LTC<sub>4</sub> synthesis was increased both in AIA and SA patients. <b><i>Conclusions:</i></b> Taken together, this study shows an increased release of the recently discovered lipid mediator EXC<sub>4</sub>, as well as the main indicator of 15-LO activity, 15-HETE, in activated eosinophils from severe and aspirin-intolerant asthmatics, and also elevated EXC<sub>4</sub> and LTC<sub>4</sub> formation in eosinophils from AIA patients after cellular activation in the presence of lysine-aspirin. The findings support a pathophysiological role of the 15-LO pathway in SA and AIA.
DOI: 10.6084/m9.figshare.5125162
title: Supplementary Material for: High Proportions of CD4+ T Cells among Residual Bone Marrow T Cells in Childhood Acute Lymphoblastic Leukemia Are Associated with Favorable Early Responses

description: Residual nonmalignant T cells in the bone marrow of patients with acute leukemias may be involved in active immune responses to leukemic cells. Here, we investigated the phenotypic signature of T cells present at diagnosis in 39 pediatric patients with acute lymphoblastic leukemia (ALL) treated within standardized ALL-BFM study protocols. Previously described age associations of lymphocyte subpopulations in the peripheral blood of healthy children were reproduced in leukemic bone marrow. Analysis of individual lymphocyte parameters and risk-associated variables using univariate linear regression models revealed a correlation of higher CD4/CD8 ratios at diagnosis with a favorable bone marrow response on day 15. Separate analysis of CD4+ cells with the CD4+CD25<sup>hi</sup>FoxP3+ T<sub>reg</sub> cell phenotype showed that the association was caused by non-T<sub>reg</sub> CD4+ cells. The association of higher CD4/CD8 ratios with a favorable bone marrow response on day 15 of treatment persisted in a cohort extended to 69 patients. We conclude that CD4+ non-T<sub>reg</sub> cells in leukemic bone marrow at diagnosis may have a role in early response to treatment. Prospective analysis of the CD4/CD8 ratio in a large cohort of pediatric patients is now needed. Moreover, future experiments will establish the functional role of the individual T cell subsets in immune control in pediatric ALL.
DOI: 10.6084/m9.figshare.5125156
title: Supplementary Material for: From Communicative Functions to Prosodic Forms

description: This is a proposal in favour of proceeding from communicative function to linguistic form, rather than the reverse, for an insightful account of how humans communicate by speech in languages. A functional framework is developed that encompasses argumentation structures, declarative and interrogative functions, and expressive intensification. Such a function orientation can become a powerful tool in comparative prosodic research across the world's languages. The potential of this approach is shown by comparing the prosodic form of Mandarin Chinese data collected in functionally contextualized scenarios with corresponding data from English and German.
DOI: 10.6084/m9.figshare.5125165
title: Supplementary Material for: Synthesis of Methoxy-X04 Derivatives and Their Evaluation in Alzheimer's Disease Pathology

description: <b><i>Background:</i></b> Alzheimer's disease is characterized by two notorious protein aggregates in the brain: extracellular senile plaques mainly consisting of amyloid-β peptides and tau-protein-derived intracellular paired helical filaments. The diagnosis of Alzheimer's disease is impaired by insufficient sensitivity and specificity of diagnostic methods to visualize these pathological hallmarks over all disease stages. <b><i>Objective:</i></b> The established fluorescence marker methoxy-X04 stains plaques, tau tangles and amyloid-derived angiopathies with good specificity, yet it is limited by slow elimination in vivo. Since the need for new markers is high, we prepared methoxy-X04 derivatives and evaluated their potential as imaging agents in Alzheimer's disease pathology. <b><i>Methods and Results: </i></b>In this study, we describe an improved synthesis for methoxy-X04 and its derivatives and their affinity determination for the respective protein targets by immunohistology and a displacement assay. <b><i>Conclusion:</i></b> This resulted in the identification of new derivatives of methoxy-X04 with improved binding affinity.
DOI: 10.6084/m9.figshare.5125168.v1
title: Supplementary Material for: ‘Born in Michigan? You're in the Biobank': Engaging Population Biobank Participants through Facebook Advertisements

description: <b><i>Background/Aims:</i></b> Despite a broad call for biobanks to use social media, data is lacking regarding the capacity of social media tools, especially advertising, to engage large populations on this topic. <b><i>Methods:</i></b> We used Facebook advertising to engage Michigan residents about the BioTrust for Health. We conducted a low-budget (<i>Results:</i> The Facebook page was viewed 1,249 times during the month of the advertising campaign, versus once in the month prior. 779,004 Michigan residents saw ads an average of 25.8 times; 4,275 clicked ads; the average click-through-ratio was 0.021%. Interactions included 516 ‘likes' and 30 photo contest entries. Cost per outcome ranged from <i>Conclusion:</i> A social media strategy to build public awareness about biobanking is not likely to be effective without a promotional ‘push' to distribute content. Social media advertisements have the capacity to scale-up engagement on biobanking while keeping costs manageable. Facebook advertisements provide necessary access points for unaware participants, with implications for public trust.
DOI: 10.6084/m9.figshare.5125147
title: Supplementary Material for: The SafeBoosC Phase II Randomised Clinical Trial: A Treatment Guideline for Targeted Near-Infrared-Derived Cerebral Tissue Oxygenation versus Standard Treatment in Extremely Preterm Infants

description: Near-infrared spectroscopy-derived regional tissue oxygen saturation of haemoglobin (rStO<sub>2</sub>) reflects venous oxygen saturation. If cerebral metabolism is stable, rStO<sub>2</sub> can be used as an estimate of cerebral oxygen delivery. The SafeBoosC phase II randomised clinical trial hypothesises that the burden of hypo- and hyperoxia can be reduced by the combined use of close monitoring of the cerebral rStO<sub>2</sub> and a treatment guideline to correct deviations in rStO<sub>2</sub> outside a predefined target range. <b><i>Aims:</i></b> To describe the rationale for and content of this treatment guideline. <b><i>Methods:</i></b> Review of the literature and assessment of the quality of evidence and the grade of recommendation for each of the interventions. <b><i>Results and Conclusions:</i></b> A clinical intervention algorithm based on the main determinants of cerebral perfusion-oxygenation changes during the first hours after birth was generated. The treatment guideline is presented to assist neonatologists in making decisions in relation to cerebral oximetry readings in preterm infants within the SafeBoosC phase II randomised clinical trial. The evidence grades were relatively low and the guideline cannot be recommended outside a research setting.
DOI: 10.6084/m9.figshare.5125150
title: Supplementary Material for: Endovascular Treatment of Distal Internal Carotid Artery Occlusions with Retrievable Stents

description: <b><i>Background:</i></b> Acute stroke due to distal intracranial internal carotid artery (ICA) occlusion has a poor natural history. Outcome in patients who receive intravenous tissue plasminogen activator (tPA) is also unsatisfactory. The objective of this study is to evaluate the effectiveness and safety of endovascular treatment with retrievable stents in these patients. <b><i>Methods:</i></b> Data from a prospective register of patients with acute stroke treated with an endovascular procedure in a single centre were analysed. <b><i>Results:</i></b> A total of 20 patients with distal ICA occlusion were collected. Mean baseline National Institutes of Health Stroke Scale score was 18. Eight cases (40%) had received previous intravenous tPA. Mean time from stroke to recanalization was 393 min. Retrievable stents with proximal occlusion and aspiration were used in all cases. In 3 patients, 2 retrievable stents were used simultaneously. Complete recanalization (thrombolysis in cerebral infarction 2b/3) was accomplished in 85% of cases. A favourable clinical outcome (modified Rankin Scale score 0-2) was achieved in 13 patients (65%). Mortality occurred in 2 cases (10%). <b><i>Conclusions:</i></b> Endovascular treatment of patients with distal ICA occlusion seems safe and effective. Retrievable stents may be the treatment of choice, although randomized clinical trials are necessary. The use of 2 retrievable stents at the same time could be an alternative technique useful in thrombi of larger size.
DOI: 10.6084/m9.figshare.5125153
title: Supplementary Material for: Clinically Relevant Effect of a New Intranasal Therapy (MP29-02) in Allergic Rhinitis Assessed by Responder Analysis

description: <b><i>Background:</i></b> It is unclear what constitutes a clinically meaningful response for allergic rhinitis (AR) outcomes. The objectives of these post hoc analyses were (1) to define a clinically meaningful response using novel efficacy analyses (including a responder analysis), and (2) to compare the efficacy of MP29-02 [a novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP)] with commercially available FP, AZE and placebo in seasonal AR (SAR) patients, using these novel analyses. <b><i>Methods:</i></b> 610 moderate-to-severe SAR patients (≥12 years old) were randomized into a double-blind, placebo-controlled, 14-day, parallel-group trial. Change from baseline in the reflective total nasal symptom score (rTNSS) over 14 days was the primary outcome. Post hoc endpoints included the sum of nasal and ocular symptoms (rT7SS), efficacy by disease severity and by predominant nasal symptom, and a set of responder analyses. <b><i>Results:</i></b> MP29-02 most effectively reduced rT7SS (relative greater improvement: 52% to FP; 56% to AZE) and both nasal and ocular symptoms irrespective of severity. More MP29-02 patients achieved a ≥30, ≥50, ≥60, ≥75 and ≥90% rTNSS reduction, which occurred days faster than with either active comparator; MP29-02 alone was superior to placebo at the ≥60% (or higher) threshold. One in 2 MP29-02 patients achieved a ≥50% rTNSS reduction and 1 in 6 achieved complete/near-to-complete response. Only MP29-02 was consistently superior to placebo for all patients, whatever their predominant symptom. <b><i>Conclusions:</i></b> MP29-02 provided faster and more complete symptom control than first-line therapies. It was consistently superior irrespective of severity, response criteria or patient-type, and may be considered the drug of choice for moderate-to-severe AR. These measures define a new standard for assessing relevance in AR.
DOI: 10.6084/m9.figshare.5125165.v1
title: Supplementary Material for: Synthesis of Methoxy-X04 Derivatives and Their Evaluation in Alzheimer's Disease Pathology

description: <b><i>Background:</i></b> Alzheimer's disease is characterized by two notorious protein aggregates in the brain: extracellular senile plaques mainly consisting of amyloid-β peptides and tau-protein-derived intracellular paired helical filaments. The diagnosis of Alzheimer's disease is impaired by insufficient sensitivity and specificity of diagnostic methods to visualize these pathological hallmarks over all disease stages. <b><i>Objective:</i></b> The established fluorescence marker methoxy-X04 stains plaques, tau tangles and amyloid-derived angiopathies with good specificity, yet it is limited by slow elimination in vivo. Since the need for new markers is high, we prepared methoxy-X04 derivatives and evaluated their potential as imaging agents in Alzheimer's disease pathology. <b><i>Methods and Results: </i></b>In this study, we describe an improved synthesis for methoxy-X04 and its derivatives and their affinity determination for the respective protein targets by immunohistology and a displacement assay. <b><i>Conclusion:</i></b> This resulted in the identification of new derivatives of methoxy-X04 with improved binding affinity.