cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5121601.v1
title: Supplementary Material for: Treatment of Growth Hormone-Deficient Infants with Recombinant Human Growth Hormone to Near-Adult Height: Patterns of Growth

description: <i>Background/Aims:</i> To determine adult statures and linear growth patterns of children with growth hormone deficiency (GHD) who began treatment with recombinant human growth hormone (rhGH) in infancy. <i>Methods:</i> Forty-seven patients with GHD in whom administration of rhGH was initiated at or before 2 years of age and who had achieved near-adult heights (NAH) were identified in the database of the Genentech National Cooperative Growth Study. <i>Results:</i> After beginning treatment at a mean age of 0.9 years and height of –2.3 SD, these subjects achieved mean statures of –0.6, –0.3, and –0.4 SD at 5 and 10 years of age and at NAH, respectively. In 23 patients whose parental heights were known, mean NAH was comparable to the target height. Patients with uncomplicated courses whose heights were normal or tall when spontaneous puberty occurred or was induced realized the tallest NAHs. Patients with severe prenatal or perinatal, congenital and acquired neurologic insults, sexual precocity, or associated illnesses achieved less optimal NAHs. <i>Conclusion:</i> A normal pattern of linear growth during childhood and adolescence and satisfactory NAHs can be achieved in the majority of patients when treatment of the GHD subject is begun during infancy.
DOI: 10.6084/m9.figshare.5121610.v1
title: Supplementary Material for: An Exploratory Study on the <i>CHRNA3-CHRNA5-CHRNB4 </i>Cluster, Smoking, and Parkinson’s Disease

description: <i>Background:</i> Smokers have a lower risk of Parkinson’s disease (PD). Recent genome-wide association studies (GWAS) have consistently linked several single nucleotide polymorphisms (SNPs) in the <i>CHRNA3-CHRNA5-CHRNB4</i> cluster on chromosome 15.q25 to smoking behaviors and nicotine dependence. Investigations into these SNPs may help explain the nature and mechanisms of the smoking-PD relationship. <i>Objective:</i> To examine whether the genetic variations that were consistently associated with smoking or nicotine dependence in recent GWAS also predict the risk of PD. <i>Methods:</i> This is a population-based case-control study of 788 physician-diagnosed PD patients and 911 controls, all non-Hispanic Whites. Seven SNPs were selected based on findings from recent GWAS on smoking and nicotine dependence, all from the nicotinic acetylcholine receptor subunits <i>(CHRN)</i> A3-A5-B4. Odds ratios (ORs) and 95% confidence intervals were derived from logistic regression models under the assumption of logit-additive allelic effects. <i>Results:</i> Four SNPs in linkage disequilibrium from the <i>CHRNA3-CHRNA5-CHRNB4</i> cluster were associated with smoking duration (OR &gt;1.3, p &lt; 0.05). However, none of the SNPs from this cluster was associated with PD risk in the overall analysis or after stratifying on smoking status. <i>Conclusion:</i> This preliminary analysis does not support a relationship between these smoking-related GWAS SNPs and PD.
DOI: 10.6084/m9.figshare.5121592
title: Supplementary Material for: Localization of the Invadopodia-Related Proteins Actinin-1 and Cortactin to Matrix-Contact-Side Cytoplasm of Cancer Cells in Surgically Resected Lung Adenocarcinomas

description: <i>Objectives:</i> Actin-associated proteins at cell-matrix-contact sites form invadopodia in cancer cells and participate in migration, matrix degradation and invasion. We investigated an alteration of subcellular localization of invadopodia-related actin-associated proteins, actinin-1 and cortactin, in lung adenocarcinomas, its clinical significance, and its possible regulatory factors. <i>Methods:</i> Invadopodia-related proteins, actinin-1 and cortactin, were immunohistochemically examined in 90 cases of lung adenocarcinomas. Expression of invadopodia-associated proteins and their possible regulators in lung adenocarcinomas were examined by real-time RT-PCR, database search, and immunohistochemistry. <i>Results:</i> Actinin-1 and cortactin showed matrix-contact-side localization in adenocarcinoma cells, but rarely in normal bronchiolar epithelial cells, alveolar cells, or precursor lesion atypical adenomatous hyperplasia cells. Immunoelectron-microscopic examination of adenocarcinoma cells revealed actinin-1 localization to matrix-contact-side cytoplasm with cytoplasmic protrusions. Matrix-contact-side localization of actinin-1 and cortactin was correlated with tumor stages, lymph node metastasis, vascular permeation, and loss of basement membrane. The tumor-specific survival rate was worse for the group in which matrix-contact-side localization of cortactin was high than for the low group. mRNA of the Rho guanine exchange factor epithelial cell transforming sequence-2 (Ect2) tended to be overexpressed in lung adenocarcinomas and cytoplasmic expression of Ect2 tended to be correlated with matrix-contact-side localization of actinin-1. <i>Conclusion:</i> Matrix-contact-side localization of invadopodia-related proteins in the lung adenocarcinoma cells were correlated with invasion, metastasis, and poor prognosis. Ect2 was a possible regulator of matrix-contact-side localization of invadopodia-related proteins.
DOI: 10.6084/m9.figshare.5121598
title: Supplementary Material for: Establishment of a Chronic Rejection Model for Orthotopic Liver Transplantation in the Rat

description: <i>Background:</i> This study aims to establish a stable chronic rejection model for orthotopic liver transplantation in the rat and to describe the pathological features of this model. <i>Methods:</i> The livers from different strains of rats were transplanted in various allogeneic donor-recipient combinations with appropriate syngeneic grafts used as controls. The rats were untreated after surgery (acute rejection model) or treated with cyclosporin A (1 mg/kg) and hydrocortisone (0.75 mg/kg) to establish chronic rejection as determined by rejection activity index scores from pathological examination of liver specimens. <i>Results:</i> Acute rejection occurred in all of the untreated recipients of allogeneic orthotopic liver transplants, and all died within 30 days. Among the treated recipients, the combinations of Lewis with brown Norway and dark agouti with Lewis rats developed acute rejection, and no changes characteristic of chronic rejection were observed in the few rats that survived beyond 30 days. In contrast, the treated Lewis recipients of livers from Sprague-Dawley rats exhibited chronic rejection in the liver specimens. <i>Conclusion:</i> We have established an animal model for chronic rejection after transplantation of livers from Sprague-Dawley to Lewis rats under short-term immunosuppression induced by small doses of cyclosporin A and hydrocortisone.
DOI: 10.6084/m9.figshare.5121586
title: Supplementary Material for: Visualization of Fine-Scale Genomic Structure by Oligonucleotide-Based High-Resolution FISH

description: The discovery of complex structural variations that exist within individual genomes has prompted a need to visualize chromosomes at a higher resolution than previously possible. To address this concern, we established a robust, high-resolution fluorescence in situ hybridization (FISH) method that utilizes probes derived from high complexity libraries of long oligonucleotides (&gt;150 mers) synthesized in massively parallel reactions. In silico selected oligonucleotides, targeted to only the most informative elements in 18 genomic regions of interest, eliminated the need for suppressive hybridization reagents. Because of the inherent flexibility in our probe design methods, we readily visualized regions as small as 6.7 kb with high specificity on human metaphase chromosomes, resulting in an overall success rate of 94%. Two-color FISH over a 479-kb duplication, initially reported as being identical in 2 individuals, revealed distinct 2-color patterns representing direct and inverted duplicons, demonstrating that visualization by high-resolution FISH provides further insight in the fine-scale complexity of genomic structures. The ability to design FISH probes for any sequenced genome along with the ease, reproducibility, and high level of accuracy of this technique suggests that it will be powerful for routine analysis of previously difficult genomic regions and structures.
DOI: 10.6084/m9.figshare.5121595
title: Supplementary Material for: Novel Variant Ph Translocation t(9;22;11)(q34;q11.2;p15)inv(9)(p13q34) in Chronic Myeloid Leukemia Involving a One-Step Mechanism

description: Chronic myeloid leukemia (CML) is a clonal malignant disorder of a pluripotent hematopoietic stem cell characterized by the presence of a Philadelphia (Ph) chromosome. Less than 10% of patients present variant Ph chromosomes involving 1 or more additional chromosomes, other than chromosomes 9 and 22, with uncertain prognosis. There are mainly 1- or 2-step mechanisms proposed to explain the genesis of variant Ph chromosomes depending on whether the involved chromosomes are simultaneously broken and rejoined or if a standard t(9;22) occurs first. By combined standard cytogenetic and FISH analysis we detected a novel variant Ph translocation among chromosomes 9, 11 and 22 in a patient with CML without progression to an accelerated phase of the disease after 7 years, with the derivative chromosome 9 also having an acquired pericentric inversion. This novel case illustrates the use of FISH in metaphase to confirm a new rearrangement not previously described in variant Ph formation and that the present karyotype could have originated by a 1-step mechanism with 4 simultaneous breakages without deletion of <i>ABL1</i>.
DOI: 10.6084/m9.figshare.5121598.v1
title: Supplementary Material for: Establishment of a Chronic Rejection Model for Orthotopic Liver Transplantation in the Rat

description: <i>Background:</i> This study aims to establish a stable chronic rejection model for orthotopic liver transplantation in the rat and to describe the pathological features of this model. <i>Methods:</i> The livers from different strains of rats were transplanted in various allogeneic donor-recipient combinations with appropriate syngeneic grafts used as controls. The rats were untreated after surgery (acute rejection model) or treated with cyclosporin A (1 mg/kg) and hydrocortisone (0.75 mg/kg) to establish chronic rejection as determined by rejection activity index scores from pathological examination of liver specimens. <i>Results:</i> Acute rejection occurred in all of the untreated recipients of allogeneic orthotopic liver transplants, and all died within 30 days. Among the treated recipients, the combinations of Lewis with brown Norway and dark agouti with Lewis rats developed acute rejection, and no changes characteristic of chronic rejection were observed in the few rats that survived beyond 30 days. In contrast, the treated Lewis recipients of livers from Sprague-Dawley rats exhibited chronic rejection in the liver specimens. <i>Conclusion:</i> We have established an animal model for chronic rejection after transplantation of livers from Sprague-Dawley to Lewis rats under short-term immunosuppression induced by small doses of cyclosporin A and hydrocortisone.
DOI: 10.6084/m9.figshare.5121589
title: Supplementary Material for: The CD6 Scavenger Receptor Is Differentially Expressed on a CD56<sup>dim</sup> Natural Killer Cell Subpopulation and Contributes to Natural Killer-Derived Cytokine and Chemokine Secretion

description: The CD6 scavenger receptor is known to be expressed on virtually all T cells and is supposed to be involved in costimulation, synapse formation, thymic selection and leukocyte migration. Here, we demonstrate that CD6 is differentially expressed by a subpopulation of peripheral CD56<sup>dim</sup> natu- ral killer (NK) cells and absent on CD56<sup>bright</sup> NK cells. CD56<sup>dim</sup>CD16<sup>+</sup> cells represent the major NK subset in the periphery, and most cells within this group are positive for CD6. Most killer immunoglobulin-like receptor- and immunoglobulin-like transcript-positive cells also belong to the CD6<sup>+</sup> subpopulation, as expected from their restricted expression on CD56<sup>dim</sup> NK cells. In addition, CD6<sup>+</sup> NK cells are similar to the newly identified CD94<sup>low</sup>CD56<sup>dim</sup> NK subpopulation and most distant from the recently defined CD27<sup>+</sup> NK subpopulation based on the reverse correlation of expression between CD6 and CD27, a marker associated primarily with CD56<sup>bright</sup> NK cells. With respect to CD6 function on NK cells, direct CD6 triggering did not result in degranulation but induced secretion of cytokines (interferon-γ and tumor necrosis factor-α) and chemokines [CXCL10 (IP-10), CXCL1 (GRO-α)]. Thus, CD6 expression on peripheral NK cells marks a novel CD56<sup>dim</sup> subpopulation associated with distinct patterns of cytokine and chemokine secretion.
DOI: 10.6084/m9.figshare.5121595.v1
title: Supplementary Material for: Novel Variant Ph Translocation t(9;22;11)(q34;q11.2;p15)inv(9)(p13q34) in Chronic Myeloid Leukemia Involving a One-Step Mechanism

description: Chronic myeloid leukemia (CML) is a clonal malignant disorder of a pluripotent hematopoietic stem cell characterized by the presence of a Philadelphia (Ph) chromosome. Less than 10% of patients present variant Ph chromosomes involving 1 or more additional chromosomes, other than chromosomes 9 and 22, with uncertain prognosis. There are mainly 1- or 2-step mechanisms proposed to explain the genesis of variant Ph chromosomes depending on whether the involved chromosomes are simultaneously broken and rejoined or if a standard t(9;22) occurs first. By combined standard cytogenetic and FISH analysis we detected a novel variant Ph translocation among chromosomes 9, 11 and 22 in a patient with CML without progression to an accelerated phase of the disease after 7 years, with the derivative chromosome 9 also having an acquired pericentric inversion. This novel case illustrates the use of FISH in metaphase to confirm a new rearrangement not previously described in variant Ph formation and that the present karyotype could have originated by a 1-step mechanism with 4 simultaneous breakages without deletion of <i>ABL1</i>.
DOI: 10.6084/m9.figshare.5121583
title: Supplementary Material for: Cognitive Function and Dialysis Adequacy: No Clear Relationship

description: <i>Background/Aims:</i> Cognitive impairment is common in hemodialysis patients and may be impacted by multiple patient and treatment characteristics. The impact of dialysis dose on cognitive function remains uncertain, particularly in the current era of increased dialysis dose and flux. <i>Methods:</i> We explored the cross-sectional relationship between dialysis adequacy and cognitive function in a cohort of maintenance hemodialysis patients. Adequacy was defined as the average of the 3 most proximate single pool Kt/V assessments. A detailed neurocognitive battery was administered during the 1st hour of dialysis. Multivariable linear regression models were adjusted for age, sex, education, race and other clinical and demographic characteristics. <i>Results:</i> Among 273 patients who underwent cognitive testing, the mean (SD) age was 63 (17) years and the median dialysis duration was 13 months, 47% were woman, 22% were African American, and 48% had diabetes. The mean (SD) Kt/V was 1.51 (0.24). In univariate, parsimonious and multivariable models, there were no significant relationships between decreased cognitive function and lower Kt/V. <i>Conclusion:</i> In contrast to several older studies, there is no association between lower Kt/V and worse cognitive performance in the current era of increased dialysis dose. Future studies should address the longitudinal relationship between adequacy of dialysis and cognitive function to confirm these findings.
DOI: 10.6084/m9.figshare.5121586.v1
title: Supplementary Material for: Visualization of Fine-Scale Genomic Structure by Oligonucleotide-Based High-Resolution FISH

description: The discovery of complex structural variations that exist within individual genomes has prompted a need to visualize chromosomes at a higher resolution than previously possible. To address this concern, we established a robust, high-resolution fluorescence in situ hybridization (FISH) method that utilizes probes derived from high complexity libraries of long oligonucleotides (&gt;150 mers) synthesized in massively parallel reactions. In silico selected oligonucleotides, targeted to only the most informative elements in 18 genomic regions of interest, eliminated the need for suppressive hybridization reagents. Because of the inherent flexibility in our probe design methods, we readily visualized regions as small as 6.7 kb with high specificity on human metaphase chromosomes, resulting in an overall success rate of 94%. Two-color FISH over a 479-kb duplication, initially reported as being identical in 2 individuals, revealed distinct 2-color patterns representing direct and inverted duplicons, demonstrating that visualization by high-resolution FISH provides further insight in the fine-scale complexity of genomic structures. The ability to design FISH probes for any sequenced genome along with the ease, reproducibility, and high level of accuracy of this technique suggests that it will be powerful for routine analysis of previously difficult genomic regions and structures.
DOI: 10.6084/m9.figshare.5121571
title: Supplementary Material for: Pregabalin Antagonizes Copper-Induced Toxicity in the Brain: In vitro and in vivo Studies

description: <i>Background:</i> Copper plays key roles in brain metabolism. Disorders of copper metabolism impact on neural signaling. The intracellular and extracellular concentrations of copper are tightly regulated. Pregabalin is a drug with multiple modes of action and has a high-affinity binding site for the alpha2delta subunit of voltage-gated calcium channels. <i>Methods:</i> Assessment of neuroprotective effects of pregabalin using cell culture, transcription studies, microdialysis and neurophysiological assessment in rats. <i>Results:</i> In vitro, copper decreased markedly the survival of neuronal cells and enhanced the production of nitric oxide (NO). Transcription of NO synthase (NOS) 1–3 and PGC-1a (a key regulator of mitochondrial biogenesis) was activated. In vivo, copper impaired the NMDA-mediated regulation of glutamate in the brain, increased the production of NO and enhanced markedly the excitability of the motor cortex. Pregabalin had antagonistic effects both in vitro and in vivo. <i>Conclusion:</i> Our experiments highlight that pregabalin antagonizes the neurotoxic effects of copper. We argue that pregabalin exerts neuroprotective effects by silencing the overexcitability state induced by copper. We propose a possible use of pregabalin for treatment of disruption of copper homeostasis.
DOI: 10.6084/m9.figshare.5121574
title: Supplementary Material for: ‘Executive’ Functions and Normal Aging: Selective Impairment in Conditional Exclusion Compared to Abstraction and Inhibition

description: <i>Background:</i> Some executive functions may be selectively impaired in normal aging over and above the general cognitive decline. <i>Methods:</i> We examined the performance of healthy high functioning young (n = 77) and older (n = 57) individuals on three ‘executive’ tests: conditional exclusion, abstraction, and inhibition of prepotent responses. We compared their relationships to each other and to other cognitive functions including attention, psychomotor speed and working memory. <i>Results:</i> Conditional exclusion was significantly more impaired than abstraction or inhibition in the elderly compared to the younger group and unlike them, showed a nonlinear relationship with age. These findings were independent of other cognitive functions. Analysis of PCET performance characteristics showed that older individuals were particularly impaired in attaining the last of the three achievable categories, were slower, and had fewer error monitoring resources compared to the younger group. <i>Conclusions:</i> Conditional exclusion shows an age-related pattern of impairment distinct from inhibition and abstraction. We propose that in healthy well-functioning individuals, it taps processes integrating task set establishment and shifting in context of accumulating information. It may thus be useful as a specific marker of complex cognitive functions in studies of normal cognitive aging and in early detection of cognitive dysfunction.
DOI: 10.6084/m9.figshare.5121580
title: Supplementary Material for: Comparison of Immunosorbent Assays for the Quantification of Biomarkers for Alzheimer’s Disease in Human Cerebrospinal Fluid

description: <i>Background:</i> The clinical diagnosis of Alzheimer’s disease in early stages may be substantiated by the quantification of the biomarkers Abeta42, Abeta40 and total-Tau (t-Tau) in cerebrospinal fluid (CSF). Different commercially available immunosorbent assays yield reliable results, yet the absolute values obtained may differ in between tests. <i>Methods:</i> We used CSF samples from patients that reported to our memory clinic. Enzyme-linked immunosorbent assays obtained from Innogenetics were used for the quantification of Abeta42 and t-Tau, test kits from IBL International were used to determine Abeta42 and Abeta40 concentrations. The multiplex assay system obtained from Mesoscale Discovery (MSD) Systems was used for the quantification of all three biomarkers. <i>Results:</i> For all biomarkers, the absolute values obtained with different test systems differ. However, the data sets highly correlate for all comparisons, with the MSD test system proving to be slightly more sensitive. Correlation coefficients (c) for the Abeta42 and Abeta40 quantifications lie between c = 0.80 and c = 0.87, and for the t-Tau quantifications we determined c = 0.99. <i>Conclusion:</i> We conclude that all assays evaluated give reliable results, yet absolute values obtained have to be assessed differently within the framework of diagnostic procedures, depending on the system used.