cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5631898
title: Obstructive and restrictive pulmonary dysfunction in long-term lymphoma survivors after high-dose therapy with autologous stem cell transplantation

description: <b>Background:</b> Obstructive and restrictive dysfunction in long-term lymphoma survivors (LSs) after high-dose therapy with autologous stem-cell transplantation (HDT-ASCT) has not been addressed systematically previously. <b>Material and methods:</b> LSs treated in Norway 1987–2008 with HDT-ASCT who performed spirometry, measurement of static lung volumes and echocardiography 2012–2014 at either Oslo or St. Olavs University Hospitals was eligible. Smoking data were recorded by questionnaire. Treatment data were collected from medical records or hospital databases. Factors associated with obstructive and restrictive impairments (dichotomous outcomes) were examined by Poisson regression. Linear regression with the margins post-estimation command was used to derive adjusted mean values of forced expiratory volume in 1 s (FEV<sub>1</sub>). We used the normative reference data recommended by the European Respiratory Society for calculating percent predicted values. <b>Results:</b> A total of 226 LSs were studied, of whom 11.5 and 5.8% had obstructive and restrictive impairment, respectively. For women and men, mean FEV<sub>1</sub> was 2.31 and 3.34 l corresponding to 11.4%- and 11.1%-points below that predicted from norms, respectively. In multivariable regression analyses, cumulative doxorubicin dose (400–775 mg/m<sup>2</sup>) and current smoking were associated with increased risk of obstructive impairment, and chest RT (&gt;13–66 Gy) was associated with increased risk of restrictive impairment. Currently smoking LSs within the highest doxorubicin category (400–775 mg/m<sup>2</sup>), had the lowest adjusted mean FEV<sub>1</sub>. <b>Conclusions:</b> Despite intensive cancer treatment, our analysis showed modest reductions in obstructive parameters among long-term LSs after HDT-ASCT compared to normative reference data. To limit obstructive impairments in LSs after HDT-ASCT, we suggest that targeted smoking-cessation advice is directed towards patients who have received high cumulative doses of doxorubicin.
DOI: 10.6084/m9.figshare.5631898.v1
title: Obstructive and restrictive pulmonary dysfunction in long-term lymphoma survivors after high-dose therapy with autologous stem cell transplantation

description: <b>Background:</b> Obstructive and restrictive dysfunction in long-term lymphoma survivors (LSs) after high-dose therapy with autologous stem-cell transplantation (HDT-ASCT) has not been addressed systematically previously. <b>Material and methods:</b> LSs treated in Norway 1987–2008 with HDT-ASCT who performed spirometry, measurement of static lung volumes and echocardiography 2012–2014 at either Oslo or St. Olavs University Hospitals was eligible. Smoking data were recorded by questionnaire. Treatment data were collected from medical records or hospital databases. Factors associated with obstructive and restrictive impairments (dichotomous outcomes) were examined by Poisson regression. Linear regression with the margins post-estimation command was used to derive adjusted mean values of forced expiratory volume in 1 s (FEV<sub>1</sub>). We used the normative reference data recommended by the European Respiratory Society for calculating percent predicted values. <b>Results:</b> A total of 226 LSs were studied, of whom 11.5 and 5.8% had obstructive and restrictive impairment, respectively. For women and men, mean FEV<sub>1</sub> was 2.31 and 3.34 l corresponding to 11.4%- and 11.1%-points below that predicted from norms, respectively. In multivariable regression analyses, cumulative doxorubicin dose (400–775 mg/m<sup>2</sup>) and current smoking were associated with increased risk of obstructive impairment, and chest RT (&gt;13–66 Gy) was associated with increased risk of restrictive impairment. Currently smoking LSs within the highest doxorubicin category (400–775 mg/m<sup>2</sup>), had the lowest adjusted mean FEV<sub>1</sub>. <b>Conclusions:</b> Despite intensive cancer treatment, our analysis showed modest reductions in obstructive parameters among long-term LSs after HDT-ASCT compared to normative reference data. To limit obstructive impairments in LSs after HDT-ASCT, we suggest that targeted smoking-cessation advice is directed towards patients who have received high cumulative doses of doxorubicin.
DOI: 10.6084/m9.figshare.5631880
title: G-Quadruplexes influence pri-microRNA processing

description: RNA G-Quadruplexes (G4) have been shown to possess many biological functions, including the regulation of microRNA (miRNA) biogenesis and function. However, their impact on pri-miRNA processing remains unknown. We identified G4 located near the Drosha cleavage site in three distinct pri-miRNAs: pri-mir200c, pri-mir451a, and pri-mir497. The folding of the potential G4 motifs was determined in solution. Subsequently, mutations disrupting G4 folding led to important changes in the mature miRNAs levels in cells. Moreover, using small antisense oligonucleotides binding to the pri-miRNA, it was possible to modulate, either positively or negatively, the mature miRNA levels. Together, these data demonstrate that G4 motifs could contribute to the regulation of pri-mRNA processing, a novel role for G4. Considering that bio-informatics screening indicates that between 9% and 50% of all pri-miRNAs contain a putative G4, these structures possess interesting potential as future therapeutic targets.
DOI: 10.6084/m9.figshare.5631880.v1
title: G-Quadruplexes influence pri-microRNA processing

description: RNA G-Quadruplexes (G4) have been shown to possess many biological functions, including the regulation of microRNA (miRNA) biogenesis and function. However, their impact on pri-miRNA processing remains unknown. We identified G4 located near the Drosha cleavage site in three distinct pri-miRNAs: pri-mir200c, pri-mir451a, and pri-mir497. The folding of the potential G4 motifs was determined in solution. Subsequently, mutations disrupting G4 folding led to important changes in the mature miRNAs levels in cells. Moreover, using small antisense oligonucleotides binding to the pri-miRNA, it was possible to modulate, either positively or negatively, the mature miRNA levels. Together, these data demonstrate that G4 motifs could contribute to the regulation of pri-mRNA processing, a novel role for G4. Considering that bio-informatics screening indicates that between 9% and 50% of all pri-miRNAs contain a putative G4, these structures possess interesting potential as future therapeutic targets.
DOI: 10.6084/m9.figshare.5631871
title: UBE3A-mediated regulation of imprinted genes and epigenome-wide marks in human neurons

description: The dysregulation of genes in neurodevelopmental disorders that lead to social and cognitive phenotypes is a complex, multilayered process involving both genetics and epigenetics. Parent-of-origin effects of deletion and duplication of the 15q11-q13 locus leading to Angelman, Prader-Willi, and Dup15q syndromes are due to imprinted genes, including <i>UBE3A</i>, which is maternally expressed exclusively in neurons. <i>UBE3A</i> encodes a ubiquitin E3 ligase protein with multiple downstream targets, including RING1B, which in turn monoubiquitinates histone variant H2A.Z. To understand the impact of neuronal UBE3A levels on epigenome-wide marks of DNA methylation, histone variant H2A.Z positioning, active H3K4me3 promoter marks, and gene expression, we took a multi-layered genomics approach. We performed an siRNA knockdown of <i>UBE3A</i> in two human neuroblastoma cell lines, including parental SH-SY5Y and the SH(15M) model of Dup15q. Genes differentially methylated across cells with differing UBE3A levels were enriched for functions in gene regulation, DNA binding, and brain morphology. Importantly, we found that altering UBE3A levels had a profound epigenetic effect on the methylation levels of up to half of known imprinted genes. Genes with differential H2A.Z peaks in SH(15M) compared to SH-SY5Y were enriched for ubiquitin and protease functions and associated with autism, hypoactivity, and energy expenditure. Together, these results support a genome-wide epigenetic consequence of altered UBE3A levels in neurons and suggest that UBE3A regulates an imprinted gene network involving DNA methylation patterning and H2A.Z deposition.
DOI: 10.6084/m9.figshare.5631871.v1
title: UBE3A-mediated regulation of imprinted genes and epigenome-wide marks in human neurons

description: The dysregulation of genes in neurodevelopmental disorders that lead to social and cognitive phenotypes is a complex, multilayered process involving both genetics and epigenetics. Parent-of-origin effects of deletion and duplication of the 15q11-q13 locus leading to Angelman, Prader-Willi, and Dup15q syndromes are due to imprinted genes, including <i>UBE3A</i>, which is maternally expressed exclusively in neurons. <i>UBE3A</i> encodes a ubiquitin E3 ligase protein with multiple downstream targets, including RING1B, which in turn monoubiquitinates histone variant H2A.Z. To understand the impact of neuronal UBE3A levels on epigenome-wide marks of DNA methylation, histone variant H2A.Z positioning, active H3K4me3 promoter marks, and gene expression, we took a multi-layered genomics approach. We performed an siRNA knockdown of <i>UBE3A</i> in two human neuroblastoma cell lines, including parental SH-SY5Y and the SH(15M) model of Dup15q. Genes differentially methylated across cells with differing UBE3A levels were enriched for functions in gene regulation, DNA binding, and brain morphology. Importantly, we found that altering UBE3A levels had a profound epigenetic effect on the methylation levels of up to half of known imprinted genes. Genes with differential H2A.Z peaks in SH(15M) compared to SH-SY5Y were enriched for ubiquitin and protease functions and associated with autism, hypoactivity, and energy expenditure. Together, these results support a genome-wide epigenetic consequence of altered UBE3A levels in neurons and suggest that UBE3A regulates an imprinted gene network involving DNA methylation patterning and H2A.Z deposition.
DOI: 10.6084/m9.figshare.5631862
title: Molecular characterization of an <i>Apple stem grooving virus</i> isolate from kiwifruit (<i>Actinidia chinensis</i>) in China

description: <i>Apple stem grooving virus</i> (ASGV) is the type species of the genus <i>Capillovirus</i> in the family <i>Betaflexiviridae</i>. The virus naturally infects several important horticultural crops. Although many ASGV isolates from apple (<i>Malus</i> spp.), pear (<i>Pyrus</i> spp.), citrus (<i>Citrus</i> spp.) and lily (<i>Lilium</i> spp.) have been characterized, the occurrence status and molecular characteristics of the virus from kiwifruit trees are still largely unknown. In this study, by employing the strategy of small RNA deep sequencing coupled with conventional RT-PCR, we provide the first complete genome sequence of an ASGV isolate (named ASGV-Ac) infecting a kiwifruit plant (<i>Actinidia chinensis</i>) grown in China. The complete genome of ASGV-Ac consisted of 6496 nucleotides, excluding poly (A) tail at its 3ʹ end. ASGV-Ac shared high nucleotide sequence identities of 96.9% and 93.5% with a kiwifruit ASGV isolate reported from New Zealand (accession no. AF522459) for their CP and MP coding regions. However, the isolate was phylogenetically distal to ASGV isolates from all other hosts by sharing 79.5–82.4% genome sequence identity, and likely represented a novel variant. RT-PCR detection revealed the presence of ASGV-infected kiwifruit in two provinces in China. The partial CP gene of nine ASGV isolates determined in this study shared 87.8–99.6% nucleotide sequence identity with the corresponding sequences of other reported ASGV isolates from kiwifruit, indicating molecular diversity of ASGV isolates from kiwifruit plants. This study provides important evidence for monitoring the viral disease and novel molecular information for developing efficient detection techniques to prevent virus spread.
DOI: 10.6084/m9.figshare.5631862.v1
title: Molecular characterization of an <i>Apple stem grooving virus</i> isolate from kiwifruit (<i>Actinidia chinensis</i>) in China

description: <i>Apple stem grooving virus</i> (ASGV) is the type species of the genus <i>Capillovirus</i> in the family <i>Betaflexiviridae</i>. The virus naturally infects several important horticultural crops. Although many ASGV isolates from apple (<i>Malus</i> spp.), pear (<i>Pyrus</i> spp.), citrus (<i>Citrus</i> spp.) and lily (<i>Lilium</i> spp.) have been characterized, the occurrence status and molecular characteristics of the virus from kiwifruit trees are still largely unknown. In this study, by employing the strategy of small RNA deep sequencing coupled with conventional RT-PCR, we provide the first complete genome sequence of an ASGV isolate (named ASGV-Ac) infecting a kiwifruit plant (<i>Actinidia chinensis</i>) grown in China. The complete genome of ASGV-Ac consisted of 6496 nucleotides, excluding poly (A) tail at its 3ʹ end. ASGV-Ac shared high nucleotide sequence identities of 96.9% and 93.5% with a kiwifruit ASGV isolate reported from New Zealand (accession no. AF522459) for their CP and MP coding regions. However, the isolate was phylogenetically distal to ASGV isolates from all other hosts by sharing 79.5–82.4% genome sequence identity, and likely represented a novel variant. RT-PCR detection revealed the presence of ASGV-infected kiwifruit in two provinces in China. The partial CP gene of nine ASGV isolates determined in this study shared 87.8–99.6% nucleotide sequence identity with the corresponding sequences of other reported ASGV isolates from kiwifruit, indicating molecular diversity of ASGV isolates from kiwifruit plants. This study provides important evidence for monitoring the viral disease and novel molecular information for developing efficient detection techniques to prevent virus spread.
DOI: 10.6084/m9.figshare.5631844
title: This is a Sage module which calculates phase diagrams using Sturm chains from Graph-facilitated resonant mode counting in stochastic interaction networks

description: Oscillations in dynamical systems are widely reported in multiple branches of physics. Critically, even a non-oscillatory deterministic system can produce cyclic trajectories when it is in a low copy number, stochastic, regime. Common methods of finding parameter ranges for stochastically driven resonances, such as direct calculation, are cumbersome for any but the smallest networks. In this paper, we provide a systematic framework to efficiently determine the number of resonant modes and parameter ranges for stochastic oscillations relying on real root counting algorithms and graph theoretic methods. We argue that stochastic resonance is a network property by showing that resonant modes only depend on the squared Jacobian matrix <i>J</i><sup>2</sup>, unlike deterministic oscillations which are determined by <i>J</i>. By using graph theoretic tools, analysis of stochastic behaviour for larger interaction networks is simplified and stochastic dynamical systems with multiple resonant modes can be identified easily.
DOI: 10.6084/m9.figshare.5631847
title: Supplementary Material for: E3 Ubiquitin Ligase RNF125 Activates Interleukin-36 Receptor Signaling and Contributes to Its Turnover

description: Signaling by the interleukin-36 receptor (IL-36R) is linked to inflammatory diseases such as psoriasis. However, the regulation of IL-36R signaling is poorly understood. Activation of IL-36R signaling in cultured cells results in an increased polyubiquitination of the receptor subunit, IL-1Rrp2. Treatment with deubiquitinases shows that the receptor subunit of IL-36R, IL-1Rrp2, is primarily polyubiquitinated at the K63 position, which is associated with endocytic trafficking and signal transduction. A minor amount of ubiquitination is at the K48 position that is associated with protein degradation. A focused siRNA screen identified RNF125, an E3 ubiquitin ligase, to ubiquitinate IL-1Rrp2 upon activation of IL-36R signaling while not affecting the activated IL-1 receptor. Knockdown of RNF125 decreases signal transduction by the IL-36R. Overexpression of RNF125 in HEK293T cells activates IL-36R signaling and increases the ubiquitination of IL-1Rrp2 and its subsequent turnover. RNF125 can coimmunoprecipitate with the IL-36R, and it traffics with IL-1Rrp2 from the cell surface to lysosomes. Mutations of Lys568 and Lys569 in the C-terminal tail of IL-1Rrp2 decrease ubiquitination by RNF125 and increase the steady-state levels of IL-1Rrp2. These results demonstrate that RNF125 has multiple regulatory roles in the signaling, trafficking, and turnover of the IL-36R.
DOI: 10.6084/m9.figshare.5631844.v1
title: This is a Sage module which calculates phase diagrams using Sturm chains from Graph-facilitated resonant mode counting in stochastic interaction networks

description: Oscillations in dynamical systems are widely reported in multiple branches of physics. Critically, even a non-oscillatory deterministic system can produce cyclic trajectories when it is in a low copy number, stochastic, regime. Common methods of finding parameter ranges for stochastically driven resonances, such as direct calculation, are cumbersome for any but the smallest networks. In this paper, we provide a systematic framework to efficiently determine the number of resonant modes and parameter ranges for stochastic oscillations relying on real root counting algorithms and graph theoretic methods. We argue that stochastic resonance is a network property by showing that resonant modes only depend on the squared Jacobian matrix <i>J</i><sup>2</sup>, unlike deterministic oscillations which are determined by <i>J</i>. By using graph theoretic tools, analysis of stochastic behaviour for larger interaction networks is simplified and stochastic dynamical systems with multiple resonant modes can be identified easily.
DOI: 10.6084/m9.figshare.5631832
title: Supplementary Material for: High Systolic Blood Pressure after Successful Endovascular Treatment Affects Early Functional Outcome in Acute Ischemic Stroke

description: <b><i>Background:</i></b> Endovascular treatment (EVT) has been shown to significantly improve functional outcome in patients with acute large cerebral vessel occlusions. To date, no evidence-based recommendations on blood pressure management after successful EVT exist. Previous studies showed an association between high pre-EVT systolic blood pressure (SBP) and functional outcome, but do not answer the question on how to manage blood pressure after successful recanalization. The purpose of this study was to determine the role of blood pressure measurements as a predictor for early functional outcome in patients with successful EVT. <b><i>Methods:</i></b> Prospectively derived data from patients with acute large vessel occlusion within the anterior circulation and EVT was analyzed in this monocentric study. Mean systolic- and maximum SBP as well as SBP-peaks have been obtained for the first 24 h after successful EVT. Predictive value of SBP for discharge modified Rankin Scale (mRS) ≤2 has been investigated using logistic regression models. <b><i>Results:</i></b> From 168 patients with successful EVT, 74 (44%) had a favorable outcome with an mRS ≤2. Mean- (127 vs. 131 mm Hg, <i>p</i> = 0.035) and maximum SBP (157 vs. 169 mm Hg, <i>p</i> &lt; 0.001) as well as the number of SBP-peaks (0 vs. 1.5, <i>p</i> = 0.004) were lower in patients with favorable outcomes. Multivariable logistic regression showed high mean- and maximum SBP to predict unfavorable outcomes. Cutoff mean SBP was 141 mm Hg and maximum SBP 159 mm Hg. <b><i>Conclusions:</i></b> High SBP in the first 24 h after recanalization of acute anterior cerebral vessel occlusions is associated with unfavorable functional outcome. Interventional studies are needed to determine the role of SBP management as a modifiable parameter in the early phase after successful EVT.
DOI: 10.6084/m9.figshare.5631832.v1
title: Supplementary Material for: High Systolic Blood Pressure after Successful Endovascular Treatment Affects Early Functional Outcome in Acute Ischemic Stroke

description: <b><i>Background:</i></b> Endovascular treatment (EVT) has been shown to significantly improve functional outcome in patients with acute large cerebral vessel occlusions. To date, no evidence-based recommendations on blood pressure management after successful EVT exist. Previous studies showed an association between high pre-EVT systolic blood pressure (SBP) and functional outcome, but do not answer the question on how to manage blood pressure after successful recanalization. The purpose of this study was to determine the role of blood pressure measurements as a predictor for early functional outcome in patients with successful EVT. <b><i>Methods:</i></b> Prospectively derived data from patients with acute large vessel occlusion within the anterior circulation and EVT was analyzed in this monocentric study. Mean systolic- and maximum SBP as well as SBP-peaks have been obtained for the first 24 h after successful EVT. Predictive value of SBP for discharge modified Rankin Scale (mRS) ≤2 has been investigated using logistic regression models. <b><i>Results:</i></b> From 168 patients with successful EVT, 74 (44%) had a favorable outcome with an mRS ≤2. Mean- (127 vs. 131 mm Hg, <i>p</i> = 0.035) and maximum SBP (157 vs. 169 mm Hg, <i>p</i> &lt; 0.001) as well as the number of SBP-peaks (0 vs. 1.5, <i>p</i> = 0.004) were lower in patients with favorable outcomes. Multivariable logistic regression showed high mean- and maximum SBP to predict unfavorable outcomes. Cutoff mean SBP was 141 mm Hg and maximum SBP 159 mm Hg. <b><i>Conclusions:</i></b> High SBP in the first 24 h after recanalization of acute anterior cerebral vessel occlusions is associated with unfavorable functional outcome. Interventional studies are needed to determine the role of SBP management as a modifiable parameter in the early phase after successful EVT.
DOI: 10.6084/m9.figshare.5631835
title: Soil properties, Meteorological, hydrological and geochemical (K+) data from the Stara Rzeka catchment (Carpathians, Poland)

description: The hydrometeorological observations 1994-2016 from Lazy Station (Poland):- monthly sums of precipitation [mm],- the monthly means of air temperature [C]- the monthly means of speciffic runoff of Stara Rzeka stream [L s-1 km-2]- the concentration of potassium in stream water during events [mg/L]- specific runoff from four streams [L s-1 km-2] (agricultural - K, forested - LP, agricultural - DP, mixed land use - SR)- ground temperature at 5, 10, 20, 50, 100 cm depth [C]- hourly precipitation during events [mm]- hourly air temperature during events [C]- soil texture, ph and exchangable K+ content