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European Journal of Human Genetics :... Jul 2024The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate pharmacogenetics implementation in clinical practice by developing evidence-based guidelines to...
The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate pharmacogenetics implementation in clinical practice by developing evidence-based guidelines to optimize pharmacotherapy based on pharmacogenetic test results. The current guideline describes the gene-drug interaction between CYP2D6 and venlafaxine, mirtazapine and duloxetine. In addition, the interaction between CYP2C19 and mirtazapine and moclobemide is presented. The DPWG identified a gene-drug interaction that requires therapy adjustment for CYP2D6 and venlafaxine. However, as the side effects do not appear to be related to plasma concentrations, it is not possible to offer a substantiated advice for dose reduction. Therefore, the DPWG recommends avoiding venlafaxine for CYP2D6 poor and intermediate metabolisers. Instead, an alternative antidepressant, which is not, or to a lesser extent, metabolized by CYP2D6 is recommended. When it is not possible to avoid venlafaxine and side effects occur, it is recommended to reduce the dose and monitor the effect and side effects or plasma concentrations. No action is required for ultra-rapid metabolisers as kinetic effects are minimal and no clinical effect has been demonstrated. In addition, a gene-drug interaction was identified for CYP2D6 and mirtazapine and CYP2C19 and moclobemide, but no therapy adjustment is required as no effect regarding effectiveness or side effects has been demonstrated for these gene-drug interactions. Finally, no gene-drug interaction and need for therapy adjustment between CYP2C19 and mirtazapine and CYP2D6 and duloxetine were identified. The DPWG classifies CYP2D6 genotyping as being "potentially beneficial" for venlafaxine, indicating that genotyping prior to treatment can be considered on an individual patient basis.
PubMed: 38956296
DOI: 10.1038/s41431-024-01648-1 -
Scientific Reports Jul 2024As the node positioning of underwater wireless sensor networks is easily affected by tidal motion, ocean current motion and multipath effect, the node positioning...
As the node positioning of underwater wireless sensor networks is easily affected by tidal motion, ocean current motion and multipath effect, the node positioning accuracy is low. In order to better improve the positioning accuracy of moving nodes of underwater wireless sensor networks, a method of locating mobile nodes of underwater wireless sensor based on tidal motion model is proposed. Firstly, the Time Difference of Arrival (TDOA) localization optimized by niche genetic algorithm is used to initialize each node. The integration of niche technology can effectively find multiple excellent solutions in the solution space, thus providing more abundant solution choices. This algorithm has excellent performance in multi-modal optimization problems, and can avoid the algorithm falling into local optimal solutions, so as to obtain more comprehensive optimization results. The simulation results show that the proposed algorithm has better positioning accuracy than the traditional Chan algorithm and Taylor algorithm. Then, each node is updated in real time by the optimized tidal movement model formula predicted by Kalman filter algorithm. The prediction algorithm is used to compare the real-time predicted update position of the node with the actual position. The positioning distance error of the prediction algorithm is also enough to meet the practical application requirements.
PubMed: 38956263
DOI: 10.1038/s41598-024-65201-2 -
Scientific Reports Jul 2024The design and radiosynthesis of [F]NT376, a high potency inhibitor of class-IIa histone deacetylases (HDAC) is reported. We utilized a three-step radiochemical approach...
The design and radiosynthesis of [F]NT376, a high potency inhibitor of class-IIa histone deacetylases (HDAC) is reported. We utilized a three-step radiochemical approach that led to the radiosynthesis of [F]NT376 in a good radiochemical yield, (17.0 ± 3%, decay corrected), high radiochemical purity (> 97%) and relatively high molar activity of 185.0 GBq/µmol (> 5.0 Ci/µmol). The repositioning of the F-radiolabel into a phenyl ring (F-Fluoro-aryl) of the class-IIa HDAC inhibitor avoided the shortcomings of the direct radiolabeling of the 5-trifluoromethyl-1,2,4-oxadiazole moiety that was reported by us previously and was associated with low molar activity (0.74-1.51 GBq/µmol, 20-41 mCi/µmol). This radiochemical approach could find a wider application for radiolabeling similar molecules with good radiochemical yield and high molar activity.
Topics: Histone Deacetylase Inhibitors; Fluorine Radioisotopes; Radiopharmaceuticals; Drug Design; Humans; Radiochemistry; Oxadiazoles
PubMed: 38956204
DOI: 10.1038/s41598-024-65668-z -
Nature Structural & Molecular Biology Jul 2024The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) long noncoding RNA (lncRNA) has key roles in regulating transcription, splicing, tumorigenesis, etc....
The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) long noncoding RNA (lncRNA) has key roles in regulating transcription, splicing, tumorigenesis, etc. Its maturation and stabilization require precise processing by RNase P, which simultaneously initiates the biogenesis of a 3' cytoplasmic MALAT1-associated small cytoplasmic RNA (mascRNA). mascRNA was proposed to fold into a transfer RNA (tRNA)-like secondary structure but lacks eight conserved linking residues required by the canonical tRNA fold. Here we report crystal structures of human mascRNA before and after processing, which reveal an ultracompact, quasi-tRNA-like structure. Despite lacking all linker residues, mascRNA faithfully recreates the characteristic 'elbow' feature of tRNAs to recruit RNase P and ElaC homolog protein 2 (ELAC2) for processing, which exhibit distinct substrate specificities. Rotation and repositioning of the D-stem and anticodon regions preclude mascRNA from aminoacylation, avoiding interference with translation. Therefore, a class of metazoan lncRNA loci uses a previously unrecognized, unusually streamlined quasi-tRNA architecture to recruit select tRNA-processing enzymes while excluding others to drive bespoke RNA biogenesis, processing and maturation.
PubMed: 38956168
DOI: 10.1038/s41594-024-01340-4 -
Scientific Reports Jul 2024Birds maintain some of the highest body temperatures among endothermic animals. Often deemed a selective advantage for heat tolerance, high body temperatures also limits...
Birds maintain some of the highest body temperatures among endothermic animals. Often deemed a selective advantage for heat tolerance, high body temperatures also limits birds' thermal safety margin before reaching lethal levels. Recent modelling suggests that sustained effort in Arctic birds might be restricted at mild air temperatures, which may require reductions in activity to avoid overheating, with expected negative impacts on reproductive performance. We measured within-individual changes in body temperature in calm birds and then in response to an experimental increase in activity in an outdoor captive population of Arctic, cold-specialised snow buntings (Plectrophenax nivalis), exposed to naturally varying air temperatures (- 15 to 36 °C). Calm buntings exhibited a modal body temperature range from 39.9 to 42.6 °C. However, we detected a significant increase in body temperature within minutes of shifting calm birds to active flight, with strong evidence for a positive effect of air temperature on body temperature (slope = 0.04 °C/ °C). Importantly, by an ambient temperature of 9 °C, flying buntings were already generating body temperatures ≥ 45 °C, approaching the upper thermal limits of organismal performance (45-47 °C). With known limited evaporative heat dissipation capacities in these birds, our results support the recent prediction that free-living buntings operating at maximal sustainable rates will increasingly need to rely on behavioural thermoregulatory strategies to regulate body temperature, to the detriment of nestling growth and survival.
Topics: Animals; Arctic Regions; Songbirds; Cold Temperature; Body Temperature Regulation; Body Temperature; Breeding; Reproduction; Female; Male; Temperature
PubMed: 38956145
DOI: 10.1038/s41598-024-65208-9 -
Scientific Reports Jul 2024Arid and semi-arid areas are among the most threatened ecosystems on the planet. The Tehuacán-Cuicatlán Biosphere Reserve (TCBR), in southeastern Mexico, is an arid...
Arid and semi-arid areas are among the most threatened ecosystems on the planet. The Tehuacán-Cuicatlán Biosphere Reserve (TCBR), in southeastern Mexico, is an arid and semi-arid area with high biological diversity and human settlements of eight ethnic groups. Two rivers drain the reserve, Río Grande (RG) and Río Salado (RS), which are not subject to water quality monitoring by government agencies; however, measures of water quality of these rivers are needed to focus conservation actions on this resource. This work aimed to test the effectiveness of participatory water quality monitoring with the participation of three actors: Reserve management leaders, local communities, and academics, to monitoring water quality in the rivers of the TCBR. Ninety-two residents were trained to carry out water quality biomonitoring using the Biological Monitoring Working Party (BMWP) index calibrated for the reserve. The BMWP uses macroinvertebrate families to display numerical and categorical water quality scores. Additionally, the Water Quality Index (WQI) was assessed and the Normalized Difference Vegetation Index (NDVI) of the riparian zones was estimated in each study site. The mean WQI scores were 69.24 for RS (no treatment necessary for most crops and necessary treatment for public water supply) and 75.16 for RG (minor purification for crops requiring high-quality water and necessary treatment for public water supply). The BMWP showed five water quality categories (Excellent, Very Good, Good, Fair, and Poor), showing higher water quality scores in the upper portion of the basins and capable of discriminating study sites with lower scores close to human settlements. At one study site, data from participatory monitoring impelled actions taken to address a pollution source and influenced policy focus, reaching the maximum level of participatory-based monitoring. This led to avoid the discharge of wastewater into the river to conserve and protect the water resource. WQI is closely related to BMWP; however, the latter was far more sensitive to detecting areas affected by domestic water discharges. The NDVI presented low values for the TCBR, being lower in RS (the driest area). Although the NDVI showed a weak relationship with BMWP values, areas with higher NDVI values generally achieved higher BMWP values. The results of this study highlight the high sensitivity of the BMWP to detect several water quality conditions in the rivers running through the TCBR when compared to WQI. In addition, the usefulness of biomonitoring using the BMWP index was evident, as well as the importance of the participation of local inhabitants contributing to the knowledge of water quality in biosphere reserves and carrying out timely measures that allow the rivers in these reserves to be maintained in good condition.
Topics: Water Quality; Mexico; Rivers; Humans; Indigenous Peoples; Citizen Science; Ecosystem; Conservation of Natural Resources; Environmental Monitoring; Water Supply; Biological Monitoring; Desert Climate
PubMed: 38956124
DOI: 10.1038/s41598-024-65903-7 -
Scientific Reports Jul 2024Blinding eye diseases are often related to changes in retinal structure, which can be detected by analysing retinal blood vessels in fundus images. However, existing...
Blinding eye diseases are often related to changes in retinal structure, which can be detected by analysing retinal blood vessels in fundus images. However, existing techniques struggle to accurately segment these delicate vessels. Although deep learning has shown promise in medical image segmentation, its reliance on specific operations can limit its ability to capture crucial details such as the edges of the vessel. This paper introduces LMBiS-Net, a lightweight convolutional neural network designed for the segmentation of retinal vessels. LMBiS-Net achieves exceptional performance with a remarkably low number of learnable parameters (only 0.172 million). The network used multipath feature extraction blocks and incorporates bidirectional skip connections for the information flow between the encoder and decoder. In addition, we have optimised the efficiency of the model by carefully selecting the number of filters to avoid filter overlap. This optimisation significantly reduces training time and improves computational efficiency. To assess LMBiS-Net's robustness and ability to generalise to unseen data, we conducted comprehensive evaluations on four publicly available datasets: DRIVE, STARE, CHASE_DB1, and HRF The proposed LMBiS-Net achieves significant performance metrics in various datasets. It obtains sensitivity values of 83.60%, 84.37%, 86.05%, and 83.48%, specificity values of 98.83%, 98.77%, 98.96%, and 98.77%, accuracy (acc) scores of 97.08%, 97.69%, 97.75%, and 96.90%, and AUC values of 98.80%, 98.82%, 98.71%, and 88.77% on the DRIVE, STARE, CHEASE_DB, and HRF datasets, respectively. In addition, it records F1 scores of 83.43%, 84.44%, 83.54%, and 78.73% on the same datasets. Our evaluations demonstrate that LMBiS-Net achieves high segmentation accuracy (acc) while exhibiting both robustness and generalisability across various retinal image datasets. This combination of qualities makes LMBiS-Net a promising tool for various clinical applications.
Topics: Retinal Vessels; Humans; Neural Networks, Computer; Deep Learning; Image Processing, Computer-Assisted; Algorithms
PubMed: 38956117
DOI: 10.1038/s41598-024-63496-9 -
Scientific Reports Jul 2024Superluminal light propagation is typically accompanied by significant absorption that might prevent its observation in realistic samples. We propose an all-optical...
Superluminal light propagation is typically accompanied by significant absorption that might prevent its observation in realistic samples. We propose an all-optical implementation exploiting the two-photon resonance in three-level media to overcome this problem. With several computational methods, we analyze three possible configurations of optically-dressed systems and identify an optimal configuration for superluminal propagation. Due to the far-detuned operating regime with low absorption, this scenario avoids the usual need for population inversion, gain assistance or nonlinear optical response. Our analysis covers a broad parameter space and aims for the identification of conditions where significant pulse advancement can be achieved at high transmission levels. In this context, a figure of merit is introduced accounting for a trade-off between the desired group-index values and transmission level. This quantity helps to identify the optimal characteristics of the dressing beam.
PubMed: 38956073
DOI: 10.1038/s41598-024-62220-x -
Scientific Reports Jul 2024Across vertebrates, adaptive behaviors, like feeding and avoiding predators, are linked to lateralized brain function. The presence of the behavioral manifestations of...
Across vertebrates, adaptive behaviors, like feeding and avoiding predators, are linked to lateralized brain function. The presence of the behavioral manifestations of these biases are associated with increased task success. Additionally, when an individual's direction of bias aligns with the majority of the population, it is linked to social advantages. However, it remains unclear if behavioral biases in humans correlate with the same advantages. This large-scale study (N = 313-1661, analyses dependent) examines whether the strength and alignment of behavioral biases associate with cognitive and social benefits respectively in humans. To remain aligned with the animal literature, we evaluate motor-sensory biases linked to motor-sequencing and emotion detection to assess lateralization. Results reveal that moderate hand lateralization is positively associated with task success and task success is, in turn, associated with language fluency, possibly representing a cascade effect. Additionally, like other vertebrates, the majority of our human sample possess a 'standard' laterality profile (right hand bias, left visual bias). A 'reversed' profile is rare by comparison, and associates higher self-reported social difficulties and increased rate of autism and/or attention deficit hyperactivity disorder. We highlight the importance of employing a comparative theoretical framing to illuminate how and why different laterization profiles associate with diverging social and cognitive phenotypes.
Topics: Humans; Cognition; Male; Female; Functional Laterality; Adult; Young Adult; Adolescent; Social Skills; Middle Aged; Emotions
PubMed: 38956070
DOI: 10.1038/s41598-024-64372-2 -
Nature Communications Jul 2024Hybrid improper ferroelectricity can effectively avoid the intrinsic chemical incompatibility of electronic mechanism for multiferroics. Perovskite superlattices, as...
Hybrid improper ferroelectricity can effectively avoid the intrinsic chemical incompatibility of electronic mechanism for multiferroics. Perovskite superlattices, as theoretically proposed hybrid improper ferroelectrics with simple structure and high technological compatibility, are conducive to device integration and miniaturization, but the experimental realization remains elusive. Here, we report a strain-driven oxygen octahedral distortion strategy for hybrid improper ferroelectricity in LaNiMnO/LaCoMnO double-perovskite superlattices. The epitaxial growth mode with mixed crystalline orientations maintains a large strain transfer distance more than 90 nm in the superlattice films with lattice mismatch less than 1%. Such epitaxial strain permits sustainable long-range modulation of oxygen octahedral rotation and tilting, thereby inducing and regulating hybrid improper ferroelectricity. A robust room-temperature ferroelectricity with remnant polarization of ~ 0.16 μC cm and piezoelectric coefficient of 2.0 pm V is obtained, and the density functional theory calculations and Landau-Ginsburg-Devonshire theory reveal the constitutive correlations between ferroelectricity, octahedral distortions, and strain. This work addresses the gap in experimental studies of hybrid improper ferroelectricity for perovskite superlattices and provides a promising research platform and idea for designing and exploring hybrid improper ferroelectricity.
PubMed: 38956065
DOI: 10.1038/s41467-024-49707-x