cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5241217
title: Erratum: Does Guideline-Adherent Therapy Improve the Outcome for Early-Onset Breast Cancer Patients?

description: <i>Background and Objective:</i> Guidelines for the treatment of early-onset breast cancer have been proposed in several countries, but to date, their impact on outcomes is unverified. The objective of this study was to evaluate the association between guideline-adherent versus nonadherent treatment and recurrence-free survival (RFS) and overall survival (OAS) in early-onset breast cancer patients. <i>Methods:</i> A total of 1,778 patients were included in the study, of whom 111 were 35 years or younger and 1,667 were between 36 and 55 years. RFS and OAS were compared between the two groups, with respect to multiple parameters. All survival data were adjusted for tumor characteristics and analyzed with respect to guideline adherence according to the German Step 3 guidelines. <i>Results:</i> Statistically significant differences between the two groups (&lt;35 years, 36–55 years) were observed with regard to breast surgery (p = 0.002) and hormone therapy (p = 0.006). Both groups were treated identically in terms of guideline adherence concerning axillary dissection (p = 0.9), radiation therapy (p = 0.7) and chemotherapy (p = 0.556). Young breast cancer patients whose treatment adhered to guideline recommendations had increased RFS and OAS [RFS: p = 0.030, hazard ratio (HR) 2.95, 95% confidence interval (CI) 1.11–7.83; OAS: p ≤ 0.001, HR 2.92, 95% CI 2.01–4.23]. <i>Conclusion:</i> Guideline-adherent treatment for early-onset breast cancer patients significantly improves OAS and RFS and should therefore be demanded for all patients.
DOI: 10.6084/m9.figshare.5241211.v1
title: Erratum: Delta-Centralization Fails to Control for Population Stratification in Genetic Association Studies

description: <i>Objective:</i> To investigate the validity of simulations and assumptions used to underpin the delta-centralization (DC) method for correcting for population stratification in genetic association studies; to assess the effectiveness of DC compared to genomic control (GC) under valid simulation conditions; and to highlight other studies employing similarly flawed simulations. <i>Methods:</i> DC and GC use data from unlinked null loci to correct the test statistic at the target locus, but differ in the way the correction is performed. We compare DC and GC under two simulation approaches: an invalid approach adopted by the originators of DC, which permits subpopulation allele frequency matching of null markers to the target locus; and a valid approach, based on the Balding-Nichols model, which does not allow subpopulation matching. <i>Results:</i> DC works under invalid simulation conditions (subpopulation allele frequency matching), but not under our valid ones. We use theoretical arguments to assert that there are no valid conditions under which DC might work. We identify several studies which have adopted similarly invalid simulation approaches in this field. <i>Conclusion:</i> DC fails to control for population stratification and should not be used. Other results from studies which have used the same invalid simulation approach should be treated cautiously.
DOI: 10.6084/m9.figshare.5241220.v1
title: Erratum: Urinary Pigment Epithelium-Derived Factor as a Marker of Diabetic Nephropathy

description: <i>Background:</i> Pigment epithelium-derived factor (PEDF), a serine protease inhibitor, regulates extracellular matrix production in the kidney. We sought the association between urinary PEDF (uPEDF) and development of nephropathy among patients with type 2 diabetes (T2DM). <i>Methods:</i> Two human studies were performed in which uPEDF was determined by ELISA. These studies included (1) a cross-sectional study of T2DM (n = 228) and healthy controls (n = 49) and (2) a longitudinal study of hypertensive T2DM with microalbuminuria (MA; n = 42) treated with irbesartan for 6 months. An animal study was performed in which PEDF was measured in the kidney and urine samples of control rats, rats rendered diabetic with streptozotocin that were also fed a high-fat diet, and diabetic rats treated with irbesartan for 3 months. <i>Results:</i> Cross-sectional study: compared to controls, uPEDF was significantly higher in patients with diabetic nephropathy. uPEDF independently correlated with MA. In the MA group, uPEDF in patients with diabetic retinopathy was significantly higher than that in patients without diabetic retinopathy. Longitudinal study: irbesartan significantly decreased uPEDF in T2DM with MA. Animal study: in diabetic rats, increased PEDF was observed in both the urine and kidney samples. uPEDF showed a significant correlation with the expression of PEDF in the kidney. Irbesartan could significantly decrease the PEDF expression in the kidneys of diabetic rats as well as uPEDF. <i>Conclusion:</i> uPEDF may serve as a novel marker for screening for nephropathy among patients with T2DM and monitoring the response to therapy.
DOI: 10.6084/m9.figshare.5241223.v1
title: Erratum: New Technologies for the Identification of Novel Genetic Markers of Disorders of Sex Development (DSD)

description: Although the genetic basis of human sexual determination and differentiation has advanced considerably in recent years, the fact remains that in most subjects with disorders of sex development (DSD) the underlying genetic cause is unknown. Where pathogenic mutations have been identified, the phenotype can be highly variable, even within families, suggesting that other genetic variants are influencing the expression of the phenotype. This situation is likely to change, as more powerful and affordable tools become widely available for detailed genetic analyses. Here, we describe recent advances in comparative genomic hybridisation, sequencing by hybridisation and next generation sequencing, and we describe how these technologies will have an impact on our understanding of the genetic causes of DSD.
DOI: 10.6084/m9.figshare.5241226.v1
title: Erratum: Impact of Molecular Genetics on Congenital Adrenal Hyperplasia Management

description: Congenital adrenal hyperplasia (CAH) is a family of autosomal recessive disorders caused by mutations in genes encoding the enzymes involved in one of the 5 steps of adrenal steroid synthesis or the electron donor P450 oxidoreductase (POR) enzyme. Steroid 21-hydroxylase deficiency (21-OHD), the principal focus of this review, accounts for about 90–95% of all CAH cases, and its biochemical and clinical severity depends on the underlying <i>CYP21A2</i> gene disruption. Molecular genetic advancements have been achieved in recent years, and the aim of this review is to attempt to highlight its contribution to the comprehension and management of the disease. When possible, we will try to achieve this goal also by providing some results from our personal experience regarding: some aspects of <i>CYP21A2</i> gene analysis, with basic genotype/phenotype relationships; its crucial role in both genetic counselling and in prenatal diagnosis and treatment in families at risk for 21-OHD; its help in the comprehension of the severity of the disease in patients diagnosed by neonatal screening and possibly treated before an evident salt-loss crisis or before performing adequate blood sampling; its usefulness in the definition of post ACTH 17-hydroxyprogesterone values, discriminating between non-classic, heterozygote and normal subjects; and finally the contribution of genes other than <i>CYP21A2</i> whose function or dysfunction could influence 21-hydroxylase activity and modify the presentation or management of the disease.
DOI: 10.6084/m9.figshare.5241199
title: Erratum: Circulating Very-Low-Density Lipoprotein Characteristics Resulting from Fatty Liver in an Insulin Resistance Rat Model

description: The close association between nonalcoholic fatty liver and insulin resistance is now widely recognized. While the former is characterized by excessive intrahepatic triglyceride accumulation, the latter induces overproduction of very-low-density lipoprotein (VLDL) particles. It has not been well elucidated whether these apparently opposite mechanisms impact on VLDL characteristics or not. The aim of the present study was to evaluate the VLDL secretion and features resulting from insulin resistance and fatty liver in rats fed a sucrose-rich diet (SRD, i.e. addition of sucrose to drinking water during 12 weeks). No differences in calorie intake were observed in comparison to controls. Both groups showed similar weight gains throughout the treatment period. However, SRD rats showed an increased proportion of body fat as assessed by X-ray absorptiometry, increased visceral obesity, liver weight and fat accumulation in the liver (p &lt; 0.04). Histological study revealed moderate micro- and macrovesicular steatosis. Fasting insulin, triglyceride and free fatty acid (FFA) levels increased while VLDLs decreased in SRD rats (p &lt; 0.05). The chemical composition of VLDLs of SRD rats showed a higher percentage of triglycerides, and the VLDL triglyceride/protein ratio, an estimator of lipoprotein size, suggests that VLDL particles of SRD rats are larger than those of controls (p &lt; 0.0005). FFA levels correlated with VLDL triglycerides (r = 0.49, p = 0.03) and liver fat content correlated with plasma triglycerides (r = 0.65), VLDL triglycerides (r = 0.55) and triglyceride/protein ratio (r = 0.52, p &lt; 0.02). The VLDL secretion rate assay showed an increase in SRD rats (p &lt; 0.02), confirming an overproduction despite liver fat accumulation. Our findings are consistent with an insulin resistance development model in which hepatic lipid content would constitute an important determinant of a triglyceride-rich, large-particle VLDL secretion; both features would increase its atherogenic potential.
DOI: 10.6084/m9.figshare.5241202
title: Erratum: A Promising Therapeutic Approach for Treatment of Posterior Uveitis: Recombinant T Cell Receptor Ligand Protects Lewis Rats from Acute and Recurrent Experimental Autoimmune Uveitis

description: <i>Introduction:</i> Chronic autoimmune uveitis is a major cause of vision loss from intraocular inflammation in humans. In this study we report that a recombinant TCR ligand (RTL220) composed of the α1 and β1 domains of MHC class II molecules linked to the uveitogenic interphotoreceptor retinoid-binding protein (IRBP) 1177–1191 peptide is effective in the suppression of acute and recurrent experimental autoimmune uveitis (EAU). <i>Material and Methods:</i> EAU was induced with IRBP1177–1191 peptide or by adoptive transfer of specific T cells in Lewis rats. The rats received 5 doses of RTL220 subcutaneously every other day starting at the onset of clinic signs of EAU. <i>Results:</i> The administration of RTL220 resulted in a delayed onset and a significant amelioration of the disease severity at clinical levels and showed protection of the retina from inflammatory damage at histological levels. In treatment of recurrent EAU, RTL220 administrated at the first or second onset of clinical disease significantly inhibited EAU, modulated immune responses and provided protection from relapses of uveitis. The systemic and local proinflammatory cytokines were significantly reduced, including IL-17. There was local and systemic increase in IL-10 and reduction in the expression of the proinflammatory chemokines CCL2, CCL3 and CCL5. <i>Conclusions:</i> Our studies demonstrate a successful treatment of acute and recurrent EAU with RTL220, which effectively suppressed the recurrence of inflammation and reversed clinical and histological EAU by altering cytokine and chemokine expression. These findings strongly support a possible clinical application of this novel class of peptide/MHC class II drugs for patients with autoimmune uveitis.
DOI: 10.6084/m9.figshare.5241205
title: Erratum: Atorvastatin Reduces Plaque Vulnerability in an Atherosclerotic Rabbit Model by Altering the 5-Lipoxygenase Pathway

description: <i>Objective:</i> The 5-lipoxygenase catalyzed formation of leukotriene lipid mediators is a mediator for inflammatory response in arteries. The present study investigated the relationship between atorvastatin and the 5-lipoxygenase pathway in an atherosclerotic rabbit model. <i>Methods:</i> Thirty male New Zealand White Rabbits were randomized into negative control, positive control and atorvastatin groups. At week 4, the rabbits were subjected to carotid balloon-dilation injury or carotid balloon-dilation injury, followed by treatment with atorvastatin. At week 12, all the animals were sacrificed. Plasma lipids, LTD<sub>4</sub>, and 15-epi-lipoxin A<sub>4</sub> were measured using the enzymatic endpoint method and ELISA, respectively. RT-PCR was performed to detect the gene expression of 5-lipoxygenase-activating protein and cysLT1R in rabbit carotid arteries. Finally, histological analysis was used to evaluate the pathophysiological changes of rabbit carotid arteries. <i>Results:</i> The results showed atorvastatin markedly lowered serum lipids and LTD<sub>4</sub> levels compared with the control group. Similarly, mRNA expression of 5-lipoxygenase-activating protein and cysLT1R was significantly inhibited by atorvastatin. Decreased carotid plaque instability was evident in atorvastatin-treated animals, as demonstrated by a thickened elastic layer, less neointima hyperplasia and macrophage proliferation. <i>Conclusions:</i> Atorvastatin may stabilize carotid plaque by regulating the 5-lipoxygenase pathway in atherosclerotic rabbits and delay the progression of atherosclerosis by exerting anti-inflammatory effects.
DOI: 10.6084/m9.figshare.5241193
title: Erratum: Copy Number Variation and Missense Mutations of the Agouti Signaling Protein (<i>ASIP)</i> Gene in Goat Breeds with Different Coat Colors

description: In goats, classical genetic studies reported a large number of alleles at the <i>Agouti</i> locus with effects on coat color and pattern distribution. From these early studies, the dominant <i>A</i><sup>Wt</sup> (white/tan) allele was suggested to cause the white color of the Saanen breed. Here, we sequenced the coding region of the goat <i>ASIP</i> gene in 6 goat breeds (Girgentana, Maltese, Derivata di Siria, Murciano-Granadina, Camosciata delle Alpi, and Saanen), with different coat colors and patterns. Five single nucleotide polymorphisms (SNPs) were identified, 3 of which caused missense mutations in conserved positions of the cysteine-rich carboxy-terminal domain of the protein (p.Ala96Gly, p.Cys126Gly, and p.Val128Gly). Allele and genotype frequencies suggested that these mutations are not associated or not completely associated with coat color in the investigated goat breeds. Moreover, genotyping and sequencing results, deviation from Hardy-Weinberg equilibrium, as well as allele copy number evaluation from semiquantitative fluorescent multiplex PCR, indicated the presence of copy number variation (CNV) in all investigated breeds. To confirm the presence of CNV and evaluate its extension, we applied a bovine-goat cross-species array comparative genome hybridization (aCGH) experiment using a custom tiling array based on bovine chromosome 13. aCGH results obtained for 8 goat DNA samples confirmed the presence of CNV affecting a region of less that 100 kb including the <i>ASIP</i> and <i>AHCY</i> genes. In Girgentana and Saanen breeds, this CNV might cause the <i>A</i><sup>Wt</sup> allele, as already suggested for a similar structural mutation in sheep affecting the <i>ASIP</i> and <i>AHCY</i> genes, providing evidence for a recurrent interspecies CNV. However, other mechanisms may also be involved in determining coat color in these 2 breeds.
DOI: 10.6084/m9.figshare.5241196
title: Erratum: Disorder in the Serotonergic System due to Tryptophan Hydroxylation Impairment: A Cause of Hypothalamic Syndrome?

description: <i>Background:</i> The hypothalamus regulates basic homeostasis such as appetite, circadian rhythm, autonomic and pituitary functions. Dysregulation in these functions results in the hypothalamic syndrome, a rare disorder of various origins. Since serotonin (5-HT) modulates most of the above-mentioned homeostasis, a defect in the serotonergic system can possibly participate in this syndrome. <i>Methods:</i> We describe a girl suffering from hypothalamic syndrome with a decreased concentration of 5-hydroxytryptophan (5-HTP) and a normal level of tryptophan in the cerebrospinal fluid (CSF) suggesting a functional defect in tryptophan hydroxylase (TPH). TPH is a rate-limiting enzyme in the synthesis of the neurotransmitter 5-HT. <i>Results:</i> Therapeutic intervention with 5-HTP, carbidopa and a specific serotonin reuptake inhibitor significantly improved her clinical symptoms and caused biochemical normalisation of neurotransmitters. <i>Conclusion:</i> The girl described had the typical symptoms of a hypothalamic disorder and a defective serotonergic metabolism, a relationship which has not been reported before. Therapeutic interventions to restore 5-HT metabolism resulted in clinical improvement. We suggest that investigation of 5-HT metabolism in CSF of patients with this rare disorder is included in the aetiological work-up.
DOI: 10.6084/m9.figshare.5241199.v1
title: Erratum: Circulating Very-Low-Density Lipoprotein Characteristics Resulting from Fatty Liver in an Insulin Resistance Rat Model

description: The close association between nonalcoholic fatty liver and insulin resistance is now widely recognized. While the former is characterized by excessive intrahepatic triglyceride accumulation, the latter induces overproduction of very-low-density lipoprotein (VLDL) particles. It has not been well elucidated whether these apparently opposite mechanisms impact on VLDL characteristics or not. The aim of the present study was to evaluate the VLDL secretion and features resulting from insulin resistance and fatty liver in rats fed a sucrose-rich diet (SRD, i.e. addition of sucrose to drinking water during 12 weeks). No differences in calorie intake were observed in comparison to controls. Both groups showed similar weight gains throughout the treatment period. However, SRD rats showed an increased proportion of body fat as assessed by X-ray absorptiometry, increased visceral obesity, liver weight and fat accumulation in the liver (p &lt; 0.04). Histological study revealed moderate micro- and macrovesicular steatosis. Fasting insulin, triglyceride and free fatty acid (FFA) levels increased while VLDLs decreased in SRD rats (p &lt; 0.05). The chemical composition of VLDLs of SRD rats showed a higher percentage of triglycerides, and the VLDL triglyceride/protein ratio, an estimator of lipoprotein size, suggests that VLDL particles of SRD rats are larger than those of controls (p &lt; 0.0005). FFA levels correlated with VLDL triglycerides (r = 0.49, p = 0.03) and liver fat content correlated with plasma triglycerides (r = 0.65), VLDL triglycerides (r = 0.55) and triglyceride/protein ratio (r = 0.52, p &lt; 0.02). The VLDL secretion rate assay showed an increase in SRD rats (p &lt; 0.02), confirming an overproduction despite liver fat accumulation. Our findings are consistent with an insulin resistance development model in which hepatic lipid content would constitute an important determinant of a triglyceride-rich, large-particle VLDL secretion; both features would increase its atherogenic potential.
DOI: 10.6084/m9.figshare.5241190
title: Erratum: Hypoxia Affected SDF-1α-CXCR4 Interaction between Bone Marrow Stem Cells and Osteoblasts via Osteoclast Modulation

description: Medicine
DOI: 10.6084/m9.figshare.5241193.v1
title: Erratum: Copy Number Variation and Missense Mutations of the Agouti Signaling Protein (<i>ASIP)</i> Gene in Goat Breeds with Different Coat Colors

description: In goats, classical genetic studies reported a large number of alleles at the <i>Agouti</i> locus with effects on coat color and pattern distribution. From these early studies, the dominant <i>A</i><sup>Wt</sup> (white/tan) allele was suggested to cause the white color of the Saanen breed. Here, we sequenced the coding region of the goat <i>ASIP</i> gene in 6 goat breeds (Girgentana, Maltese, Derivata di Siria, Murciano-Granadina, Camosciata delle Alpi, and Saanen), with different coat colors and patterns. Five single nucleotide polymorphisms (SNPs) were identified, 3 of which caused missense mutations in conserved positions of the cysteine-rich carboxy-terminal domain of the protein (p.Ala96Gly, p.Cys126Gly, and p.Val128Gly). Allele and genotype frequencies suggested that these mutations are not associated or not completely associated with coat color in the investigated goat breeds. Moreover, genotyping and sequencing results, deviation from Hardy-Weinberg equilibrium, as well as allele copy number evaluation from semiquantitative fluorescent multiplex PCR, indicated the presence of copy number variation (CNV) in all investigated breeds. To confirm the presence of CNV and evaluate its extension, we applied a bovine-goat cross-species array comparative genome hybridization (aCGH) experiment using a custom tiling array based on bovine chromosome 13. aCGH results obtained for 8 goat DNA samples confirmed the presence of CNV affecting a region of less that 100 kb including the <i>ASIP</i> and <i>AHCY</i> genes. In Girgentana and Saanen breeds, this CNV might cause the <i>A</i><sup>Wt</sup> allele, as already suggested for a similar structural mutation in sheep affecting the <i>ASIP</i> and <i>AHCY</i> genes, providing evidence for a recurrent interspecies CNV. However, other mechanisms may also be involved in determining coat color in these 2 breeds.
DOI: 10.6084/m9.figshare.5241184
title: Erratum: Why Do the Clients of Georgian Needle Exchange Programmes Inject Buprenorphine?

description: <i>Aim:</i> The aim of the study was to understand the prevalence and patterns of the non-medical injecting use of buprenorphine among drug injectors in Georgia. <i>Method:</i> A self-administered questionnaire was distributed among injecting drug users enrolled in Georgian needle exchange programmes. The questions covered topics related to drug use career, patterns (frequency, history, dosage) and reasons for the use of buprenorphine. <i>Results:</i> Pharmaceutical buprenorphine in the form of Subutex® was the most commonly injected drug in terms of lifetime (95.5%) and last-month (75%) prevalence of use. 48% of those study participants who had injected Subutex at some point reported having used it to cope with withdrawal or to give up other opioids. 90.5% of Subutex injectors used 1–2 mg as a single dose, and the mean frequency of its injection was 6 times per month. 75% of Subutex injectors had used 3 or more types of illegal drugs during the last 30 days. <i>Conclusion:</i> While widely misused by Georgian drug injectors, Subutex is neither the principal nor the favourite drug, and it is rather used as self-treatment. The authors consider the introduction of buprenorphine maintenance treatment to be a promising effective measure to decrease its non-medical and illegal use.