cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5241157.v1
title: Erratum: Reduction of Arteriosclerotic Nanoplaque Formation and Size by n-3 Fatty Acids in Patients after Valvular Defect Operation

description: <i>Background/Methods: </i>Coating a silica surface with the isolated lipoprotein receptor heparan sulfate proteoglycan (HS-PG) from arterial endothelium and vascular matrices, we could observe the very earliest stages of arteriosclerotic plaque development by ellipsometric techniques in vitro (patent EP 0 946 876). This so-called nanoplaque formation is represented by the ternary aggregational complex of the HS-PG receptor, lipoprotein particles and calcium ions. The model was validated in several clinical studies on statins in cardiovascular high-risk patients applying their native blood lipoprotein fractions. <i>Results: </i>In 7 patients who had undergone a valvular defect operation, the reduction of arteriosclerotic nanoplaque formation in normal Krebs solution amounted to 6.1 ± 2.3% (p &lt; 0.0156) and of nanoplaque size to 37.5 ± 13.2% (p &lt; 0.0312), respectively, after a 3-month therapy with n-3 fatty acids (3 ··3 g daily, Ameu® 500 mg). Additionally, the quotient oxLDL/LDL was lowered by 6.8 ± 2.1% (p &lt; 0.0166), the MDA concentration remained unchanged and the lipoprotein(a) concentration decreased by 15.8 ± 5.6% (p &lt; 0.0469) in the patients’ blood. The concentration of the nanoplaque promoting particles VLDL and total triglycerides was diminished by 34.1 ± 11.6% (p &lt; 0.0469) and 26.7 ± 10.8% (p &lt; 0.0156), respectively. Furthermore, the ratio of the strongly atherogenic small dense to the total LDL cholesterol (LDL5+LDL6)/LDLtot decreased by 9.9 ± 3.0% (p &lt; 0.0174). <i>Conclusions: </i>A combinatorial regression analysis revealed a basis for a mechanistic explanation of nanoplaque reduction under n-3 fatty acid treatment. This effect was possibly due to the beneficial changes in lipid concentrations and an attenuation of the risk factors oxLDL/LDL and (LDL5+LDL6)/LDLtot.
DOI: 10.6084/m9.figshare.5241160.v1
title: Erratum: Phase IV Study of Bevacizumab in Combination with Infusional Fluorouracil, Leucovorin and Irinotecan (FOLFIRI) in First-Line Metastatic Colorectal Cancer

description: <i>Background:</i> Bevacizumab (Avastin®) significantly improves overall survival (OS) and progression-free survival (PFS) when combined with first-line irinotecan (IFL) plus bolus 5-fluorouracil (5-FU) and leucovorin (LV) in patients with metastatic colorectal cancer (CRC). This open-label, phase IV trial evaluated the efficacy and safety of first-line bevacizumab in combination with IFL and infusional 5-FU/LV (FOLFIRI). <i>Methods:</i> Two-hundred and nine treatment-naïve metastatic CRC patients were enrolled and received bevacizumab and FOLFIRI every 2 weeks. Treatment was continued until disease progression. The primary objective was PFS, with additional determinations of OS, response and toxicity. <i>Results:</i> Median PFS was 11.1 months and is comparable to that observed in published phase III and community-based trials using first-line bevacizumab plus FOLFIRI, and to phase III trials using bevacizumab in combination with bolus 5-FU/LV plus IFL. Median OS was 22.2 months. Overall response rate was 53.1% and the disease control rate 85.6%. Most adverse events were grade 1/2 and were manageable. The most common grade 3/4 adverse events (≥10%) were neutropenia, venous thromboembolic events, diarrhea, and fatigue. <i>Conclusion:</i> Bevacizumab combined with first-line FOLFIRI is an effective and well-tolerated therapy option for patients with metastatic CRC.
DOI: 10.6084/m9.figshare.5241163.v1
title: Erratum: Targeted Disruption of the Mouse <i>Npal3</i> Gene Leads to Deficits in Behavior, Increased IgE Levels, and Impaired Lung Function

description: The non-imprinted in Prader-Willi/Angelman syndrome (NIPA) proteins are highly conserved receptors or transporters. Translocation of <i>NIPA</i> genes were found in patients with Prader-Willi syndrome, and loss-of-function of the <i>NIPA1</i> gene was identified in hereditary spastic paraplegia. The family of NIPA-like domain containing (NPAL) proteins is closely related to the NIPA proteins, but to date nothing is known about their function. Here, we could demonstrate that both human <i>NPAL3 </i>and mouse <i>Npal3 </i>are ubiquitously expressed and encode highly conserved proteins. To further elucidate the function of the <i>Npal3</i> gene, knockout <i>(Npal3</i><sup>–/–</sup><i>)</i> mice were generated. Intensive phenotypic analyses revealed that disruption of the <i>Npal3</i> gene results in a pleiotropic phenotype. The function of the nervous system was impaired in both mutant males and females which could be demonstrated in behavioral tests. In addition, in <i>Npal3 </i>mutants the number of NK cells was decreased and changes in IgM, IgG<sub>2</sub>, and IgA were observed, indicating that the immune system is also affected. Interestingly, increased IgE levels as well as impaired lung functions were observed in mutant males but not in mutant females. It should be noted that the human <i>NPAL3</i> gene is located at 1p36.12→p35.1, and atopic diseases were previously linked to this genomic region. Thus, the <i>Npal3</i><sup>–/–</sup> mice could serve as a valuable model system for studying atopic diseases.
DOI: 10.6084/m9.figshare.5241148
title: Erratum: A Synergistic Association of ACE I/D and eNOS G894T Gene Variants with the Progression of Immunoglobulin A Nephropathy – A Pilot Study

description: <i>Background:</i> Individual variability in the natural history and response to therapy of immunoglobulin A nephropathy (IgAN) suggests a complex multifactorial pathogenesis. We investigated whether single nucleotide polymorphisms (SNPs) involved in the non-immunologic progression of renal disease are related with disease progression. <i>Methods:</i> This is a pilot historic cohort study of 64 Caucasian patients with biopsy-proven IgAN and a median follow-up of 70 months. Three SNPs of the renin-angiotensin system genes (angiotensin I converting enzyme insertion/deletion (ACE I/D), angiotensinogen (AGT) M235T, and angiotensin II type 1 receptor (AT<sub>1</sub>R) 1166A/C), 2 of the endothelial nitric oxide synthase (eNOS), 4a/b and G894T, and 1 of the bradykinin 1 receptor, G–699C, were genotyped. The primary outcome was ‘kidney survival’ defined as a 30% decrease of baseline creatinine clearance; annualized decrease of glomerular filtration rate was also calculated. <i>Results:</i> Proteinuria, histological lesions, and mean arterial pressure were related to an unfavorable outcome. The simultaneous presence of the DD and GG variants of the ACE and eNOS genes was related to an unfavorable outcome as compared with other combinations [hazard ratio ranging from 4.7 (95% CI 1.52–14.33) to 8.4 (95% CI 2.45–29.10)] after controlling for proteinuria, mean arterial pressure and baseline histological lesions. <i>Conclusion:</i> This study suggests that in our population with IgAN, an interaction between ACE and eNOS polymorphisms may be a prognostic factor for renal function deterioration.
DOI: 10.6084/m9.figshare.5241151
title: Erratum: Common Variable Immunodeficiency: Etiological and Treatment Issues

description: One of the great advances in clinical medicine was the recognition of the pleomorphism of the immune response and the multiple afferent and efferent limbs of antigen processing and responsiveness. A significant contribution to this understanding was derived from studies of human immunodeficiency states, including both inherited and acquired syndromes. Amongst these syndromes, one of the most common, and least understood, is common variable immune deficiency (CVID). CVID is a syndrome that leads to a reduction in serum immunoglobulins and complications including recurrent infections. Management includes immunoglobulin replacement therapy; however, patients with CVID are at risk for complications of exogenous immunoglobulin administration as well as CVID-associated diseases such as autoimmune processes and malignancies. To assess the current state of knowledge in the field, we performed a literature review of a total of 753 publications covering the period of 1968 until 2008. From this list, 189 publications were selected for discussion. In this review, we demonstrate that while the molecular basis of CVID in many cases remains incompletely understood, significant strides have been made and it is now clear that there is involvement of several pathways of immune activation, with contributions from both T and B cells. Furthermore, despite the current gaps in our knowledge of the molecular pathogenesis of the syndrome, there have been dramatic advances in management that have led to improved survival and significantly reduced morbidity in affected patients.
DOI: 10.6084/m9.figshare.5241154
title: Erratum: Involvement of the Mitochondrial Pathway in p53-Independent Apoptosis Induced by <i>p28GANK</i> Knockdown in Hep3B Cells

description: It is well known that <i>TP53</i> may mediate apoptosis triggered by anticancer drugs. However, accumulating evidence indicates that <i>TP53</i> may be inactivated by mutations and/or deletions in about 50% of human cancers and, as such, may lead to pronounced resistance to therapeutic agents. Thus, the development of new approaches to improve the efficiency of therapeutic agents in cancer cells harboring mutant <i>TP53</i> may have a significant impact on cancer treatment. It has been reported that knockdown by RNA interference (RNAi) of <i>p28GANK</i> (an alias of the gene <i>PSMD10</i>), a novel oncogene over-expressed in hepatocellular carcinoma (HCC), can induce apoptosis in HepG2, a <i>TP53</i>-intact HCC cell line. Because of the high frequency <i>TP53</i> mutations in HCC, it is relevant to know whether <i>p28GANK</i> knockdown-induced apoptosis is also operational in <i>TP53</i>-negative HCC cells. Here, we investigated Adsi<i>p28GANK</i>-induced apoptosis in the <i>TP53</i>-negative HCC cell line Hep3B. Our results indicate that <i>p28GANK</i>-knockdown induces the generation of reactive oxygen species (ROS), which in turn activates p38. Since p38 can signal to Bax, its activation may lead to mitochondrial transmembrane potential (Δψm) loss, cytochrome c release from mitochondria to cytosol, and caspase-9 activation, eventually triggering the mitochondrial pathway of apoptosis.
DOI: 10.6084/m9.figshare.5241145
title: Erratum: Ischemic Preconditioning Attenuates Renal Ischemia-Reperfusion Injury by Inhibiting Activation of IKKβ and Inflammatory Response

description: <i>Background:</i> Renal ischemia-reperfusion (I/R) injury is a major cause of acute renal failure (ARF). The transcription factor nuclear factor-κB (NF-κB) has been implicated as a key mediator of reperfusion injury. Activation of NF-κB is dependent upon the phosphorylation of its inhibitor, IκB, by the specific inhibitory κB kinase (IKK) subunit, IKKβ. We hypothesized that ischemic preconditioning (IPC) reduces acute renal damage following I/R injury by inhibiting activation of IKKβ. As neutrophil gelatinase-associated lipocalin (NGAL), an early predictive biomarker of acute kidney injury, is regulated by NF-κB, we approached the relationship between NGAL and IKKβ. <i>Method:</i> Thirty male Sprague-Dawley rats were randomly divided into 3 groups after right kidney nephrectomy. Group A rats were sham-operated controls. Group B rats were 45-min ischemic in the left renal artery while Group C rats were pre-treated with 3 cycles of 2-min ischemia and 5-min reperfusion. All the rats were sacrificed at 24 h after reperfusion. We harvested kidneys and serum to do further analysis, including histological and functional parameters, expressions of NGAL and IKKβ in renal tissues. <i>Results:</i> Compared with rats subjected to I/R injury, pre-treated rats had a significant decrease in serum creatinine level (Scr) and tubulointerstitial injury scores (Scr, 86.79 ± 12.98 vs. 205.89 ± 19.16 μmol/l, p &lt; 0.01; tubulointerstitial injury scores, 1.3 ± 0.48 vs. 3.8 ± 0.79, p &lt; 0.01). In addition, expressions of IKKβ (0.95 ± 0.21 vs. 1.74 ± 0.17, p &lt; 0.05) and NGAL (1.71 ± 0.032 vs. 2.66 ± 0.078, p &lt; 0.05) at renal tubule in pre-treated rats were attenuated significantly compared with rats subjected to ischemia-reperfusion injury. Moreover, our study showed that IKKβ and NGAL were in positive correlation (R = 0.965 &gt; R<sub>0.01</sub>(30) = 0.448, p &lt; 0.01). <i>Conclusions:</i> The evidence suggests that IKKβ may play a role in renal I/R injury and give rise to the generation of NGAL. It appears that IPC may attenuate renal injury and the expression of NGAL following acute I/R injury. IKKβ may offer a clinically accessible target for preventing renal injury following I/R.
DOI: 10.6084/m9.figshare.5241142
title: Erratum: Analysis of a Promoter Polymorphism in the SMDF Neuregulin 1 Isoform in Schizophrenia

description: <i>Background/Aims:</i> Neuregulin 1 (<i>NRG1</i>) is a positional candidate gene in schizophrenia (SZ). Two major susceptibility loci in the <i>NRG1</i> gene approximately one million nucleotides apart have been identified in genetic studies. Several candidate functional allelic variants have been described that might be involved in disease susceptibility. However, the findings are still preliminary. We recently mapped active promoters and other regulatory domains in several SZ and bipolar disorder (BD) candidate genes using ChIP-chip (chromatin immunoprecipitation hybridized to microarrays). One was the promoter for the <i>NRG1</i> isoform, <i>SMDF</i>, which maps to the 3′ end of the gene complex. Analysis of the SNP database revealed several polymorphisms within the approximate borders of the region immunoprecipitated in our ChIP-chip experiments, one of which is rs7825588. <i>Methods:</i> This SNP was analyzed in patients with SZ and BD and its effect on promoter function was assessed by electromobility gel shift assays and luciferase reporter constructs. <i>Results:</i> A significant increase in homozygosity for the minor allele was found in patients with SZ (genotype distribution χ<sup>2</sup> = 7.32, p = 0.03) but not in BD (genotype distribution χ<sup>2</sup> = 0.52, p = 0.77). Molecular studies demonstrated modest, but statistically significant allele-specific differences in protein binding and promoter function. <i>Conclusion:</i> The findings suggest that homozygosity for rs725588 could be a risk genotype for SZ.
DOI: 10.6084/m9.figshare.5241148.v1
title: Erratum: A Synergistic Association of ACE I/D and eNOS G894T Gene Variants with the Progression of Immunoglobulin A Nephropathy – A Pilot Study

description: <i>Background:</i> Individual variability in the natural history and response to therapy of immunoglobulin A nephropathy (IgAN) suggests a complex multifactorial pathogenesis. We investigated whether single nucleotide polymorphisms (SNPs) involved in the non-immunologic progression of renal disease are related with disease progression. <i>Methods:</i> This is a pilot historic cohort study of 64 Caucasian patients with biopsy-proven IgAN and a median follow-up of 70 months. Three SNPs of the renin-angiotensin system genes (angiotensin I converting enzyme insertion/deletion (ACE I/D), angiotensinogen (AGT) M235T, and angiotensin II type 1 receptor (AT<sub>1</sub>R) 1166A/C), 2 of the endothelial nitric oxide synthase (eNOS), 4a/b and G894T, and 1 of the bradykinin 1 receptor, G–699C, were genotyped. The primary outcome was ‘kidney survival’ defined as a 30% decrease of baseline creatinine clearance; annualized decrease of glomerular filtration rate was also calculated. <i>Results:</i> Proteinuria, histological lesions, and mean arterial pressure were related to an unfavorable outcome. The simultaneous presence of the DD and GG variants of the ACE and eNOS genes was related to an unfavorable outcome as compared with other combinations [hazard ratio ranging from 4.7 (95% CI 1.52–14.33) to 8.4 (95% CI 2.45–29.10)] after controlling for proteinuria, mean arterial pressure and baseline histological lesions. <i>Conclusion:</i> This study suggests that in our population with IgAN, an interaction between ACE and eNOS polymorphisms may be a prognostic factor for renal function deterioration.
DOI: 10.6084/m9.figshare.5241154.v1
title: Erratum: Involvement of the Mitochondrial Pathway in p53-Independent Apoptosis Induced by <i>p28GANK</i> Knockdown in Hep3B Cells

description: It is well known that <i>TP53</i> may mediate apoptosis triggered by anticancer drugs. However, accumulating evidence indicates that <i>TP53</i> may be inactivated by mutations and/or deletions in about 50% of human cancers and, as such, may lead to pronounced resistance to therapeutic agents. Thus, the development of new approaches to improve the efficiency of therapeutic agents in cancer cells harboring mutant <i>TP53</i> may have a significant impact on cancer treatment. It has been reported that knockdown by RNA interference (RNAi) of <i>p28GANK</i> (an alias of the gene <i>PSMD10</i>), a novel oncogene over-expressed in hepatocellular carcinoma (HCC), can induce apoptosis in HepG2, a <i>TP53</i>-intact HCC cell line. Because of the high frequency <i>TP53</i> mutations in HCC, it is relevant to know whether <i>p28GANK</i> knockdown-induced apoptosis is also operational in <i>TP53</i>-negative HCC cells. Here, we investigated Adsi<i>p28GANK</i>-induced apoptosis in the <i>TP53</i>-negative HCC cell line Hep3B. Our results indicate that <i>p28GANK</i>-knockdown induces the generation of reactive oxygen species (ROS), which in turn activates p38. Since p38 can signal to Bax, its activation may lead to mitochondrial transmembrane potential (Δψm) loss, cytochrome c release from mitochondria to cytosol, and caspase-9 activation, eventually triggering the mitochondrial pathway of apoptosis.
DOI: 10.6084/m9.figshare.5241139
title: Erratum: Induced Endothelial Cells Enhance Osteogenesis and Vascularization of Mesenchymal Stem Cells

description: Adequate vascularization remains one of the major challenges in bone tissue engineering. Since the microvascular endothelium is of benefit to osteogenesis and vascularization when in direct contact with bone marrow mesenchymal stem cells (BM-MSCs), we investigated whether endothelial cells induced from BM-MSCs have the same effect on BM-MSCs in vitro and in vivo. BM-MSCs were isolated, characterized and induced into endothelial-like cells (induced endothelial cells, IECs) in endothelial cell growth medium 2. BM-MSCs and IECs were co-cultured with direct contact. In vitro, IECs were evaluated in terms of their characteristics of endothelial cells and their effects on the osteogenic potential of BM-MSCs by cell morphology, immunofluorescent staining, alkaline phosphatase activity and osteocalcin synthesis. In vivo, scaffolds consisting of β-tricalcium phosphate co-seeded with IECs and BM-MSCs were transplanted into mouse dorsal pockets, and a histological analysis was performed to determine the extent of new bone and blood vessel formation. Isolated BM-MSCs were positive for the markers CD105 and CD29 and negative for hematopoietic markers CD34, CD45 and CD14. They were able to differentiate into adipocytes, osteocytes and chondrocytes in respective media. Immunofluorescent analysis with von Willebrand factor and CD31 staining showed that BM-MSCs could differentiate into endothelial cells. The alkaline phosphatase activity and the osteocalcin content of the co-culture group were obviously higher than those of any other group (p &lt; 0.05). Histologically, newly formed bone and vessels were more evident in the culture group (p &lt; 0.05). Our findings suggest that IECs could efficiently stimulate the in vitro differentiation of osteoblast-like cells and promote osteogenesis in vivo by direct contact with BM-MSCs.
DOI: 10.6084/m9.figshare.5241142.v1
title: Erratum: Analysis of a Promoter Polymorphism in the SMDF Neuregulin 1 Isoform in Schizophrenia

description: <i>Background/Aims:</i> Neuregulin 1 (<i>NRG1</i>) is a positional candidate gene in schizophrenia (SZ). Two major susceptibility loci in the <i>NRG1</i> gene approximately one million nucleotides apart have been identified in genetic studies. Several candidate functional allelic variants have been described that might be involved in disease susceptibility. However, the findings are still preliminary. We recently mapped active promoters and other regulatory domains in several SZ and bipolar disorder (BD) candidate genes using ChIP-chip (chromatin immunoprecipitation hybridized to microarrays). One was the promoter for the <i>NRG1</i> isoform, <i>SMDF</i>, which maps to the 3′ end of the gene complex. Analysis of the SNP database revealed several polymorphisms within the approximate borders of the region immunoprecipitated in our ChIP-chip experiments, one of which is rs7825588. <i>Methods:</i> This SNP was analyzed in patients with SZ and BD and its effect on promoter function was assessed by electromobility gel shift assays and luciferase reporter constructs. <i>Results:</i> A significant increase in homozygosity for the minor allele was found in patients with SZ (genotype distribution χ<sup>2</sup> = 7.32, p = 0.03) but not in BD (genotype distribution χ<sup>2</sup> = 0.52, p = 0.77). Molecular studies demonstrated modest, but statistically significant allele-specific differences in protein binding and promoter function. <i>Conclusion:</i> The findings suggest that homozygosity for rs725588 could be a risk genotype for SZ.
DOI: 10.6084/m9.figshare.5241136
title: Erratum: Reexamination of Caries and Fluorosis Experience of Children in an Area of Jamaica with Relatively High Fluorosis Prevalence

description: The aim of this cross-sectional study was to reexamine in 2006 caries and fluorosis experience among 5- to 6- and 11- to 12-year-olds (n = 789) in St. Elizabeth, Jamaica, an area found to have a high prevalence of dental fluorosis in 1999. Mean (± SD) dmft/DMFT scores were 2.4 ± 3.1 (n = 275) and 2.2 ± 2.3 (n = 133), fluorosis prevalence (tooth surface index of dental fluorosis &gt;0) of upper central incisors was 67% (n = 109) and 39% (n = 132) among 6- and 12-year-olds, respectively. Results indicate slightly reduced caries experience for 6-year-olds compared to 1999. Fluorosis prevalence was high particularly in 6-year-olds. Thus, risks and benefits from use of fluorides from multiple sources should be monitored carefully.