cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5123134
title: Supplementary Material for: A Combined Functional Annotation Score for Non-Synonymous Variants

description: <i>Aims:</i> Next-generation sequencing has opened the possibility of large-scale sequence-based disease association studies. A major challenge in interpreting whole-exome data is predicting which of the discovered variants are deleterious or neutral. To address this question in silico, we have developed a score called Combined Annotation scoRing toOL (CAROL), which combines information from 2 bioinformatics tools: PolyPhen-2 and SIFT, in order to improve the prediction of the effect of non-synonymous coding variants. <i>Methods:</i> We used a weighted <i>Z</i> method that combines the probabilistic scores of PolyPhen-2 and SIFT. We defined 2 dataset pairs to train and test CAROL using information from the dbSNP: ‘HGMD-PUBLIC’ and 1000 Genomes Project databases. The training pair comprises a total of 980 positive control (disease-causing) and 4,845 negative control (non-disease-causing) variants. The test pair consists of 1,959 positive and 9,691 negative controls.<i> Results:</i> CAROL has higher predictive power and accuracy for the effect of non-synonymous variants than each individual annotation tool (PolyPhen-2 and SIFT) and benefits from higher coverage. <i>Conclusion:</i> The combination of annotation tools can help improve automated prediction of whole-genome/exome non-synonymous variant functional consequences.
DOI: 10.6084/m9.figshare.5123140
title: Supplementary Material for: Survival of Patients with Small Cell Lung Carcinoma in Taiwan

description: <i>Background:</i> Small cell lung cancer (SCLC) is the most aggressive form of lung cancer. The prognosis for SCLC patients remains unsatisfactory despite advances in chemotherapy. In this study, we sought to clarify the prognosis and treatment patterns of patients with SCLC. <i>Methods:</i> A cohort comprising all patients diagnosed with SCLC between January 2004 and December 2006 was assembled from the Taiwan Cancer Database. Patients were followed up until December 31, 2009, to determine overall survival. Patient survival was estimated using the Kaplan-Meier method, and Cox’s proportional hazard model was used to determine the relationship between prognostic factors and median survival time. <i>Results:</i> Among the 1,684 patients diagnosed with SCLC, 1,215 (72%) were diagnosed with extensive-stage disease and 469 (28%) with limited-stage disease. Most of the patients were male (90%). The median survival duration of patients with limited-stage and extensive-stage SCLC was 10.3 months and 5.6 months, respectively. For limited-stage patients, surgery, chemotherapy, and combined chemotherapy and radiotherapy resulted in better survival than best supportive care (HR 0.20, p &lt; 0.001; HR 0.61, p &lt; 0.001, and HR 0.37, p &lt; 0.001, respectively). For extensive-stage patients, male gender was significantly associated with a poor prognosis (HR 1.45, p &lt; 0.001) and chemotherapy was shown to improve overall survival more effectively than best supportive care (HR 0.37, p &lt; 0.001). <i>Conclusion:</i> For limited-stage SCLC patients, surgery, chemotherapy, and combined chemotherapy and radiotherapy improved survival compared to best supportive care. Extensive-stage SCLC patients benefited more from chemotherapy treatment than from best supportive care.
DOI: 10.6084/m9.figshare.5123143.v1
title: Supplementary Material for: Loss-of-Function <i>CNKSR2</i> Mutation Is a Likely Cause of Non-Syndromic X-Linked Intellectual Disability

description: In a non-dysmorphic 5-year-old boy with developmental delay, well-controlled epilepsy, and microcephaly, a 234-kb deletion of Xp22.12 was detected by copy number analysis. The maternally inherited deletion removed the initial 15 of the 21 exons of the connector enhancer of KSR-2 gene called <i>CNKSR2 </i>or <i>CNK2</i>. Our finding suggests that loss of <i>CNKSR2</i> is a novel cause of non-syndromic X-linked mental retardation, an assumption supported by high gene expression in the brain, localization to the post-synaptic density, and a role in RAS/MAPK-dependent signal transduction.
DOI: 10.6084/m9.figshare.5123131
title: Supplementary Material for: The Frequency and Risk of Preclinical Coronary Artery Disease Detected Using Multichannel Cardiac Computed Tomography in Patients with Ischemic Stroke

description: <i>Background:</i> Atherosclerosis is a systemic disease. Many ischemic stroke patients may have concomitant coronary artery disease (CAD). Detection and treatment of preclinical CAD in stroke patients may improve long-term outcome and survival because CAD is a major cause of death during follow-up in stroke patients. However, association between coronary and cerebral artery atherosclerosis in stroke patients has not fully been investigated. This study aimed at examining the frequency and high-risk groups of CAD in ischemic stroke patients. <i>Methods:</i> Consecutive patients who were admitted due to acute ischemic stroke between July 2006 and June 2010 were prospectively enrolled in this study. A total of 1,304 patients who underwent MSCT coronary angiography and cerebral angiography were included in this study. By using 64-multislice computed tomography coronary angiography, we investigated the frequency of CAD and association between coronary and cerebral artery atherosclerosis in terms of location and burden (severity and extent) in stroke patients. We also sought to identify high-risk groups for CAD among stroke patients. <i>Results:</i> The frequency of significant (≧50%) CAD was 32.3% and the frequency of any degree of CAD was 70.1%. Diabetes mellitus, serum levels of total cholesterol, high-density lipoprotein cholesterol and triglyceride, and significant stenosis of the extracranial carotid, intracranial vertebral and basilar arteries were independently associated with CAD. However, no association was found between CAD and significant stenosis of the anterior, middle and posterior cerebral arteries. The association between CAD and cerebral atherosclerosis was stronger with increased severity and extent of cerebral atherosclerosis. When compared to patients with &lt;2 risk factors and without significant cerebral atherosclerosis, those with multiple (≧2) risk factors and atherosclerosis in both the carotid and the vertebrobasilar arteries had very high risks of CAD [odds ratio (OR) 8.36; 95% confidence interval (CI) 4.15–16.87]. The risk was also high in patients with multiple risk factors and atherosclerosis in either the carotid or the vertebrobasilar artery (OR 4.13; 95% CI 2.62–6.51), and in those with &lt;2 risk factors but atherosclerosis in both the carotid and the vertebrobasilar arteries (OR 3.40; 95% CI 1.22–9.47). <i>Conclusions:</i> A substantial portion of stroke patients had preclinical CAD, and there was a clear relationship between coronary and cerebral artery atherosclerosis in terms of location and burden. The risk of CAD was particularly high in stroke patients with multiple risk factors and atherosclerosis of the carotid and/or vertebrobasilar arteries.
DOI: 10.6084/m9.figshare.5123137.v1
title: Supplementary Material for: The Expression of Preaxial Polydactyly Is Influenced by Modifying Genetic Elements and Is Not Maintained by Chromosomal Inversion in an Avian Biomedical Model

description: Polydactyly (Po) is a common mutation found in many vertebrates. The UCD-Po.003 congenic chicken line was previously characterized for Po inheritance (autosomal dominant) and the mutation was mapped to chromosome 2p. Here, we describe for the first time the range and variability of the phenotype in this congenic line. Further, we studied the hypothesis that a chromosomal inversion was responsible for the maintenance of a large (6.3 Mb) candidate gene region. Fluorescence in situ hybridization employing BACs encompassing a 10.7-Mb region of GGA2p showed that the Po chromosome was normal, i.e. exhibits the wild-type BAC order. Continued fine-mapping along with a change in breeding strategy reduced the size of the causative region to 1.43 Mb. Recent research indicates that the cause of preaxial Po resides within a 794-bp highly conserved zone of polarizing activity regulatory sequence (ZRS) element located in intron 5 of the <i>LMBR1</i> gene; however, the ZRS polymorphism of interest is found in some but not all breeds of polydactylous chicken. Therefore, we sequenced the ZRS in 101 heterozygous and 30 unaffected (wild-type) individuals to establish the relevance of this region to the Po condition in the UCD-Po.003 congenic line. A single point mutation (C/A at coordinate GGA2p: 8,414,121) within the ZRS segregated with carrier status. The polydactylous UCD-Silkie line also maintains this SNP in addition to a single base deletion. An inheritance analysis of the phenotypic variation in UCD-Po.003 suggests recessive epistasis as the mode of inheritance for the additional modifying genetic elements, residing outside the ZRS, to impact the preaxial polydactyl phenotype. These results contribute to our understanding of the cause of Po in an important vertebrate model.
DOI: 10.6084/m9.figshare.5123128
title: Supplementary Material for: Wirksamkeit von Arbeitszeitrestriktion in der Prokrastinationsbehandlung

description: <i>Hintergrund: </i>Pathologisches Aufschieben (Prokrastination) ist eine klinisch bedeutsame Störung der Selbststeuerung, die besonders in Beratungs- und Psychotherapieeinrichtungen an Universitäten gut bekannt ist. Trotzdem gibt es bisher kaum systematisch evaluierte Behandlungsmethoden. In der vorliegenden Studie wird die Wirksamkeit der Methode der Arbeitszeitrestriktion in der Prokrastinationsbehandlung dargestellt. <i>Patienten und Methoden: </i>Untersucht wurden 116 Studierende, die unter Prokrastination litten und deshalb in der Psychotherapie- Ambulanz des Instituts für Psychologie der Universität Münster vorstellig wurden. Die Arbeitszeitrestriktion beruht auf der Idee, die Arbeitszeit zu verknappen und dadurch kostbar zu machen. Betroffene dürfen nur noch zu bestimmten Zeiten arbeiten; auf diese Weise wird die Trennung von Arbeitszeit und Freizeit wiederhergestellt. Erst wenn ein definierter Anteil der vorgesehenen Arbeitszeit effektiv genutzt wurde, darf zusätzliche Arbeitszeit geplant werden. Neben Fragebogendaten zu State- und Trait-Prokrastination, Planung, Zeitmanagement und Gestaltung der Lernumgebung wurden Verhaltensmaße in Form von täglich im «Münsteraner Arbeitstagebuch» protokolliertem Arbeitsverhalten erhoben. Die Fragebogendaten wurden zu 4 Messzeitpunkten erhoben. <i>Ergebnisse: </i>Alle selbstberichteten Maße und das täglich protokollierte Arbeitsverhalten verbesserten sich signifikant. Die State- Prokrastination (Academic Procrastination State Inventory (APSI)) verbesserte sich mit einer Effektstärke von 2,24 und die Trait-Prokrastination (Aitken Procrastination Scale (APS)) mit einer Effektstärke von 1,30. <i>Schlussfolgerung: </i>Die Arbeitszeitrestriktion ist ein vielversprechender Ansatz zur Behandlung von Prokrastination.
DOI: 10.6084/m9.figshare.5123134.v1
title: Supplementary Material for: A Combined Functional Annotation Score for Non-Synonymous Variants

description: <i>Aims:</i> Next-generation sequencing has opened the possibility of large-scale sequence-based disease association studies. A major challenge in interpreting whole-exome data is predicting which of the discovered variants are deleterious or neutral. To address this question in silico, we have developed a score called Combined Annotation scoRing toOL (CAROL), which combines information from 2 bioinformatics tools: PolyPhen-2 and SIFT, in order to improve the prediction of the effect of non-synonymous coding variants. <i>Methods:</i> We used a weighted <i>Z</i> method that combines the probabilistic scores of PolyPhen-2 and SIFT. We defined 2 dataset pairs to train and test CAROL using information from the dbSNP: ‘HGMD-PUBLIC’ and 1000 Genomes Project databases. The training pair comprises a total of 980 positive control (disease-causing) and 4,845 negative control (non-disease-causing) variants. The test pair consists of 1,959 positive and 9,691 negative controls.<i> Results:</i> CAROL has higher predictive power and accuracy for the effect of non-synonymous variants than each individual annotation tool (PolyPhen-2 and SIFT) and benefits from higher coverage. <i>Conclusion:</i> The combination of annotation tools can help improve automated prediction of whole-genome/exome non-synonymous variant functional consequences.
DOI: 10.6084/m9.figshare.5123119
title: Supplementary Material for: MC4R Dimerization in the Paraventricular Nucleus and GHSR/MC3R Heterodimerization in the Arcuate Nucleus: Is There Relevance for Body Weight Regulation?

description: The worldwide obesity epidemic is increasing, yet at this time, no long-acting and specific pharmaceutical therapies are available. Peripheral hormonal signals communicate metabolic status to the hypothalamus by activating their corresponding receptors in the arcuate nucleus (ARC). In this brain region, a variety of G protein-coupled receptors (GPCRs) are expressed that are potentially involved in weight regulation, but so far, the detailed function of most hypothalamic GPCRs is only partially understood. An important and underappreciated feature of GPCRs is the capacity for regulation via di- and heterodimerization. Increasing evidence implicates that heterodimerization of GPCRs results in profound functional consequences. Recently, we could demonstrate that interaction of the melanocortin 3 receptor (MC3R) and the growth hormone secretagogue receptor (GHSR)-1a results in a modulation of function in both receptors. Although the physiological role of GPCR-GPCR interaction in the hypothalamus is yet to be elucidated, this concept promises new avenues for investigation and understanding of hypothalamic functions dependent on GPCR signaling. Since GPCRs are important targets for drugs to combat many diseases, identification of heterodimers may be a prerequisite for highly specific drugs. Therefore, a detailed understanding of the mechanisms and their involvement in weight regulation is necessary. Fundamental to this understanding is the interplay of GPCR-GPCR in the hypothalamic nuclei in energy metabolism. In this review, we summarize the current knowledge on melanocortin receptors and GHSR-1a in hypothalamic weight regulation, especially as they pertain to possible drug targets. Furthermore, we include available evidence for the participation and significance of GPCR dimerization.
DOI: 10.6084/m9.figshare.5123122
title: Supplementary Material for: Outcomes of Acute Phase Cognitive Therapy in Outpatients with Anxious versus Nonanxious Depression

description: <i>Objective:</i> Compared to nonanxious depressed patients, anxious depressed patients respond less to pharmacotherapy, prompting consideration of alternate treatments. Based on the transdiagnostic principles of cognitive therapy (CT), we predicted that anxious depressed patients would respond as well to CT as nonanxious depressed patients. <i>Method:</i> Adults (n = 523) with recurrent major depressive disorder received 12–14 weeks of CT as part of the Continuation Phase Cognitive Therapy Relapse Prevention Trial. Anxious depressed patients (n = 264; 50.4%) were compared to nonanxious depressed patients (n = 259; 49.6%) on demographic variables, initial severity, attrition, and rates and patterns of response and remission. <i>Results:</i> Anxious depressed patients presented with greater illness severity and had significantly lower response (55.3 vs. 68.3%) and remission rates (26.9 vs. 40.2%) based on clinician-administered measures. By contrast, smaller between-group differences for attrition, and for response (59.1 vs. 64.9%) and remission (41.7 vs. 48.7%) rates on self-report measures were not significant. Further, anxious depressed patients had greater speed of improvement on self-reported anxiety symptom severity and clinician-rated depressive and anxiety symptom severity measures. <i>Conclusion:</i> Consistent with prior reports, anxious depressed patients presented with greater severity and, following CT, had lower response and remission rates on clinician-administered scales. However, anxious depressed patients improved more rapidly and response and remission rates on self-report measures were not significantly different from nonanxious depressed patients. Our findings suggest that anxious depressed patients may simply need additional time or more CT sessions to reach outcomes fully comparable to those of less anxious patients.
DOI: 10.6084/m9.figshare.5123125
title: Supplementary Material for: Analysis of p16<sub><i>CDKN2A</i></sub> Methylation and HPV-16 Infection in Oral Mucosal Dysplasia

description: <i>Objective:</i> The purpose of this study was to investigate the relationship between <i>p16</i><sub><i>CDKN2A</i></sub> methylation and epithelial dysplasia (ED). We also evaluated the expressions of proteins related to methylation (DNMT3B and DNMT1). Finally, we tested whether HPV-16/18 or the <i>dmt3b</i> (C46359T) polymorphism is associated with <i>p16</i><sub><i>CDKN2A</i></sub> methylation status. <i>Methods:</i> To test the hypothesis, a case-control study with 72 (control, n = 24; ED, n = 48) tissue samples from subjects was performed. Methylation-specific PCR, RFLP, and immunohistochemical analyses were performed to evaluate <i>p16</i><sub><i>CDKN2A</i></sub> methylation status, <i>dmt3b</i> (C46359T) genotyping, and protein levels, respectively. <i>Results:</i> The methylation of <i>p16</i><sub><i>CDKN2A</i></sub> and HPV-16 was associated with ED gradation (p = 0.001 and 0.002, respectively). In addition, most HPV-16-positive samples (77.8%) exhibited <i>p16</i><sub><i>CDKN2A</i></sub> methylation; however, changes in DNMT3B and DNMT1 protein levels were not observed in HPV-positive samples. Neither HPV-18 nor the <i>dmt3b</i> polymorphism was associated with <i>p16</i><sub><i>CDKN2A</i></sub> methylation. <i>Conclusions:</i> There is an association between the presence of HPV-16 in ED and the occurrence of <i>p16</i><sub><i>CDKN2A</i></sub> methylation. Both variables are also associated with ED development, but further studies are necessary to clarify if they operate independently and if they have any impact on OD malignization.
DOI: 10.6084/m9.figshare.5123125.v1
title: Supplementary Material for: Analysis of p16<sub><i>CDKN2A</i></sub> Methylation and HPV-16 Infection in Oral Mucosal Dysplasia

description: <i>Objective:</i> The purpose of this study was to investigate the relationship between <i>p16</i><sub><i>CDKN2A</i></sub> methylation and epithelial dysplasia (ED). We also evaluated the expressions of proteins related to methylation (DNMT3B and DNMT1). Finally, we tested whether HPV-16/18 or the <i>dmt3b</i> (C46359T) polymorphism is associated with <i>p16</i><sub><i>CDKN2A</i></sub> methylation status. <i>Methods:</i> To test the hypothesis, a case-control study with 72 (control, n = 24; ED, n = 48) tissue samples from subjects was performed. Methylation-specific PCR, RFLP, and immunohistochemical analyses were performed to evaluate <i>p16</i><sub><i>CDKN2A</i></sub> methylation status, <i>dmt3b</i> (C46359T) genotyping, and protein levels, respectively. <i>Results:</i> The methylation of <i>p16</i><sub><i>CDKN2A</i></sub> and HPV-16 was associated with ED gradation (p = 0.001 and 0.002, respectively). In addition, most HPV-16-positive samples (77.8%) exhibited <i>p16</i><sub><i>CDKN2A</i></sub> methylation; however, changes in DNMT3B and DNMT1 protein levels were not observed in HPV-positive samples. Neither HPV-18 nor the <i>dmt3b</i> polymorphism was associated with <i>p16</i><sub><i>CDKN2A</i></sub> methylation. <i>Conclusions:</i> There is an association between the presence of HPV-16 in ED and the occurrence of <i>p16</i><sub><i>CDKN2A</i></sub> methylation. Both variables are also associated with ED development, but further studies are necessary to clarify if they operate independently and if they have any impact on OD malignization.
DOI: 10.6084/m9.figshare.5123128.v1
title: Supplementary Material for: Wirksamkeit von Arbeitszeitrestriktion in der Prokrastinationsbehandlung

description: <i>Hintergrund: </i>Pathologisches Aufschieben (Prokrastination) ist eine klinisch bedeutsame Störung der Selbststeuerung, die besonders in Beratungs- und Psychotherapieeinrichtungen an Universitäten gut bekannt ist. Trotzdem gibt es bisher kaum systematisch evaluierte Behandlungsmethoden. In der vorliegenden Studie wird die Wirksamkeit der Methode der Arbeitszeitrestriktion in der Prokrastinationsbehandlung dargestellt. <i>Patienten und Methoden: </i>Untersucht wurden 116 Studierende, die unter Prokrastination litten und deshalb in der Psychotherapie- Ambulanz des Instituts für Psychologie der Universität Münster vorstellig wurden. Die Arbeitszeitrestriktion beruht auf der Idee, die Arbeitszeit zu verknappen und dadurch kostbar zu machen. Betroffene dürfen nur noch zu bestimmten Zeiten arbeiten; auf diese Weise wird die Trennung von Arbeitszeit und Freizeit wiederhergestellt. Erst wenn ein definierter Anteil der vorgesehenen Arbeitszeit effektiv genutzt wurde, darf zusätzliche Arbeitszeit geplant werden. Neben Fragebogendaten zu State- und Trait-Prokrastination, Planung, Zeitmanagement und Gestaltung der Lernumgebung wurden Verhaltensmaße in Form von täglich im «Münsteraner Arbeitstagebuch» protokolliertem Arbeitsverhalten erhoben. Die Fragebogendaten wurden zu 4 Messzeitpunkten erhoben. <i>Ergebnisse: </i>Alle selbstberichteten Maße und das täglich protokollierte Arbeitsverhalten verbesserten sich signifikant. Die State- Prokrastination (Academic Procrastination State Inventory (APSI)) verbesserte sich mit einer Effektstärke von 2,24 und die Trait-Prokrastination (Aitken Procrastination Scale (APS)) mit einer Effektstärke von 1,30. <i>Schlussfolgerung: </i>Die Arbeitszeitrestriktion ist ein vielversprechender Ansatz zur Behandlung von Prokrastination.
DOI: 10.6084/m9.figshare.5123107
title: Supplementary Material for: Pretransplant Physical Activity Predicts All-Cause Mortality in Kidney Transplant Recipients

description: <i>Background:</i> Low physical activity (PA) has been associated with higher rates of cardiovascular disease (CVD) and mortality in the general population. Despite the benefits of kidney transplantation, kidney transplant recipients (KTRs) remain at elevated risk for CVD and mortality compared to individuals without kidney disease. <i>Methods:</i> A prospective cohort of 507 adult KTRs from three academic centers completed the Physical Activity Scale for the Elderly (PASE) at transplantation. PASE scores were divided into tertiles. <i>Results:</i> PA was lower with older age, history of CVD, smoking, and diabetes. During the median 8-year follow-up period, 128 individuals died, among whom 101 had a functioning allograft. In multivariable Cox regression for all-cause mortality, greater PA was strongly associated with better survival (HR: 0.52 for most active vs. inactive tertiles, 95% CI: 0.31–0.87, p = 0.01). Secondary analyses, in which (1) death with a functioning graft was the primary outcome, and (2) PASE scores were converted to the metabolic equivalent of task, revealed similar results. We did not find an association between change of PA after transplantation and mortality. <i>Conclusions:</i> PA at the time of kidney transplantation is a strong predictor of all-cause mortality and death with graft function. Evaluation of PA level among kidney transplant candidates may be a useful method to risk-stratify patients for survival after kidney transplantation. Kidney transplant candidates and recipients should also be encouraged to be physically active.