cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5123089
title: Supplementary Material for: <i>Staphylococcus aureus</i> Virulence Is Enhanced by Secreted Factors That Block Innate Immune Defenses

description: <i>Staphylococcus aureus</i> is a leading human pathogen that causes a large variety of diseases. In vitro studies have shown that <i>S. aureus</i> secretes several small proteins that block specific elements of the host innate immune system, but their role in bacterial pathogenicity is unknown. For instance, the extracellular complement-binding protein (Ecb) impairs complement activation by binding to the C3d domain of C3. Its homolog, the extracellular fibrinogen-binding protein (Efb), is known to block both complement activation and neutrophil adhesion to fibrinogen. Here, we show that targeted inactivation of the genes encoding Ecb and Efb strongly attenuates <i>S. aureus</i> virulence in a murine infection model: mice experienced significantly higher mortality rates upon intravenous infection with wild-type bacteria (79%) than with an isogenic ΔEcbΔEfb mutant (21%). In addition, Ecb and Efb are both required for staphylococcal persistence in host tissues and abscess formation in the kidneys (27% for wild-type vs. 7% for the ΔEcbΔEfb mutant). During staphylococcal pneumonia, Ecb and Efb together promote bacterial survival in the lungs (p = 0.03) and block neutrophil influx into the lungs. Thus, Ecb and Efb are essential to <i>S. aureus</i> virulence in vivo and could be attractive targets in future vaccine development efforts.
DOI: 10.6084/m9.figshare.5123095.v1
title: Supplementary Material for: Diagnosis of Neonatal Sepsis by Broad-Range 16S Real-Time Polymerase Chain Reaction

description: <i>Background:</i> The standard diagnostic test (blood culture) for suspected neonatal sepsis has limitations in sensitivity and specificity, and 16S polymerase chain reaction (PCR) has been suggested as a new diagnostic tool for neonatal sepsis. <i>Objectives:</i> To develop and evaluate a new real-time PCR method for detection of bacterial DNA in blood samples collected from infants with suspected neonatal sepsis. <i>Methods:</i> Immediately after blood culture, a study sample of 0.5–1.0 ml whole blood was collected and used for a novel 16S real-time PCR assay. All positive samples were sequenced. Detailed case studies were performed in all cases with conflicting results, to verify if PCR could detect pathogens in culture negative sepsis. <i>Results:</i> 368 samples from 317 infants were included. When compared with blood culture, the assay yielded a sensitivity of 79%, a specificity of 90%, a positive predictive value of 59%, and a negative predictive value of 96%. Seven of the 31 samples with a positive PCR result and a negative blood culture had definite or suspected bacterial sepsis. In five samples, PCR (but not blood culture) could detect a pathogen that was present in a blood culture collected more than 24 h prior to the PCR sample. <i>Conclusions:</i> This study presents an evaluation of a new real-time PCR technique that can detect culture-positive sepsis, and suggests that PCR has the potential to detect bacteria in culture-negative samples even after the initiation of intravenous antibiotics.
DOI: 10.6084/m9.figshare.5123092.v1
title: Supplementary Material for: Effects of 22-Oxa-Calcitriol on Podocyte Injury in Adriamycin-Induced Nephrosis

description: <i>Background:</i> In various animal studies, vitamin D has been shown to have a significant effect on reduction of proteinuria and the progression of kidney disease. However, little is known on its renoprotective effect in adriamycin (ADR)-induced nephrosis mice. The present study was intended to determine the therapeutic benefit of 22-oxa-calcitriol (OCT), a vitamin D analog, in reducing proteinuria and its renoprotective effect, i.e. preventing podocyte injury on ADR-induced nephrosis mice. <i>Methods:</i> Three experimental groups were used as follows: (1) nephrosis mice, established by a single intravenous injection of ADR; (2) ADR+OCT mice, nephrosis mice treated with OCT, and (3) mice treated only with OCT as the control group. Podocyte injury was assessed by podocyte apoptosis using the TUNEL assay, podocyte counting, podocyte-specific expressed protein by immunofluorescence and Western blot analysis, and foot process effacement using electron microscopy. <i>Results:</i> Lower proteinuria was observed in ADR+OCT mice. Improvement in glomerulosclerosis and interstitial fibrosis, and prevention of glomerular hyperfiltration were observed in ADR+OCT mice. Immunofluorescence and Western blot analyses showed restoration of downregulated expression of nephrin, CD2AP and podocin. Nevertheless, dendrin expression was not restored. An insignificant reduction in podocyte numbers was found in ADR+OCT mice. Complete foot process effacement was partially prevented in ADR+OCT mice. <i>Conclusions:</i> The results indicate that OCT reduces podocyte injury and has renoprotective effects in ADR nephrosis mice.
DOI: 10.6084/m9.figshare.5123098.v1
title: Supplementary Material for: Submicroscopic Deletion of <i>FGFR1</i> Gene Is Recurrently Detected in Myeloid and Lymphoid Neoplasms Associated with <i>ZMYM2-FGFR1</i> Rearrangements: A Case Study

description: Medicine
DOI: 10.6084/m9.figshare.5123080
title: Supplementary Material for: Loss of <i>R-Spondin1</i> and <i>Foxl2</i> Amplifies Female-to-Male Sex Reversal in XX Mice

description: In vertebrates, 2 main genetic pathways have been shown to regulate ovarian development. Indeed, a loss of function mutations in <i>Rspo1</i> and <i>Foxl2</i> promote partial female-to-male sex reversal. In mice, it has been shown that the secreted protein RSPO1 is involved in ovarian differentiation and the transcription factor FOXL2 is required for follicular formation. Here, we analysed the potential interactions between these 2 genetic pathways and have shown that while <i>Rspo1</i> expression seems to be independent of <i>Foxl2 </i>up-regulation, <i>Foxl2</i> expression partly depends of <i>Rspo1 </i>signalisation. This suggests that different <i>Foxl2</i>-positive somatic cell lineages exist within the ovaries. In addition, a combination of both mutated genes in XX <i>Foxl2</i><sup>–/–</sup><i>/Rspo1</i><sup>–/–</sup> gonads promotes sex reversal, detectable at earlier stages than in XX <i>Rspo1</i><sup>–/–</sup> mutants. Ectopic development of the steroidogenic lineage is more pronounced in XX <i>Foxl2</i><sup>–/–</sup><i>/Rspo1</i><sup>–/–</sup> gonads than in XX <i>Rspo1</i><sup>–/–</sup> embryos, suggesting that <i>Foxl2</i> is involved in preventing ectopic steroidogenesis in foetal ovaries.
DOI: 10.6084/m9.figshare.5123083
title: Supplementary Material for: Well-Differentiated Hand Liposarcoma with Bone Metastases Treated Successfully with Zoledronic Acid

description: <i>Background: </i>Well-differentiated liposarcomas of the upper extremities, such as the hand or forearm, are extremely rare and are commonly misdiagnosed and considered benign. They are frequently reported as having low metastatic potential. <i>Case Report: </i>We report the case of a 58-year-old man with well-differentiated hand liposarcoma and diffuse bone metastases. The patient initially presented with a tumor of the thenar eminence and was treated with marginal surgical excision and external beam irradiation. 4 months after this treatment, soft tissue local recurrence and skeletal metastases were detected. Zoledronic acid treatment (4 mg per month) was initiated, and both the tumor and the metastases regressed. The patient remains cancer-free 3.5 years after diagnosis of the metastatic disease. <i>Conclusion: </i>Significant metastatic disease can develop in patients with well-differentiated liposarcomas. The beneficial effect of zoledronic acid observed in this case may be related to its anticancer properties, as described in phase III trials in various tumor types.
DOI: 10.6084/m9.figshare.5123086
title: Supplementary Material for: Activity, Expression and Genetic Variation of Canine β-Defensin 103: A Multifunctional Antimicrobial Peptide in the Skin of Domestic Dogs

description: The skin functions as more than a physical barrier to infection. Epithelial cells of the skin can synthesize antimicrobial peptides, including defensins, which exhibit direct antimicrobial activity. Here we characterize the expression pattern, genetic variation and activity of the major β-defensin expressed in canine skin, canine β-defensin 103 (CBD103). The gene encoding CBD103 exhibits two forms of polymorphism: a common 3-basepair deletion allele and a gene copy-number variation. Golden retrievers and Labrador retrievers were the only breeds that encoded the variant allele of <i>CBD103,</i> termed <i>CBD103</i>Δ<i>G23</i>. Both these breeds also exhibited a <i>CBD103</i> gene copy-number polymorphism that ranged from 2 to 4 gene-copies per diploid genome. Recombinant CBD103 and CBD103ΔG23, as well as the human ortholog human β-defensin 3 (hBD3) and hBD3ΔG23, showed potent and comparable antimicrobial killing against both methicillin-susceptible and methicillin-resistant <i>Staphylococcus pseudintermedius</i>. Skin biopsy specimens from dogs with atopic dermatitis revealed <i>CBD103</i> expression levels similar to those in healthy controls and comparable at lesional and nonlesional sites. This expression pattern in dogs differs from the previously reported reduced expression of the human ortholog in atopic dermatitis. Overall, the similarities of CBD103 and its human ortholog reported here support the notion that the domestic dog may serve as a valuable model for studying β-defensin biology in the skin.
DOI: 10.6084/m9.figshare.5123074
title: Supplementary Material for: Biomarker Discovery in Serum from Patients with Carotid Atherosclerosis

description: <i>Background:</i> Blood-based biomarkers of atherosclerosis have been used to identify patients at high risk for developing stroke. We hypothesized that patients with carotid artery disease would have a distinctive proteomic signature in blood as compared to a healthy control population without carotid artery disease. In order to discover protein biomarkers associated with increased atherosclerotic risk, we used two different strategies to identify biomarkers from patients with clinically defined atherosclerosis who were undergoing endarterectomy for atherosclerotic carotid artery disease. These patients were compared with healthy matched controls. <i>Methods:</i> Serum was obtained from patients undergoing endarterectomy (EA; n = 38) and compared to a group of age-matched healthy controls (n = 40). Serum was fractionated using anion exchange chromatography and three different surface-enhanced laser desorption/ionization (SELDI) chip surfaces and then evaluated with mass spectrometry (MS) and two-dimensional difference gel electrophoresis (2D-DIGE). <i>Results:</i> A random forest (RF) analysis of the SELDI-MS protein peak data distinguished these two groups with 69.2% sensitivity and 73.2% specificity. Four unique SELDI peaks (4.2, 4.4, 16.7 and 28 kDa, all p&lt; 0.01) showed the greatest influence in the RF model. The EA patients with a history of prior clinical atherosclerotic plaque rupture manifested as either stroke or transient ischemic attack (symptomatic; n = 16) were compared to patients with carotid atherosclerosis but no clinical evidence of plaque rupture (asymptomatic; n = 22). Analysis of the SELDI spectra did not separate these two patient subgroups. A subgroup analysis using 2D-DIGE images obtained from albumin-depleted serum comparing symptomatic (n = 10) to asymptomatic EA patients (n = 10) found 4 proteins that were differentially expressed (p &lt; 0.01) in the symptomatic patients. These proteins were identified as α<sub>1</sub>-antitrypsin, haptoglobin and vitamin D binding protein that were downregulated and α<sub>2</sub>-glycoprotein precursor that was upregulated in the symptomatic EA group. <i>Conclusions:</i> SELDI-MS data analysis of fractionated serum suggests that a distinct protein signature exists in patients with carotid atherosclerosis compared to age-matched healthy controls. Identification of 4 proteins in a subset of patients with symptomatic and asymptomatic carotid atherosclerosis suggests that these and other protein biomarkers may assist in identifying high-risk patients with carotid atherosclerosis.
DOI: 10.6084/m9.figshare.5123077
title: Supplementary Material for: Expression Profiling of Wnt Signaling Genes during Gonadal Differentiation and Gametogenesis in Rainbow Trout

description: Wnt signaling plays major roles in various processes, including ovarian differentiation and development in mammals. In order to explore its potential implication during gonadal development in a nonmammalian vertebrate species, expression of Wnt signaling genes was investigated in rainbow trout during gonadal differentiation and gametogenesis. Multiple Wnt pathway genes were expressed and exhibited distinct expression patterns. In ovary, <i>tcf7</i> was highly expressed during early differentiation, whereas no sexually dimorphic expression of <i>rspo1</i> was detected. During later ovarian development,<i> wnt11</i> was highly expressed in granulosa cells and oocytes suggesting an implication in folliculogenesis and oogenesis, whereas <i>wnt9b</i> was principally detected in granulosa cells. In testis, Wnt pathway genes were mostly expressed during early spermatogenesis. Overall, these present results suggest that Wnt signaling is implicated in multiple processes of male and female gonadal development and provide basis for future studies on Wnt signaling functions in teleost fish gonads.
DOI: 10.6084/m9.figshare.5123086.v1
title: Supplementary Material for: Activity, Expression and Genetic Variation of Canine β-Defensin 103: A Multifunctional Antimicrobial Peptide in the Skin of Domestic Dogs

description: The skin functions as more than a physical barrier to infection. Epithelial cells of the skin can synthesize antimicrobial peptides, including defensins, which exhibit direct antimicrobial activity. Here we characterize the expression pattern, genetic variation and activity of the major β-defensin expressed in canine skin, canine β-defensin 103 (CBD103). The gene encoding CBD103 exhibits two forms of polymorphism: a common 3-basepair deletion allele and a gene copy-number variation. Golden retrievers and Labrador retrievers were the only breeds that encoded the variant allele of <i>CBD103,</i> termed <i>CBD103</i>Δ<i>G23</i>. Both these breeds also exhibited a <i>CBD103</i> gene copy-number polymorphism that ranged from 2 to 4 gene-copies per diploid genome. Recombinant CBD103 and CBD103ΔG23, as well as the human ortholog human β-defensin 3 (hBD3) and hBD3ΔG23, showed potent and comparable antimicrobial killing against both methicillin-susceptible and methicillin-resistant <i>Staphylococcus pseudintermedius</i>. Skin biopsy specimens from dogs with atopic dermatitis revealed <i>CBD103</i> expression levels similar to those in healthy controls and comparable at lesional and nonlesional sites. This expression pattern in dogs differs from the previously reported reduced expression of the human ortholog in atopic dermatitis. Overall, the similarities of CBD103 and its human ortholog reported here support the notion that the domestic dog may serve as a valuable model for studying β-defensin biology in the skin.
DOI: 10.6084/m9.figshare.5123074.v1
title: Supplementary Material for: Biomarker Discovery in Serum from Patients with Carotid Atherosclerosis

description: <i>Background:</i> Blood-based biomarkers of atherosclerosis have been used to identify patients at high risk for developing stroke. We hypothesized that patients with carotid artery disease would have a distinctive proteomic signature in blood as compared to a healthy control population without carotid artery disease. In order to discover protein biomarkers associated with increased atherosclerotic risk, we used two different strategies to identify biomarkers from patients with clinically defined atherosclerosis who were undergoing endarterectomy for atherosclerotic carotid artery disease. These patients were compared with healthy matched controls. <i>Methods:</i> Serum was obtained from patients undergoing endarterectomy (EA; n = 38) and compared to a group of age-matched healthy controls (n = 40). Serum was fractionated using anion exchange chromatography and three different surface-enhanced laser desorption/ionization (SELDI) chip surfaces and then evaluated with mass spectrometry (MS) and two-dimensional difference gel electrophoresis (2D-DIGE). <i>Results:</i> A random forest (RF) analysis of the SELDI-MS protein peak data distinguished these two groups with 69.2% sensitivity and 73.2% specificity. Four unique SELDI peaks (4.2, 4.4, 16.7 and 28 kDa, all p&lt; 0.01) showed the greatest influence in the RF model. The EA patients with a history of prior clinical atherosclerotic plaque rupture manifested as either stroke or transient ischemic attack (symptomatic; n = 16) were compared to patients with carotid atherosclerosis but no clinical evidence of plaque rupture (asymptomatic; n = 22). Analysis of the SELDI spectra did not separate these two patient subgroups. A subgroup analysis using 2D-DIGE images obtained from albumin-depleted serum comparing symptomatic (n = 10) to asymptomatic EA patients (n = 10) found 4 proteins that were differentially expressed (p &lt; 0.01) in the symptomatic patients. These proteins were identified as α<sub>1</sub>-antitrypsin, haptoglobin and vitamin D binding protein that were downregulated and α<sub>2</sub>-glycoprotein precursor that was upregulated in the symptomatic EA group. <i>Conclusions:</i> SELDI-MS data analysis of fractionated serum suggests that a distinct protein signature exists in patients with carotid atherosclerosis compared to age-matched healthy controls. Identification of 4 proteins in a subset of patients with symptomatic and asymptomatic carotid atherosclerosis suggests that these and other protein biomarkers may assist in identifying high-risk patients with carotid atherosclerosis.
DOI: 10.6084/m9.figshare.5123077.v1
title: Supplementary Material for: Expression Profiling of Wnt Signaling Genes during Gonadal Differentiation and Gametogenesis in Rainbow Trout

description: Wnt signaling plays major roles in various processes, including ovarian differentiation and development in mammals. In order to explore its potential implication during gonadal development in a nonmammalian vertebrate species, expression of Wnt signaling genes was investigated in rainbow trout during gonadal differentiation and gametogenesis. Multiple Wnt pathway genes were expressed and exhibited distinct expression patterns. In ovary, <i>tcf7</i> was highly expressed during early differentiation, whereas no sexually dimorphic expression of <i>rspo1</i> was detected. During later ovarian development,<i> wnt11</i> was highly expressed in granulosa cells and oocytes suggesting an implication in folliculogenesis and oogenesis, whereas <i>wnt9b</i> was principally detected in granulosa cells. In testis, Wnt pathway genes were mostly expressed during early spermatogenesis. Overall, these present results suggest that Wnt signaling is implicated in multiple processes of male and female gonadal development and provide basis for future studies on Wnt signaling functions in teleost fish gonads.
DOI: 10.6084/m9.figshare.5123080.v1
title: Supplementary Material for: Loss of <i>R-Spondin1</i> and <i>Foxl2</i> Amplifies Female-to-Male Sex Reversal in XX Mice

description: In vertebrates, 2 main genetic pathways have been shown to regulate ovarian development. Indeed, a loss of function mutations in <i>Rspo1</i> and <i>Foxl2</i> promote partial female-to-male sex reversal. In mice, it has been shown that the secreted protein RSPO1 is involved in ovarian differentiation and the transcription factor FOXL2 is required for follicular formation. Here, we analysed the potential interactions between these 2 genetic pathways and have shown that while <i>Rspo1</i> expression seems to be independent of <i>Foxl2 </i>up-regulation, <i>Foxl2</i> expression partly depends of <i>Rspo1 </i>signalisation. This suggests that different <i>Foxl2</i>-positive somatic cell lineages exist within the ovaries. In addition, a combination of both mutated genes in XX <i>Foxl2</i><sup>–/–</sup><i>/Rspo1</i><sup>–/–</sup> gonads promotes sex reversal, detectable at earlier stages than in XX <i>Rspo1</i><sup>–/–</sup> mutants. Ectopic development of the steroidogenic lineage is more pronounced in XX <i>Foxl2</i><sup>–/–</sup><i>/Rspo1</i><sup>–/–</sup> gonads than in XX <i>Rspo1</i><sup>–/–</sup> embryos, suggesting that <i>Foxl2</i> is involved in preventing ectopic steroidogenesis in foetal ovaries.
DOI: 10.6084/m9.figshare.5123083.v1
title: Supplementary Material for: Well-Differentiated Hand Liposarcoma with Bone Metastases Treated Successfully with Zoledronic Acid

description: <i>Background: </i>Well-differentiated liposarcomas of the upper extremities, such as the hand or forearm, are extremely rare and are commonly misdiagnosed and considered benign. They are frequently reported as having low metastatic potential. <i>Case Report: </i>We report the case of a 58-year-old man with well-differentiated hand liposarcoma and diffuse bone metastases. The patient initially presented with a tumor of the thenar eminence and was treated with marginal surgical excision and external beam irradiation. 4 months after this treatment, soft tissue local recurrence and skeletal metastases were detected. Zoledronic acid treatment (4 mg per month) was initiated, and both the tumor and the metastases regressed. The patient remains cancer-free 3.5 years after diagnosis of the metastatic disease. <i>Conclusion: </i>Significant metastatic disease can develop in patients with well-differentiated liposarcomas. The beneficial effect of zoledronic acid observed in this case may be related to its anticancer properties, as described in phase III trials in various tumor types.
DOI: 10.6084/m9.figshare.5123068
title: Supplementary Material for: Myocardial Strain Abnormalities in Fetal Congenital Heart Disease Assessed by Speckle Tracking Echocardiography

description: <b><i>Objectives:</i></b> To compare myocardial deformation patterns in fetuses with congenital heart disease (CHD) with our reference range using speckle tracking echocardiography. <b><i>Methods:</i></b> We prospectively stored and analyzed 4-chamber loops of 28 fetuses with CHD (median gestation 27 weeks, range 20.9–37.0). The peak longitudinal left (LVs) and right (RVs) ventricular free wall Lagrangian strain and LV/RV strain ratio were measured from Syngo VVI software- (Siemens) derived original coordinates. Strain values from the first examination were compared with normative data from the same population using ANOVA with post hoc tests and serial examinations described in 14 fetuses. <b><i>Results:</i></b> Simple shunt lesions (0.82) and shunts with pulmonary stenosis or atresia (0.93) had reduced mean LV/RV strain ratios compared to normal fetuses (1.01; 95% CI 0.97–1.05). Fetuses with hypoplastic left heart had the lowest (0.29), and those with Ebstein the highest (1.55), LV:RV ratio. Serial measurements showed increased LVs in aortic coarctation and aortic stenosis, but not in one developing important mitral regurgitation. Increased right ventricular loading in a fetus developing pulmonary regurgitation was associated with increasing RVs. <b><i>Conclusions:</i></b> Myocardial strain reflects the changing physiology of fetal CHD. Speckle tracking might be a useful tool to study the progress of myocardial function in affected fetuses.