cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5125300.v1
title: Supplementary Material for: Efficacy and Tolerability of Benzodiazepines versus Antidepressants in Anxiety Disorders: A Systematic Review and Meta-Analysis

description: <b><i>Background:</i></b> Placebo-controlled trials showed that both benzodiazepines (BDZ) and antidepressant drugs (AD) are effective in treating anxiety disorders. However, in the last years a progressive shift in the prescribing pattern from BDZ to newer AD has taken place. The aim of this systematic review and meta-analysis is to analyze whether controlled comparisons support such a shift. <b><i>Methods:</i></b> CINHAL, the Cochrane Library, MEDLINE, PubMed and Web of Science were searched from inception up to December 2012. A total of 22 studies met the criteria for inclusion. They were mostly concerned with tricyclic antidepressants (TCA; 18/22) and involved different anxiety disorders. In order to reduce clinical heterogeneity, only the 10 investigations that dealt with the comparison between TCA and BDZ in panic disorder were submitted to meta-analysis, whereas the remaining papers were individually summarized and critically examined. <b><i>Results:</i></b> According to the systematic review, no consistent evidence emerged supporting the advantage of using TCA over BDZ in treating generalized anxiety disorder (GAD), complex phobias and mixed anxiety-depressive disorders. Indeed, BDZ showed fewer treatment withdrawals and adverse events than AD. In panic disorder with and without agoraphobia our meta-analysis found BDZ treatments more effective in reducing the number of panic attacks than TCA (risk ratio, RR = 1.13; 95% CI = 1.01-1.27). Furthermore, BDZ medications were significantly better tolerated than TCA drugs, causing less discontinuation (RR = 0.40; 95% CI = 0.20-0.57) and side effects (RR = 0.41; 95% CI = 0.34-0.50). As to newer AD, BDZ trials resulted in comparable or greater improvements and fewer adverse events in patients suffering from GAD or panic disorder. <b><i>Conclusions:</i></b> The change in the prescribing pattern favoring newer AD over BDZ in the treatment of anxiety disorders has occurred without supporting evidence. Indeed, the role and usefulness of BDZ need to be reappraised.
DOI: 10.6084/m9.figshare.5125288
title: Supplementary Material for: Class IA Phosphatidylinositol 3-Kinase Inhibition Inhibits Cell Growth and Proliferation in Mantle Cell Lymphoma

description: <b><i>Background/Aims:</i></b> Constitutive activation of the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin signaling pathway preferentially occurs in aggressive blastoid variants of mantle cell lymphoma (MCL) and is implicated in the pathogenesis of this disease. In this study, we investigated the role of PI3K isoforms on proliferation of aggressive MCL cells. <b><i>Methods:</i></b> The changes in cell viability, cell cycle distribution and apoptosis induction by the PI3K isoform-selective inhibitors were evaluated. The molecular basis underlying the effects of the specific inhibition of PI3K isoforms was investigated by Western blot analysis. <b><i>Results:</i></b> Our results demonstrated that a class IA PI3K isoform is most commonly involved in the constitutive activation of Akt in aggressive MCL. Treatment with a p110α isoform-specific inhibitor induced prominent cell cycle arrest followed by apoptosis through complete abolishment of phosphorylated (p)-Akt and its downstream targets. An inhibitor of isoform p110δ induced moderate cell cycle arrest with downregulation of p-Akt and p-S6K. A dual inhibitor of p110α and p110δ GDC-0941 caused more prominent cell growth inhibition compared to selective p110α or p110δ inhibitors. Inhibition of the class IB PI3K isoform p110γ did not cause cell cycle arrest or induce apoptosis in MCL cells. <b><i>Conclusion:</i></b> These findings suggest that the therapeutic ablation of class IA PI3K may be a promising strategy for the treatment of refractory, aggressive MCL.
DOI: 10.6084/m9.figshare.5125279
title: Supplementary Material for: Significance of Interdialytic Weight Gain versus Chronic Volume Overload: Consensus Opinion

description: Predialysis volume overload is the sum of interdialytic weight gain (IDWG) and residual postdialysis volume overload. It results mostly from failure to achieve an adequate volume status at the end of the dialysis session. Recent developments in bioimpedance spectroscopy and possibly relative plasma volume monitoring permit noninvasive volume status assessment in hemodialysis patients. A large proportion of patients have previously been shown to be chronically volume overloaded predialysis (defined as &gt;15% above ‘normal' extracellular fluid volume, equivalent to &gt;2.5 liters on average), and to exhibit a more than twofold increased mortality risk. By contrast, the magnitude of the mortality risk associated with IDWG is much smaller and only evident with very large weight gains. Here we review the available evidence on volume overload and IDWG, and question the use of IDWG as an indicator of ‘nonadherence' by describing its association with postdialysis volume depletion. We also demonstrate the relationship between IDWG, volume overload and predialysis serum sodium concentration, and comment on salt intake. Discriminating between volume overload and IDWG will likely lead to a more appropriate management of fluid withdrawal during dialysis. Consensually, the present authors agree that this discrimination should be among the primary goals for dialysis caretakers today. In consequence, we recommend objective measures of volume status beyond mere evaluations of IDWG.
DOI: 10.6084/m9.figshare.5125282
title: Supplementary Material for: Inductive Ability of Human Developing and Differentiated Dental Mesenchyme

description: The development of cell-based therapeutic strategies to bioengineer tooth tissue is a promising approach for the treatment of lost or damaged tooth tissue. The lack of a readily available cell source for human dental epithelial cells (ECs) severely constrains the progress of tooth bioengineering. Previous studies in model organisms have demonstrated that developing dental mesenchyme can instruct nondental epithelium to differentiate into enamel-forming epithelium. In this study, we characterized the ability of fetal and adult human dental mesenchyme to promote differentiation of human embryonic stem cell (hESC)-derived ECs (ES-ECs) into ameloblast-lineage cells. ES-ECs were co-cultured either with human fetal dental mesenchymal cells (FDMCs) or with adult dental mesenchymal cells (ADMCs) in either a three-dimensional culture system, or in the renal capsules of SCID mice. When co-cultured with FDMCs in vitro, ES-ECs polarized and expressed amelogenin. Tooth organ-like structures assembled with epithelium and encased mesenchyme and developing enamel-like structures could be detected in the complexes resulting from in vitro and ex vivo co-culture of ES-ECs and FDMCs. In contrast, co-cultured ES-ECs and ADMCs formed amorphous spherical structures and occasionally formed hair<i>.</i> Transcription factors were significantly upregulated in FDMCs compared to ADMCs including <i>MSX1</i>, <i>GLI1</i>, <i>LHX6</i>, <i>LHX8,</i><i>LEF1</i> and <i>TBX1</i>. In summary, FDMCs but not ADMCs had the capacity to induce differentiation of ES-ECs into ameloblast lineage cells. Further characterization of the functional differences between these two types of dental mesenchyme could enable reprogramming of ADMCs to enhance their odontogenic inductive competence.
DOI: 10.6084/m9.figshare.5125276
title: Supplementary Material for: Declining Mortality Rates despite Increases in Clinical Coronary Artery Disease among US Dialysis Patients: A National Registry Study

description: <b><i>Background/Aims:</i></b> Coronary artery disease (CAD) is a major risk factor for death on dialysis. The objective of this study was to compare prevalent trends and patterns of survival in successive national cohorts. <b><i>Methods:</i></b> National data on 823,753 incident dialysis patients, aged 18 and over, were analyzed from the US Renal Data System from 1995 to 2004. The prevalence of CAD was compared across calendar years by sex and race categorized as; White, Black, Asian and Native American/Alaskan Native (Native Am). Two-year mortality rates were determined for annual cohorts and multivariable Cox regression compared hazard ratios (HR) and 95% confidence intervals. <b><i>Results:</i></b> From 1995 to 2004, the annual prevalence of CAD increased significantly in men from 25.2 to 30.1% and in women from 22.1 to 25.3%, p &lt; 0.001. For men, the rise in prevalence was largely due to increases among Black men and older White men. For women, the pattern was similar. During this period, death rates decreased significantly from 379 to 348 and from 396 to 357 per 1,000 person-years in men and women respectively. Multivariate analysis identified significant reductions in mortality with advancing calendar year for White (HR 0.98 (0.98-0.99)), Asian (HR 0.93 (0.91-0.96)), and Native Am men (HR 0.95 (0.90-0.99)), and for White (HR 0.99 (0.98-0.99)) and Native Am women (HR 0.93 (0.89-0.98)). No significant trends were observed for Black patients. <b><i>Conclusions:</i></b> Despite a rising burden of CAD among incident US dialysis patients, mortality rates have fallen for most groups. Substantial racial disparities remain.
DOI: 10.6084/m9.figshare.5125279.v1
title: Supplementary Material for: Significance of Interdialytic Weight Gain versus Chronic Volume Overload: Consensus Opinion

description: Predialysis volume overload is the sum of interdialytic weight gain (IDWG) and residual postdialysis volume overload. It results mostly from failure to achieve an adequate volume status at the end of the dialysis session. Recent developments in bioimpedance spectroscopy and possibly relative plasma volume monitoring permit noninvasive volume status assessment in hemodialysis patients. A large proportion of patients have previously been shown to be chronically volume overloaded predialysis (defined as &gt;15% above ‘normal' extracellular fluid volume, equivalent to &gt;2.5 liters on average), and to exhibit a more than twofold increased mortality risk. By contrast, the magnitude of the mortality risk associated with IDWG is much smaller and only evident with very large weight gains. Here we review the available evidence on volume overload and IDWG, and question the use of IDWG as an indicator of ‘nonadherence' by describing its association with postdialysis volume depletion. We also demonstrate the relationship between IDWG, volume overload and predialysis serum sodium concentration, and comment on salt intake. Discriminating between volume overload and IDWG will likely lead to a more appropriate management of fluid withdrawal during dialysis. Consensually, the present authors agree that this discrimination should be among the primary goals for dialysis caretakers today. In consequence, we recommend objective measures of volume status beyond mere evaluations of IDWG.
DOI: 10.6084/m9.figshare.5125288.v1
title: Supplementary Material for: Class IA Phosphatidylinositol 3-Kinase Inhibition Inhibits Cell Growth and Proliferation in Mantle Cell Lymphoma

description: <b><i>Background/Aims:</i></b> Constitutive activation of the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin signaling pathway preferentially occurs in aggressive blastoid variants of mantle cell lymphoma (MCL) and is implicated in the pathogenesis of this disease. In this study, we investigated the role of PI3K isoforms on proliferation of aggressive MCL cells. <b><i>Methods:</i></b> The changes in cell viability, cell cycle distribution and apoptosis induction by the PI3K isoform-selective inhibitors were evaluated. The molecular basis underlying the effects of the specific inhibition of PI3K isoforms was investigated by Western blot analysis. <b><i>Results:</i></b> Our results demonstrated that a class IA PI3K isoform is most commonly involved in the constitutive activation of Akt in aggressive MCL. Treatment with a p110α isoform-specific inhibitor induced prominent cell cycle arrest followed by apoptosis through complete abolishment of phosphorylated (p)-Akt and its downstream targets. An inhibitor of isoform p110δ induced moderate cell cycle arrest with downregulation of p-Akt and p-S6K. A dual inhibitor of p110α and p110δ GDC-0941 caused more prominent cell growth inhibition compared to selective p110α or p110δ inhibitors. Inhibition of the class IB PI3K isoform p110γ did not cause cell cycle arrest or induce apoptosis in MCL cells. <b><i>Conclusion:</i></b> These findings suggest that the therapeutic ablation of class IA PI3K may be a promising strategy for the treatment of refractory, aggressive MCL.
DOI: 10.6084/m9.figshare.5125267
title: Supplementary Material for: Karyotype Reorganization with Conserved Genomic Compartmentalization in Dot-Shaped Microchromosomes in the Japanese Mountain Hawk-Eagle (<i>Nisaetus nipalensis orientalis</i>, Accipitridae)

description: The karyotype of the Japanese mountain hawk-eagle <i>(Nisaetus nipalensis</i><b> </b><i>orientalis)</i> (2n = 66) consists of a large number of medium-sized and small chromosomes but only 4 pairs of dot-shaped microchromosomes, in contrast to the typical avian karyotype with a small number of macrochromosomes and many indistinguishable microchromosomes. To investigate the drastic karyotype reorganization in this species, we performed a molecular cytogenetic characterization employing chromosome in situ hybridization and molecular cloning of centromeric heterochromatin. Cross-species chromosome painting with chicken chromosome-specific probes 1-9 and Z and a paint pool of 20 microchromosome pairs revealed that the <i>N. n. orientalis</i> karyotype differs from chicken by at least 13 fissions of macrochromosomes and 15 fusions between microchromosomes and between micro- and macrochromosomes. A novel family of satellite DNA sequences (NNO-<i>Apa</i>I) was isolated, consisting of a GC-rich 173-bp repeated sequence element. The NNO-<i>Apa</i>I sequence was localized to the C-positive centromeric heterochromatin of 4 pairs of microchromosomes, which evolved concertedly by homogenization between the microchromosomes. These results suggest that the 4 pairs of dot-shaped microchromosomes have retained their genomic compartmentalization from other middle-sized and small chromosomes.
DOI: 10.6084/m9.figshare.5125270
title: Supplementary Material for: Inflammatory Activation after Experimental Cardiac Tamponade

description: <b><i>Background/Purpose:</i></b> Cardiac tamponade is a medical emergency situation associated with a high rate of life-threatening complications, even after immediate interventions. Our aim was to characterize the acute inflammatory consequences of this event in a clinically relevant large animal model. <b><i>Methods:</i></b> Cardiac tamponade was induced for 60 min in anesthetized, ventilated and thoracotomized minipigs by intrapericardial fluid administration, the mean arterial pressure (MAP) being maintained in the interval of 40-45 mm Hg (n = 8). A further group (n = 7) served as sham-operated control. The global macrohemodynamics, including the right- and left-heart end-diastolic volumes (RHEDV and LHEDV), the pulmonary vascular resistance index (PVRI) and the superior mesenteric artery (SMA) flow, were monitored for 240 min, and the intestinal microcirculatory changes (pCO<sub>2</sub> gap) were evaluated by indirect tonometry. Blood samples were taken for the determination of cardiac troponin T and vasoactive inflammatory mediators, including histamine, nitrite/nitrate, big-endothelin, superoxide and high-mobility group box protein-1 levels in association with intestinal leukocyte and complement activation. <b><i>Results:</i></b> The cardiac tamponade induced significant decreases in MAP, cardiac output, LHEDV and SMA flow, while the PVRI and the pCO<sub>2</sub> gap increased significantly. After the removal of fluid from the pericardial sac, the MAP and the LHEDV were decreased, while the PVRI and the pCO<sub>2</sub> gap remained elevated when compared with those in the sham-operated group. In the posttamponade period, the abrupt release of inflammatory mediators was accompanied by a significant splanchnic leukocyte accumulation and complement activation. <b><i>Conclusions:</i></b> The macrocirculatory and splanchnic microcirculatory disturbances were accompanied by a significant proinflammatory reaction; endothelin and the complement system may be significant components of the inflammatory cascade that is activated in this porcine model of pericardial tamponade.
DOI: 10.6084/m9.figshare.5125273
title: Supplementary Material for: Close Relations between Podocyte Injuries and Membranous Proliferative Glomerulonephritis in Autoimmune Murine Models

description: <b><i>Background:</i></b> Membranous proliferative glomerulonephritis (MPGN) is a major primary cause of chronic kidney disease (CKD). Podocyte injury is crucial in the pathogenesis of glomerular disease with proteinuria, leading to CKD. To assess podocyte injuries in MPGN, the pathological features of spontaneous murine models were analyzed. <b><i>Methods:</i></b> The autoimmune-prone mice strains BXSB/MpJ-<i>Yaa</i> and B6.MRL-(<i>D1Mit202</i>-<i>D1Mit403</i>) were used as the MPGN models, and BXSB/MpJ-<i>Yaa</i><sup>+</sup> and C57BL/6 were used as the respective controls. In addition to clinical parameters and glomerular histopathology, the protein and mRNA levels of podocyte functional markers were evaluated as indices for podocyte injuries. The relation between MPGN pathology and podocyte injuries was analyzed by statistical correlation. <b><i>Results:</i></b> Both models developed MPGN with albuminuria and elevated serum anti-double-strand DNA (dsDNA) antibody levels. BXSB/MpJ-<i>Yaa</i> and B6.MRL showed severe proliferative lesions with T and B cell infiltrations and membranous lesions with T cell infiltrations, respectively. Foot process effacement and microvillus-like structure formation were observed ultrastructurally in the podocytes of both MPGN models. Furthermore, both MPGN models showed a decrease in immune-positive areas of nephrin, podocin and synaptopodin in the glomerulus, and in the mRNA expression of <i>Nphs1</i>, <i>Nphs2</i>, <i>Synpo</i>, <i>Actn4</i>, <i>Cd2ap</i>, and <i>Podxl </i>in the isolated glomerulus. Significant negative correlations were detected between serum anti-dsDNA antibody levels and glomerular <i>Nphs1</i> expression, and between urinary albumin-to-creatinine ratio and glomerular expression of <i>Nphs1</i>, <i>Synpo</i>, <i>Actn4</i>, <i>Cd2ap</i>, or <i>Podxl.</i><b><i>Conclusion:</i></b> MPGN models clearly developed podocyte injuries characterized by the decreased expression of podocyte functional markers with altered morphology. These data emphasized the importance of regulation of podocyte injuries in MPGN.
DOI: 10.6084/m9.figshare.5125276.v1
title: Supplementary Material for: Declining Mortality Rates despite Increases in Clinical Coronary Artery Disease among US Dialysis Patients: A National Registry Study

description: <b><i>Background/Aims:</i></b> Coronary artery disease (CAD) is a major risk factor for death on dialysis. The objective of this study was to compare prevalent trends and patterns of survival in successive national cohorts. <b><i>Methods:</i></b> National data on 823,753 incident dialysis patients, aged 18 and over, were analyzed from the US Renal Data System from 1995 to 2004. The prevalence of CAD was compared across calendar years by sex and race categorized as; White, Black, Asian and Native American/Alaskan Native (Native Am). Two-year mortality rates were determined for annual cohorts and multivariable Cox regression compared hazard ratios (HR) and 95% confidence intervals. <b><i>Results:</i></b> From 1995 to 2004, the annual prevalence of CAD increased significantly in men from 25.2 to 30.1% and in women from 22.1 to 25.3%, p &lt; 0.001. For men, the rise in prevalence was largely due to increases among Black men and older White men. For women, the pattern was similar. During this period, death rates decreased significantly from 379 to 348 and from 396 to 357 per 1,000 person-years in men and women respectively. Multivariate analysis identified significant reductions in mortality with advancing calendar year for White (HR 0.98 (0.98-0.99)), Asian (HR 0.93 (0.91-0.96)), and Native Am men (HR 0.95 (0.90-0.99)), and for White (HR 0.99 (0.98-0.99)) and Native Am women (HR 0.93 (0.89-0.98)). No significant trends were observed for Black patients. <b><i>Conclusions:</i></b> Despite a rising burden of CAD among incident US dialysis patients, mortality rates have fallen for most groups. Substantial racial disparities remain.
DOI: 10.6084/m9.figshare.5125261
title: Supplementary Material for: Cognitive Patterns in Relation to Biomarkers of Cerebrovascular Disease and Vascular Risk Factors

description: <b><i>Background:</i></b> Risk factors for vascular cognitive impairment (VCI) are the same as traditional risk factors for cerebrovascular disease (CVD). Early identification of subjects at higher risk of VCI is important for the development of effective preventive strategies. In addition to traditional vascular risk factors (VRF), circulating biomarkers have emerged as potential tools for early diagnoses, as they could provide in vivo measures of the underlying pathophysiology. While VRF have been consistently linked to a VCI profile (i.e., deficits in executive functions and processing speed), the cognitive correlates of CVD biomarkers remain unclear. In this population-based study, the aim was to study and compare cognitive patterns in relation to VRF and circulating biomarkers of CVD. <b><i>Methods:</i></b> The<b> </b>Barcelona-AsIA Neuropsychology Study included 747 subjects older than 50, without a prior history of stroke or coronary disease and with a moderate to high vascular risk (mean age, 66 years; 34.1% women). Three cognitive domains were derived from factoral analysis: visuospatial skills/speed, verbal memory and verbal fluency. Multiple linear regression was used to assess relationships between cognitive performance (multiple domains) and a panel of circulating biomarkers, including indicators of inflammation, C-reactive protein (CRP) and resistin, endothelial dysfunction, asymmetric dimethylarginine (ADMA), thrombosis, plasminogen activator inhibitor 1 (PAI-1), as well as traditional VRF, metabolic syndrome and insulin resistance (homeostatic model assessment for insulin resistance index). Analyses were adjusted for age, gender, years of education and depressive symptoms. <b><i>Results:</i></b> Traditional VRF were related to lower performance in verbal fluency, insulin resistance accounted for lower performance in visuospatial skills/speed and the metabolic syndrome predicted lower performance in both cognitive domains. From the biomarkers of CVD, CRP was negatively related to verbal fluency performance and increasing ADMA levels were associated with lower performance in verbal memory. Resistin and PAI-1 did not relate to cognitive function performance. <b><i>Conclusion: </i></b>Vascular risk factors, and markers of inflammation and endothelial dysfunction predicted lower performance in several cognitive domains. Specifically, cognitive functions associated with CRP are typically affected in VCI and overlap those related to VRF. ADMA indicated a dissociation in the cognitive profile involving verbal memory. These findings suggest that inflammation and endothelial dysfunction might play a role in the predementia cognitive impairment stages.