cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.15468/dl.jc2w5k
title: Occurrence Download

description: A dataset containing 202 species occurrences available in GBIF matching the query:
{
 "and" : [
 "Country is Peru",
 "TaxonKey is Tapirus terrestris (Linnaeus, 1758)"
 ]
}

 The dataset includes 202 records from 13 constituent datasets; see https://api.gbif.org/v1/occurrence/download/0013287-241024112534372/datasets/export for details.
 
Data from some individual datasets included in this download may be licensed under less restrictive terms.
DOI: 10.15468/dl.crndqx
title: Occurrence Download

description: A dataset containing 6525 species occurrences available in GBIF matching the query:
{
 "TaxonKey" : [
 "is Betula platyphylla Sukaczev"
 ]
}

 The dataset includes 6525 records from 118 constituent datasets; see https://api.gbif.org/v1/occurrence/download/0013288-241024112534372/datasets/export for details.
 
Data from some individual datasets included in this download may be licensed under less restrictive terms.
DOI: 10.6084/m9.figshare.27043128
title: A systematic review of allometric scaling exponents for IgG mAbs

description: Increasing complexity of mAbs in development creates challenges in predicting human pharmacokinetic (PK) parameters from preclinical data. The aim of this analysis was to identify optimal allometric scaling exponents.Data were extracted from literature to create a central database (currently the largest available published database) of two-compartment model parameters for mAbs (<i>n</i> = 59) in cynomolgus monkey (CM) and human.Global allometric exponents were calculated and drug-dependent factors were investigated as potential variables in determining the optimal scaling factor.The global exponents for scaling CM mAb PK data were 0.74 (CL), 0.80 (CL with Fc-modified mAbs excluded), 0.44 (CL with Fc-modified mAbs only), 0.71 (Q), 1.12 (V1), and 0.99 (V2). These values are in line with previously published literature values. Increasing complexity of mAbs in development creates challenges in predicting human pharmacokinetic (PK) parameters from preclinical data. The aim of this analysis was to identify optimal allometric scaling exponents. Data were extracted from literature to create a central database (currently the largest available published database) of two-compartment model parameters for mAbs (<i>n</i> = 59) in cynomolgus monkey (CM) and human. Global allometric exponents were calculated and drug-dependent factors were investigated as potential variables in determining the optimal scaling factor. The global exponents for scaling CM mAb PK data were 0.74 (CL), 0.80 (CL with Fc-modified mAbs excluded), 0.44 (CL with Fc-modified mAbs only), 0.71 (Q), 1.12 (V1), and 0.99 (V2). These values are in line with previously published literature values.
DOI: 10.6084/m9.figshare.27043128.v1
title: A systematic review of allometric scaling exponents for IgG mAbs

description: Increasing complexity of mAbs in development creates challenges in predicting human pharmacokinetic (PK) parameters from preclinical data. The aim of this analysis was to identify optimal allometric scaling exponents.Data were extracted from literature to create a central database (currently the largest available published database) of two-compartment model parameters for mAbs (<i>n</i> = 59) in cynomolgus monkey (CM) and human.Global allometric exponents were calculated and drug-dependent factors were investigated as potential variables in determining the optimal scaling factor.The global exponents for scaling CM mAb PK data were 0.74 (CL), 0.80 (CL with Fc-modified mAbs excluded), 0.44 (CL with Fc-modified mAbs only), 0.71 (Q), 1.12 (V1), and 0.99 (V2). These values are in line with previously published literature values. Increasing complexity of mAbs in development creates challenges in predicting human pharmacokinetic (PK) parameters from preclinical data. The aim of this analysis was to identify optimal allometric scaling exponents. Data were extracted from literature to create a central database (currently the largest available published database) of two-compartment model parameters for mAbs (<i>n</i> = 59) in cynomolgus monkey (CM) and human. Global allometric exponents were calculated and drug-dependent factors were investigated as potential variables in determining the optimal scaling factor. The global exponents for scaling CM mAb PK data were 0.74 (CL), 0.80 (CL with Fc-modified mAbs excluded), 0.44 (CL with Fc-modified mAbs only), 0.71 (Q), 1.12 (V1), and 0.99 (V2). These values are in line with previously published literature values.
DOI: 10.6084/m9.figshare.25650432
title: MicroRNA-mediated Krüppel-like factor 4 upregulation induces alternatively activated macrophage-associated marker and chemokine transcription in 4,4’-methylene diphenyl diisocyanate exposed macrophages

description: 1. Occupational exposure to 4,4’-methylene diphenyl diisocyanate (MDI) is associated with occupational asthma (OA) development. Alveolar macrophage-induced recruitment of immune cells to the lung microenvironment plays an important role during asthma pathogenesis. Previous studies identified that MDI/MDI-glutathione (GSH)-exposure downregulates endogenous <i>hsa-miR-206-3p</i>/<i>hsa-miR-381-3p</i>. Our prior report shows that alternatively activated (M2) macrophage-associated markers/chemokines are induced by MDI/MDI-GSH-mediated Krüppel-Like Factor 4 (KLF4) upregulation in macrophages and stimulates immune cell chemotaxis. However, the underlying molecular mechanism(s) by which MDI/MDI-GSH upregulates KLF4 remain unclear. 2. Following MDI-GSH exposure, microRNA(miR)-inhibitors/mimics or plasmid transfection, endogenous <i>hsa-miR-206-3p</i>/<i>hsa-miR-381-3p,</i> KLF4, or M2 macrophage-associated markers (<i>CD206</i>, <i>TGM2</i>), and chemokines (<i>CCL17, CCL22, CCL24</i>) were measured by either RT-qPCR, western blot, or luciferase assay. 3. MDI-GSH exposure downregulates <i>hsa-miR-206-3p</i>/<i>hsa-miR-381-3p</i> by 1.46- to 9.75-fold whereas upregulates <i>KLF4</i> by 1.68- to 1.99-fold, respectively. <i>In silico</i> analysis predicts binding between <i>hsa-miR-206-3p/hsa-miR-381-3p</i> and <i>KLF4.</i> Gain- and loss-of-function, luciferase reporter assays and RNA-induced silencing complex-immunoprecipitation (RISC-IP) studies confirm the posttranscriptional regulatory roles of <i>hsa-miR-206-3p/hsa-miR-381-3p</i> and <i>KLF4</i> in macrophages. Furthermore, <i>hsa-miR-206-3p</i>/<i>hsa-miR-381-3p</i> regulate the expression of M2 macrophage-associated markers and chemokines <i>via</i> KLF4. 4. In conclusion, <i>hsa-miR-206-3p/hsa-miR-381-3p</i> play a major role in regulation of MDI/MDI-GSH-induced M2 macrophage-associated markers and chemokines by targeting the <i>KLF4</i> transcript, and KLF4-mediated regulation in macrophages.
DOI: 10.6084/m9.figshare.25650432.v2
title: MicroRNA-mediated Krüppel-like factor 4 upregulation induces alternatively activated macrophage-associated marker and chemokine transcription in 4,4’-methylene diphenyl diisocyanate exposed macrophages

description: 1. Occupational exposure to 4,4’-methylene diphenyl diisocyanate (MDI) is associated with occupational asthma (OA) development. Alveolar macrophage-induced recruitment of immune cells to the lung microenvironment plays an important role during asthma pathogenesis. Previous studies identified that MDI/MDI-glutathione (GSH)-exposure downregulates endogenous <i>hsa-miR-206-3p</i>/<i>hsa-miR-381-3p</i>. Our prior report shows that alternatively activated (M2) macrophage-associated markers/chemokines are induced by MDI/MDI-GSH-mediated Krüppel-Like Factor 4 (KLF4) upregulation in macrophages and stimulates immune cell chemotaxis. However, the underlying molecular mechanism(s) by which MDI/MDI-GSH upregulates KLF4 remain unclear. 2. Following MDI-GSH exposure, microRNA(miR)-inhibitors/mimics or plasmid transfection, endogenous <i>hsa-miR-206-3p</i>/<i>hsa-miR-381-3p,</i> KLF4, or M2 macrophage-associated markers (<i>CD206</i>, <i>TGM2</i>), and chemokines (<i>CCL17, CCL22, CCL24</i>) were measured by either RT-qPCR, western blot, or luciferase assay. 3. MDI-GSH exposure downregulates <i>hsa-miR-206-3p</i>/<i>hsa-miR-381-3p</i> by 1.46- to 9.75-fold whereas upregulates <i>KLF4</i> by 1.68- to 1.99-fold, respectively. <i>In silico</i> analysis predicts binding between <i>hsa-miR-206-3p/hsa-miR-381-3p</i> and <i>KLF4.</i> Gain- and loss-of-function, luciferase reporter assays and RNA-induced silencing complex-immunoprecipitation (RISC-IP) studies confirm the posttranscriptional regulatory roles of <i>hsa-miR-206-3p/hsa-miR-381-3p</i> and <i>KLF4</i> in macrophages. Furthermore, <i>hsa-miR-206-3p</i>/<i>hsa-miR-381-3p</i> regulate the expression of M2 macrophage-associated markers and chemokines <i>via</i> KLF4. 4. In conclusion, <i>hsa-miR-206-3p/hsa-miR-381-3p</i> play a major role in regulation of MDI/MDI-GSH-induced M2 macrophage-associated markers and chemokines by targeting the <i>KLF4</i> transcript, and KLF4-mediated regulation in macrophages.
DOI: 10.6084/m9.figshare.27024848
title: How predictive are isolated perfused liver data of <i>in vivo</i> hepatic clearance? A meta-analysis of isolated perfused rat liver data

description: Isolated perfused rat liver (IPRL) experiments have been used to answer clearance-related questions, including evaluating the impact of pathological and physiological processes on hepatic clearance (<i>CL<sub>H</sub></i>). However, to date, IPRL data has not been evaluated for <i>in vivo CL<sub>H</sub></i> prediction accuracy.In addition to a detailed overview of available IPRL literature, we present an in-depth analysis of the performance of IPRL in <i>CL<sub>H</sub></i> prediction.While the entire dataset poorly predicted <i>CL<sub>H</sub></i> (GAFE = 3.2; 64% within 3-fold), IPRL conducted under optimal experimental conditions, such as in the presence of plasma proteins and with a perfusion rate within 2-fold of physiological liver blood flow and corrected for unbound fraction in the presence of red blood cells, can accurately predict rat <i>CL<sub>H</sub></i> (GAFE = 2.0; 78% within 3-fold). Careful consideration of experimental conditions is needed to allow proper data analysis.Further, isolated perfused liver experiments in other species, including human livers, may allow us to address the current <i>in vitro</i>-<i>in vivo</i> disconnects of hepatic metabolic clearance and improve our methodology for <i>CL<sub>H</sub></i> predictions. Isolated perfused rat liver (IPRL) experiments have been used to answer clearance-related questions, including evaluating the impact of pathological and physiological processes on hepatic clearance (<i>CL<sub>H</sub></i>). However, to date, IPRL data has not been evaluated for <i>in vivo CL<sub>H</sub></i> prediction accuracy. In addition to a detailed overview of available IPRL literature, we present an in-depth analysis of the performance of IPRL in <i>CL<sub>H</sub></i> prediction. While the entire dataset poorly predicted <i>CL<sub>H</sub></i> (GAFE = 3.2; 64% within 3-fold), IPRL conducted under optimal experimental conditions, such as in the presence of plasma proteins and with a perfusion rate within 2-fold of physiological liver blood flow and corrected for unbound fraction in the presence of red blood cells, can accurately predict rat <i>CL<sub>H</sub></i> (GAFE = 2.0; 78% within 3-fold). Careful consideration of experimental conditions is needed to allow proper data analysis. Further, isolated perfused liver experiments in other species, including human livers, may allow us to address the current <i>in vitro</i>-<i>in vivo</i> disconnects of hepatic metabolic clearance and improve our methodology for <i>CL<sub>H</sub></i> predictions.
DOI: 10.6084/m9.figshare.27024848.v2
title: How predictive are isolated perfused liver data of <i>in vivo</i> hepatic clearance? A meta-analysis of isolated perfused rat liver data

description: Isolated perfused rat liver (IPRL) experiments have been used to answer clearance-related questions, including evaluating the impact of pathological and physiological processes on hepatic clearance (<i>CL<sub>H</sub></i>). However, to date, IPRL data has not been evaluated for <i>in vivo CL<sub>H</sub></i> prediction accuracy.In addition to a detailed overview of available IPRL literature, we present an in-depth analysis of the performance of IPRL in <i>CL<sub>H</sub></i> prediction.While the entire dataset poorly predicted <i>CL<sub>H</sub></i> (GAFE = 3.2; 64% within 3-fold), IPRL conducted under optimal experimental conditions, such as in the presence of plasma proteins and with a perfusion rate within 2-fold of physiological liver blood flow and corrected for unbound fraction in the presence of red blood cells, can accurately predict rat <i>CL<sub>H</sub></i> (GAFE = 2.0; 78% within 3-fold). Careful consideration of experimental conditions is needed to allow proper data analysis.Further, isolated perfused liver experiments in other species, including human livers, may allow us to address the current <i>in vitro</i>-<i>in vivo</i> disconnects of hepatic metabolic clearance and improve our methodology for <i>CL<sub>H</sub></i> predictions. Isolated perfused rat liver (IPRL) experiments have been used to answer clearance-related questions, including evaluating the impact of pathological and physiological processes on hepatic clearance (<i>CL<sub>H</sub></i>). However, to date, IPRL data has not been evaluated for <i>in vivo CL<sub>H</sub></i> prediction accuracy. In addition to a detailed overview of available IPRL literature, we present an in-depth analysis of the performance of IPRL in <i>CL<sub>H</sub></i> prediction. While the entire dataset poorly predicted <i>CL<sub>H</sub></i> (GAFE = 3.2; 64% within 3-fold), IPRL conducted under optimal experimental conditions, such as in the presence of plasma proteins and with a perfusion rate within 2-fold of physiological liver blood flow and corrected for unbound fraction in the presence of red blood cells, can accurately predict rat <i>CL<sub>H</sub></i> (GAFE = 2.0; 78% within 3-fold). Careful consideration of experimental conditions is needed to allow proper data analysis. Further, isolated perfused liver experiments in other species, including human livers, may allow us to address the current <i>in vitro</i>-<i>in vivo</i> disconnects of hepatic metabolic clearance and improve our methodology for <i>CL<sub>H</sub></i> predictions.
DOI: 10.6084/m9.figshare.25650432.v1
title: MicroRNA-mediated Krüppel-like factor 4 upregulation induces alternatively activated macrophage-associated marker and chemokine transcription in 4,4’-methylene diphenyl diisocyanate exposed macrophages

description: 1. Occupational exposure to 4,4’-methylene diphenyl diisocyanate (MDI) is associated with occupational asthma (OA) development. Alveolar macrophage-induced recruitment of immune cells to the lung microenvironment plays an important role during asthma pathogenesis. Previous studies identified that MDI/MDI-glutathione (GSH)-exposure downregulates endogenous <i>hsa-miR-206-3p</i>/<i>hsa-miR-381-3p</i>. Our prior report shows that alternatively activated (M2) macrophage-associated markers/chemokines are induced by MDI/MDI-GSH-mediated Krüppel-Like Factor 4 (KLF4) upregulation in macrophages and stimulates immune cell chemotaxis. However, the underlying molecular mechanism(s) by which MDI/MDI-GSH upregulates KLF4 remain unclear. 2. Following MDI-GSH exposure, microRNA(miR)-inhibitors/mimics or plasmid transfection, endogenous <i>hsa-miR-206-3p</i>/<i>hsa-miR-381-3p,</i> KLF4, or M2 macrophage-associated markers (<i>CD206</i>, <i>TGM2</i>), and chemokines (<i>CCL17, CCL22, CCL24</i>) were measured by either RT-qPCR, western blot, or luciferase assay. 3. MDI-GSH exposure downregulates <i>hsa-miR-206-3p</i>/<i>hsa-miR-381-3p</i> by 1.46- to 9.75-fold whereas upregulates <i>KLF4</i> by 1.68- to 1.99-fold, respectively. <i>In silico</i> analysis predicts binding between <i>hsa-miR-206-3p/hsa-miR-381-3p</i> and <i>KLF4.</i> Gain- and loss-of-function, luciferase reporter assays and RNA-induced silencing complex-immunoprecipitation (RISC-IP) studies confirm the posttranscriptional regulatory roles of <i>hsa-miR-206-3p/hsa-miR-381-3p</i> and <i>KLF4</i> in macrophages. Furthermore, <i>hsa-miR-206-3p</i>/<i>hsa-miR-381-3p</i> regulate the expression of M2 macrophage-associated markers and chemokines <i>via</i> KLF4. 4. In conclusion, <i>hsa-miR-206-3p/hsa-miR-381-3p</i> play a major role in regulation of MDI/MDI-GSH-induced M2 macrophage-associated markers and chemokines by targeting the <i>KLF4</i> transcript, and KLF4-mediated regulation in macrophages.
DOI: 10.6084/m9.figshare.26539350
title: Improved preclinical drug metabolism and pharmacokinetics of pibothiadine (HEC121210), a novel hepatitis B virus capsid assembly modulator

description: Pibothiadine (PBD; HEC121120) is a novel hepatitis B virus capsid assembly modulator based on GLS4 (morphothiadine) and has inhibitory activities against resistant strains.To assess the overall preclinical drug metabolism and pharmacokinetics (DMPK) properties of PBD, <i>in vivo</i> pharmacokinetics studies in rats and dogs have been performed along with a series of <i>in vitro</i> metabolism assays.The oral bioavailability of PBD in rats and dogs might be related to its medium permeability in Caco-2 cells and largely be impacted by the pH-dependent solubility. PBD was highly distributed to the liver where the local exposure was 16.4 fold of the system exposure. PBD showed relatively low metabolic rate in recombinant human cytochrome P450 enzymes, whereas low to moderate <i>in vitro</i> clearance in liver microsomes and low (dog) to moderate (rat) <i>in vivo</i> clearance. Furthermore, β-oxidation and dehydrogenation were proposed as the primary metabolic pathways of PBD in rats.Compared to GLS4, the higher systemic exposure of PBD might be attributed to its improved oral absorption and metabolic stability. In addition, the enhanced liver/plasma exposure ratio could further increase the local exposure around the target. These improved DMPK properties might indicate better development of PBD in the clinical phase. Pibothiadine (PBD; HEC121120) is a novel hepatitis B virus capsid assembly modulator based on GLS4 (morphothiadine) and has inhibitory activities against resistant strains. To assess the overall preclinical drug metabolism and pharmacokinetics (DMPK) properties of PBD, <i>in vivo</i> pharmacokinetics studies in rats and dogs have been performed along with a series of <i>in vitro</i> metabolism assays. The oral bioavailability of PBD in rats and dogs might be related to its medium permeability in Caco-2 cells and largely be impacted by the pH-dependent solubility. PBD was highly distributed to the liver where the local exposure was 16.4 fold of the system exposure. PBD showed relatively low metabolic rate in recombinant human cytochrome P450 enzymes, whereas low to moderate <i>in vitro</i> clearance in liver microsomes and low (dog) to moderate (rat) <i>in vivo</i> clearance. Furthermore, β-oxidation and dehydrogenation were proposed as the primary metabolic pathways of PBD in rats. Compared to GLS4, the higher systemic exposure of PBD might be attributed to its improved oral absorption and metabolic stability. In addition, the enhanced liver/plasma exposure ratio could further increase the local exposure around the target. These improved DMPK properties might indicate better development of PBD in the clinical phase.
DOI: 10.6084/m9.figshare.26539350.v1
title: Improved preclinical drug metabolism and pharmacokinetics of pibothiadine (HEC121210), a novel hepatitis B virus capsid assembly modulator

description: Pibothiadine (PBD; HEC121120) is a novel hepatitis B virus capsid assembly modulator based on GLS4 (morphothiadine) and has inhibitory activities against resistant strains.To assess the overall preclinical drug metabolism and pharmacokinetics (DMPK) properties of PBD, <i>in vivo</i> pharmacokinetics studies in rats and dogs have been performed along with a series of <i>in vitro</i> metabolism assays.The oral bioavailability of PBD in rats and dogs might be related to its medium permeability in Caco-2 cells and largely be impacted by the pH-dependent solubility. PBD was highly distributed to the liver where the local exposure was 16.4 fold of the system exposure. PBD showed relatively low metabolic rate in recombinant human cytochrome P450 enzymes, whereas low to moderate <i>in vitro</i> clearance in liver microsomes and low (dog) to moderate (rat) <i>in vivo</i> clearance. Furthermore, β-oxidation and dehydrogenation were proposed as the primary metabolic pathways of PBD in rats.Compared to GLS4, the higher systemic exposure of PBD might be attributed to its improved oral absorption and metabolic stability. In addition, the enhanced liver/plasma exposure ratio could further increase the local exposure around the target. These improved DMPK properties might indicate better development of PBD in the clinical phase. Pibothiadine (PBD; HEC121120) is a novel hepatitis B virus capsid assembly modulator based on GLS4 (morphothiadine) and has inhibitory activities against resistant strains. To assess the overall preclinical drug metabolism and pharmacokinetics (DMPK) properties of PBD, <i>in vivo</i> pharmacokinetics studies in rats and dogs have been performed along with a series of <i>in vitro</i> metabolism assays. The oral bioavailability of PBD in rats and dogs might be related to its medium permeability in Caco-2 cells and largely be impacted by the pH-dependent solubility. PBD was highly distributed to the liver where the local exposure was 16.4 fold of the system exposure. PBD showed relatively low metabolic rate in recombinant human cytochrome P450 enzymes, whereas low to moderate <i>in vitro</i> clearance in liver microsomes and low (dog) to moderate (rat) <i>in vivo</i> clearance. Furthermore, β-oxidation and dehydrogenation were proposed as the primary metabolic pathways of PBD in rats. Compared to GLS4, the higher systemic exposure of PBD might be attributed to its improved oral absorption and metabolic stability. In addition, the enhanced liver/plasma exposure ratio could further increase the local exposure around the target. These improved DMPK properties might indicate better development of PBD in the clinical phase.