cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.4738153.v1
title: Cost effectiveness of the occupation-based approach for subacute stroke patients: result of a randomized controlled trial

description: <b>Background and purpose:</b> The cost effectiveness of occupational therapy for subacute stroke patients is unclear in the extant literature. Consequently, this study determined the cost effectiveness of the occupation-based approach using Aid for Decision-Making in Occupation Choice (ADOC) for subacute stroke patients compared with an impairment-based approach. <b>Methods:</b> We conducted an economic evaluation from a societal perspective alongside a pilot randomized controlled trial, with a single blind assessor for participants in 10 subacute rehabilitation units in Japan. The intervention group received occupation-based goal setting using ADOC, with interventions focused on meaningful occupations. The control group received an impairment-based approach focused on restoring capacities. For both groups, occupational-therapy intervention was administered more than five times per week, for over 40 min each time, and they received physical and speech therapy prior to discharge. The main outcomes were quality-adjusted life years (QALYs) and total costs. Further, sensitivity analyses were performed to examine the influence of parameter uncertainty on the base case results. <b>Results:</b> The final number of participants was 24 in each of the two groups. In terms of QALYs, the intervention group is significantly higher than the control group (<i>p</i> = 0.001, difference 95% CI: 0.002–0.008) and total costs are not statistically significant. Applying a willingness-to-pay threshold of JPY 5 million/QALY, the probability of the occupation-based approach using ADOC being cost effective was estimated to be 65.3%. <b>Conclusions:</b> The results show that the occupation-based approach is associated with significantly improved QALYs and has potential cost effectiveness, compared with the impairment-based approach.
DOI: 10.6084/m9.figshare.4738123
title: Utility of registries for post-marketing evaluation of medicines. A survey of Swedish health care quality registries from a regulatory perspective

description: <b>Aim:</b> The aim of this study was to describe content and procedures in some selected Swedish health care quality registries (QRs) of relevance to regulatory decision-making. <b>Methods:</b> A workshop was organized with participation of seven Swedish QRs which subsequently answered a questionnaire regarding registry content on drug treatments and outcomes. Patient populations, coverage, data handling and quality control, as well as legal and ethical aspects are presented. Scientific publications from the QRs are used as a complementary measure of quality and scientific relevance. <b>Results:</b> The registries under study collect clinical data of high relevance to regulatory and health technology agencies. Five out of seven registries provide information on the drug of interest. When applying external quality criteria, we found a high degree of fulfillment, although information on medication was not sufficient to answer all questions of regulatory interest. A notable strength is the option for linkage to the Prescribed Drug Registry and to information on education and socioeconomic status. Data on drugs used during hospitalization were also collected to some extent. Outcome measures collected resemble those used in relevant clinical trials. All registries collected patient-reported outcome measures. The number of publications from the registries was substantial, with studies of appropriate design, including randomized registry trials. <b>Conclusions:</b> Quality registries may provide a valuable source of post-marketing data on drug effectiveness, safety, and cost-effectiveness. Closer collaboration between registries and regulators to improve quality and usefulness of registry data could benefit both regulatory utility and value for health care providers.
DOI: 10.6084/m9.figshare.4738114
title: Inhibition of NMDA receptor function with an anti-GluN1-S2 antibody impairs human platelet function and thrombosis

description: GluN1 is a mandatory component of <i>N</i>-methyl-D-aspartate receptors (NMDARs) best known for their roles in the brain, but with increasing evidence for relevance in peripheral tissues, including platelets. Certain anti-GluN1 antibodies reduce brain infarcts in rodent models of ischaemic stroke. There is also evidence that human anti-GluN1 autoantibodies reduce neuronal damage in stroke patients, but the underlying mechanism is unclear. This study investigated whether anti-GluN1-mediated neuroprotection involves inhibition of platelet function. Four commercial anti-GluN1 antibodies were screened for their abilities to inhibit human platelet aggregation. Haematological parameters were examined in rats vaccinated with GluN1. Platelet effects of a mouse monoclonal antibody targeting the glycine-binding region of GluN1 (GluN1-S2) were tested in assays of platelet activation, aggregation and thrombus formation. The epitope of anti-GluN1-S2 was mapped and the mechanism of antibody action modelled using crystal structures of GluN1. Our work found that rats vaccinated with GluN1 had a mildly prolonged bleeding time and carried antibodies targeting mostly GluN1-S2. The monoclonal anti-GluN1-S2 antibody (from BD Biosciences) inhibited activation and aggregation of human platelets in the presence of adrenaline, adenosine diphosphate, collagen, thrombin and a protease-activated receptor 1-activating peptide. When human blood was flowed over collagen-coated surfaces, anti-GluN1-S2 impaired thrombus growth and stability. The epitope of anti-GluN1-S2 was mapped to α-helix H located within the glycine-binding clamshell of GluN1, where the antibody binding was computationally predicted to impair opening of the NMDAR channel. Our results indicate that anti-GluN1-S2 inhibits function of human platelets, including dense granule release and thrombus growth. Findings add to the evidence that platelet NMDARs regulate thrombus formation and suggest a novel mechanism by which anti-GluN1 autoantibodies limit stroke-induced neuronal damage.
DOI: 10.6084/m9.figshare.4738123.v1
title: Utility of registries for post-marketing evaluation of medicines. A survey of Swedish health care quality registries from a regulatory perspective

description: <b>Aim:</b> The aim of this study was to describe content and procedures in some selected Swedish health care quality registries (QRs) of relevance to regulatory decision-making. <b>Methods:</b> A workshop was organized with participation of seven Swedish QRs which subsequently answered a questionnaire regarding registry content on drug treatments and outcomes. Patient populations, coverage, data handling and quality control, as well as legal and ethical aspects are presented. Scientific publications from the QRs are used as a complementary measure of quality and scientific relevance. <b>Results:</b> The registries under study collect clinical data of high relevance to regulatory and health technology agencies. Five out of seven registries provide information on the drug of interest. When applying external quality criteria, we found a high degree of fulfillment, although information on medication was not sufficient to answer all questions of regulatory interest. A notable strength is the option for linkage to the Prescribed Drug Registry and to information on education and socioeconomic status. Data on drugs used during hospitalization were also collected to some extent. Outcome measures collected resemble those used in relevant clinical trials. All registries collected patient-reported outcome measures. The number of publications from the registries was substantial, with studies of appropriate design, including randomized registry trials. <b>Conclusions:</b> Quality registries may provide a valuable source of post-marketing data on drug effectiveness, safety, and cost-effectiveness. Closer collaboration between registries and regulators to improve quality and usefulness of registry data could benefit both regulatory utility and value for health care providers.
DOI: 10.6084/m9.figshare.4738105
title: Features of the attenuation and single-sided imaging potential of near-infrared laser radiation in tissue-like liquid turbid media

description: Tissue-like phantoms are important tools in studying light propagation and scattering in biological tissues and in the development, testing and calibration of novel optical diagnostic and therapeutic methods and instruments. This motivates the interest in characterizing the optical properties of tissue-simulating turbid media. In the present work, using an original approach, the specific features have been revealed experimentally and interpreted physically (as owing to the polydispersity of the ensemble of scatterers) of the generally non-linear behaviour of the extinction (total attenuation) coefficient of Intralipid-20% dilutions in distilled water, depending on the Intralipid concentration, for near-infrared laser radiation of different wavelengths. At relatively low incremental concentrations, the values obtained of the extinction coefficient are shown to increase linearly being in agreement at each wavelength of concern with results for the integral scattering coefficient predicted by empiric formulae found by other authors. Comparative estimation has been performed as well, depending on the radiation wavelength, of the potentialities of single-sided optical sensing of tissue-like media. The estimates obtained outline the advantage of the wavelengths around the upper limit of the tissue optical window.
DOI: 10.6084/m9.figshare.4738114.v1
title: Inhibition of NMDA receptor function with an anti-GluN1-S2 antibody impairs human platelet function and thrombosis

description: GluN1 is a mandatory component of <i>N</i>-methyl-D-aspartate receptors (NMDARs) best known for their roles in the brain, but with increasing evidence for relevance in peripheral tissues, including platelets. Certain anti-GluN1 antibodies reduce brain infarcts in rodent models of ischaemic stroke. There is also evidence that human anti-GluN1 autoantibodies reduce neuronal damage in stroke patients, but the underlying mechanism is unclear. This study investigated whether anti-GluN1-mediated neuroprotection involves inhibition of platelet function. Four commercial anti-GluN1 antibodies were screened for their abilities to inhibit human platelet aggregation. Haematological parameters were examined in rats vaccinated with GluN1. Platelet effects of a mouse monoclonal antibody targeting the glycine-binding region of GluN1 (GluN1-S2) were tested in assays of platelet activation, aggregation and thrombus formation. The epitope of anti-GluN1-S2 was mapped and the mechanism of antibody action modelled using crystal structures of GluN1. Our work found that rats vaccinated with GluN1 had a mildly prolonged bleeding time and carried antibodies targeting mostly GluN1-S2. The monoclonal anti-GluN1-S2 antibody (from BD Biosciences) inhibited activation and aggregation of human platelets in the presence of adrenaline, adenosine diphosphate, collagen, thrombin and a protease-activated receptor 1-activating peptide. When human blood was flowed over collagen-coated surfaces, anti-GluN1-S2 impaired thrombus growth and stability. The epitope of anti-GluN1-S2 was mapped to α-helix H located within the glycine-binding clamshell of GluN1, where the antibody binding was computationally predicted to impair opening of the NMDAR channel. Our results indicate that anti-GluN1-S2 inhibits function of human platelets, including dense granule release and thrombus growth. Findings add to the evidence that platelet NMDARs regulate thrombus formation and suggest a novel mechanism by which anti-GluN1 autoantibodies limit stroke-induced neuronal damage.
DOI: 10.6084/m9.figshare.4738099
title: Nanoethosomes for transdermal delivery of tropisetron HCl: multi-factorial predictive modeling, characterization, and <i>ex vivo</i> skin permeation

description: <b>Objective:</b> The aim of the present work is to exclusively optimize and model the effect of phospholipid type either egg phosphatidylcholine (EPC) or soybean phosphatidylcholine (SPC), together with other formulation variables, on the development of nano-ethosomal systems for transdermal delivery of a water-soluble antiemetic drug. Tropisetron HCl (TRO) is available as hard gelatin capsules and IV injections. The transdermal delivery of TRO is considered as a novel alternative route supposing to improve BAV as well as patient convenience. <b>Methods:</b> TRO-loaded ethanolic vesicular systems were prepared by hot technique. The effect of formulation variables were optimized through a response surface methodology using 3 × 2<sup>2</sup>-level full factorial design. The concentrations of both PC (A) and ethanol (B) and PC type (C) were the factors, while entrapment efficiency (<i>Y</i><sub>1</sub>), vesicle size (<i>Y</i><sub>2</sub>), polydispersity index (<i>Y</i><sub>3</sub>), and zeta potential (<i>Y</i><sub>4</sub>) were the responses. The drug permeation across rat skin from selected formulae was studied. Particle morphology, drug–excipient interactions, and vesicle stability were also investigated. <b>Results:</b> The results proved the critical role of all formulation variables on ethosomal characteristics. The suggested models for all responses showed good predictability. Only the concentration of phospholipid, irrespective to PC type, had a significant effect on the transdermal flux (<i>p</i> <b>Conclusion:</b> The study suggests the applicability of statistical modeling as a promising tool for prediction of ethosomal characteristics. The ethanolic vesicles were considered as novel potential nanocarriers for accentuated transdermal TRO delivery.
DOI: 10.6084/m9.figshare.4738093
title: Instrumental political support: bringing policy preferences back into explanations of EU support

description: There is a joint development towards Europeanisation of public policies and an increasing visibility and politicisation of European issues in EU member states. In this context, the degree of fit between individuals’ policy preferences and European norms could be expected to influence support for the EU: this support might increase when Europeanisation makes the desired policies more likely, and decrease when it hinders these policies. Multilevel analyses of the 2014 wave of the European Election Study confirms the existence of such instrumental support for the EU. The findings demonstrate that this support is shaped by policy preferences on state intervention, immigration, moral issues and environmental protection. The results also show that the impact of these policy preferences is modulated by the level of integration of the designated policy, by the weight of the policy issue in the country and, in some cases, by the level of individual political knowledge.
DOI: 10.6084/m9.figshare.4738099.v1
title: Nanoethosomes for transdermal delivery of tropisetron HCl: multi-factorial predictive modeling, characterization, and <i>ex vivo</i> skin permeation

description: <b>Objective:</b> The aim of the present work is to exclusively optimize and model the effect of phospholipid type either egg phosphatidylcholine (EPC) or soybean phosphatidylcholine (SPC), together with other formulation variables, on the development of nano-ethosomal systems for transdermal delivery of a water-soluble antiemetic drug. Tropisetron HCl (TRO) is available as hard gelatin capsules and IV injections. The transdermal delivery of TRO is considered as a novel alternative route supposing to improve BAV as well as patient convenience. <b>Methods:</b> TRO-loaded ethanolic vesicular systems were prepared by hot technique. The effect of formulation variables were optimized through a response surface methodology using 3 × 2<sup>2</sup>-level full factorial design. The concentrations of both PC (A) and ethanol (B) and PC type (C) were the factors, while entrapment efficiency (<i>Y</i><sub>1</sub>), vesicle size (<i>Y</i><sub>2</sub>), polydispersity index (<i>Y</i><sub>3</sub>), and zeta potential (<i>Y</i><sub>4</sub>) were the responses. The drug permeation across rat skin from selected formulae was studied. Particle morphology, drug–excipient interactions, and vesicle stability were also investigated. <b>Results:</b> The results proved the critical role of all formulation variables on ethosomal characteristics. The suggested models for all responses showed good predictability. Only the concentration of phospholipid, irrespective to PC type, had a significant effect on the transdermal flux (<i>p</i> <b>Conclusion:</b> The study suggests the applicability of statistical modeling as a promising tool for prediction of ethosomal characteristics. The ethanolic vesicles were considered as novel potential nanocarriers for accentuated transdermal TRO delivery.
DOI: 10.6084/m9.figshare.4738093.v1
title: Instrumental political support: bringing policy preferences back into explanations of EU support

description: There is a joint development towards Europeanisation of public policies and an increasing visibility and politicisation of European issues in EU member states. In this context, the degree of fit between individuals’ policy preferences and European norms could be expected to influence support for the EU: this support might increase when Europeanisation makes the desired policies more likely, and decrease when it hinders these policies. Multilevel analyses of the 2014 wave of the European Election Study confirms the existence of such instrumental support for the EU. The findings demonstrate that this support is shaped by policy preferences on state intervention, immigration, moral issues and environmental protection. The results also show that the impact of these policy preferences is modulated by the level of integration of the designated policy, by the weight of the policy issue in the country and, in some cases, by the level of individual political knowledge.
DOI: 10.6084/m9.figshare.4738054
title: Mitochondrial super-haplogroup U diversity in Serbians

description: <b>Background:</b> Available mitochondrial (mtDNA) data demonstrate genetic differentiation among South Slavs inhabiting the Balkan Peninsula. However, their resolution is insufficient to elucidate the female-specific aspects of the genetic history of South Slavs, including the genetic impact of various migrations which were rather common within the Balkans, a region having a turbulent demographic history. <b>Aim:</b> The aim was to thoroughly study complete mitogenomes of Serbians, a population linking westward and eastward South Slavs. <b>Subjects and methods:</b> Forty-six predominantly Serbian super-haplogroup U complete mitogenomes were analysed phylogenetically against ∼4000 available complete mtDNAs of modern and ancient Western Eurasians. <b>Results:</b> Serbians share a number of U mtDNA lineages with Southern, Eastern-Central and North-Western Europeans. Putative Balkan-specific lineages (e.g. U1a1c2, U4c1b1, U5b3j, K1a4l and K1a13a1) and lineages shared among Serbians (South Slavs) and West and East Slavs were detected (e.g. U2e1b1, U2e2a1d, U4a2a, U4a2c, U4a2g1, U4d2b and U5b1a1). <b>Conclusion:</b> The exceptional diversity of maternal lineages found in Serbians may be associated with the genetic impact of both autochthonous pre-Slavic Balkan populations whose mtDNA gene pool was affected by migrations of various populations over time (e.g. Bronze Age pastoralists) and Slavic and Germanic newcomers in the early Middle Ages.
DOI: 10.6084/m9.figshare.4738036
title: Efficient solvation free energy simulations: impact of soft-core potential and a new adaptive λ-spacing method

description: The calculation of Gibbs free energy of solvation Δ<i>G</i> is commonly applied to predict the solubility of solutes in different solvents. The transition path between the thermodynamic end states of full and non-existent solute–solvent interactions is described by the spacing of intermediate states and the soft-core potential employed to scale the interactions. The choice of both, the soft-core potential and the distribution of intermediate states, has a large impact on the simulated Δ<i>G</i>. In this work, we determine the free energy of hydration for 10 neutral amino acid side chain analogues to analyse the impact of different soft-core potentials on the consistency of results from two different free energy methods, i.e. thermodynamic integration and free energy perturbation. Additionally, we propose a new method to improve the alchemical pathway by adaptive spacing of intermediate states. Our technique is easy to implement and not limited to any simulation package or free energy technique in particular, making it easily adaptable to a variety of workflows. Exploiting the ability to systematically optimise alchemical pathways, we introduce a scheme to define a suitable number of windows based on prescribed configurational space overlap. With this, excessive sampling is avoided and computational costs can be reduced.
DOI: 10.6084/m9.figshare.4738021
title: Adenomyosis and adverse perinatal outcomes: increased risk of second trimester miscarriage, preeclampsia, and placental malposition

description: <b>Objective:</b> To evaluate the potential impact of adenomyosis on the pregnancy outcomes by retrospectively investigating adenomyosis-complicated pregnancy cases. <b>Methods:</b> We performed a retrospective case–control study. Forty-nine singleton pregnancy cases complicated with adenomyosis were included in this study. The controls (<i>n</i> = 245) were singleton pregnant women without adenomyosis and were frequency matched to adenomyosis cases by age, parity, and the need for assisted reproductive technology for this conception. The incidence of obstetrical complications and delivery and neonatal outcomes were examined. <b>Results:</b> Patients in the adenomyosis group were significantly more likely to have a second trimester miscarriage (12.2% versus 1.2%, odds ratio (OR): 11.2, 95% confidence interval (95% CI): 2.2–71.2), preeclampsia (18.3% versus 1.2%, OR: 21.0, 95% CI: 4.8–124.5), placental malposition (14.2% versus 3.2%, OR: 4.9, 95% CI: 1.4–16.3), and preterm delivery (24.4% versus 9.3%, OR: 3.1, 95% CI: 1.2–7.2), compared with the control group. <b>Conclusion:</b> Adenomyosis was associated not only with an increased incidence of preterm delivery, as previously reported, but also with an increased risk of second trimester miscarriage, preeclampsia, and placental malposition, which could lead to poor perinatal outcomes.
DOI: 10.6084/m9.figshare.4738027
title: Quantum virial coefficients of molecular nitrogen

description: We report virial coefficients up to third order in density for molecular nitrogen, investigating 103 temperatures in the range (15 K, 3000 K). All calculations are based on an <i>ab initio</i>-based potential taken from the literature. Path-integral Monte Carlo (PIMC) is applied to account for nuclear quantum effects, and these results are compared to a more approximate but faster semiclassical treatment. Additionally, we examine a PIMC approach that employs semiclassical beads for the path-integral images, but find that it offers marginal advantage. A recently developed orientation sampling algorithm is used in conjunction with Mayer sampling to compute precise virial coefficients. We find that, within the precision of our calculations of the second-order coefficient (<i>B</i><sub>2</sub>), semiclassical methods are adequate for temperatures greater than 250 K, and are needed to correct classical behaviour for temperatures as high as 800 K. For the third-order coefficient (<i>B</i><sub>3</sub>), the semiclassical methods are adequate above 150 K, and are required up to the highest temperature examined (3000 K) in order to correct the classical treatment within the precision of the calculations. However, three-body contributions to the potential are much more significant than nuclear quantum effects for the evaluation of <i>B</i><sub>3</sub>.