cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.2065605.v1
title: Gene promoter methylation signature predicts survival of head and neck squamous cell carcinoma patients

description: Infection with high-risk types of human papilloma virus (HPV) is currently the best-established prognostic marker for head and neck squamous cell carcinoma (HNSCC), one of the most common and lethal human malignancies worldwide. Clinical trials have been launched to address the concept of treatment de-escalation for HPV-positive HNSCC with the final aim to reduce treatment related toxicity and debilitating long-term impacts on the quality of life. However, HPV-related tumors are mainly restricted to oropharyngeal SCC (OPSCC) and there is an urgent need to establish reliable biomarkers for all patients at high risk for treatment failure. A patient cohort (n=295) with mainly non-OPSCC (72.9%) and a low prevalence of HPV16-related tumors (8.8%) was analyzed by MassARRAY to determine a previously established prognostic methylation score (MS). Kaplan-Meier revealed a highly significant correlation between a high MS and a favorable survival for OPSCC (<i>P</i>=0.0004) and for non-OPSCC (<i>P</i>&lt;0.0001), which was confirmed for all HNSCC by multivariate Cox regression models (HR: 9.67, 95% CI [4.61–20.30], <i>P</i>&lt;0.0001). Next, we established a minimal methylation signature score (MMSS), which consists of ten most informative of the originally 62 CpG units used for the MS. The prognostic value of the MMSS was confirmed by Kaplan-Meier analysis for all HNSCC (<i>P</i>&lt;0.0001) and non-OPSCC (<i>P</i>=0.0002), and was supported by multivariate Cox regression models for all HNSCC (HR: 2.15, 95% CI [1.36–3.41], <i>P</i>=0.001). In summary, the MS and the MMSS exhibit an excellent performance as prognosticators for survival, which is not limited by the anatomical site, and both could be implemented in future clinical trials.
DOI: 10.6084/m9.figshare.2065614.v3
title: Quantitative evaluation of first, second, and third generation hairpin systems reveals the limit of mammalian vector-based RNAi

description: Incorporating miRNA-like features into vector-based hairpin scaffolds has been shown to augment small RNA processing and RNAi efficiency. Therefore, defining an optimal, native hairpin context may obviate a need for hairpin-specific targeting design schemes, which confound the movement of functional siRNAs into shRNA/artificial miRNA backbones, or large-scale screens to identify efficacious sequences. Thus, we used quantitative cell-based assays to compare separate third generation artificial miRNA systems, miR-E (based on miR-30a) and miR-3G (based on miR-16-2 and first described in this study) to widely-adopted, first and second generation formats in both Pol-II and Pol-III expression vector contexts. Despite their unique structures and strandedness, and in contrast to first and second-generation RNAi triggers, the third generation formats operated with remarkable similarity to one another, and strong silencing was observed with a significant fraction of the evaluated target sequences within either promoter context. By pairing an established siRNA design algorithm with the third generation vectors we could readily identify targeting sequences that matched or exceeded the potency of those discovered through large-scale sensor-based assays. We find that third generation hairpin systems enable the maximal level of siRNA function, likely through enhanced processing and accumulation of precisely-defined guide RNAs. Therefore, we predict future gains in RNAi potency will come from improved hairpin expression and identification of optimal siRNA-intrinsic silencing properties rather than further modification of these scaffolds. Consequently, third generation systems should be the primary format for vector-based RNAi studies; miR-3G is advantageous due to its small expression cassette and simplified, cost-efficient cloning scheme.
DOI: 10.6084/m9.figshare.2065563
title: A potential role for sensory neuroplasticity in major depressive disorder.pdf

description: Brain imaging and electrophysiological recordings of primary and secondary sensory cortices indicate that each is arranged into sub-regions that process specific subsets of environmental stimuli. The sizes of these regions, termed cortical response fields (CRFs), have been correlated with the consciously perceived intensity of their respective stimuli and with the neural processing power devoted to analyzing such stimuli. Typically, CRFs are highly plastic, and their experience-dependent plasticity is modulated by attention and reinforcement. Because of this, disorders with negative attentional bias, such as major depressive disorder (MDD), have the potential to significantly alter these maps in psychologically harmful ways. We review literature suggesting that sensory map plasticity plays a role in the initiation and maintenance of major depressive disorder. Such a role would suggest possible new treatments for MDD, and may help explain mechanisms of existing treatments.
DOI: 10.6084/m9.figshare.2065578
title: Gene expression profile of <i>zeitlupe/lov kelch protein1</i> T-DNA insertion mutants in <i>Arabidopsis thaliana</i>: Downregulation of auxin-inducible genes in hypocotyls

description: Elongation of hypocotyl cells has been studied as a model for elucidating the contribution of cellular expansion to plant organ growth. ZEITLUPE (ZTL) or LOV KELCH PROTEIN1 (LKP1) is a positive regulator of warmth-induced hypocotyl elongation under white light in <i>Arabidopsis</i>, although the molecular mechanisms by which it promotes hypocotyl cell elongation remain unknown. Microarray analysis showed that 134 genes were upregulated and 204 genes including 15 auxin-inducible genes were downregulated in the seedlings of 2 <i>ztl</i> T-DNA insertion mutants grown under warm conditions with continuous white light. Application of a polar auxin transport inhibitor, an auxin antagonist or an auxin biosynthesis inhibitor inhibited hypocotyl elongation of control seedlings to the level observed with the <i>ztl</i> mutant. Our data suggest the involvement of auxin and auxin-inducible genes in ZTL-mediated hypocotyl elongation.
DOI: 10.6084/m9.figshare.2065578.v1
title: Gene expression profile of <i>zeitlupe/lov kelch protein1</i> T-DNA insertion mutants in <i>Arabidopsis thaliana</i>: Downregulation of auxin-inducible genes in hypocotyls

description: Elongation of hypocotyl cells has been studied as a model for elucidating the contribution of cellular expansion to plant organ growth. ZEITLUPE (ZTL) or LOV KELCH PROTEIN1 (LKP1) is a positive regulator of warmth-induced hypocotyl elongation under white light in <i>Arabidopsis</i>, although the molecular mechanisms by which it promotes hypocotyl cell elongation remain unknown. Microarray analysis showed that 134 genes were upregulated and 204 genes including 15 auxin-inducible genes were downregulated in the seedlings of 2 <i>ztl</i> T-DNA insertion mutants grown under warm conditions with continuous white light. Application of a polar auxin transport inhibitor, an auxin antagonist or an auxin biosynthesis inhibitor inhibited hypocotyl elongation of control seedlings to the level observed with the <i>ztl</i> mutant. Our data suggest the involvement of auxin and auxin-inducible genes in ZTL-mediated hypocotyl elongation.
DOI: 10.6084/m9.figshare.2065575
title: Genome-wide methylation profiling identifies novel methylated genes in neuroblastoma tumors

description: Neuroblastoma is a very heterogeneous tumor of childhood. The clinical spectra range from very aggressive metastatic disease to spontaneous regression, even without therapy. Aberrant DNA methylation pattern is a common feature of most cancers. For neuroblastoma, it has been demonstrated both for single genes as well as genome-wide, where a so-called methylator phenotype has been described. Here, we present a study using Illumina 450K methylation arrays on 60 neuroblastoma tumors. We show that aggressive tumors, characterized by International Neuroblastoma Risk Group (INRG) as stage M, are hypermethylated compared to low-grade tumors. On the contrary, INRG stage L tumors display more non-CpG methylation. The genes with the highest number of hypermethylated CpG sites in INRG M tumors are <i>TERT, PCDHGA4, DLX5</i>, and <i>DLX6-AS1</i>. Gene ontology analysis showed a representation of neuronal tumor relevant gene functions among the differentially methylated genes. For validation, we used a set of independent tumors previously analyzed with the Illumina 27K methylation arrays, which confirmed the differentially methylated sites. Top candidate genes with aberrant methylation were analyzed for altered gene expression through the R2 platform (http://r2.amc.nl), and for correlations between methylation and gene expression in a public dataset. Altered expression in nonsurvivors was found for the genes <i>B3GALT4</i> and <i>KIAA1949, CLIC5, DLX6-AS, TERT</i>, and <i>PIRT</i>, and strongest correlations were found for <i>TRIM36, KIAA0513</i>, and <i>PIRT</i>. Our data indicate that methylation profiling can be used for patient stratification and informs on epigenetically deregulated genes with the potential of increasing our knowledge about the underlying mechanisms of tumor development.
DOI: 10.6084/m9.figshare.2065575.v1
title: Genome-wide methylation profiling identifies novel methylated genes in neuroblastoma tumors

description: Neuroblastoma is a very heterogeneous tumor of childhood. The clinical spectra range from very aggressive metastatic disease to spontaneous regression, even without therapy. Aberrant DNA methylation pattern is a common feature of most cancers. For neuroblastoma, it has been demonstrated both for single-genes as well as genome-wide, where a so-called methylator phenotype has been described. Here, we present a study using Illumina 450K methylation arrays on 60 neuroblastoma tumors. We show that aggressive tumors, characterised by International Neuroblastoma Risk Group (INRG) stage M are hypermethylated compared to low-grade tumors. On the contrary, INRG stage L tumors display more non-CpG methylation. The genes with the highest number of hypermethylated CpG sites in INRG M tumors are <i>TERT, PCDHGA4, DLX5</i>, and <i>DLX6-AS1</i>. Gene ontology analysis showed a representation of neuronal tumor relevant gene functions among the differentially methylated genes. For validation, we used a set of independent tumors previously analyzed with the Illumina 27K methylation arrays, which confirmed the differentially methylated sites. Top candidate genes with aberrant methylation were analyzed for altered gene expression through the R2 platform (http://r2.amc.nl), and for correlations between methylation and gene expression in a public dataset. Altered expression in nonsurvivors was found for the genes <i>B3GALT4</i> and <i>KIAA1949, CLIC5, DLX6-AS, TERT</i>, and <i>PIRT</i>, and strongest correlations were found for <i>TRIM36, KIAA0513</i>, and <i>PIRT</i>. Our data indicate that methylation profiling can be used for patient stratification and informs on epigenetically deregulated genes with the potential of increasing our knowledge about the underlying mechanisms of tumor development.
DOI: 10.6084/m9.figshare.2065602.v2
title: Research compendium for a report on archaeological excavations at Khao Toh Chong, Krabi, Thailand

description: Supplementary information for the publication on KTC. Development repository is at https://github.com/benmarwick/ktc11
DOI: 10.6084/m9.figshare.2065563.v2
title: A potential role for sensory neuroplasticity in major depressive disorder.pdf

description: Brain imaging and electrophysiological recordings of primary and secondary sensory cortices indicate that each is arranged into sub-regions that process specific subsets of environmental stimuli. The sizes of these regions, termed cortical response fields (CRFs), have been correlated with the consciously perceived intensity of their respective stimuli and with the neural processing power devoted to analyzing such stimuli. Typically, CRFs are highly plastic, and their experience-dependent plasticity is modulated by attention and reinforcement. Because of this, disorders with negative attentional bias, such as major depressive disorder (MDD), have the potential to significantly alter these maps in psychologically harmful ways. We review literature suggesting that sensory map plasticity plays a role in the initiation and maintenance of major depressive disorder. Such a role would suggest possible new treatments for MDD, and may help explain mechanisms of existing treatments.
DOI: 10.6084/m9.figshare.2065575.v3
title: Genome-wide methylation profiling identifies novel methylated genes in neuroblastoma tumors

description: Neuroblastoma is a very heterogeneous tumor of childhood. The clinical spectra range from very aggressive metastatic disease to spontaneous regression, even without therapy. Aberrant DNA methylation pattern is a common feature of most cancers. For neuroblastoma, it has been demonstrated both for single genes as well as genome-wide, where a so-called methylator phenotype has been described. Here, we present a study using Illumina 450K methylation arrays on 60 neuroblastoma tumors. We show that aggressive tumors, characterized by International Neuroblastoma Risk Group (INRG) as stage M, are hypermethylated compared to low-grade tumors. On the contrary, INRG stage L tumors display more non-CpG methylation. The genes with the highest number of hypermethylated CpG sites in INRG M tumors are <i>TERT, PCDHGA4, DLX5</i>, and <i>DLX6-AS1</i>. Gene ontology analysis showed a representation of neuronal tumor relevant gene functions among the differentially methylated genes. For validation, we used a set of independent tumors previously analyzed with the Illumina 27K methylation arrays, which confirmed the differentially methylated sites. Top candidate genes with aberrant methylation were analyzed for altered gene expression through the R2 platform (http://r2.amc.nl), and for correlations between methylation and gene expression in a public dataset. Altered expression in nonsurvivors was found for the genes <i>B3GALT4</i> and <i>KIAA1949, CLIC5, DLX6-AS, TERT</i>, and <i>PIRT</i>, and strongest correlations were found for <i>TRIM36, KIAA0513</i>, and <i>PIRT</i>. Our data indicate that methylation profiling can be used for patient stratification and informs on epigenetically deregulated genes with the potential of increasing our knowledge about the underlying mechanisms of tumor development.
DOI: 10.6084/m9.figshare.2065602.v4
title: Research compendium for a report on archaeological excavations at Khao Toh Chong, Krabi, Thailand

description: Supplementary information for the publication on KTC. Development repository is at https://github.com/benmarwick/ktc11
DOI: 10.6084/m9.figshare.2065545
title: A Simple Generic Model for Estimating Saturated Vapor Pressure

description: Arguably, the most important of the basic thermodynamic properties of fluids, vapor pressure has been the focus of investigation for over a century. The two main drawbacks of the models currently used for its correlation are that they either exhibit large deviations near critical temperature and triple point or that they have a large number of compound-specific adjusted parameters and hence the inconvenient necessity of having at hand large tabulations of hundreds of model parameters. In this study, by employing the up and coming procedure of genetic programming, a new model, which to a large extent remedies these shortcomings, is proposed. Essentially, having only two compound-specific adjusted parameters and also using two readily available substance parameters of molecular weight and normal boiling point ensure a high level of convenience, yet precision and applicability over a large portion of the vapor–liquid coexistence curve. Concisely, a sizable database comprised of 58,272 data points was gathered for 243 organic and inorganic compounds and elements belonging to a diverse set of chemical families; these were then used in both developing and validating the proposed model and reporting generic and compound/element-specific adjusted parameters. Average absolute relative deviations (AARDs) of 1.47% (for a subset of 40,852 data points) and 1.82% (for a subset of 17,420 data points) for the general model and a slightly modified model applicable to hydrogen-bonded alcohols and phenols, respectively, are a testament to the reliability of the new proposed model.
DOI: 10.6084/m9.figshare.2065575.v2
title: Genome-wide methylation profiling identifies novel methylated genes in neuroblastoma tumors

description: Neuroblastoma is a very heterogeneous tumor of childhood. The clinical spectra range from very aggressive metastatic disease to spontaneous regression, even without therapy. Aberrant DNA methylation pattern is a common feature of most cancers. For neuroblastoma, it has been demonstrated both for single-genes as well as genome-wide, where a so-called methylator phenotype has been described. Here, we present a study using Illumina 450K methylation arrays on 60 neuroblastoma tumors. We show that aggressive tumors, characterised by International Neuroblastoma Risk Group (INRG) stage M are hypermethylated compared to low-grade tumors. On the contrary, INRG stage L tumors display more non-CpG methylation. The genes with the highest number of hypermethylated CpG sites in INRG M tumors are <i>TERT, PCDHGA4, DLX5</i>, and <i>DLX6-AS1</i>. Gene ontology analysis showed a representation of neuronal tumor relevant gene functions among the differentially methylated genes. For validation, we used a set of independent tumors previously analyzed with the Illumina 27K methylation arrays, which confirmed the differentially methylated sites. Top candidate genes with aberrant methylation were analyzed for altered gene expression through the R2 platform (http://r2.amc.nl), and for correlations between methylation and gene expression in a public dataset. Altered expression in nonsurvivors was found for the genes <i>B3GALT4</i> and <i>KIAA1949, CLIC5, DLX6-AS, TERT</i>, and <i>PIRT</i>, and strongest correlations were found for <i>TRIM36, KIAA0513</i>, and <i>PIRT</i>. Our data indicate that methylation profiling can be used for patient stratification and informs on epigenetically deregulated genes with the potential of increasing our knowledge about the underlying mechanisms of tumor development.
DOI: 10.6084/m9.figshare.2065563.v3
title: A potential role for sensory neuroplasticity in major depressive disorder.pdf

description: Brain imaging and electrophysiological recordings of primary and secondary sensory cortices indicate that each is arranged into sub-regions that process specific subsets of environmental stimuli. The sizes of these regions, termed cortical response fields (CRFs), have been correlated with the consciously perceived intensity of their respective stimuli and with the neural processing power devoted to analyzing such stimuli. Typically, CRFs are highly plastic, and their experience-dependent plasticity is modulated by attention and reinforcement. Because of this, disorders with negative attentional bias, such as major depressive disorder (MDD), have the potential to significantly alter these maps in psychologically harmful ways. We review literature suggesting that sensory map plasticity plays a role in the initiation and maintenance of major depressive disorder. Such a role would suggest possible new treatments for MDD, and may help explain mechanisms of existing treatments.
DOI: 10.6084/m9.figshare.2065602.v3
title: Research compendium for a report on archaeological excavations at Khao Toh Chong, Krabi, Thailand

description: Supplementary information for the publication on KTC. Development repository is at https://github.com/benmarwick/ktc11
DOI: 10.6084/m9.figshare.2065563.v4
title: A potential role for sensory neuroplasticity in major depressive disorder.pdf

description: Brain imaging and electrophysiological recordings of primary and secondary sensory cortices indicate that each is arranged into sub-regions that process specific subsets of environmental stimuli. The sizes of these regions, termed cortical response fields (CRFs), have been correlated with the consciously perceived intensity of their respective stimuli and with the neural processing power devoted to analyzing such stimuli. Typically, CRFs are highly plastic, and their experience-dependent plasticity is modulated by attention and reinforcement. Because of this, disorders with negative attentional bias, such as major depressive disorder (MDD), have the potential to significantly alter these maps in psychologically harmful ways. We review literature suggesting that sensory map plasticity plays a role in the initiation and maintenance of major depressive disorder. Such a role would suggest possible new treatments for MDD, and may help explain mechanisms of existing treatments.
DOI: 10.6084/m9.figshare.2065545.v1
title: A Simple Generic Model for Estimating Saturated Vapour Pressure

description: Arguably, the most important of the basic thermodynamic properties of fluids, vapour pressure has been the focus of investigation for over a century. The two main drawbacks of the models currently used for its correlation are that they either exhibit large deviations near critical temperature and triple point or that they have a large number of compound-specific adjusted parameters; hence the inconvenient necessity of having at hand large tabulations of hundreds of model parameters. In this study, by employing the up and coming procedure of genetic programming, a new model, which to a large extent remedies these shortcomings, is proposed. Essentially, having only two compound-specific adjusted parameters and also using two readily available substance parameters of molecular weight and normal boiling point, ensures a high level of convenience, yet precision and applicability over a large portion of vapour-liquid coexistence curve. Concisely, a sizable database comprised of 58272 data points was gathered for 243 organic and inorganic compounds and elements belonging to a diverse set of chemical families; which was then used in both developing and validating the proposed model and reporting generic and compound/element specific adjusted parameters. AARDs of 1.47% (for a subset of 40852 data points) and 1.82% (for a subset of 17420 data points) for the general model and a slightly modified model applicable to hydrogen-bonded alcohols and phenols, respectively, are a testament to the reliability of the new proposed model.
DOI: 10.6084/m9.figshare.2065563.v5
title: A potential role for sensory neuroplasticity in major depressive disorder.pdf

description: Brain imaging and electrophysiological recordings of primary and secondary sensory cortices indicate that each is arranged into sub-regions that process specific subsets of environmental stimuli. The sizes of these regions, termed cortical response fields (CRFs), have been correlated with the consciously perceived intensity of their respective stimuli and with the neural processing power devoted to analyzing such stimuli. Typically, CRFs are highly plastic, and their experience-dependent plasticity is modulated by attention and reinforcement. Because of this, disorders with negative attentional bias, such as major depressive disorder (MDD), have the potential to significantly alter these maps in psychologically harmful ways. We review literature suggesting that sensory map plasticity plays a role in the initiation and maintenance of major depressive disorder. Such a role would suggest possible new treatments for MDD, and may help explain mechanisms of existing treatments.