cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5127976
title: Supplementary Material for: High Titer Anti-Basement Membrane Antibodies in a Subset of Patients with Pediatric Systemic Lupus Erythematosus

description: <b><i>Background/Aims:</i></b> There is a critical need for more noninvasive biomarkers to identify nephritis in patients with systemic lupus erythematosus (SLE). Recent studies in a model mouse and an adult SLE patient cohort suggest that anti-basement membrane antibody levels correlate well with lupus activity and kidney injury. The purpose of this study was to assess the anti-basement membrane reactivity in pediatric SLE (pSLE) patients with or without nephritis. <b><i>Methods:</i></b> Auto-antibodies to basement membrane antigens were assessed using an anti-matrigel ELISA. Endpoint titers were measured in pSLE patients and healthy children, as well as in autoimmune and non-immune mice, with good reproducing capabilities. Findings were also analyzed with respect to the presence or absence of nephritis, dsDNA antibodies, and other manifestations of pSLE. <b><i>Results:</i></b> MRL/lpr mice developed high-titer anti-matrigel antibodies, whereas C57BL/6 mice did not. In a cohort of 21 pSLE patients and 22 pediatric controls, high-titer anti-matrigel IgG, IgM and IgA antibody levels were specific for pSLE. High-titer anti-matrigel IgG3 levels could distinguish with good sensitivity the 13 pSLE patients with a history of nephritis from the 8 non-renal pSLE patients. High-titer anti-matrigel IgG, IgA, IgM or IgG3 did not correlate with positive anti-double stranded DNA, but defined an overlapping subset of patients. <b><i>Conclusion:</i></b> The addition of anti-basement membrane antibody testing to serologic testing in pSLE may help to monitor disease activity or to define important subsets of patients with risks for specific disease manifestations.
DOI: 10.6084/m9.figshare.5127976.v1
title: Supplementary Material for: High Titer Anti-Basement Membrane Antibodies in a Subset of Patients with Pediatric Systemic Lupus Erythematosus

description: <b><i>Background/Aims:</i></b> There is a critical need for more noninvasive biomarkers to identify nephritis in patients with systemic lupus erythematosus (SLE). Recent studies in a model mouse and an adult SLE patient cohort suggest that anti-basement membrane antibody levels correlate well with lupus activity and kidney injury. The purpose of this study was to assess the anti-basement membrane reactivity in pediatric SLE (pSLE) patients with or without nephritis. <b><i>Methods:</i></b> Auto-antibodies to basement membrane antigens were assessed using an anti-matrigel ELISA. Endpoint titers were measured in pSLE patients and healthy children, as well as in autoimmune and non-immune mice, with good reproducing capabilities. Findings were also analyzed with respect to the presence or absence of nephritis, dsDNA antibodies, and other manifestations of pSLE. <b><i>Results:</i></b> MRL/lpr mice developed high-titer anti-matrigel antibodies, whereas C57BL/6 mice did not. In a cohort of 21 pSLE patients and 22 pediatric controls, high-titer anti-matrigel IgG, IgM and IgA antibody levels were specific for pSLE. High-titer anti-matrigel IgG3 levels could distinguish with good sensitivity the 13 pSLE patients with a history of nephritis from the 8 non-renal pSLE patients. High-titer anti-matrigel IgG, IgA, IgM or IgG3 did not correlate with positive anti-double stranded DNA, but defined an overlapping subset of patients. <b><i>Conclusion:</i></b> The addition of anti-basement membrane antibody testing to serologic testing in pSLE may help to monitor disease activity or to define important subsets of patients with risks for specific disease manifestations.
DOI: 10.6084/m9.figshare.5127985.v1
title: Supplementary Material for: Modulation of Clr Ligand Expression and NKR-P1 Receptor Function during Murine Cytomegalovirus Infection

description: Viruses are known to induce pathological cellular states that render infected cells susceptible or resistant to immune recognition. Here, we characterize an MHC-I-independent natural killer (NK) cell recognition mechanism that involves modulation of inhibitory NKR-P1B:Clr-b receptor-ligand interactions in response to mouse cytomegalovirus (MCMV) infection. We demonstrate that mouse Clr-b expression on healthy cells is rapidly lost at the cell surface and transcript levels in a time- and dose-dependent manner upon MCMV infection. In addition, cross-species infections using rat cytomegalovirus (RCMV) infection of mouse fibroblasts and MCMV infection of rat fibroblasts suggest that this response is conserved during host-pathogen interactions. Active viral infection appears to be necessary for Clr-b loss, as cellular stimulation using UV-inactivated whole virus or agonists of many innate pattern recognition receptors failed to elicit efficient Clr-b downregulation. Notably, Clr-b loss could be partially blocked by titrated cycloheximide treatment, suggesting that early viral or nascent host proteins are required for Clr-b downregulation. Interestingly, reporter cell assays suggest that MCMV may encode a novel Clr-b-independent immunoevasin that functionally engages the NKR-P1B receptor. Together, these data suggest that Clr-b modulation is a conserved innate host cell response to virus infection that is subverted by multiple CMV immune evasion strategies.
DOI: 10.6084/m9.figshare.5127970
title: Supplementary Material for: Cognitive Behavioral Analysis System of Psychotherapy versus Escitalopram in Chronic Major Depression

description: <b><i>Background:</i></b> A specific psychotherapy for chronic depression, the Cognitive Behavioral Analysis System of Psychotherapy (CBASP), was compared to escitalopram (ESC). <b><i>Methods:</i></b> Sixty patients with chronic major depression were randomized to ‘CBASP' (22 sessions) or ‘ESC plus clinical management' (ESC/CM) at two treatment sites. The primary outcome measure was the score on the Montgomery-Asberg Depression Rating Scale (MADRS) after 8 weeks of acute treatment assessed by blinded raters. In the case of nonimprovement (&lt;20% reduction in the MADRS score), the other condition was augmented for the following 20 weeks of extended treatment. Secondary end points were, among others, depressive symptoms, remission (MADRS score of ≤9) and response rates (reduction of MADRS score of ≥50%) 28 weeks after randomization. <b><i>Results:</i></b> An intent-to-treat analysis revealed that clinician-rated depression scores decreased significantly after 8 and 28 weeks with no significant differences between the groups. The response rates after 28 weeks of treatment were high (CBASP: 68.4%, ESC/CM: 60.0%), and the remission rates were moderate (CBASP: 36.8%, ESC/CM: 50.0%) with neither group being superior. Nonimprovers to the initial treatment caught up with the initial improvers in terms of depression scores and response and remission rates by the end of the treatment after being augmented with the respective other condition. <b><i>Conclusions:</i></b> CBASP and ESC/CM appear to be equally effective treatment options for chronically depressed outpatients. For nonimprovers to the initial treatment, it is efficacious to augment with medication in the case of nonresponse to CBASP and vice versa.
DOI: 10.6084/m9.figshare.5127979.v1
title: Supplementary Material for: Variants of Base Excision Repair Genes <b><i>MUTYH</i></b>, <b><i>PARP1</i></b> and <b><i>XRCC1</i></b> in Alzheimer's Disease Risk

description: <b><i>Background:</i></b> Many clinical studies have shown that oxidative stress pathways and the efficiency of the oxidative DNA damage base excision repair (BER) system are associated with the pathogenesis of Alzheimer's disease (AD). Reduced BER efficiency may result from polymorphisms of BER-related genes. In the present study, we examine whether single nucleotide polymorphisms (SNPs) of BER genes are associated with increased risk of AD. <b><i>Methods:</i></b> SNP genotyping was carried out on DNA isolated from peripheral blood mononuclear cells obtained from 120 patients with AD and 110 healthy volunteers. Samples were genotyped for the presence of BER-related SNPs, i.e. <i>XRCC1</i>-rs1799782, rs25487; <i>MUTYH</i>-rs3219489, and <i>PARP1</i>-rs1136410. <b><i>Results:</i></b> We found a positive association between AD risk and the presence of G/A genotype variant of the<i> XRCC1</i> rs25487 polymorphism [odds ratio (OR) = 3.762, 95% CI: 1.793-7.891]. The presence of the A/A genotype of this polymorphism reduced the risk of AD (OR = 0.485, 95% CI: 0.271-0.870). In cases of the <i>PARP1 </i>gene rs1136410 polymorphism, we observed that the T/C variant increases (OR = 4.159, 95% CI: 1.978-8.745) while the T/T variant reduces risk (OR = 0.240, 95% CI: 0.114-0.556) of AD. <b><i>Conclusions:</i></b> We conclude that BER gene polymorphisms may play an important role in the etiology of AD. Diagnosing the presence or absence of particular genetic variants may be an important marker of AD. Further research on a larger population is needed. There is also a need to examine polymorphisms of other BER in the context of AD risk.
DOI: 10.6084/m9.figshare.5127961
title: Supplementary Material for: Outcomes of Systemic Therapy for Patients with Metastatic Angiosarcoma

description: <b><i>Background:</i></b> Angiosarcomas (AS) are rare tumors of vascular origin with a variable behavior and overall poor prognosis. We sought to assess the outcomes of patients treated for metastatic disease. <b><i>Methods:</i></b> We performed a retrospective analysis of 119 patients treated for metastatic AS. Outcomes and efficacy measurements of the first and subsequent lines of treatment were analyzed. <b><i>Results:</i></b> Median age was 61 years, and the most frequent primary sites were chest wall/breast (31%), viscera (22%) and head/neck (20%). Seventy-three (61%) and 46 (39%) patients received ≥2 and ≥3 lines of therapy, respectively. The most commonly used agents included taxanes and anthracyclines. Median overall survival was 12.1 months. Median times to tumor progression were 3.5 months for first line, 3.7 months for second line and 2.7 months for third line. Among 48 patients evaluable per RECIST, the overall response rate to first line was 30% and &lt;10% in subsequent lines. Doxorubicin, liposomal doxorubicin and taxanes resulted in similar response rates and survival, and there was no apparent benefit for combination chemotherapy. <b><i>Conclusion:</i></b> Despite reasonable response rates in the first-line setting, benefit from systemic therapy is short-lived in metastatic AS, and outcomes are poor. Doxorubicin, liposomal doxorubicin and taxanes are reasonable and appropriate choices for monotherapy.
DOI: 10.6084/m9.figshare.5127964
title: Supplementary Material for: Parameters Used to Discontinue Dialysis in Acute Kidney Injury Recovery: A Survey of United States Nephrologists

description: <b><i>Background:</i></b> Despite advances in the approach to cure acute kidney injury (AKI), including definition, classification and treatment methods, there are no standard criteria to withdraw dialysis in the setting of improving AKI. We conducted this survey to elucidate parameters that United States (US) nephrologists used to determine when to stop dialysis with improving renal function in AKI. We hypothesized that there would be a difference in approach to weaning a patient off dialysis based on years in practice or the number of cases of AKI treated per year. <b><i>Methods:</i></b> This was an anonymous electronic survey of practicing nephrologists who treated AKI. Data was de-identified and analyzed using descriptive statistics. <b><i>Results:</i></b> The commonest criteria used to stop dialysis when renal function improved was, in decreasing order of importance, resolution in oliguria (51%), resolution of volume overload (29%), improvement in serum creatinine (26.7%) and resolution of hyperkalemia (21%). The most common reasons for re-starting dialysis within 28 days did not show a specific trend but respondents (20%) reported re-starting if estimated glomerular filtration rates (eGFR) declined. There was no significant pattern in approach to withdrawing dialysis or resuming dialysis based on the number of years in nephrology practice. However, responses of nephrologists who saw more than 20 AKI patients/year were significantly different in stopping dialysis with clinical stabilization of blood pressure (p &lt; 0.001), improvement in respiratory parameters (p = 0.005), improvement in pre-dialysis blood urea nitrogen (BUN) levels despite the same dose of dialysis (p = 0.05) and resolution of oliguria (p = 0.025) compared to those who saw fewer cases. <b><i>Conclusion:</i></b> Resolution of oliguria was the commonest factor used to help deciding to stop dialysis in improving AKI. However, considerable variation was noted among US nephrologists who participated in this survey, regarding what criteria they used to withdraw dialysis in the setting of improving AKI. These results call for more studies in withdrawing dialysis in the setting of AKI that could lead to guideline formulation.
DOI: 10.6084/m9.figshare.5127967
title: Supplementary Material for: Dialysis Amyloid Deposition in the Aortic Valve and Its Association with Aortic Stenosis

description: <b><i>Background:</i></b> The relationship between dialysis amyloid (DA) deposition in the aortic valve (AV) and aortic stenosis (AS) is unknown. <b><i>Methods:</i></b> This was a cross-sectional study. AV specimens of dialysis patients (median vintage: 8.8 years) consecutively collected from cardiac surgeries (n = 56) or autopsies (n = 13) were examined by a board-certified pathologist blinded to clinical data. DAs were considered to be present if deposits were stained both by Congo red with apple-green birefringence under polarized light and by anti-β2-microblobulin antibody. Degree of deposition was graded as follows: Amyloid (-), no deposit; Amyloid (1+), occasional small deposits; Amyloid (2+), multiple small to large deposits or a single large deposit. Calcification was defined as a calcified deposit with a diameter &gt;1 mm in the specimen. Severe AS (sAS) was defined as a mean gradient &gt;50 mm Hg by echocardiogram. We examined the proportion of DAs and the association between DAs and the sAS. <b><i>Results:</i></b> DAs were present in 71% (n = 49) of specimens and primarily co-localized with calcification. Non-dialysis related amyloid was found in one specimen. After excluding this specimen, sAS was associated with ‘Amyloid (1+) and Calcification &gt;1 mm' and ‘Amyloid (2+) and Calcification &gt;1 mm' (vs. ‘Amyloid (-) and Calcification ≤1 mm', odds ratios (ORs): 13.5 and 34.2, respectively). Furthermore, after adjustment for covariates, sAS was found to be associated with ‘Amyloid (2+) and Calcification &gt;1 mm' (OR: 24.3). <b><i>Conclusions:</i></b> DA deposition in the AV was prevalent among dialysis patients. DA deposition with accompanying calcification might contribute to the severity of AS.
DOI: 10.6084/m9.figshare.5127970.v1
title: Supplementary Material for: Cognitive Behavioral Analysis System of Psychotherapy versus Escitalopram in Chronic Major Depression

description: <b><i>Background:</i></b> A specific psychotherapy for chronic depression, the Cognitive Behavioral Analysis System of Psychotherapy (CBASP), was compared to escitalopram (ESC). <b><i>Methods:</i></b> Sixty patients with chronic major depression were randomized to ‘CBASP' (22 sessions) or ‘ESC plus clinical management' (ESC/CM) at two treatment sites. The primary outcome measure was the score on the Montgomery-Asberg Depression Rating Scale (MADRS) after 8 weeks of acute treatment assessed by blinded raters. In the case of nonimprovement (&lt;20% reduction in the MADRS score), the other condition was augmented for the following 20 weeks of extended treatment. Secondary end points were, among others, depressive symptoms, remission (MADRS score of ≤9) and response rates (reduction of MADRS score of ≥50%) 28 weeks after randomization. <b><i>Results:</i></b> An intent-to-treat analysis revealed that clinician-rated depression scores decreased significantly after 8 and 28 weeks with no significant differences between the groups. The response rates after 28 weeks of treatment were high (CBASP: 68.4%, ESC/CM: 60.0%), and the remission rates were moderate (CBASP: 36.8%, ESC/CM: 50.0%) with neither group being superior. Nonimprovers to the initial treatment caught up with the initial improvers in terms of depression scores and response and remission rates by the end of the treatment after being augmented with the respective other condition. <b><i>Conclusions:</i></b> CBASP and ESC/CM appear to be equally effective treatment options for chronically depressed outpatients. For nonimprovers to the initial treatment, it is efficacious to augment with medication in the case of nonresponse to CBASP and vice versa.
DOI: 10.6084/m9.figshare.5127973.v1
title: Supplementary Material for: Endothelial Repair in Childhood Arterial Ischaemic Stroke with Cerebral Arteriopathy

description: <b><i>Background:</i></b> We have previously shown that recurrent arterial ischaemic stroke (AIS) in children with cerebral arteriopathy is associated with increased circulating endothelial cells and endothelial microparticles, consistent with ongoing endothelial injury. To date, however, little is known about endothelial repair responses in childhood AIS. We examined the relationship between the number and function of circulating endothelial progenitor cells (EPC), the levels of brain-derived neurotrophic factor (BDNF) and AIS recurrence. <b><i>Methods:</i></b> Flow cytometry was used to identify peripheral blood mononuclear cells positive for CD34/kinase insert domain-containing receptor (KDR). In a subgroup of patients (5 in each group selected at random), monocytic EPC function was assessed by colony-forming unit (EPC-CFU) capacity and incorporation into endothelial cell networks in Matrigel. BDNF was measured using ELISA. <b><i>Results:</i></b> Thirty-five children, aged 12 years (range: 5-16.5; 9 males), with AIS and cerebral arteriopathy were studied; 10 had recurrent AIS. CD34+/KDR+ cells were significantly higher in recurrent AIS compared to non-recurrent AIS patients (p = 0.005) and controls (p = 0.0002). EPC-CFU and EPC incorporation into endothelial cell networks were significantly reduced in recurrent compared to non-recurrent AIS patients (p = 0.04 and p = 0.01, respectively). Levels of BDNF were significantly higher in recurrent compared to non-recurrent AIS patients (p = 0.0008) and controls (p = 0.0002). <b><i>Conclusions:</i></b> Children with recurrent AIS and cerebral arteriopathy had increased circulating CD34+/KDR+ cells and BDNF consistent with an endothelial repair response. However, EPC function was impaired. Future studies are needed to examine whether suboptimal endothelial repair contributes to childhood AIS recurrence.
DOI: 10.6084/m9.figshare.5127958
title: Supplementary Material for: Systemic Treatment Approaches for Sporadic Desmoid-Type Fibromatosis: Scarce Evidence and Recommendations

description: Desmoid-type fibromatosis (DF) is a rare disease characterized by a monoclonal, fibroblastic proliferation and a variable and often unpredictable clinical course. Although histologically benign, DF is locally invasive and associated with a high local recurrence rate, but lacks any metastatic potential. As there is no established or evidence-based treatment approach available as of today, an individualized treatment strategy is fundamental in the light of highly variable clinical presentations, anatomic locations, and biological behaviors. Surgery with negative margins has been the cornerstone of DF treatment; however, an overall reassessment of the management of DF patients has taken place in the last few years, and preservation of function and quality of life has become a priority in these patients. Evidence is scarce for systemic treatment; different pharmacological options can be proposed and will be reviewed here. To better define possible therapeutic strategies, a consensus approach has been initiated, bringing together sarcoma experts from the European Organisation for Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group (STBSG) with patient advocates from Sarcoma Patients EuroNet (SPAEN). As a prerequisite, patients should be discussed in a multidisciplinary setting in centers/networks with specific expertise and experience in this disease.
DOI: 10.6084/m9.figshare.5127955
title: Supplementary Material for: Global Individual Ancestry Using Principal Components for Family Data

description: Studies of complex human diseases and traits associated with candidate genes are potentially vulnerable to bias (confounding) due to population stratification and inbreeding, especially in admixed population. In GWAS, the principal components (PCs) method provides a global ancestry value per subject, allowing corrections for population stratification. However, these coefficients are typically estimated assuming unrelated individuals, and if family structure is present and ignored, such substructures may induce artifactual PCs. Extensions of the PCs method have been proposed by Konishi and Rao [Biometrika 1992;79:631-641], taking into account only siblings' relatedness, and by Oualkacha et al. [Stat Appl Genet Mol Biol 2012, DOI: 10.2202/1544-6115.1711], taking into account large pedigrees and high-dimensional phenotype data. In this work, we extend these methods to estimate the global individual ancestry coefficients from PCs derived from different variance component matrix estimators using SNPs from two simulated data sets and two real data sets: the GENOA sibship data consisting of European and African-American subjects and the Baependi Heart Study consisting of 80 extended Brazilian families, both with genotyping data from the Affymetrix 6.0 chip. Our results show that the family structure plays an important role in the estimation of the global individual ancestry value for extended pedigrees but not for sibships.