cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.4567723
title: Data relative age plos.sav

description: Row / Data1. Child number<br>2. Schoolyear3. Combiclass (0 = no / 1 = yes)4. Gender (0 = male / 1 = female)<br>5. Used (0 = no / 1 = yes)<br><br>6. Combination class (y/n)<br>7. Total emotional problems<br>8. Total conduct problems<br>9. Total problems with hyperactivity<br>10. Total problems with peers<br>11. Total pro-social behavior<br>12. Total problems<br>13. Teacher number<br>14. Schoolnumber<br>15. Year of birth16. Month of birth17. Day of the year<br>18. Relative day of the year<br>
DOI: 10.6084/m9.figshare.4567723.v1
title: Data relative age plos.sav

description: Row / Data1. Child number<br>2. Schoolyear3. Combiclass (0 = no / 1 = yes)4. Gender (0 = male / 1 = female)<br>5. Used (0 = no / 1 = yes)<br><br>6. Combination class (y/n)<br>7. Total emotional problems<br>8. Total conduct problems<br>9. Total problems with hyperactivity<br>10. Total problems with peers<br>11. Total pro-social behavior<br>12. Total problems<br>13. Teacher number<br>14. Schoolnumber<br>15. Year of birth16. Month of birth17. Day of the year<br>18. Relative day of the year<br>
DOI: 10.6084/m9.figshare.4567999.v7
title: Statistical Considerations in Demonstrating CMC Analytical Similarity for a Biosimilar Product

description: Demonstration of analytical similarity between a reference product and a biosimilar product is required as part of the biosimilarity approval process. A statistical two one-sided test (TOST) based on the difference of means proposed in the literature and recommended by the FDA for Tier 1 quality attributes is demonstrated to have a type I error rate greater than the specified level, which cannot be corrected by increasing sample size. In this paper, an alternative TOST based on the effect size is demonstrated to maintain the desired type I error rate, and in some situations, provide greater power than the TOST based on the mean difference. Results are demonstrated both analytically and with computer simulations. An example with calculations is provided in the paper.
DOI: 10.6084/m9.figshare.4565344
title: Intravenous Lidocaine and Buprenorphine Effects on Postoperative Pain and Gastrointestinal Motility in New Zealand White Rabbits Following Ovariohysterectomy

description: Line plots of fecal production over time in female rabbits undergoing ovariohysterectomy under two different analgesia protocols (lidocaine CRI and buprenorphine). Error bars represent SEM.
DOI: 10.6084/m9.figshare.4565344.v1
title: Intravenous Lidocaine and Buprenorphine Effects on Postoperative Pain and Gastrointestinal Motility in New Zealand White Rabbits Following Ovariohysterectomy

description: Line plots of fecal production over time in female rabbits undergoing ovariohysterectomy under two different analgesia protocols (lidocaine CRI and buprenorphine). Error bars represent SEM.
DOI: 10.6084/m9.figshare.4567999.v8
title: Statistical Considerations in Demonstrating CMC Analytical Similarity for a Biosimilar Product

description: Demonstration of analytical similarity between a reference product and a biosimilar product is required as part of the biosimilarity approval process. A statistical two one-sided test (TOST) based on the difference of means proposed in the literature and recommended by the FDA for Tier 1 quality attributes is demonstrated to have a Type I error rate greater than the specified level, which cannot be corrected by increasing sample size. In this article, an alternative TOST based on the effect size is demonstrated to maintain the desired Type I error rate, and in some situations, provide greater power than the TOST based on the mean difference. Results are demonstrated both analytically and with computer simulations. An example with calculations is provided in the article. Supplementary materials for this article are avalilable online.
DOI: 10.6084/m9.figshare.4567999.v9
title: Statistical Considerations in Demonstrating CMC Analytical Similarity for a Biosimilar Product

description: Demonstration of analytical similarity between a reference product and a biosimilar product is required as part of the biosimilarity approval process. A statistical two one-sided test (TOST) based on the difference of means proposed in the literature and recommended by the FDA for Tier 1 quality attributes is demonstrated to have a type I error rate greater than the specified level, which cannot be corrected by increasing sample size. In this paper, an alternative TOST based on the effect size is demonstrated to maintain the desired type I error rate, and in some situations, provide greater power than the TOST based on the mean difference. Results are demonstrated both analytically and with computer simulations. An example with calculations is provided in the paper.
DOI: 10.6084/m9.figshare.4565281
title: How could thermal stratification affect horizontal distribution of depth-integrated metazooplankton communities in the Gulf of Gabes (Tunisia)?

description: The spatial and temporal variability of metazooplankton communities in relation to environmental and trophic factors were studied in the Gulf of Gabes during three periods of increasing thermal stratification in June, July and September. Non-metric multi-dimensional scaling (NMDS) revealed the time and space succession of three zooplankton communities in relation to the degree of thermal stratification. A co-inertia analysis showed the association between these communities and the trophic conditions (abundance and composition of microplankton) driven by stratification. Three divergent communities were evident. The first, characterized by annelid larvae and coastal copepods, was associated with shallow mixed and microplankton-rich water (June, coastal). The second, characterized by euphausiids, amphipods, doliolids and several deep-water copepods, corresponded to highly stratified microplankton-poor water (September). The third, characterized by the most ubiquitous and abundant species, was linked to intermediate water (June deep and July). Temperature and salinity conditions also explained the distribution of key species. <i>Clausocalanus furcatus</i>, <i>Oithona plumifera</i> and <i>Triconia conifera</i> were clearly associated with warm and highly stratified water (September). Enhanced thermal stratification led to higher surface salinity, explaining the emergence of euryhaline taxa such as <i>Oithona plumifera</i>.
DOI: 10.6084/m9.figshare.4565281.v1
title: How could thermal stratification affect horizontal distribution of depth-integrated metazooplankton communities in the Gulf of Gabes (Tunisia)?

description: The spatial and temporal variability of metazooplankton communities in relation to environmental and trophic factors were studied in the Gulf of Gabes during three periods of increasing thermal stratification in June, July and September. Non-metric multi-dimensional scaling (NMDS) revealed the time and space succession of three zooplankton communities in relation to the degree of thermal stratification. A co-inertia analysis showed the association between these communities and the trophic conditions (abundance and composition of microplankton) driven by stratification. Three divergent communities were evident. The first, characterized by annelid larvae and coastal copepods, was associated with shallow mixed and microplankton-rich water (June, coastal). The second, characterized by euphausiids, amphipods, doliolids and several deep-water copepods, corresponded to highly stratified microplankton-poor water (September). The third, characterized by the most ubiquitous and abundant species, was linked to intermediate water (June deep and July). Temperature and salinity conditions also explained the distribution of key species. <i>Clausocalanus furcatus</i>, <i>Oithona plumifera</i> and <i>Triconia conifera</i> were clearly associated with warm and highly stratified water (September). Enhanced thermal stratification led to higher surface salinity, explaining the emergence of euryhaline taxa such as <i>Oithona plumifera</i>.
DOI: 10.6084/m9.figshare.4567999.v10
title: Statistical Considerations in Demonstrating CMC Analytical Similarity for a Biosimilar Product

description: Demonstration of analytical similarity between a reference product and a biosimilar product is required as part of the biosimilarity approval process. A statistical two one-sided test (TOST) based on the difference of means proposed in the literature and recommended by the FDA for Tier 1 quality attributes is demonstrated to have a Type I error rate greater than the specified level, which cannot be corrected by increasing sample size. In this article, an alternative TOST based on the effect size is demonstrated to maintain the desired Type I error rate, and in some situations, provide greater power than the TOST based on the mean difference. Results are demonstrated both analytically and with computer simulations. An example with calculations is provided in the article. Supplementary materials for this article are avalilable online.
DOI: 10.6084/m9.figshare.4567999.v11
title: Statistical Considerations in Demonstrating CMC Analytical Similarity for a Biosimilar Product

description: Demonstration of analytical similarity between a reference product and a biosimilar product is required as part of the biosimilarity approval process. A statistical two one-sided test (TOST) based on the difference of means proposed in the literature and recommended by the FDA for Tier 1 quality attributes is demonstrated to have a type I error rate greater than the specified level, which cannot be corrected by increasing sample size. In this paper, an alternative TOST based on the effect size is demonstrated to maintain the desired type I error rate, and in some situations, provide greater power than the TOST based on the mean difference. Results are demonstrated both analytically and with computer simulations. An example with calculations is provided in the paper.
DOI: 10.6084/m9.figshare.4567999.v12
title: Statistical Considerations in Demonstrating CMC Analytical Similarity for a Biosimilar Product

description: Demonstration of analytical similarity between a reference product and a biosimilar product is required as part of the biosimilarity approval process. A statistical two one-sided test (TOST) based on the difference of means proposed in the literature and recommended by the FDA for Tier 1 quality attributes is demonstrated to have a Type I error rate greater than the specified level, which cannot be corrected by increasing sample size. In this article, an alternative TOST based on the effect size is demonstrated to maintain the desired Type I error rate, and in some situations, provide greater power than the TOST based on the mean difference. Results are demonstrated both analytically and with computer simulations. An example with calculations is provided in the article. Supplementary materials for this article are avalilable online.
DOI: 10.6084/m9.figshare.4567999.v13
title: Statistical Considerations in Demonstrating CMC Analytical Similarity for a Biosimilar Product

description: Demonstration of analytical similarity between a reference product and a biosimilar product is required as part of the biosimilarity approval process. A statistical two one-sided test (TOST) based on the difference of means proposed in the literature and recommended by the FDA for Tier 1 quality attributes is demonstrated to have a type I error rate greater than the specified level, which cannot be corrected by increasing sample size. In this paper, an alternative TOST based on the effect size is demonstrated to maintain the desired type I error rate, and in some situations, provide greater power than the TOST based on the mean difference. Results are demonstrated both analytically and with computer simulations. An example with calculations is provided in the paper.
DOI: 10.6084/m9.figshare.4567999.v14
title: Statistical Considerations in Demonstrating CMC Analytical Similarity for a Biosimilar Product

description: Demonstration of analytical similarity between a reference product and a biosimilar product is required as part of the biosimilarity approval process. A statistical two one-sided test (TOST) based on the difference of means proposed in the literature and recommended by the FDA for Tier 1 quality attributes is demonstrated to have a Type I error rate greater than the specified level, which cannot be corrected by increasing sample size. In this article, an alternative TOST based on the effect size is demonstrated to maintain the desired Type I error rate, and in some situations, provide greater power than the TOST based on the mean difference. Results are demonstrated both analytically and with computer simulations. An example with calculations is provided in the article. Supplementary materials for this article are avalilable online.
DOI: 10.6084/m9.figshare.4565185
title: PLK1 (polo like kinase 1) inhibits MTOR complex 1 and promotes autophagy

description: Mechanistic target of rapamycin complex 1 (MTORC1) and polo like kinase 1 (PLK1) are major drivers of cancer cell growth and proliferation, and inhibitors of both protein kinases are currently being investigated in clinical studies. To date, MTORC1′s and PLK1′s functions are mostly studied separately, and reports on their mutual crosstalk are scarce. Here, we identify PLK1 as a physical MTORC1 interactor in human cancer cells. PLK1 inhibition enhances MTORC1 activity under nutrient sufficiency and in starved cells, and PLK1 directly phosphorylates the MTORC1 component RPTOR/RAPTOR in vitro. PLK1 and MTORC1 reside together at lysosomes, the subcellular site where MTORC1 is active. Consistent with an inhibitory role of PLK1 toward MTORC1, PLK1 overexpression inhibits lysosomal association of the PLK1-MTORC1 complex, whereas PLK1 inhibition promotes lysosomal localization of MTOR. PLK1-MTORC1 binding is enhanced by amino acid starvation, a condition known to increase autophagy. MTORC1 inhibition is an important step in autophagy activation. Consistently, PLK1 inhibition mitigates autophagy in cancer cells both under nutrient starvation and sufficiency, and a role of PLK1 in autophagy is also observed in the invertebrate model organism <i>Caenorhabditis elegans</i>. In summary, PLK1 inhibits MTORC1 and thereby positively contributes to autophagy. Since autophagy is increasingly recognized to contribute to tumor cell survival and growth, we propose that cautious monitoring of MTORC1 and autophagy readouts in clinical trials with PLK1 inhibitors is needed to develop strategies for optimized (combinatorial) cancer therapies targeting MTORC1, PLK1, and autophagy.
DOI: 10.6084/m9.figshare.4565230
title: Antisense transcription of the myotonic dystrophy locus yields low-abundant RNAs with and without (CAG)n repeat

description: The unstable (CTG·CAG)n trinucleotide repeat in the myotonic dystrophy type 1 (DM1) locus is bidirectionally transcribed from genes with terminal overlap. By transcription in the sense direction, the <i>DMPK</i> gene produces various alternatively spliced mRNAs with a (CUG)n repeat in their 3′ UTR. Expression in opposite orientation reportedly yields (CAG)n-repeat containing RNA, but both structure and biological significance of this antisense gene (<i>DM1-AS</i>) are largely unknown. Via a combinatorial approach of computational and experimental analyses of RNA from unaffected individuals and DM1 patients we discovered that <i>DM1-AS</i> spans &gt;6 kb, contains alternative transcription start sites and uses alternative polyadenylation sites up- and downstream of the (CAG)n repeat. Moreover, its primary transcripts undergo alternative splicing, whereby the (CAG)n segment is removed as part of an intron. Thus, in patients a mixture of <i>DM1-AS</i> RNAs with and without expanded (CAG)n repeat are produced. <i>DM1-AS</i> expression appears upregulated in patients, but transcript abundance remains very low in all tissues analyzed. Our data suggest that <i>DM1-AS</i> transcripts belong to the class of long non-coding RNAs. These and other biologically relevant implications for how (CAG)n-expanded transcripts may contribute to DM1 pathology can now be explored experimentally.
DOI: 10.6084/m9.figshare.4565185.v1
title: PLK1 (polo like kinase 1) inhibits MTOR complex 1 and promotes autophagy

description: Mechanistic target of rapamycin complex 1 (MTORC1) and polo like kinase 1 (PLK1) are major drivers of cancer cell growth and proliferation, and inhibitors of both protein kinases are currently being investigated in clinical studies. To date, MTORC1′s and PLK1′s functions are mostly studied separately, and reports on their mutual crosstalk are scarce. Here, we identify PLK1 as a physical MTORC1 interactor in human cancer cells. PLK1 inhibition enhances MTORC1 activity under nutrient sufficiency and in starved cells, and PLK1 directly phosphorylates the MTORC1 component RPTOR/RAPTOR in vitro. PLK1 and MTORC1 reside together at lysosomes, the subcellular site where MTORC1 is active. Consistent with an inhibitory role of PLK1 toward MTORC1, PLK1 overexpression inhibits lysosomal association of the PLK1-MTORC1 complex, whereas PLK1 inhibition promotes lysosomal localization of MTOR. PLK1-MTORC1 binding is enhanced by amino acid starvation, a condition known to increase autophagy. MTORC1 inhibition is an important step in autophagy activation. Consistently, PLK1 inhibition mitigates autophagy in cancer cells both under nutrient starvation and sufficiency, and a role of PLK1 in autophagy is also observed in the invertebrate model organism <i>Caenorhabditis elegans</i>. In summary, PLK1 inhibits MTORC1 and thereby positively contributes to autophagy. Since autophagy is increasingly recognized to contribute to tumor cell survival and growth, we propose that cautious monitoring of MTORC1 and autophagy readouts in clinical trials with PLK1 inhibitors is needed to develop strategies for optimized (combinatorial) cancer therapies targeting MTORC1, PLK1, and autophagy.
DOI: 10.6084/m9.figshare.4567999.v15
title: Statistical Considerations in Demonstrating CMC Analytical Similarity for a Biosimilar Product

description: Demonstration of analytical similarity between a reference product and a biosimilar product is required as part of the biosimilarity approval process. A statistical two one-sided test (TOST) based on the difference of means proposed in the literature and recommended by the FDA for Tier 1 quality attributes is demonstrated to have a type I error rate greater than the specified level, which cannot be corrected by increasing sample size. In this paper, an alternative TOST based on the effect size is demonstrated to maintain the desired type I error rate, and in some situations, provide greater power than the TOST based on the mean difference. Results are demonstrated both analytically and with computer simulations. An example with calculations is provided in the paper.
DOI: 10.6084/m9.figshare.4565230.v1
title: Antisense transcription of the myotonic dystrophy locus yields low-abundant RNAs with and without (CAG)n repeat

description: The unstable (CTG·CAG)n trinucleotide repeat in the myotonic dystrophy type 1 (DM1) locus is bidirectionally transcribed from genes with terminal overlap. By transcription in the sense direction, the <i>DMPK</i> gene produces various alternatively spliced mRNAs with a (CUG)n repeat in their 3′ UTR. Expression in opposite orientation reportedly yields (CAG)n-repeat containing RNA, but both structure and biologic significance of this antisense gene (<i>DM1-AS</i>) are largely unknown. Via a combinatorial approach of computational and experimental analyses of RNA from unaffected individuals and DM1 patients we discovered that <i>DM1-AS</i> spans &gt;6 kb, contains alternative transcription start sites and uses alternative polyadenylation sites up- and downstream of the (CAG)n repeat. Moreover, its primary transcripts undergo alternative splicing, whereby the (CAG)n segment is removed as part of an intron. Thus, in patients a mixture of <i>DM1-AS</i> RNAs with and without expanded (CAG)n repeat are produced. <i>DM1-AS</i> expression appears upregulated in patients, but transcript abundance remains very low in all tissues analyzed. Our data suggest that <i>DM1-AS</i> transcripts belong to the class of long non-coding RNAs. These and other biologically relevant implications for how (CAG)n-expanded transcripts may contribute to DM1 pathology can now be explored experimentally.
DOI: 10.6084/m9.figshare.4565161
title: The effect of precrash velocity reduction on occupant response using a human body finite element model

description: <b>Objective</b>: The objective of this study is to use a validated finite element model of the human body and a certified model of an anthropomorphic test dummy (ATD) to evaluate the effect of simulated precrash braking on driver kinematics, restraint loads, body loads, and computed injury criteria in 4 commonly injured body regions. <b>Methods</b>: The Global Human Body Models Consortium (GHBMC) 50th percentile male occupant (M50-O) and the Humanetics Hybrid III 50th percentile models were gravity settled in the driver position of a generic interior equipped with an advanced 3-point belt and driver airbag. Fifteen simulations per model (30 total) were conducted, including 4 scenarios at 3 severity levels: median, severe, and the U.S. New Car Assessment Program (U.S.-NCAP) and 3 extra per model with high-intensity braking. The 4 scenarios were no precollision system (no PCS), forward collision warning (FCW), FCW with prebraking assist (FCW+PBA), and FCW and PBA with autonomous precrash braking (FCW + PBA + PB). The baseline ΔV was 17, 34, and 56.4 kph for median, severe, and U.S.-NCAP scenarios, respectively, and were based on crash reconstructions from NASS/CDS. Pulses were then developed based on the assumed precrash systems equipped. Restraint properties and the generic pulse used were based on literature. <b>Results</b>: In median crash severity cases, little to no risk (&lt;10% risk for Abbreviated injury Scale [AIS] 3+) was found for all injury measures for both models. In the severe set of cases, little to no risk for AIS 3+ injury was also found for all injury measures. In NCAP cases, highest risk was typically found with No PCS and lowest with FCW + PBA + PB. In the higher intensity braking cases (1.0–1.4 g), head injury criterion (HIC), brain injury criterion (BrIC), and chest deflection injury measures increased with increased braking intensity. All other measures for these cases tended to decrease. The ATD also predicted and trended similar to the human body models predictions for both the median, severe, and NCAP cases. Forward excursion for both models decreased across median, severe, and NCAP cases and diverged from each other in cases above 1.0 g of braking intensity. <b>Conclusions</b>: The addition of precrash systems simulated through reduced precrash speeds caused reductions in some injury criteria, whereas others (chest deflection, HIC, and BrIC) increased due to a modified occupant position. The human model and ATD models trended similarly in nearly all cases with greater risk indicated in the human model. These results suggest the need for integrated safety systems that have restraints that optimize the occupant's position during precrash braking and prior to impact.