cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.3494837
title: Supplementary Material for: Distinct Gene Expression Patterns Defining Human Osteoblasts' Response to BMP2 Treatment: Is the Therapeutic Success All a Matter of Timing?

description: <i>Background:</i> Bone morphogenetic proteins (BMPs) play a key role in bone formation. Local application of BMP2 (Dibotermin alfa) supports bone formation when applied to complex fractures. However, up to 33% of patients do not respond to this therapy.<i>Purpose:</i> Aiming to investigate whether inter-individual responses to BMP2 treatment can be predicted by gene expression patterns, we investigated the effect of BMP2 on primary human osteoblasts and THP-1 cell-derived osteoclasts from 110 donors. <i>Methods:</i> Osteoblasts were obtained by collagenase digestion of spongy bone tissues. Osteoclasts were differentiated from THP-1 cells using the conditioned media of the osteoblasts. Viability was determined by resazurin conversion. As functional characteristics AP and Trap5B activity were measured. Gene expression levels were determined by RT-PCR in 21 of the 110 evaluated donors and visualized by electrophoresis. <i>Results:</i> Based on our data, we could classify three response groups: (i) In 51.8% of all donors, BMP2 treatment induced osteoblast function. These donors strongly expressed the BMP2 inhibitor Noggin <i>(NOG)</i>, the alternative BMP2 receptors repulsive guidance molecule B <i>(RGMb)</i> and activin receptor-like kinase 6<i>(Alk6)</i>, as well as the Wnt inhibitor sclerostin <i>(SOST)</i>. (ii) In 17.3% of all donors, BMP2 treatment induced viability. In these donors, the initial high <i>SOST</i> expression significantly dropped with BMP2 treatment. (iii) 30.9% of all donors were not directly affected by BMP2 treatment. These donors expressed high levels of the pseudoreceptor BMP and activin membrane-bound inhibitor <i>(BAMBI)</i> and lacked <i>SOST</i>expression. In all donors, <i>SOST</i> expression correlated directly with receptor activator of NF-κB ligand <i>(RANKL)</i> expression, defining the cells' potential to stimulate osteoclastogenesis. <i>Conclusions:</i> Our data identified three donor groups profiting from BMP2 treatment either directly via stimulation of osteoblast function or viability and/or indirectly via inhibition of osteoclastogenesis, depending on their expression of <i>BAMBI</i>, <i>SOST</i>, <i>NOG</i>, and <i>RANKL</i>. On the basis of patients' respective expression profiles, the clinical application of BMP2 as well as its timing might be modified in order to better fit the patients' needs to promote bone formation or to inhibit bone resorption.
DOI: 10.6084/m9.figshare.3494837.v1
title: Supplementary Material for: Distinct Gene Expression Patterns Defining Human Osteoblasts' Response to BMP2 Treatment: Is the Therapeutic Success All a Matter of Timing?

description: <i>Background:</i> Bone morphogenetic proteins (BMPs) play a key role in bone formation. Local application of BMP2 (Dibotermin alfa) supports bone formation when applied to complex fractures. However, up to 33% of patients do not respond to this therapy.<i>Purpose:</i> Aiming to investigate whether inter-individual responses to BMP2 treatment can be predicted by gene expression patterns, we investigated the effect of BMP2 on primary human osteoblasts and THP-1 cell-derived osteoclasts from 110 donors. <i>Methods:</i> Osteoblasts were obtained by collagenase digestion of spongy bone tissues. Osteoclasts were differentiated from THP-1 cells using the conditioned media of the osteoblasts. Viability was determined by resazurin conversion. As functional characteristics AP and Trap5B activity were measured. Gene expression levels were determined by RT-PCR in 21 of the 110 evaluated donors and visualized by electrophoresis. <i>Results:</i> Based on our data, we could classify three response groups: (i) In 51.8% of all donors, BMP2 treatment induced osteoblast function. These donors strongly expressed the BMP2 inhibitor Noggin <i>(NOG)</i>, the alternative BMP2 receptors repulsive guidance molecule B <i>(RGMb)</i> and activin receptor-like kinase 6<i>(Alk6)</i>, as well as the Wnt inhibitor sclerostin <i>(SOST)</i>. (ii) In 17.3% of all donors, BMP2 treatment induced viability. In these donors, the initial high <i>SOST</i> expression significantly dropped with BMP2 treatment. (iii) 30.9% of all donors were not directly affected by BMP2 treatment. These donors expressed high levels of the pseudoreceptor BMP and activin membrane-bound inhibitor <i>(BAMBI)</i> and lacked <i>SOST</i>expression. In all donors, <i>SOST</i> expression correlated directly with receptor activator of NF-κB ligand <i>(RANKL)</i> expression, defining the cells' potential to stimulate osteoclastogenesis. <i>Conclusions:</i> Our data identified three donor groups profiting from BMP2 treatment either directly via stimulation of osteoblast function or viability and/or indirectly via inhibition of osteoclastogenesis, depending on their expression of <i>BAMBI</i>, <i>SOST</i>, <i>NOG</i>, and <i>RANKL</i>. On the basis of patients' respective expression profiles, the clinical application of BMP2 as well as its timing might be modified in order to better fit the patients' needs to promote bone formation or to inhibit bone resorption.
DOI: 10.6084/m9.figshare.3494834
title: Supplementary Material for: Progranulin Levels in Plasma and Cerebrospinal Fluid in Granulin Mutation Carriers

description: <i>Background:</i> Pathogenic mutations in the granulin gene <i>(GRN)</i> are causative in 5-10% of patients with frontotemporal dementia (FTD), mostly leading to reduced progranulin protein (PGRN) levels. Upcoming therapeutic trials focus on enhancing PGRN levels. <i>Methods:</i> Fluctuations in plasma PGRN (n = 41) and its relationship with cerebrospinal fluid (CSF, n = 32) and specific single nucleotide polymorphisms were investigated in pre- and symptomatic <i>GRN</i> mutation carriers and controls. <i>Results:</i>Plasma PGRN levels were lower in carriers than in controls and showed a mean coefficient of variation of 5.3% in carriers over 1 week. Although plasma PGRN correlated with CSF PGRN in carriers (r = 0.54, p = 0.02), plasma only explained 29% of the variability in CSF PGRN. rs5848, rs646776 and rs1990622 genotypes only partly explained the variability of PGRN levels between subjects. <i>Conclusions:</i> Plasma PGRN is relatively stable over 1 week and therefore seems suitable for treatment monitoring of PGRN-enhancing agents. Since plasma PGRN only moderately correlated with CSF PGRN, CSF sampling will additionally be needed in therapeutic trials.
DOI: 10.6084/m9.figshare.3494834.v1
title: Supplementary Material for: Progranulin Levels in Plasma and Cerebrospinal Fluid in Granulin Mutation Carriers

description: <i>Background:</i> Pathogenic mutations in the granulin gene <i>(GRN)</i> are causative in 5-10% of patients with frontotemporal dementia (FTD), mostly leading to reduced progranulin protein (PGRN) levels. Upcoming therapeutic trials focus on enhancing PGRN levels. <i>Methods:</i> Fluctuations in plasma PGRN (n = 41) and its relationship with cerebrospinal fluid (CSF, n = 32) and specific single nucleotide polymorphisms were investigated in pre- and symptomatic <i>GRN</i> mutation carriers and controls. <i>Results:</i>Plasma PGRN levels were lower in carriers than in controls and showed a mean coefficient of variation of 5.3% in carriers over 1 week. Although plasma PGRN correlated with CSF PGRN in carriers (r = 0.54, p = 0.02), plasma only explained 29% of the variability in CSF PGRN. rs5848, rs646776 and rs1990622 genotypes only partly explained the variability of PGRN levels between subjects. <i>Conclusions:</i> Plasma PGRN is relatively stable over 1 week and therefore seems suitable for treatment monitoring of PGRN-enhancing agents. Since plasma PGRN only moderately correlated with CSF PGRN, CSF sampling will additionally be needed in therapeutic trials.
DOI: 10.6084/m9.figshare.3494831
title: Ligand_Receptor_Prediction

description: Identifying of ligand-receptor interactions via a noval computational method.
DOI: 10.6084/m9.figshare.3494822
title: LiMP data.sav

description: The data pertains to the Literacy in Musculoskeletal Problems questionnaire for use in a Mokken analysis.<br>
DOI: 10.6084/m9.figshare.3494819
title: Assistive technology in resource-limited environments: a scoping review

description: <b>Purpose:</b> It is estimated that only 5–15% of people in low and middle income countries (LMICs) who need assistive technologies (AT) have access to them. This scoping review was conducted to provide a comprehensive picture of the current evidence base on AT within LMICs and other resource limited environments. <b>Method:</b> The scoping review involved locating evidence, extracting data, and summarizing characteristics of all included research publications. <b>Results:</b> Of the 252 publications included, over 80% focused on types of AT that address mobility (45.2%) and vision (35.5%) needs, with AT types of spectacles and prosthetics comprising over 50% of all publications. Evidence on AT that addresses hearing, communication, and cognition is the most underrepresented within the existing evidence base. The vast majority of study designs are observational (63%). <b>Conclusions:</b> Evidence on AT in resource-limited environments is limited in quantity and quality, and not evenly distributed across types of AT. To advance this field, we recommend using appropriate evidence review approaches that allow for heterogeneous study designs, and developing a common language by creating a typology of AT research focus areas. Funders and researchers must commit much greater resources to the AT field to ameliorate the paucity of evidence available.Implications for RehabilitationAn increase in the quality and quantity of research is required in resource limited environments, where 80% of the global population of people with disabilities reside. Improved and increased evidence is needed to identify and understand needs, inform policy and practice, and assess progress made in increasing access to and availability of appropriate AT.Over 80% of the existing research publications on assistive technologies in resource limited environments address mobility and vision. More research is needed on AT that address hearing, communication and cognition.The use of a common language would facilitate the advancement of the global AT research field. Specifically there is a need for researchers to use a common definition of AT (i.e., ISO 9999) and typology of AT research focus areas. An increase in the quality and quantity of research is required in resource limited environments, where 80% of the global population of people with disabilities reside. Improved and increased evidence is needed to identify and understand needs, inform policy and practice, and assess progress made in increasing access to and availability of appropriate AT. Over 80% of the existing research publications on assistive technologies in resource limited environments address mobility and vision. More research is needed on AT that address hearing, communication and cognition. The use of a common language would facilitate the advancement of the global AT research field. Specifically there is a need for researchers to use a common definition of AT (i.e., ISO 9999) and typology of AT research focus areas.
DOI: 10.6084/m9.figshare.3494819.v1
title: Assistive technology in resource-limited environments: a scoping review

description: <b>Purpose:</b> It is estimated that only 5–15% of people in low and middle income countries (LMICs) who need assistive technologies (AT) have access to them. This scoping review was conducted to provide a comprehensive picture of the current evidence base on AT within LMICs and other resource limited environments. <b>Method:</b> The scoping review involved locating evidence, extracting data, and summarizing characteristics of all included research publications. <b>Results:</b> Of the 252 publications included, over 80% focused on types of AT that address mobility (45.2%) and vision (35.5%) needs, with AT types of spectacles and prosthetics comprising over 50% of all publications. Evidence on AT that addresses hearing, communication, and cognition is the most underrepresented within the existing evidence base. The vast majority of study designs are observational (63%). <b>Conclusions:</b> Evidence on AT in resource-limited environments is limited in quantity and quality, and not evenly distributed across types of AT. To advance this field, we recommend using appropriate evidence review approaches that allow for heterogeneous study designs, and developing a common language by creating a typology of AT research focus areas. Funders and researchers must commit much greater resources to the AT field to ameliorate the paucity of evidence available.Implications for RehabilitationAn increase in the quality and quantity of research is required in resource limited environments, where 80% of the global population of people with disabilities reside. Improved and increased evidence is needed to identify and understand needs, inform policy and practice, and assess progress made in increasing access to and availability of appropriate AT.Over 80% of the existing research publications on assistive technologies in resource limited environments address mobility and vision. More research is needed on AT that address hearing, communication and cognition.The use of a common language would facilitate the advancement of the global AT research field. Specifically there is a need for researchers to use a common definition of AT (i.e., ISO 9999) and typology of AT research focus areas. An increase in the quality and quantity of research is required in resource limited environments, where 80% of the global population of people with disabilities reside. Improved and increased evidence is needed to identify and understand needs, inform policy and practice, and assess progress made in increasing access to and availability of appropriate AT. Over 80% of the existing research publications on assistive technologies in resource limited environments address mobility and vision. More research is needed on AT that address hearing, communication and cognition. The use of a common language would facilitate the advancement of the global AT research field. Specifically there is a need for researchers to use a common definition of AT (i.e., ISO 9999) and typology of AT research focus areas.
DOI: 10.6084/m9.figshare.3494744
title: HEA acts against P. xylostella via adenosine receptors

description: The diamondback moth, <i>Plutella xylostella,</i> is one of the most important pests of cruciferous crops. We have earlier shown that N<sup>6</sup>-(2-hydroxyethyl)-adenosine (HEA) exhibits insecticidal activity against <i>P. xylostella</i>. In the present study we investigated the possible mechanism of insecticidal action of HEA on <i>P. xylostella</i>. HEA is a derivative of adenosine, therefore, we speculated whether it acts via <i>P. xylostella</i> adenosine receptor (<i>PxAdoR</i>). We used RNAi approach to silence <i>PxAdoR</i><i> </i>gene and used antagonist of denosine receptor (AdoR) to study the insecticidal effect of HEA. We cloned the<i> </i>whole sequence of <i>PxAdoR</i> gene.
DOI: 10.6084/m9.figshare.3494744.v1
title: data.zip

description: The diamondback moth, <i>Plutella xylostella,</i> is one of the most important pests of cruciferous crops. We have earlier shown that N<sup>6</sup>-(2-hydroxyethyl)-adenosine (HEA) exhibits insecticidal activity against <i>P. xylostella</i>. In the present study we investigated the possible mechanism of insecticidal action of HEA on <i>P. xylostella</i>. HEA is a derivative of adenosine, therefore, we speculated whether it acts via <i>P. xylostella</i> adenosine receptor (<i>PxAdoR</i>). We used RNAi approach to silence <i>PxAdoR</i><i> </i>gene and used antagonist of denosine receptor (AdoR) to study the insecticidal effect of HEA. We cloned the<i> </i>whole sequence of <i>PxAdoR</i> gene. A BLAST search using NCBI protein database showed a 61% identity with the <i>Drosophila</i> adenosine receptor (DmAdoR) and a 32-35% identity with human AdoR. Though the amino acids sequence of <i>PxAdoR </i>was different compared to other adenosine receptors, most of the amino acids that are known to be important for adenosine receptor ligand binding and signaling were present, But only 30% binding sites key residues was similar between PxAdoR and A1R. HEA, at a dose of 1 mg/mL, was found to be lethal to the second-instar larvae of<i> P</i>. <i>xylostella</i>, and a significant reduction of mortality and growth inhibition ratio were obtained when HEA was administered to the larvae along with <i>PxAdoR</i>-dsRNA<i> </i>or antagonist of AdoR (SCH58261) for 36, 48, or 60 h. Especially at 48 h, the rate of growth inhibition of the <i>PxAdoR </i>knockdown group was 3.5-fold less than that of the HEA group, and the corrected mortality of SCH58261 group was reduced almost 2-fold compared with the HEA group. Our findings show that HEA may exert its insecticidal activity against <i>P. xylo</i><i>s</i><i>tella</i> larvae via acting on PxAdoR.
DOI: 10.6084/m9.figshare.3494744.v4
title: HEA acts against P. xylostella via adenosine receptors

description: The diamondback moth, <i>Plutella xylostella,</i> is one of the most important pests of cruciferous crops. We have earlier shown that N<sup>6</sup>-(2-hydroxyethyl)-adenosine (HEA) exhibits insecticidal activity against <i>P. xylostella</i>. In the present study we investigated the possible mechanism of insecticidal action of HEA on <i>P. xylostella</i>. HEA is a derivative of adenosine, therefore, we speculated whether it acts via <i>P. xylostella</i> adenosine receptor (<i>PxAdoR</i>). We used RNAi approach to silence <i>PxAdoR</i><i> </i>gene and used antagonist of denosine receptor (AdoR) to study the insecticidal effect of HEA. We cloned the<i> </i>whole sequence of <i>PxAdoR</i> gene.
DOI: 10.6084/m9.figshare.3494582
title: Gene Expression Profile of Extracellular Matrix and Adhesion Molecules in the Human Normal Corneal Stroma

description: <i>Purpose</i>: There is limited information on region-specific gene expression in the human corneal stroma. In this study, we aimed to investigate the expression profile of the extracellular matrix and adhesion molecules in the normal corneal stroma using laser capture microdissection (LCM) and molecular techniques. <i>Methods</i>: Frozen sections of human cornea without ocular disease were used to isolate the central and peripheral corneal stromal keratocytes by LCM. RNA was extracted from LCM-captured tissues and the RT<sup>2</sup> Profiler PCR Arrays were used to examine the expression profile of extracellular matrix and adhesion molecules in the central and peripheral stroma. Real-time quantitative PCR was used to quantify gene expression. Proteomic and western blotting (WB) analyses were performed to confirm gene expression at protein level. Function association network was generated via the web tools String and Cytoscape. <i>Results</i>: The gene expression profiling demonstrated that 35 out of the 84 extracellular matrix and adhesion molecules represented in the array were expressed in stromal keratocytes. Among them, 24 genes were not previously described in the corneal stroma. Two genes were found more abundantly expressed in the central stroma than in the periphery: TGFBI, COL6A2 (<i>p</i> &lt; 0.05). ADAMTS13 was detected only in the central stroma. Proteomics and WB analysis confirmed the expression of 10 genes. Functional analysis revealed that most identified genes were presented in a core cluster that had multiple and strong associations with other genes. <i>Conclusion</i>: This study identified genes not previously described in the corneal stroma, revealed regional differences in gene expression between central and peripheral stroma, and also detected some interesting candidate genes that may play important roles in corneal function. These observations serve as the foundation to further investigate the molecular and cellular mechanisms regulating the pathogenesis of regional corneal stromal disorders such as keratoconus.
DOI: 10.6084/m9.figshare.3494582.v1
title: Gene Expression Profile of Extracellular Matrix and Adhesion Molecules in the Human Normal Corneal Stroma

description: <i>Purpose</i>: There is limited information on region-specific gene expression in the human corneal stroma. In this study, we aimed to investigate the expression profile of the extracellular matrix and adhesion molecules in the normal corneal stroma using laser capture microdissection (LCM) and molecular techniques. <i>Methods</i>: Frozen sections of human cornea without ocular disease were used to isolate the central and peripheral corneal stromal keratocytes by LCM. RNA was extracted from LCM-captured tissues and the RT<sup>2</sup> Profiler PCR Arrays were used to examine the expression profile of extracellular matrix and adhesion molecules in the central and peripheral stroma. Real-time quantitative PCR was used to quantify gene expression. Proteomic and western blotting (WB) analyses were performed to confirm gene expression at protein level. Function association network was generated via the web tools String and Cytoscape. <i>Results</i>: The gene expression profiling demonstrated that 35 out of the 84 extracellular matrix and adhesion molecules represented in the array were expressed in stromal keratocytes. Among them, 24 genes were not previously described in the corneal stroma. Two genes were found more abundantly expressed in the central stroma than in the periphery: TGFBI, COL6A2 (<i>p</i> &lt; 0.05). ADAMTS13 was detected only in the central stroma. Proteomics and WB analysis confirmed the expression of 10 genes. Functional analysis revealed that most identified genes were presented in a core cluster that had multiple and strong associations with other genes. <i>Conclusion</i>: This study identified genes not previously described in the corneal stroma, revealed regional differences in gene expression between central and peripheral stroma, and also detected some interesting candidate genes that may play important roles in corneal function. These observations serve as the foundation to further investigate the molecular and cellular mechanisms regulating the pathogenesis of regional corneal stromal disorders such as keratoconus.
DOI: 10.6084/m9.figshare.3494564
title: Data supporting: Seasonal shifts in accumulation of glycerol biosynthetic gene transcripts in mountain pine beetle, Dendroctonus ponderosae Hopkins (Coleoptera: Curculionidae), larvae

description: Seasonal temperature data along with transcript accumulation data for a variety of genes associated with glycerol biosynthesis in the mountain pine beetle.
DOI: 10.6084/m9.figshare.3494564.v1
title: Data supporting: Seasonal shifts in accumulation of glycerol biosynthetic gene transcripts in mountain pine beetle, Dendroctonus ponderosae Hopkins (Coleoptera: Curculionidae), larvae

description: Seasonal temperature data along with transcript accumulation data for a variety of genes associated with glycerol biosynthesis in the mountain pine beetle.
DOI: 10.6084/m9.figshare.3494549
title: A Statistical Inference Course Based on <i>p</i>-Values

description: Introductory statistical inference texts and courses treat the point estimation, hypothesis testing, and interval estimation problems separately, with primary emphasis on large-sample approximations. Here, I present an alternative approach to teaching this course, built around <i>p</i>-values, emphasizing provably valid inference for all sample sizes. Details about computation and marginalization are also provided, with several illustrative examples, along with a course outline. Supplementary materials for this article are available online.