cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5126713
title: Supplementary Material for: G-Protein-Coupled Receptor Cell Signaling Pathways Mediating Embryonic Chick Retinal Growth Cone Collapse Induced by Lysophosphatidic Acid and Sphingosine-1-Phosphate

description: In the development of the nervous system, one of the critical aspects is the proper navigation of axons to their targets, i.e. the problem of axonal guidance. We used the chick visual system as a model to investigate the role of the lysophospholipids lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) as potential axon guidance cues. We showed that both LPA and S1P cause a specific, dose-dependent growth cone collapse of retinal neurons in vitro in the chick model system, with slight differences compared to the mouse but very similar to observations in <i>Xenopus.</i> Because LPA and S1P receptors are G-protein-coupled receptors, we analyzed the intracellular signaling pathways using pharmacological inhibitors in chick retinal neurons. Blocking rho kinase (ROCK) prevented growth cone collapse by LPA and S1P, while blocking PLC or chelating calcium had no effect on growth cone collapse. Inhibition of G<sub>i/o</sub> with pertussis toxin resulted in a partial reduction of growth cone collapse, both with LPA and with S1P. Inhibition of p38 blocked growth cone collapse mediated by LPA but not S1P. Thus, in addition to the involvement of the G<sub>12/13</sub>-ROCK pathway, LPA- and S1P-induced collapse of chick retinal growth cones has a partial requirement for G<sub>i/o</sub>.
DOI: 10.6084/m9.figshare.5126701
title: Supplementary Material for: Unspecific Abdominal Symptoms and Pneumobilia: A Rare Case of Gastrointestinal Obstruction

description: The case of a 77-year-old woman with symptoms of gastric outlet obstruction is presented. Transabdominal ultrasonography findings were suspicious of Bouveret's syndrome. Upper endoscopy confirmed this diagnosis. Bouveret's syndrome is a rare complication of gallstone disease caused by a bilioenteric fistula leading to gastric outlet obstruction by a gallstone and should be suspected in any patient who presents with pneumobilia without recent endoscopic retrograde cholangiopancreatography or biliary surgery.
DOI: 10.6084/m9.figshare.5126704
title: Supplementary Material for: Duodenal Hemorrhage from Pancreatic Cancer Infiltration Controlled through Combination Therapy with Gemcitabine and S-1

description: 2.6% of pancreatic cancer patients have the primary manifestation of gastrointestinal bleeding. It is not feasible to stop the duodenal hemorrhage caused by the pancreatic cancer infiltration. A 43-year-old woman who was diagnosed as having pancreatic cancer with multiple hepatic metastases and duodenal infiltration was administered gemcitabine and S-1 combination therapy. During the chemotherapy, initially, bleeding occurred due to duodenal infiltration. However, we continued the chemotherapy and duodenal infiltration was markedly reduced in size and did not rebleed. Aggressive chemotherapy contributed to maintenance of performance status as well as improvement of quality of life for the patient.
DOI: 10.6084/m9.figshare.5126710
title: Supplementary Material for: Reduced ING4 Expression Is Associated with the Malignancy of Human Bladder

description: <b><i>Introduction:</i></b> Inhibitor of growth 4 (ING4) is a tumor suppressor. However the role of ING4 in human bladder malignancy is unknown. In this study, ING4 expression in human bladder cancer and its potential effects were studied. <b><i>Materials and Methods:</i></b> ING4 expression in 47 human bladder cancer tissues and paired adjacent normal tissues was detected by Western blotting, quantitative reverse transcription-polymerase chain reaction, and immunohistochemistry. The migration and cell cycle progression of SV-HUC-1 and T24 cells with aberrant ING4 expression were examined. <b><i>Results:</i></b> ING4 protein and mRNA were significantly decreased in bladder cancer tissues. ING4 protein level was significantly lower in the group of patients over 50 years of age. ING4 knockdown caused more rapid cell migration and increased the population of SV-HUC-1 and T24 cells in the G2-M phase. <b><i>Conclusion:</i></b> Our data suggest a close connection between aberrant ING4 expression and the carcinogenesis of human bladder cells. ING4 may be a potential target for bladder cancer chemotherapy.
DOI: 10.6084/m9.figshare.5126707.v1
title: Supplementary Material for: Are Respiratory Abnormalities Specific for Panic Disorder? A Meta-Analysis

description: <b><i>Objectives:</i></b> There is evidence of baseline respiratory abnormalities in panic disorder (PD), but whether they are specific to PD remains unclear. To investigate this issue, we meta-analyzed results from studies comparing baseline respiratory and hematic variables between subjects with PD and subjects with other anxiety disorders. <b><i>Methods:</i></b> A literature search in bibliographic databases was performed. Fixed-effects models were applied. Several moderator analyses and publication bias diagnostics were performed. <b><i>Results:</i></b> We found: (1) significantly lower mean end-tidal partial pressure of CO<sub>2</sub> (et-pCO<sub>2</sub>) in subjects with PD than in those with social phobia (SP) or generalized anxiety disorder (GAD), and (2) higher mean respiratory rate, lower venous et-pCO<sub>2</sub> and HCO<sub>3</sub><sup>-</sup> concentration in subjects with PD than in those with SP. No publication bias was found. <b><i>Conclusions:</i></b> Subjects with PD show a condition of baseline hyperventilation when compared to subjects with SP or GAD. Hematic variables suggest that the hyperventilation may be chronic. These results support the idea that baseline respiratory abnormalities are specific to PD pathophysiology. Further studies are needed to clarify whether these abnormalities are related to a malfunction of the respiratory system or to specific cognitive/emotional/behavioral factors in this population.
DOI: 10.6084/m9.figshare.5126710.v1
title: Supplementary Material for: Reduced ING4 Expression Is Associated with the Malignancy of Human Bladder

description: <b><i>Introduction:</i></b> Inhibitor of growth 4 (ING4) is a tumor suppressor. However the role of ING4 in human bladder malignancy is unknown. In this study, ING4 expression in human bladder cancer and its potential effects were studied. <b><i>Materials and Methods:</i></b> ING4 expression in 47 human bladder cancer tissues and paired adjacent normal tissues was detected by Western blotting, quantitative reverse transcription-polymerase chain reaction, and immunohistochemistry. The migration and cell cycle progression of SV-HUC-1 and T24 cells with aberrant ING4 expression were examined. <b><i>Results:</i></b> ING4 protein and mRNA were significantly decreased in bladder cancer tissues. ING4 protein level was significantly lower in the group of patients over 50 years of age. ING4 knockdown caused more rapid cell migration and increased the population of SV-HUC-1 and T24 cells in the G2-M phase. <b><i>Conclusion:</i></b> Our data suggest a close connection between aberrant ING4 expression and the carcinogenesis of human bladder cells. ING4 may be a potential target for bladder cancer chemotherapy.
DOI: 10.6084/m9.figshare.5126713.v1
title: Supplementary Material for: G-Protein-Coupled Receptor Cell Signaling Pathways Mediating Embryonic Chick Retinal Growth Cone Collapse Induced by Lysophosphatidic Acid and Sphingosine-1-Phosphate

description: In the development of the nervous system, one of the critical aspects is the proper navigation of axons to their targets, i.e. the problem of axonal guidance. We used the chick visual system as a model to investigate the role of the lysophospholipids lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) as potential axon guidance cues. We showed that both LPA and S1P cause a specific, dose-dependent growth cone collapse of retinal neurons in vitro in the chick model system, with slight differences compared to the mouse but very similar to observations in <i>Xenopus.</i> Because LPA and S1P receptors are G-protein-coupled receptors, we analyzed the intracellular signaling pathways using pharmacological inhibitors in chick retinal neurons. Blocking rho kinase (ROCK) prevented growth cone collapse by LPA and S1P, while blocking PLC or chelating calcium had no effect on growth cone collapse. Inhibition of G<sub>i/o</sub> with pertussis toxin resulted in a partial reduction of growth cone collapse, both with LPA and with S1P. Inhibition of p38 blocked growth cone collapse mediated by LPA but not S1P. Thus, in addition to the involvement of the G<sub>12/13</sub>-ROCK pathway, LPA- and S1P-induced collapse of chick retinal growth cones has a partial requirement for G<sub>i/o</sub>.
DOI: 10.6084/m9.figshare.5126695
title: Supplementary Material for: Congenital Adrenal Hyperplasia, Ovarian Failure and Ehlers-Danlos Syndrome due to a 6p Deletion

description: Cryptic deletions in balanced de novo translocations represent a frequent cause of abnormal phenotypes, including Mendelian diseases. In this study, we describe a patient with multiple congenital abnormalities, such as late-onset congenital adrenal hyperplasia (CAH), primary ovarian failure and Ehlers-Danlos syndrome (EDS), who carries a de novo t(6;14)(p21;q32) translocation. Genomic array analysis identified a cryptic 1.1-Mb heterozygous deletion, adjacent to the breakpoint on chromosome 6, extending from 6p21.33 to 6p21.32 and affecting 85 genes, including <i>CYP21A2,</i><i>TNXB</i> and <i>MSH5</i>. Multiplex ligation-dependent probe amplification analysis of the 6p21.3 region was performed in the patient and her family and revealed a 30-kb deletion in the patient's normal chromosome 6, inherited from her mother, resulting in homozygous loss of genes <i>CYP21A1P</i> and <i>C4B</i>. <i>CYP21A2 </i>sequencing showed that its promoter region was not affected by the 30-kb deletion, suggesting that the deletion of other regulatory sequences in the normal chromosome 6 caused a loss of function of the <i>CYP21A2</i> gene. EDS and primary ovarian failure phenotypes could be explained by the loss of genes <i>TNXB</i> and <i>MSH5</i>, a finding that may contribute to the characterization of disease-causing genes. The detection of this de novo microdeletion drastically reduced the estimated recurrence risk for CAH in the family.
DOI: 10.6084/m9.figshare.5126689
title: Supplementary Material for: Establishment and Characterization of Immortalized Gingival Epithelial and Fibroblastic Cell Lines for the Development of Organotypic Cultures

description: In vitro studies using 3D co-cultures of gingival cells can resemble their in vivo counterparts much better than 2D models that typically only utilize monolayer cultures with short-living primary cells. However, the use of 3D gingival models is still limited through lack of appropriate cell lines. We aimed to establish immortalized cell line models of primary human gingival epithelium keratinocytes (HGEK) and gingival fibroblasts (GFB). Immortalized cell lines (HGEK-16 and GFB-16) were induced by E6 and E7 oncoproteins of human papillomavirus. In addition, 3D multilayered organotypic cultures were formed by embedding GFB-16 cells within a collagen (Col) matrix and seeding of HGEK-16 cells on the upper surfaces. Cell growth was analyzed in both immortalized cell lines and their parental primary cells. The expression levels of cell type-specific markers, i.e. cytokeratin (CK) 10, CK13, CK16, CK18, CK19 for HGEK-16 and Col I and Col II for GFB-16, were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Expansion of the primary cultures was impeded at early passages, while the transformed immortalized cell lines could be expanded for more than 30 passages. In 3D cultures, immortalized HGEK formed a multilayer of epithelial cells. qRT-PCR showed that cell-specific marker expression in the 3D cultures was qualitatively and quantitatively closer to that in human gingival tissue than to monolayer cultures. These results indicate that immortalized gingival fibroblastic and epithelial cell lines can successfully form organotypic multilayered cultures and, therefore, may be useful tools for studying gingival tissue in vitro.
DOI: 10.6084/m9.figshare.5126692
title: Supplementary Material for: Duration of Gestation and Mode of Delivery Affect the Genes of Transepithelial Sodium Transport in Pulmonary Adaptation

description: <b><i>Background:</i></b> Respiratory distress due to inadequate lung liquid clearance is a significant problem in infants delivered late preterm or early term, especially by elective cesarean delivery (CD). Lung liquid clearance depends on epithelial ion transport and in animals is induced by glucocorticoids. <b><i>Objectives:</i></b> In newborn late preterm and term infants to study airway epithelial gene expressions of epithelial sodium channel (ENaC), and the serum and glucocorticoid-inducible kinase 1 (SGK1), and their association with cortisol, mode of delivery, and gestational age (GA). <b><i>Methods:</i></b> Infants were delivered at 35<sup>0/7</sup>-41<sup>6/7</sup> weeks. Cortisol in umbilical cord plasma was analyzed with liquid chromatography-tandem mass spectrometry. ENaC and SGK1 mRNAs in airway epithelial cells obtained within 3 h and at 1 day postnatally were quantified with real-time PCR. <b><i>Results:</i></b> ENaC and SGK1 mRNAs were significantly lower in late preterm and early term infants than in those ≥39<sup>0/7</sup> weeks. Significant correlations existed between both ENaC and SGK1 and cord cortisol and GA. In term infants, SGK1 mRNA at 1.5 h was higher after vaginal delivery than elective CD. <b><i>Conclusions:</i></b> In late preterm and early term infants, low expression of ENaC and SGK1 may parallel insufficient lung liquid clearance predisposing to respiratory distress. Lower SGK1 expression after term CD could translate into insufficient sodium and lung liquid absorption. The findings demonstrate a central role for cortisol in regulation of ENaC and potentially perinatal sodium and lung liquid clearance.
DOI: 10.6084/m9.figshare.5126698
title: Supplementary Material for: Evaluating Dissociated Optic Nerve Fiber Layer Appearance Using En Face Layer Imaging Produced by Optical Coherence Tomography

description: <b><i>Purpose:</i></b> To investigate the incidence of and risk factors for a dissociated optic nerve fiber layer (DONFL) appearance after pars plana vitrectomy (PPV). <b><i>Methods:</i></b> We retrospectively reviewed 189 eyes that underwent PPV with internal limiting membrane removal and judged the presence/absence of an apparent DONFL based on en face layer images produced by spectral-domain optical coherence tomography (SD-OCT). <b><i>Results:</i></b> An apparent DONFL was observed in 47 (24.9%) eyes. The incidence of an apparent DONFL was significantly higher in the macular hole (MH) group (76.5%) than in the non-MH group (epiretinal membrane, diabetic macular edema, retinal vein occlusion, and others; 4.9%; p &lt; 0.001). In the logistic regression analysis, surgical indication for MH was identified as the most significant DONFL risk factor (odds ratio 63.7; p = 1.05 × 10<sup>-8</sup>). <b><i>Conclusion:</i></b> Postoperative OCT en face layer imaging clarified that MH eyes are liable to have an apparent DONFL following PPV.
DOI: 10.6084/m9.figshare.5126686
title: Supplementary Material for: A New System Identification Approach to Identify Genetic Variants in Sequencing Studies for a Binary Phenotype

description: We propose in this paper a set-valued (SV) system model, which is a generalized form of logistic (LG) and Probit (Probit) regression, to be considered as a method for discovering genetic variants, especially rare genetic variants in next-generation sequencing studies, for a binary phenotype. We propose a new SV system identification method to estimate all underlying key system parameters for the Probit model and compare it with the LG model in the setting of genetic association studies. Across an extensive series of simulation studies, the Probit method maintained type I error control and had similar or greater power than the LG method, which is robust to different distributions of noise: logistic, normal, or t distributions. Additionally, the Probit association parameter estimate was 2.7-46.8-fold less variable than the LG log-odds ratio association parameter estimate. Less variability in the association parameter estimate translates to greater power and robustness across the spectrum of minor allele frequencies (MAFs), and these advantages are the most pronounced for rare variants. For instance, in a simulation that generated data from an additive logistic model with an odds ratio of 7.4 for a rare single nucleotide polymorphism with a MAF of 0.005 and a sample size of 2,300, the Probit method had 60% power whereas the LG method had 25% power at the α = 10<sup>-6</sup> level. Consistent with these simulation results, the set of variants identified by the LG method was a subset of those identified by the Probit method in two example analyses. Thus, we suggest the Probit method may be a competitive alternative to the LG method in genetic association studies such as candidate gene, genome-wide, or next-generation sequencing studies for a binary phenotype.
DOI: 10.6084/m9.figshare.5126680
title: Supplementary Material for: Diffusion Tensor Imaging, Intracranial Vascular Resistance and Cognition in Middle-Aged Asymptomatic Subjects

description: <b><i>Background:</i></b> The contribution of traditional vascular risk factors to cognitive impairment and dementia is well known. However, in order to obtain possible targets for prevention of vascular cognitive impairment (VCI), it may be important to identify other early and noninvasive markers in asymptomatic middle-aged adults. The calculation of middle cerebral artery-pulsatility index (MCA-PI) is an ultrasonologic, noninvasive, validated and easily reproducible technique to assess increased distal resistance to blood flow. This study aims to assess the relationship between MCA-PI, microstructural white matter (WM) integrity and cognition in a middle-aged asymptomatic population. <b><i>Methods:</i></b> Ninety-five participants from the Barcelona-Asymptomatic Intracranial Atherosclerosis (AsIA) neuropsychology study were included. Subjects were 50-65 years old, free from dementia and without history of vascular disease. Transcranial color-coded duplex ultrasound examination was performed to assess MCA-PI as a measure of vascular resistance. WM integrity was evaluated by fractional anisotropy (FA) measurements of diffusion tensor images (DTI) acquired on a 3T-MRI. The neuropsychological battery was specifically selected to be sensitive to VCI, and included tests that were grouped into six cognitive domains: executive functioning, attention, verbal fluency, memory, visuospatial skills and psychomotor speed. A multivariate linear regression model adjusted for age, gender, years of education, diabetes and hypertension was performed. <b><i>Results:</i></b> MCA-PI was significantly associated with WM disintegration in different tracts (fornix, corticospinal and anterior thalamic), all p &lt; 0.05 uncorrected. Both mean MCA-PI and mean FA of those significant tracts were independently associated with poor performance in attention, psychomotor speed, and visuospatial skills after adjustment for age, gender, years of education, and vascular risk factors (all p &lt; 0.05). MCA-PI was independently associated with lower scores in all cognitive domains, except for visuospatial skills. <b><i>Conclusions:</i></b> Our data suggest that MCA-PI may be related to WM disintegration and early vascular cognitive impairment in middle-aged subjects. Although further prospective studies are needed to provide evidence for its validity in longitudinal studies, our results support the proposal of including MCA-PI as part of clinical assessment in order to identify targets for VCI prevention.
DOI: 10.6084/m9.figshare.5126683
title: Supplementary Material for: Direct Evidence for Self-Propagation of Different Amyloid-β Fibril Conformations

description: <b><i>Background:</i></b> Amyloid fibrils formed by amyloid-β (Aβ) peptides are associated with Alzheimer's disease and can occur in a range of distinct morphologies that are not uniquely determined by the Aβ sequence. Whether distinct conformations of Aβ fibrils can be stably propagated over multiple cycles of seeding and fibril growth has not been established experimentally. <b><i>Objective:</i></b> The ability of the 40-residue peptide Aβ<sub>1-40</sub> to assemble into fibrils with the conformation of the mutant Aβ<sub>1-40</sub> peptide containing the ‘Osaka' mutation E22Δ was investigated. <b><i>Methods:</i></b> Fibril formation of highly pure, recombinant Aβ<sub>1-40</sub> in the presence of distinct, preformed seeds in vitro was recorded with thioflavin T fluorescence, and distinct fibrillar structures were identified and distinguished by fluorescence spectroscopy and electron microscopy. <b><i>Results:</i></b> We propagated the specific quaternary structure of Aβ<sub>1-40</sub> E22Δ fibrils with wild-type Aβ<sub>1-40</sub> over up to seven cycles of seeding and fibril elongation. As a result of a 10<sup>7</sup>-fold dilution of the initially present Aβ<sub>1-40</sub> E22Δ seeds, the vast majority of fibrils formed after the seventh propagation cycle with Aβ<sub>1-40</sub> did not contain a single molecule of Aβ<sub>1-40</sub> E22Δ, but still retained the conformation of the initial Aβ<sub>1-40</sub> E22Δ seeds. Increased critical concentrations of Aβ<sub>1-40</sub> fibrils formed in the presence of Aβ<sub>1-40</sub> E22Δ nuclei suggest that these fibrils are less stable than homologously seeded Aβ<sub>1-40</sub> fibrils, consistent with a kinetically controlled mechanism of fibril formation. <b><i>Conclusion:</i></b> The propagation of a distinct Aβ fibril conformation over multiple cycles of seeded fibril growth demonstrates the basic ability of the Aβ peptide to form amyloid strains that in turn may cause phenotypes in Alzheimer's disease.
DOI: 10.6084/m9.figshare.5126689.v1
title: Supplementary Material for: Establishment and Characterization of Immortalized Gingival Epithelial and Fibroblastic Cell Lines for the Development of Organotypic Cultures

description: In vitro studies using 3D co-cultures of gingival cells can resemble their in vivo counterparts much better than 2D models that typically only utilize monolayer cultures with short-living primary cells. However, the use of 3D gingival models is still limited through lack of appropriate cell lines. We aimed to establish immortalized cell line models of primary human gingival epithelium keratinocytes (HGEK) and gingival fibroblasts (GFB). Immortalized cell lines (HGEK-16 and GFB-16) were induced by E6 and E7 oncoproteins of human papillomavirus. In addition, 3D multilayered organotypic cultures were formed by embedding GFB-16 cells within a collagen (Col) matrix and seeding of HGEK-16 cells on the upper surfaces. Cell growth was analyzed in both immortalized cell lines and their parental primary cells. The expression levels of cell type-specific markers, i.e. cytokeratin (CK) 10, CK13, CK16, CK18, CK19 for HGEK-16 and Col I and Col II for GFB-16, were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Expansion of the primary cultures was impeded at early passages, while the transformed immortalized cell lines could be expanded for more than 30 passages. In 3D cultures, immortalized HGEK formed a multilayer of epithelial cells. qRT-PCR showed that cell-specific marker expression in the 3D cultures was qualitatively and quantitatively closer to that in human gingival tissue than to monolayer cultures. These results indicate that immortalized gingival fibroblastic and epithelial cell lines can successfully form organotypic multilayered cultures and, therefore, may be useful tools for studying gingival tissue in vitro.