cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5126227.v1
title: Supplementary Material for: Chlorthalidone for Poorly Controlled Hypertension in Chronic Kidney Disease: An Interventional Pilot Study

description: To test the hypothesis that thiazide-type diuretics effectively lower blood pressure (BP) in moderate to advanced chronic kidney disease (CKD; estimated GFR 20-45 ml/min/ 1.73 m<sup>2</sup>), after confirming poorly controlled hypertension with 24-hour ambulatory BP monitoring, chlorthalidone was added to existing medications in a dose of 25 mg/day, and the dose doubled every 4 weeks if the BP remained elevated. The average age of the 14 subjects was 67.5 years, a median of 4 antihypertensive drugs were used and estimated GFR was 26.8 ± 8.8 ml/min/1.73 m<sup>2</sup>. Twelve subjects completed the 12-week treatment phase, and the 24-hour BP, which was 143.1/75.1 mm Hg at baseline, was reduced by 10.5/ 3.1 mm Hg (p = 0.01/p = 0.17). Home BP prior to initiating chlorthalidone was 152.4/82.6 mm Hg and fell at 4, 8, and 12 weeks by 10.2/4.8, 13.4/6.0, and 9.4/3.7 mm Hg (all p &lt; 0.05). Maximal reduction in body weight and total body volume (measured by air displacement plethysmography) was seen at 8 weeks, concurrent with the maximal elevation in serum creatinine concentration and plasma renin activity. Albuminuria was significantly reduced by 40-45%. Adverse events were seen following chlorthalidone therapy in 7 subjects who experienced 18 events as follows: hypokalemia (n = 4), hyperuricemia (4), hyponatremia (3), transient creatinine changes (3), dizziness (2), hyperglycemia (1), and constipation (1). One subject had ischemic stroke during the study. In conclusion, among people with moderate to advanced CKD with poorly controlled hypertension, chlorthalidone may significantly reduce BP via volume contraction; a randomized trial is needed to define the risks and benefits. Adverse effects may occur within a few weeks and should be carefully monitored.
DOI: 10.6084/m9.figshare.5126233.v1
title: Supplementary Material for: Projections of Trends in Overweight in the Elderly Population in Germany until 2030 and International Comparison

description: <b><i>Background/Aims:</i></b> To project the numbers of pre-obese (BMI 25-29.99 kg/m²) and obese (BMI &gt; 30 kg/m²) men and women aged 50+ in Germany until 2030 and to compare our estimates with actual figures from four European countries and the USA. Estimates are based on six scenarios encompassing improvements as well as worsenings of current trends. <b><i>Methods:</i></b> We used pooled data from 1999 to 2009 of the German Microcensus (n = 1,472,547). Using multinomial logistic regression models we estimated age-specific probabilities of pre-obesity and obesity and applied them to the 12th population projection of the Federal Statistical Office. <b><i>Results:</i></b> We project overall increases in absolute numbers of pre-obesity ranging between 14.2 and 18.2 million. However, the prevalence of pre-obesity is likely to decrease slightly. In contrast, absolute and relative numbers of obesity are projected to increase, ranging between 7.2 and 15.8 million. The international comparison revealed that pre-obesity prevalences will remain among the highest in Germany, while obesity is projected to fall below current levels of the UK or the USA. <b><i>Conclusion:</i></b> Pre-obesity and, particularly, obesity are likely to become a more prominent health issue in Germany in the near future which could have large repercussions for the public health system.
DOI: 10.6084/m9.figshare.5126224.v1
title: Supplementary Material for: Identification of Responders to Sorafenib in Hepatocellular Carcinoma: Is Tumor Volume Measurement the Way Forward?

description: Objectives: Early assessment of hepatocellular carcinoma (HCC) response during sorafenib (SO) treatment is challenging, since tumor necrosis, extension and radiological appearance can be inhomogeneous. We evaluated the predictive value of different imaging criteria - such as Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, European Association for the Study of the Liver (EASL), modified RECIST (mRECIST), tumor density and volume variations - in the early follow-up of SO treatment. Methods: The study included 22 patients. CT images from baseline and 2 months were reviewed to assess response according to RECIST 1.1, mRECIST, EASL, Choi's criteria (decreased tumor density by ≥15%) and arterial-enhancing tumor volume ratio; α-fetoprotein (AFP) variations were expressed as AFP ratio. Results: The response criteria and volume measurements were reproducible (k &gt; 0.80). The overall disease control rate was 40.9% by EASL and mRECIST, and 27.3% by RECIST 1.1; a ≥15% decrease in tumor density was observed in 9 patients (40.9%). The mean volume ratio was 1.73 ± 2.12, the mean AFP ratio 14 ± 37. The 1-year survival rate was 65.9%. Volume ratio was the only predictive factor for survival, with 1-year cumulative survival rates of 90% for volume ratios ≤1.1 and of 45.4% for volume ratios &gt;1.1 (p = 0.04). Conclusions: Tumor volume measurements are reproducible and might provide an early predictive marker of response in HCC patients treated with SO.
DOI: 10.6084/m9.figshare.5126215
title: Supplementary Material for: Hierarchical Maturation of Innate Immune Defences in Very Preterm Neonates

description: <b><i>Background:</i></b> Preterm neonates are highly vulnerable to infection. <b><i>Objectives:</i></b> To investigate the developmental contribution of prematurity, chorioamnionitis and antenatal corticosteroids (ANS) on the maturation of neonatal microbial pathogen recognition responses. <b><i>Methods:</i></b> Using standardized protocols, we assayed multiple inflammatory cytokine responses (IL-1β, IL-6, TNF-α and IL-12/23p40) to three prototypic Toll-like receptor (TLR) agonists, i.e. TLR4 (lipopolysaccharide), TLR5 (flagellin) and TLR7/8 (R848), and to the non-TLR retinoic acid-inducible gene I (RIG-I)-like receptor agonist, in cord blood mononuclear cells from neonates born before 33 weeks of gestation and at term. <b><i>Results:</i></b> TLR responses develop asynchronously in preterm neonates, whereby responses to TLR7/8 were more mature and were followed by the development of TLR4 responses, which were also heterogeneous. Responses to TLR5 were weakest and most immature. Maturity in TLR responses was not influenced by sex. Overall, we detected no significant contribution of ANS and chorioamnionitis to the developmental attenuation of either TLR or RIG-I responses. <b><i>Conclusions:</i></b> The maturation of anti-microbial responses in neonates born early in gestation follows an asynchronous developmental hierarchy independently of an exposure to chorioamnionitis and ANS. Our data provide an immunological basis for the predominance of specific microbial infections in this age group.
DOI: 10.6084/m9.figshare.5126218
title: Supplementary Material for: Longitudinal Changes in Circulating Testosterone Levels Determined by LC-MS/MS and by a Commercially Available Radioimmunoassay in Healthy Girls and Boys during the Pubertal Transition

description: <b><i>Background:</i></b> Accurate and selective assessment of testosterone requires use of a sensitive LC-MS/MS method, especially at low levels as those seen in young children. <b><i>Methods:</i></b> The present longitudinal study of 20 healthy children from the Copenhagen Puberty Study followed every 6 months for 5 years evaluates the longitudinal increase in serum testosterone before, during and after pubertal onset quantified by a newly developed LC-MS/MS method in comparison with immunoassay. Testosterone concentrations in serum samples (n = 177) were determined by LC-MS/MS (detection limit 0.1 nmol/l) and by immunoassay (detection limit 0.23 nmol/l). <b><i>Results:</i></b> Serum concentrations of testosterone increased gradually with age by both methods. However, serum testosterone was quantifiable in 9/10 girls prior to pubic hair development measured with LC-MS/MS, and in 2/10 girls measured with immunoassay. In boys, testosterone was quantifiable in 10/10 boys 1 year prior to pubic hair development measured with LC-MS/MS, and only in 1/10 boys measured with immunoassay. Serum testosterone levels were quantifiable 1.5 years (range 0.5-2.5) earlier using LC-MS/MS. <b><i>Conclusion:</i></b> Assessment of longitudinal circulating levels of serum testosterone using a selective LC-MS/MS method proved to be more sensitive in predicting early peripubertal changes in healthy children compared to levels determined by immunoassay.
DOI: 10.6084/m9.figshare.5126230.v1
title: Supplementary Material for: Combination of Cross-Sectional and Molecular Imaging Studies in the Localization of Gastroenteropancreatic Neuroendocrine Tumors

description: Molecular imaging modalities exploit aspects of neuroendocrine tumors (NET) pathophysiology for both diagnostic imaging and therapeutic purposes. The characteristic metabolic pathways of NET determine which tracers are useful for their visualization. In this review, we summarize the diagnostic value of all available molecular imaging studies, present data about their use in daily practice in NET centers globally, and finally make recommendations about the appropriate use of those modalities in specific clinical scenarios. Somatostatin receptor scintigraphy (SRS) continues to have a central role in the diagnostic workup of patients with NET, as it is also widely available. However, and despite the lack of prospective randomized studies, many NET experts predict that Gallium-68 (<sup>68</sup>Ga)-DOTA positron emission tomography (PET) techniques may replace SRS in the future, not only because of their technical advantages, but also because they are superior in patients with small-volume disease, in patients with skeletal metastases, and in those with occult primary tumors. Carbon-11 (<sup>11</sup>C)-5-hydroxy-L-tryptophan (5-HTP) PET and <sup>18</sup>F-dihydroxyphenylalanine (<sup>18</sup>F-DOPA) PET are new molecular imaging techniques of limited availability, and based on retrospective data, their sensitivities seem to be inferior to that of <sup>68</sup>Ga-DOTA PET. Glucagon-like-peptide-1 (GLP-1) receptor imaging seems promising for localization of the primary in benign insulinomas, but is currently available only in a few centers. Fluorine-18 (<sup>18</sup>F)-fluorodeoxyglucose (<sup>18</sup>F-FDG) PET was initially thought to be of limited value in NET, due to their usually slow-growing nature. However, according to subsequent data, <sup>18</sup>F-FDG PET is particularly helpful for visualizing the more aggressive NET, such as poorly differentiated neuroendocrine carcinomas, and well-differentiated tumors with Ki67 values &gt;10%. According to limited data, <sup>18</sup>F-FDG-avid tumor lesions, even in slow-growing NET, may indicate a more aggressive disease course. When a secondary malignancy has already been established or is strongly suspected, combining molecular imaging techniques (e.g. <sup>18</sup>F-FDG PET and <sup>68</sup>Ga-DOTA PET) takes advantage of the diverse avidities of different tumor types to differentiate lesions of different origins. All the above-mentioned molecular imaging studies should always be reviewed and interpreted in a multidisciplinary (tumor board) meeting in combination with the conventional cross-sectional imaging, as the latter remains the imaging of choice for the evaluation of treatment response and disease follow-up.
DOI: 10.6084/m9.figshare.5126212
title: Supplementary Material for: Parents' Preferences for Return of Results in Pediatric Genomic Research

description: <b><i>Background:</i></b> The aim of this study was to ascertain parental preferences for the return of genetic research results on themselves and their children and their choices for genetic research results to receive. <b><i>Methods:</i></b> A mail survey was sent to 6,874 families seen at Boston Children's Hospital. The survey included questions assessing the respondents' preferences regarding the types of result they wanted to receive on themselves and their children. <b><i>Results:</i></b> Most of the 1,060 respondents ‘probably' or ‘definitely' wanted to receive genetic research results about themselves (84.6%) and their children (88.0%). Among those who wanted to receive results, 83.4% wanted to receive all research results for themselves and 87.8% for their children. When questions about specific types of research results were combined into a composite measure, fewer respondents chose to receive all results for themselves (53.5%) and for their children (56.9%). <b><i>Conclusion:</i></b> Although most parents report a desire to receive all research results on a general question, almost half chose to receive only a subset of research results when presented with specific types of research results. Our findings suggest that participants might not understand the implications of their choice of individual research results to receive unless faced with specific types of results.
DOI: 10.6084/m9.figshare.5126215.v1
title: Supplementary Material for: Hierarchical Maturation of Innate Immune Defences in Very Preterm Neonates

description: <b><i>Background:</i></b> Preterm neonates are highly vulnerable to infection. <b><i>Objectives:</i></b> To investigate the developmental contribution of prematurity, chorioamnionitis and antenatal corticosteroids (ANS) on the maturation of neonatal microbial pathogen recognition responses. <b><i>Methods:</i></b> Using standardized protocols, we assayed multiple inflammatory cytokine responses (IL-1β, IL-6, TNF-α and IL-12/23p40) to three prototypic Toll-like receptor (TLR) agonists, i.e. TLR4 (lipopolysaccharide), TLR5 (flagellin) and TLR7/8 (R848), and to the non-TLR retinoic acid-inducible gene I (RIG-I)-like receptor agonist, in cord blood mononuclear cells from neonates born before 33 weeks of gestation and at term. <b><i>Results:</i></b> TLR responses develop asynchronously in preterm neonates, whereby responses to TLR7/8 were more mature and were followed by the development of TLR4 responses, which were also heterogeneous. Responses to TLR5 were weakest and most immature. Maturity in TLR responses was not influenced by sex. Overall, we detected no significant contribution of ANS and chorioamnionitis to the developmental attenuation of either TLR or RIG-I responses. <b><i>Conclusions:</i></b> The maturation of anti-microbial responses in neonates born early in gestation follows an asynchronous developmental hierarchy independently of an exposure to chorioamnionitis and ANS. Our data provide an immunological basis for the predominance of specific microbial infections in this age group.
DOI: 10.6084/m9.figshare.5126209
title: Supplementary Material for: Bioavailability and Allergoprotective Capacity of Milk-Associated Conjugated Linoleic Acid in a Murine Model of Allergic Airway Inflammation

description: <b><i>Background:</i></b> Cross-sectional epidemiological studies have demonstrated that farm milk from traditional farm settings possesses allergoprotective properties. Up to now, it has not been clarified which milk ingredient is responsible for protection against allergic diseases. As farm milk is rich in conjugated linoleic acids (CLA), it is hypothesized that this n-3 polyunsaturated fatty acid family contributes to the allergoprotective capacity of farm milk. We aim to prove this hypothesis in a murine model of allergic airway inflammation. <b><i>Methods:</i></b> To prove the bioavailability and allergoprotective capacity of milk-associated CLA in a standardized protocol, milk batches that differed significantly in terms of their CLA content were spray dried and incorporated into a basic diet by substituting the regular sunflower fat fraction. Initially, the milk CLA uptake from the diet was monitored via measurement of the CLA content in plasma and erythrocyte membranes obtained from supplemented mice. To determine whether a milk CLA-enriched diet possesses allergoprotective properties, female Balb/c mice were fed the milk CLA-enriched diet ahead of sensitization and a challenge with ovalbumin (OVA) and the parameters of airway inflammation and eisosanoid pattern were measured. <b><i>Results:</i></b> In animals, supplementation with a diet rich in milk CLA resulted in elevated CLA levels in plasma and erythrocyte membranes, indicating bioavailability of milk fatty acids. Though membrane-associated phospholipid patterns were affected by supplementation with milk CLA, this application neither reduced the hallmarks of allergic airway inflammation in sensitized and OVA-challenged mice nor modified the eiconsanoid pattern in the bronchoalveolar lavage fluid of these animals. <b><i>Conclusion:</i></b> Milk-associated CLA was not capable of preventing murine allergic airway inflammation in an animal model of OVA-induced allergic airway inflammation.
DOI: 10.6084/m9.figshare.5126218.v1
title: Supplementary Material for: Longitudinal Changes in Circulating Testosterone Levels Determined by LC-MS/MS and by a Commercially Available Radioimmunoassay in Healthy Girls and Boys during the Pubertal Transition

description: <b><i>Background:</i></b> Accurate and selective assessment of testosterone requires use of a sensitive LC-MS/MS method, especially at low levels as those seen in young children. <b><i>Methods:</i></b> The present longitudinal study of 20 healthy children from the Copenhagen Puberty Study followed every 6 months for 5 years evaluates the longitudinal increase in serum testosterone before, during and after pubertal onset quantified by a newly developed LC-MS/MS method in comparison with immunoassay. Testosterone concentrations in serum samples (n = 177) were determined by LC-MS/MS (detection limit 0.1 nmol/l) and by immunoassay (detection limit 0.23 nmol/l). <b><i>Results:</i></b> Serum concentrations of testosterone increased gradually with age by both methods. However, serum testosterone was quantifiable in 9/10 girls prior to pubic hair development measured with LC-MS/MS, and in 2/10 girls measured with immunoassay. In boys, testosterone was quantifiable in 10/10 boys 1 year prior to pubic hair development measured with LC-MS/MS, and only in 1/10 boys measured with immunoassay. Serum testosterone levels were quantifiable 1.5 years (range 0.5-2.5) earlier using LC-MS/MS. <b><i>Conclusion:</i></b> Assessment of longitudinal circulating levels of serum testosterone using a selective LC-MS/MS method proved to be more sensitive in predicting early peripubertal changes in healthy children compared to levels determined by immunoassay.
DOI: 10.6084/m9.figshare.5126200
title: Supplementary Material for: Etiologic Spectrum and Prognosis of Longitudinally Extensive Transverse Myelopathies

description: <b><i>Background:</i></b> Patients with a first episode of longitudinal extensive transverse myelopathy (LETM) were reviewed with two objectives: to evaluate the clinical spectrum of LETM and to analyze the related clinical and laboratory variables that can be used as functional prognostic markers. <b><i>Methods:</i></b> A retrospective review was conducted of clinical, radiologic and biochemical data of patients admitted for LETM between 1993 and 2011. <b><i>Results:</i></b> Our cohort included 72 patients [median age 41 years, interquartile range (IQR) 29-61.5]. Median follow-up was 34 months (IQR 17.2-63). The modified Rankin Scale (mRS) score was ≥2 at the end of follow-up in 72.2%. The final diagnosis was idiopathic LETM in 22 patients, multiple sclerosis in 18, parainfectious disease in 11, systemic disease in 9, spinal cord infarction and neuromyelitis optica spectrum disorders in 3 patients each, and acute demyelinating encephalomyelitis, dural fistula, and tumor-related LETM in 2 patients each. Unfavorable outcome was associated with mRS ≥2 at admission [odds ratio (OR) 1.39, 95% confidence interval (CI) 1.16-1.66] and older age (OR 1.06, 95% CI 1.01-1.11). <b><i>Conclusion:</i></b> Idiopathic LETM was the most frequent diagnosis at the end of follow-up. Older age and clinically severe disease at onset were independent prognostic factors of poorer functional recovery.
DOI: 10.6084/m9.figshare.5126203
title: Supplementary Material for: Factors Influencing the Accuracy of Fetal Weight Estimation with a Focus on Preterm Birth at the Limit of Viability: A Systematic Literature Review

description: <b><i>Background:</i></b> Fetal weight estimation (FWE) is an important factor for clinical management decisions, especially in imminent preterm birth at the limit of viability between 23<sup>0/7</sup> and 26<sup>0/7</sup> weeks of gestation. It is crucial to detect and eliminate factors that have a negative impact on the accuracy of FWE. <b><i>Data Sources:</i></b> In this systematic literature review, we investigated 14 factors that may influence the accuracy of FWE, in particular in preterm neonates born at the limit of viability. <b><i>Results:</i></b> We found that gestational age, maternal body mass index, amniotic fluid index and ruptured membranes, presentation of the fetus, location of the placenta and the presence of multiple fetuses do not seem to have an impact on FWE accuracy. The influence of the examiner's grade of experience and that of fetal gender were discussed controversially. Fetal weight, time interval between estimation and delivery and the use of different formulas seem to have an evident effect on FWE accuracy. No results were obtained on the impact of active labor. <b><i>Discussion:</i></b> This review reveals that only few studies investigated factors possibly influencing the accuracy of FWE in preterm neonates at the limit of viability. Further research in this specific age group on potential confounding factors is needed.
DOI: 10.6084/m9.figshare.5126209.v1
title: Supplementary Material for: Bioavailability and Allergoprotective Capacity of Milk-Associated Conjugated Linoleic Acid in a Murine Model of Allergic Airway Inflammation

description: <b><i>Background:</i></b> Cross-sectional epidemiological studies have demonstrated that farm milk from traditional farm settings possesses allergoprotective properties. Up to now, it has not been clarified which milk ingredient is responsible for protection against allergic diseases. As farm milk is rich in conjugated linoleic acids (CLA), it is hypothesized that this n-3 polyunsaturated fatty acid family contributes to the allergoprotective capacity of farm milk. We aim to prove this hypothesis in a murine model of allergic airway inflammation. <b><i>Methods:</i></b> To prove the bioavailability and allergoprotective capacity of milk-associated CLA in a standardized protocol, milk batches that differed significantly in terms of their CLA content were spray dried and incorporated into a basic diet by substituting the regular sunflower fat fraction. Initially, the milk CLA uptake from the diet was monitored via measurement of the CLA content in plasma and erythrocyte membranes obtained from supplemented mice. To determine whether a milk CLA-enriched diet possesses allergoprotective properties, female Balb/c mice were fed the milk CLA-enriched diet ahead of sensitization and a challenge with ovalbumin (OVA) and the parameters of airway inflammation and eisosanoid pattern were measured. <b><i>Results:</i></b> In animals, supplementation with a diet rich in milk CLA resulted in elevated CLA levels in plasma and erythrocyte membranes, indicating bioavailability of milk fatty acids. Though membrane-associated phospholipid patterns were affected by supplementation with milk CLA, this application neither reduced the hallmarks of allergic airway inflammation in sensitized and OVA-challenged mice nor modified the eiconsanoid pattern in the bronchoalveolar lavage fluid of these animals. <b><i>Conclusion:</i></b> Milk-associated CLA was not capable of preventing murine allergic airway inflammation in an animal model of OVA-induced allergic airway inflammation.