cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5104537
title: Supplementary Material for: The ‘Double Lung Point’: An Ultrasound Sign Diagnostic of Transient Tachypnea of the Newborn

description: <i>Background:</i> Transient tachypnea of the newborn (TTN) is a mild form of neonatal respiratory distress which early in its course needs to be differentiated from other severe respiratory disorders. At present the diagnosis is based on radiological findings and clinical course. Lung sonography in TTN has not yet been assessed. <i>Objectives:</i> The aim of the study was to define the ultrasonographic appearance of TTN and evaluate its clinical relevance. <i>Methods:</i> Lung sonography was performed in 32 newborn infants with radiological and clinical signs of TTN within the first hour after birth and the findings were compared with those of 60 normal infants, 29 with respiratory distress syndrome, 6 with pneumonia, 5 with pulmonary hemorrhage and 5 with atelectasis. <i>Results:</i> In the infants with TTN, lung sonography showed a difference in lung echogenicity between the upper and lower lung areas. There were very compact comet-tail artifacts in the inferior fields while these were rare in the superior fields. We designated this finding the ‘double lung point’ and it was not observed in healthy infants, infants with respiratory distress syndrome, actelectasis, pneumothorax, pneumonia, or pulmonary hemorrhage. Sensitivity and specificity of the double lung point was 100% for the diagnosis of TTN. <i>Conclusion:</i> We found lung sonography reliable for the early diagnosis of TTN. We suggest that it should become the first approach for imaging of neonatal respiratory distress although further prospective studies with good blinding need to be performed.
DOI: 10.6084/m9.figshare.5104543
title: Supplementary Material for: Candidate-Gene Association Study of Mothers with Pre-Eclampsia, and Their Infants, Analyzing 775 SNPs in 190 Genes

description: Pre-eclampsia (PE) affects 5–7% of pregnancies in the US, and is a leading cause of maternal death and perinatal morbidity and mortality worldwide. To identify genes with a role in PE, we conducted a large-scale association study evaluating 775 SNPs in 190 candidate genes selected for a potential role in obstetrical complications. SNP discovery was performed by DNA sequencing, and genotyping was carried out in a high-throughput facility using the MassARRAY<sup>TM</sup> System. Women with PE (n = 394) and their offspring (n = 324) were compared with control women (n = 602) and their offspring (n = 631) from the same hospital-based population. Haplotypes were estimated for each gene using the EM algorithm, and empirical p values were obtained for a logistic regression-based score test, adjusted for significant covariates. An interaction model between maternal and offspring genotypes was also evaluated. The most significant findings for association with PE were <i>COL1A1</i> (p = 0.0011) and <i>IL1A</i> (p = 0.0014) for the maternal genotype, and <i>PLAUR</i> (p = 0.0008) for the offspring genotype. Common candidate genes for PE, including <i>MTHFR </i>and <i>NOS3</i>, were not significantly associated with PE. For the interaction model, SNPs within <i>IGF1</i> (p = 0.0035) and <i>IL4R</i> (p = 0.0036) gave the most significant results. This study is one of the most comprehensive genetic association studies of PE to date, including an evaluation of offspring genotypes that have rarely been considered in previous studies. Although we did not identify statistically significant evidence of association for any of the candidate loci evaluated here after adjusting for multiple testing using the false discovery rate, additional compelling evidence exists, including multiple SNPs with nominally significant p values in COL1A1 and the IL1A region, and previous reports of association for IL1A, to support continued interest in these genes as candidates for PE. Identification of the genetic regulators of PE may have broader implications, since women with PE are at increased risk of death from cardiovascular diseases later in life.
DOI: 10.6084/m9.figshare.5104549
title: Supplementary Material for: Wilson’s Disease: A Great Masquerader

description: <i>Background:</i> Wilson’s disease (WD) is a treatable autosomal recessive metabolic disorder which could lead to protean hepatic or neurologic manifestations. WD could mimic many neurologic disorders and is often diagnosed with a long delay. This study describes central nervous system manifestations of a group of Iranian patients with neurologic WD. <i>Methods:</i> Data from case records of patients with neurologic WD presenting at a referral university hospital and a private clinic in Tehran from 1984 to 2004 were analyzed. <i>Results:</i> Fifty patients from 44 unrelated families with WD were identified, whose mean duration of follow-up was 51.8 (±58.5) months. The median age of onset of neurologic symptoms in 37 patients with primary neurologic or simultaneous hepatic-neurologic presentation was 16 (10–38) years, whereas in 13 patients with prior hepatic damage, this was 18.5 (11–34) years. The 6 most common manifestations were dysarthria (80%), drooling (48%), tremor in limbs (44%), abnormal gait (44%), psychiatric and/or sleep symptoms (44%), and dystonia in limbs (42%). <i>Conclusion:</i> Neurologic WD has heterogeneous manifestations and should be considered in young patients presenting with dysarthria, drooling, any kind of movement disorders or psychiatric symptoms.
DOI: 10.6084/m9.figshare.5104552
title: Supplementary Material for: Two-Photon Microscopy of Vital Murine Elastic and Muscular Arteries

description: Understanding vascular pathologies requires insight in the structure and function, and, hence, an imaging technique combining subcellular resolution, large penetration depth, and optical sectioning. We evaluated the applicability of two-photon laser-scanning microscopy (TPLSM) in large elastic and small muscular arteries under physiological conditions. Elastic (carotid) and muscular (uterine, mesenteric) arteries of C57BL/6 mice were mounted in a perfusion chamber. TPLSM was used to assess the viability of arteries and to visualize the structural components elastin, collagen, nuclei, and endothelial glycocalyx (EG). Functionality was determined using diameter changes in response to noradrenaline and acetylcholine. Viability and functionality were maintained up to 4 h, enabling the assessment of structure-function relationships. Structural vessel wall components differed between elastic and muscular arteries: size (1.3 vs. 2.1 µm) and density (0.045 vs. 0.57 µm<sup>–2</sup>) of internal elastic lamina fenestrae, smooth muscle cell density (3.50 vs. 1.53 µm<sup>–3</sup>), number of elastic laminae (3 vs. 2), and adventitial collagen structure (tortuous vs. straight). EG in elastic arteries was 4.5 µm thick, covering 66% of the endothelial surface. TPLSM enables visualization and quantification of subcellular structures in vital and functional elastic and muscular murine arteries, allowing unraveling of structure-function relationships in healthy and diseased arteries.
DOI: 10.6084/m9.figshare.5104525
title: Supplementary Material for: The Ruler Is Dead: An Analysis of Carotid Plaque Motion

description: Factors involved in atherosclerotic plaque progression are still a topic of hot debate. With the advance of new ultrasound techniques it has been possible to identify atherosclerotic plaque characteristics that may reflect a higher risk of vulnerability. Among the various proposed mechanisms, one of the least investigated is plaque motion, i.e. plaque stability in respect to the arterial wall. We report here two asymptomatic patients with internal carotid stenosis that showed differences in plaque motion, a finding that could determine a change in their future treatment.
DOI: 10.6084/m9.figshare.5104531
title: Supplementary Material for: Sex and Age Specificity of Susceptibility Genes Modulating Survival at Old Age

description: <i>Objective:</i> We aimed to investigate the influence of the genetic variability of candidate genes on survival at old age in good health. <i>Methods:</i> First, on the basis of a synthetic survival curve constructed using historic mortality data taken from the Italian population from 1890 onward, we defined three age classes ranging from 18 to 106 years. Second, we assembled a multinomial logistic regression model to evaluate the effect of dichotomous variables (genotypes) on the probability to be assigned to a specific category (age class). Third, we applied the regression model to a cross-sectional dataset (10 genes; 972 subjects selected for healthy status) categorized according to age and sex. <i>Results:</i> We found that genetic factors influence survival at advanced age in good health in a sex- and age-specific way. Furthermore, we found that genetic variability plays a stronger role in males than in females and that, in both genders, its impact is especially important at very old ages. <i>Conclusions:</i> The analyses presented here underline the age-specific effect of the gene network in modulating survival at advanced age in good health.
DOI: 10.6084/m9.figshare.5104543.v1
title: Supplementary Material for: Candidate-Gene Association Study of Mothers with Pre-Eclampsia, and Their Infants, Analyzing 775 SNPs in 190 Genes

description: Pre-eclampsia (PE) affects 5–7% of pregnancies in the US, and is a leading cause of maternal death and perinatal morbidity and mortality worldwide. To identify genes with a role in PE, we conducted a large-scale association study evaluating 775 SNPs in 190 candidate genes selected for a potential role in obstetrical complications. SNP discovery was performed by DNA sequencing, and genotyping was carried out in a high-throughput facility using the MassARRAY<sup>TM</sup> System. Women with PE (n = 394) and their offspring (n = 324) were compared with control women (n = 602) and their offspring (n = 631) from the same hospital-based population. Haplotypes were estimated for each gene using the EM algorithm, and empirical p values were obtained for a logistic regression-based score test, adjusted for significant covariates. An interaction model between maternal and offspring genotypes was also evaluated. The most significant findings for association with PE were <i>COL1A1</i> (p = 0.0011) and <i>IL1A</i> (p = 0.0014) for the maternal genotype, and <i>PLAUR</i> (p = 0.0008) for the offspring genotype. Common candidate genes for PE, including <i>MTHFR </i>and <i>NOS3</i>, were not significantly associated with PE. For the interaction model, SNPs within <i>IGF1</i> (p = 0.0035) and <i>IL4R</i> (p = 0.0036) gave the most significant results. This study is one of the most comprehensive genetic association studies of PE to date, including an evaluation of offspring genotypes that have rarely been considered in previous studies. Although we did not identify statistically significant evidence of association for any of the candidate loci evaluated here after adjusting for multiple testing using the false discovery rate, additional compelling evidence exists, including multiple SNPs with nominally significant p values in COL1A1 and the IL1A region, and previous reports of association for IL1A, to support continued interest in these genes as candidates for PE. Identification of the genetic regulators of PE may have broader implications, since women with PE are at increased risk of death from cardiovascular diseases later in life.
DOI: 10.6084/m9.figshare.5104528
title: Supplementary Material for: Reporting Data on Homeopathic Treatments (RedHot): A Supplement to CONSORT*

description: When homeopathy is tested in clinical trials, understanding and appraisal are likely to be improved if published reports contain details of prescribing strategies and treatments. An international Delphi panel was convened to develop consensus guidelines for reporting homeopathic methods and treatments. The panel agreed 28 treatment- and provider-specific items that supplement the CONSORT (Consolidated Standards of Reporting Trials) Statement items 2, 3, 4 and 19. The authors recommend these for adoption by authors and journals when reporting trials of homeopathy.
DOI: 10.6084/m9.figshare.5104534
title: Supplementary Material for: Genomic structure and transcript variants of the bovine <i>DAZL</i> gene

description: The Deleted in AZoospermia Like <i>(DAZL)</i> gene is a member of the DAZ family and encodes an RNA-binding protein that is expressed in prenatal and postnatal germ cells of males and females. In the human, there are five highly-related members in the DAZ family, four <i>(DAZ1–4)</i> on the Y chromosome and one <i>(DAZL)</i> on an autosome (HSA3). Mutations in these genes have been linked to severe spermatogenic failure and infertility in men. In the present study, we have cloned and characterized the bovine <i>DAZL</i> (b<i>DAZL</i>) gene. The full-length b<i>DAZL</i> cDNA is predicted to encode a protein of 295 amino acids with an RNA recognition motif. The deduced protein sequence of bDAZL is 96 and 97% similar to human and mouse DAZL, respectively. Fluorescence in situ hybridization (FISH) maps b<i>DAZL</i> to the distal region on BTA1q. The b<i>DAZL</i> gene consists of 11 exons and 10 introns. A b<i>DAZL</i> pseudogene was identified on BTA16. Expression analysis of b<i>DAZL</i> in 13 different tissues by RT-PCR shows that two transcripts, variant 1 (2,996 bp) and variant 2 (1,373 bp), of the b<i>DAZL</i> gene are detected only in testis mRNA. The variants probably result from alternative RNA splicing as variant 1 contains an additional 1,623-bp insertion in the 3′ UTR. Our results lay the groundwork for possible single nucleotide polymorphism (SNP) and functional studies of the <i>DAZL</i> gene in cattle.
DOI: 10.6084/m9.figshare.5104525.v1
title: Supplementary Material for: The Ruler Is Dead: An Analysis of Carotid Plaque Motion

description: Factors involved in atherosclerotic plaque progression are still a topic of hot debate. With the advance of new ultrasound techniques it has been possible to identify atherosclerotic plaque characteristics that may reflect a higher risk of vulnerability. Among the various proposed mechanisms, one of the least investigated is plaque motion, i.e. plaque stability in respect to the arterial wall. We report here two asymptomatic patients with internal carotid stenosis that showed differences in plaque motion, a finding that could determine a change in their future treatment.
DOI: 10.6084/m9.figshare.5104531.v1
title: Supplementary Material for: Sex and Age Specificity of Susceptibility Genes Modulating Survival at Old Age

description: <i>Objective:</i> We aimed to investigate the influence of the genetic variability of candidate genes on survival at old age in good health. <i>Methods:</i> First, on the basis of a synthetic survival curve constructed using historic mortality data taken from the Italian population from 1890 onward, we defined three age classes ranging from 18 to 106 years. Second, we assembled a multinomial logistic regression model to evaluate the effect of dichotomous variables (genotypes) on the probability to be assigned to a specific category (age class). Third, we applied the regression model to a cross-sectional dataset (10 genes; 972 subjects selected for healthy status) categorized according to age and sex. <i>Results:</i> We found that genetic factors influence survival at advanced age in good health in a sex- and age-specific way. Furthermore, we found that genetic variability plays a stronger role in males than in females and that, in both genders, its impact is especially important at very old ages. <i>Conclusions:</i> The analyses presented here underline the age-specific effect of the gene network in modulating survival at advanced age in good health.
DOI: 10.6084/m9.figshare.5104534.v1
title: Supplementary Material for: Genomic structure and transcript variants of the bovine <i>DAZL</i> gene

description: The Deleted in AZoospermia Like <i>(DAZL)</i> gene is a member of the DAZ family and encodes an RNA-binding protein that is expressed in prenatal and postnatal germ cells of males and females. In the human, there are five highly-related members in the DAZ family, four <i>(DAZ1–4)</i> on the Y chromosome and one <i>(DAZL)</i> on an autosome (HSA3). Mutations in these genes have been linked to severe spermatogenic failure and infertility in men. In the present study, we have cloned and characterized the bovine <i>DAZL</i> (b<i>DAZL</i>) gene. The full-length b<i>DAZL</i> cDNA is predicted to encode a protein of 295 amino acids with an RNA recognition motif. The deduced protein sequence of bDAZL is 96 and 97% similar to human and mouse DAZL, respectively. Fluorescence in situ hybridization (FISH) maps b<i>DAZL</i> to the distal region on BTA1q. The b<i>DAZL</i> gene consists of 11 exons and 10 introns. A b<i>DAZL</i> pseudogene was identified on BTA16. Expression analysis of b<i>DAZL</i> in 13 different tissues by RT-PCR shows that two transcripts, variant 1 (2,996 bp) and variant 2 (1,373 bp), of the b<i>DAZL</i> gene are detected only in testis mRNA. The variants probably result from alternative RNA splicing as variant 1 contains an additional 1,623-bp insertion in the 3′ UTR. Our results lay the groundwork for possible single nucleotide polymorphism (SNP) and functional studies of the <i>DAZL</i> gene in cattle.
DOI: 10.6084/m9.figshare.5104510
title: Supplementary Material for: mRNA Expression Analysis and the Molecular Basis of Neonatal Testis Defects in <i>Dmrt1</i> Mutant Mice

description: Transcriptional regulators containing the DM domain DNA binding motif have been found to control sexual differentiation in a diverse group of metazoan animals including vertebrates, insects, and nematodes, suggesting that these proteins may comprise a very ancient group of sexual regulators. <i>Dmrt1</i>, 1 of 7 mammalian DM domain genes, is essential for several aspects of testicular differentiation in mice. The <i>Dmrt1</i> mutant phenotype becomes apparent shortly after birth, and culminates in severe testicular dysgenesis. To better understand the roles of <i>Dmrt1</i> in testicular development we have performed a more detailed analysis of its mutant phenotypes, and we have used mRNA expression profiling to identify genes misregulated in the neonatal <i>Dmrt1</i> mutant testis. We find that <i>Dmrt1</i> mutant germ cells fail to undergo several of the normal postnatal events of germ cell development, including radial movement, mitotic proliferation, differentiation into spermatogonia, and initiation of meiosis, and they die by P14. During this period <i>Dmrt1</i> mutant Sertoli cells fail to polarize and form tight junctions, and fail to cease proliferation, eventually filling the seminiferous tubules. Expression profiling at P1 and P2 in <i>Dmrt1</i> mutant testes indicates defects in several important testicular signaling pathways (Gdnf, retinoic acid, TGFβ, FSH), and detects elevated expression of the pluripotency marker <i>Stella/Dppa3/Pgc7</i>, providing insight into the molecular basis of <i>Dmrt1</i> testis defects. This work also identifies a number of new candidate testicular regulators for further investigation.
DOI: 10.6084/m9.figshare.5104522
title: Supplementary Material for: Linkage Disequilibrium and Haplotype Homozygosity in Population Samples Genotyped at a High Marker Density

description: <i>Objective:</i> Analyze the information contained in homozygous haplotypes detected with high density genotyping. <i>Methods:</i> We analyze the genotypes of ∼2,500 markers on chr 22 in 12 population samples, each including 200 individuals. We develop a measure of disequilibrium based on haplotype homozygosity and an algorithm to identify genomic segments characterized by non-random homozygosity (NRH), taking into account allele frequencies, missing data, genotyping error, and linkage disequilibrium. <i>Results:</i> We show how our measure of linkage disequilibrium based on homozygosity leads to results comparable to those of <i>R</i><sup>2</sup>, as well as the importance of correcting for small sample variation when evaluating <i>D</i>′. We observe that the regions that harbor NRH segments tend to be consistent across populations, are gene rich, and are characterized by lower recombination. <i>Conclusions:</i> It is crucial to take into account LD patterns when interpreting long stretches of homozygous markers.
DOI: 10.6084/m9.figshare.5104507
title: Supplementary Material for: Impact of low copy repeats on the generation of balanced and unbalanced chromosomal aberrations in mental retardation

description: Low copy repeats (LCRs) are stretches of duplicated DNA that are more than 1 kb in size and share a sequence similarity that exceeds 90%. Non-allelic homologous recombination (NAHR) between highly similar LCRs has been implicated in numerous genomic disorders. This study aimed at defining the impact of LCRs on the generation of balanced and unbalanced chromosomal rearrangements in mentally retarded patients. A cohort of 22 patients, preselected for the presence of submicroscopic imbalances, was analysed using submegabase resolution tiling path array CGH and the results were compared with a set of 41 patients with balanced translocations and breakpoints that were mapped to the BAC level by FISH. Our data indicate an accumulation of LCRs at breakpoints of both balanced and unbalanced rearrangements. LCRs with high sequence similarity in both breakpoint regions, suggesting NAHR as the most likely cause of rearrangement, were observed in 6/22 patients with chromosomal imbalances, but not in any of the balanced translocation cases studied. In case of chromosomal imbalances, the likelihood of NAHR seems to be inversely related to the size of the aberration. Our data also suggest the presence of additional mechanisms coinciding with or dependent on the presence of LCRs that may induce an increased instability at these chromosomal sites.
DOI: 10.6084/m9.figshare.5104519
title: Supplementary Material for: Global Gene Expression Profiling of <i>Bacillus subtilis</i> in Response to Ammonium and Tryptophan Starvation as Revealed by Transcriptome and Proteome Analysis

description: The global gene expression profile of <i>Bacillus subtilis</i> in response to ammonium and tryptophan starvation was analyzed using transcriptomics and proteomics which gained novel insights into these starvation responses. The results demonstrate that both starvation conditions induce specific, overlapping and general starvation responses. The TnrA regulon, the glutamine synthetase (<i>glnA</i>) as well as the σ<sup>L</sup>-dependent <i>bkd</i> and <i>roc</i> operons were most strongly and specifically induced after ammonium starvation. These are involved in the uptake and utilization of ammonium and alternative nitrogen sources such as amino acids, γ-aminobutyrate, nitrate/nitrite, uric acid/urea and oligopeptides. In addition, several carbon catabolite-controlled genes (e.g. <i>acsA</i>, <i>citB</i>), the α-acetolactate synthase/-decarboxylase <i>alsSD </i>operon and several aminotransferase genes were specifically induced after ammonium starvation. The induction of σ<sup>F</sup>- and σ<sup>E</sup>-dependent sporulation proteins at later time points in ammonium-starved cells was accompanied by an increased sporulation frequency. The specific response to tryptophan starvation includes the TRAP-regulated tryptophan biosynthesis genes, some RelA-dependent genes (e.g. <i>adeC, ald</i>) as well as <i>spo0E</i>. Furthermore, we recognized overlapping responses between ammonium and tryptophan starvation (e.g. <i>dat</i>, <i>maeN</i>) as well as the common induction of the CodY and σ<sup>H</sup> general starvation regulons and the RelA-dependent stringent response. Many genes encoding proteins of so far unknown functions could be assigned to specifically or commonly induced genes.