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Illegal collecting of wild Venus flytraps (Dionaea muscipula) for the horticultural trade represents a persistent threat to populations of the species across their endemic range in the coastal plain of North and South Carolina (United States). Although wild collecting of Venus flytraps is not a novel threat, there has been very little research on the impacts of collecting on the species' conservation to date or why an illegal trade persists alongside a legal one. We drew on qualitative expert stakeholder elicitation to contextualize the threat of illegal collecting to the long-term conservation of Venus flytraps in relation to other anthropogenic threats. Expert elicitation included botanical and conservation researchers, cognizant state and federal agency staff, land managers, and conservation nonprofit actors. The workshop included mapping of supply chain structures and prioritization of social and environmental harms. Expert consensus determined illegal collecting is an ongoing problem for Venus flytrap conservation, but habitat destruction, degradation, and fire suppression are the most significant threats to flytrap conservation. Supply chain analysis showed that observable social and environmental harms of the trade are focused at the supply stage and that less is known about transit and demand stages. Key research gaps identified include a lack of understanding of plant laundering practices relevant to a range of desirable plant taxa; the role of commercial nurseries in illicit horticultural supply chains; motivations for engaging in Venus flytrap collecting; and the persistent demand for illegally harvested plants when cultivated, legally obtainable plants are readily available. Our findings and methodology are relevant to a range of ornamental plants affected by illegal trade for which robust social data on illegal collecting drivers are lacking., (© 2024 The Author(s). Conservation Biology published by Wiley Periodicals LLC on behalf of Society for Conservation Biology.)

Advances in neuroimaging acquisition protocols and denoising techniques, along with increasing magnetic field strengths, have dramatically improved the temporal signal-to-noise ratio (tSNR) in functional magnetic resonance imaging (fMRI). This permits spatial resolution with submillimeter voxel sizes and ultrahigh temporal resolution and opens a route toward performing precision fMRI in the brains of individuals. Yet ultrahigh spatial and temporal resolution comes at a cost: it reduces tSNR and, therefore, the sensitivity to the blood oxygen level-dependent (BOLD) effect and other functional contrasts across the brain. Here we investigate the potential of various smoothing filters to improve BOLD sensitivity while preserving the spatial accuracy of activated clusters in single-subject analysis. We introduce adaptive-weight smoothing with optimized metrics (AWSOM), which addresses this challenge extremely well. AWSOM employs a local inference approach that is as sensitive as cluster-corrected inference of data smoothed with large Gaussian kernels, but it preserves spatial details across multiple tSNR levels. This is essential for examining whole-brain fMRI data because tSNR varies across the entire brain, depending on the distance of a brain region from the receiver coil, the type of setup, acquisition protocol, preprocessing, and resolution. We found that cluster correction in single subjects results in inflated family-wise error and false positive rates. AWSOM effectively suppresses false positives while remaining sensitive even to small clusters of activated voxels. Furthermore, it preserves signal integrity, that is, the relative activation strength of significant voxels, making it a valuable asset for a wide range of fMRI applications. Here we demonstrate these features and make AWSOM freely available to the research community for download., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Cannabidiol (CBD) is a non-intoxicating phytocannabinoid which has been proposed to possess anti-inflammatory and analgesic properties. Given the potential for perceptions of pain to limit exercise performance, the aim of the present study was to investigate if 3 weeks of daily CBD supplementation (150 mg day -1 ) improved performance in a 10-min performance-trial on a cycle ergometer. In a randomized, double-blind and placebo-controlled study, 22 healthy participants (n = 11 male and n = 11 female) completed two 10-min performance trials on a WattBike cycle ergometer interspersed with a 3-week supplementation period. Supplementation involved either 150 mg day -1 oral CBD or 150 mg day -1 of a visually identical placebo (PLA). During trials, ratings of perceived exertion (RPE [6-20]), heart rate (HR) and blood lactate (BLa) were collected every 2 min. Mean power (W) was also taken throughout the exercise at each time point. All data were analyzed using two-way ANOVAs. There were no significant differences (P > 0.05) between CBD or PLA groups for mean power (W) during the 10-min performance trial. There were also no significant differences (P > 0.05) in any of the physiological or perceptual parameters (HR, BLa and RPE) between conditions. Three weeks supplementation of a broad-spectrum CBD supplement did not improve performance via any change in RPE during a 10-min time trial on a cycle ergometer, and as such, this evidence does not support the claim that broad-spectrum CBD supplements could be performance-enhancing in this exercise modality., (© 2024 The Authors. European Journal of Sport Science published by Wiley‐VCH GmbH on behalf of European College of Sport Science.)

Purpose: The increasing incidence of kidney diseases is a global concern, and current biomarkers and treatments are inadequate. Changes in renal tubule luminal volume fraction (TVF) serve as a rapid biomarker for kidney disease and improve understanding of renal (patho)physiology. This study uses the amplitude of the long T 2 component as a surrogate for TVF in rats, by applying multiexponential analysis of the T 2 -driven signal decay to examine micromorphological changes in renal tissue., Methods: Simulations were conducted to identify a low mean absolute error (MAE) protocol and an accelerated protocol customized for the in vivo study of T 2 mapping of the rat kidney at 9.4 T. We then validated our bi-exponential approach in a phantom mimicking the relaxation properties of renal tissue. This was followed by a proof-of-principle demonstration using in vivo data obtained during a transient increase of renal pelvis and tubular pressure., Results: Using the low MAE protocol, our approach achieved an accuracy of MAE < 1% on the mechanical phantom. The T 2 mapping protocol customized for in vivo study achieved an accuracy of MAE < 3%. Transiently increasing pressure in the renal pelvis and tubules led to significant changes in TVF in renal compartments: ΔTVF cortex  = 4.9%, ΔTVF outer&#95;medulla  = 4.5%, and ΔTVF inner&#95;medulla  = -14.6%., Conclusion: These results demonstrate that our approach is promising for research into quantitative assessment of renal TVF in in vivo applications. Ultimately, these investigations have the potential to help reveal mechanism in acute renal injury that may lead to chronic kidney disease, which will support research into renal disorders., (© 2024 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Magnetic Resonance Imaging (MRI) datasets from epidemiological studies often show a lower prevalence of motion artifacts than what is encountered in clinical practice. These artifacts can be unevenly distributed between subject groups and studies which introduces a bias that needs addressing when augmenting data for machine learning purposes. Since unreconstructed multi-channel k-space data is typically not available for population-based MRI datasets, motion simulations must be performed using signal magnitude data. There is thus a need to systematically evaluate how realistic such magnitude-based simulations are. We performed magnitude-based motion simulations on a dataset (MR-ART) from 148 subjects in which real motion-corrupted reference data was also available. The similarity of real and simulated motion was assessed by using image quality metrics (IQMs) including Coefficient of Joint Variation (CJV), Signal-to-Noise-Ratio (SNR), and Contrast-to-Noise-Ratio (CNR). An additional comparison was made by investigating the decrease in the Dice-Sørensen Coefficient (DSC) of automated segmentations with increasing motion severity. Segmentation of the cerebral cortex was performed with 6 freely available tools: FreeSurfer, BrainSuite, ANTs, SAMSEG, FastSurfer, and SynthSeg+. To better mimic the real subject motion, the original motion simulation within an existing data augmentation framework (TorchIO), was modified. This allowed a non-random motion paradigm and phase encoding direction. The mean difference in CJV/SNR/CNR between the real motion-corrupted images and our modified simulations (0.004±0.054/-0.7±1.8/-0.09±0.55) was lower than that of the original simulations (0.015±0.061/0.2±2.0/-0.29±0.62). Further, the mean difference in the DSC between the real motion-corrupted images was lower for our modified simulations (0.03±0.06) compared to the original simulations (-0.15±0.09). SynthSeg+ showed the highest robustness towards all forms of motion, real and simulated. In conclusion, reasonably realistic synthetic motion artifacts can be induced on a large-scale when only magnitude MR images are available to obtain unbiased data sets for the training of machine learning based models., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: HO is currently employed by Philips Healthcare. Remaining authors have declared that no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Olsson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Biological membranes have a stunning ability to adapt their composition in response to physiological stress and metabolic challenges. Little is known how such perturbations affect individual organelles in eukaryotic cells. Pioneering work has provided insights into the subcellular distribution of lipids in the yeast Saccharomyces cerevisiae, but the composition of the endoplasmic reticulum (ER) membrane, which also crucially regulates lipid metabolism and the unfolded protein response, remains insufficiently characterized. Here, we describe a method for purifying organelle membranes from yeast, MemPrep. We demonstrate the purity of our ER membrane preparations by proteomics, and document the general utility of MemPrep by isolating vacuolar membranes. Quantitative lipidomics establishes the lipid composition of the ER and the vacuolar membrane. Our findings provide a baseline for studying membrane protein biogenesis and have important implications for understanding the role of lipids in regulating the unfolded protein response (UPR). The combined preparative and analytical MemPrep approach uncovers dynamic remodeling of ER membranes in stressed cells and establishes distinct molecular fingerprints of lipid bilayer stress., (© 2024. The Author(s).)

Pump sizing is the process of dimensional matching of an impeller and stator to provide a satisfactory performance test result and good service life during the operation of progressive cavity pumps. In this process, historical data analysis and dimensional monitoring are done manually, consuming a large number of man-hours and requiring a deep knowledge of progressive cavity pump behavior. This paper proposes the use of graph neural networks in the construction of a prototype to recommend interference during the pump sizing process in a progressive cavity pump. For this, data from different applications is used in addition to individual control spreadsheets to build the database used in the prototype. From the pre-processed data, complex network techniques and the betweenness centrality metric are used to calculate the degree of importance of each order confirmation, as well as to calculate the dimensionality of the rotors. Using the proposed method a mean squared error of 0.28 is obtained for the cases where there are recommendations for order confirmations. Based on the results achieved, it is noticeable that there is a similarity of the dimensions defined by the project engineers during the pump sizing process, and this outcome can be used to validate the new design definitions., (© 2023. Springer Nature Limited.)

Thermal Magnetic Resonance (ThermalMR) is a theranostic concept that combines diagnostic magnetic resonance imaging (MRI) with targeted thermal therapy in the hyperthermia (HT) range using a radiofrequency (RF) applicator in an integrated system. ThermalMR adds a therapeutic dimension to a diagnostic MRI device. Focused, targeted RF heating of deep-seated brain tumors, accurate non-invasive temperature monitoring and high-resolution MRI are specific requirements of ThermalMR that can be addressed with novel concepts in RF applicator design. This work examines hybrid RF applicator arrays combining loop and self-grounded bow-tie (SGBT) dipole antennas for ThermalMR of brain tumors, at magnetic field strengths of 7.0 T, 9.4 T and 10.5 T. These high-density RF arrays improve the feasible transmission channel count, and provide additional degrees of freedom for RF shimming not afforded by using dipole antennas only, for superior thermal therapy and MRI diagnostics. These improvements are especially relevant for ThermalMR theranostics of deep-seated brain tumors because of the small surface area of the head. ThermalMR RF applicators with the hybrid loop+SGBT dipole design outperformed applicators using dipole-only and loop-only designs, with superior MRI performance and targeted RF heating. Array variants with a horse-shoe configuration covering an arc (270°) around the head avoiding the eyes performed better than designs with 360° coverage, with a 1.3 °C higher temperature rise inside the tumor while sparing healthy tissue. Our EMF and temperature simulations performed on a virtual patient with a clinically realistic intracranial tumor provide a technical foundation for implementation of advanced RF applicators tailored for ThermalMR theranostics of brain tumors.

Theranostic imaging methods could greatly enhance our understanding of the distribution of CNS-acting drugs in individual patients. Fluorine-19 magnetic resonance imaging ( 19 F MRI) offers the opportunity to localize and quantify fluorinated drugs non-invasively, without modifications and without the application of ionizing or other harmful radiation. Here we investigated siponimod, a sphingosine 1-phosphate (S 1 P) receptor antagonist indicated for secondary progressive multiple sclerosis (SPMS), to determine the feasibility of in vivo 19 F MR imaging of a disease modifying drug. Methods: The 19 F MR properties of siponimod were characterized using spectroscopic techniques. Four MRI methods were investigated to determine which was the most sensitive for 19 F MR imaging of siponimod under biological conditions. We subsequently administered siponimod orally to 6 mice and acquired 19 F MR spectra and images in vivo directly after administration, and in ex vivo tissues. Results: The 19 F transverse relaxation time of siponimod was 381 ms when dissolved in dimethyl sulfoxide, and substantially reduced to 5 ms when combined with serum, and to 20 ms in ex vivo liver tissue. Ultrashort echo time (UTE) imaging was determined to be the most sensitive MRI technique for imaging siponimod in a biological context and was used to map the drug in vivo in the stomach and liver. Ex vivo images in the liver and brain showed an inhomogeneous distribution of siponimod in both organs. In the brain, siponimod accumulated predominantly in the cerebrum but not the cerebellum. No secondary 19 F signals were detected from metabolites. From a translational perspective, we found that acquisitions done on a 3.0 T clinical MR scanner were 2.75 times more sensitive than acquisitions performed on a preclinical 9.4 T MR setup when taking changes in brain size across species into consideration and using equivalent relative spatial resolution. Conclusion: Siponimod can be imaged non-invasively using 19 F UTE MRI in the form administered to MS patients, without modification. This study lays the groundwork for more extensive preclinical and clinical investigations. With the necessary technical development, 19 F MRI has the potential to become a powerful theranostic tool for studying the time-course and distribution of CNS-acting drugs within the brain, especially during pathology., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

(1) Background: Radial RARE-EPI MRI facilitates simultaneous T 2 and T 2 * mapping (2in1-RARE-EPI). With modest undersampling (R = 2), the speed gain of 2in1-RARE-EPI relative to Multi-Spin-Echo and Multi-Gradient-Recalled-Echo references is limited. Further reduction in scan time is crucial for clinical studies investigating T 2 and T 2 * as imaging biomarkers. We demonstrate the feasibility of further acceleration, utilizing compressed sensing (CS) reconstruction of highly undersampled 2in1-RARE-EPI. (2) Methods: Two-fold radially-undersampled 2in1-RARE-EPI data from phantoms, healthy volunteers ( n = 3), and multiple sclerosis patients ( n = 4) were used as references, and undersampled (R extra = 1-12, effective undersampling R eff = 2-24). For each echo time, images were reconstructed using CS-reconstruction. For T 2 (RARE module) and T 2 * mapping (EPI module), a linear least-square fit was applied to the images. T 2 and T 2 * from CS-reconstruction of undersampled data were benchmarked against values from CS-reconstruction of the reference data. (3) Results: We demonstrate accelerated simultaneous T 2 and T 2 * mapping using undersampled 2in1-RARE-EPI with CS-reconstruction is feasible. For R extra = 6 (TA = 01:39 min), the overall MAPE was ≤8% (T 2 *) and ≤4% (T 2 ); for R extra = 12 (TA = 01:06 min), the overall MAPE was <13% (T 2 *) and <5% (T 2 ). (4) Conclusion: Substantial reductions in scan time are achievable for simultaneous T 2 and T 2 * mapping of the brain using highly undersampled 2in1-RARE-EPI with CS-reconstruction.

Purpose: Low SNR in fluorine-19 ( 19 F) MRI benefits from cryogenically-cooled transceive surface RF probes (CRPs), but strong B 1 inhomogeneities hinder quantification. Rapid acquisition with refocused echoes (RARE) is an SNR-efficient method for MRI of neuroinflammation with perfluorinated compounds but lacks an analytical signal intensity equation to retrospectively correct B 1 inhomogeneity. Here, a workflow was proposed and validated to correct and quantify 19 F-MR signals from the inflamed mouse brain using a 19 F-CRP., Methods: In vivo 19 F-MR images were acquired in a neuroinflammation mouse model with a quadrature 19 F-CRP using an imaging setup including 3D-printed components to acquire co-localized anatomical and 19 F images. Model-based corrections were validated on a uniform 19 F phantom and in the neuroinflammatory model. Corrected 19 F-MR images were benchmarked against reference images and overlaid on in vivo 1 H-MR images. Computed concentration uncertainty maps using Monte Carlo simulations served as a measure of performance of the B 1 corrections., Results: Our study reports on the first quantitative in vivo 19 F-MR images of an inflamed mouse brain using a 19 F-CRP, including in vivo T 1 calculations for 19 F-nanoparticles during pathology and B 1 corrections for 19 F-signal quantification. Model-based corrections markedly improved 19 F-signal quantification from errors > 50% to < 10% in a uniform phantom (p < 0.001). Concentration uncertainty maps ex vivo and in vivo yielded uncertainties that were generally < 25%. Monte Carlo simulations prescribed SNR ≥ 10.1 to reduce uncertainties < 10%, and SNR ≥ 4.25 to achieve uncertainties < 25%., Conclusion: Our model-based correction method facilitated 19 F signal quantification in the inflamed mouse brain when using the SNR-boosting 19 F-CRP technology, paving the way for future low-SNR 19 F-MRI applications in vivo., (© 2021 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Fluorine ( 19 F) magnetic resonance imaging (MRI) is severely limited by a low signal-to noise ratio (SNR), and tapping it for 19 F drug detection in vivo still poses a significant challenge. However, it bears the potential for label-free theranostic imaging. Recently, we detected the fluorinated dihydroorotate dehydrogenase (DHODH) inhibitor teriflunomide (TF) noninvasively in an animal model of multiple sclerosis (MS) using 19 F MR spectroscopy (MRS). In the present study, we probed distinct modifications to the CF 3 group of TF to improve its SNR. This revealed SF 5 as a superior alternative to the CF 3 group. The value of the SF 5 bioisostere as a 19 F MRI reporter group within a biological or pharmacological context is by far underexplored. Here, we compared the biological and pharmacological activities of different TF derivatives and their 19 F MR properties (chemical shift and relaxation times). The 19 F MR SNR efficiency of three MRI methods revealed that SF 5 -substituted TF has the highest 19 F MR SNR efficiency in combination with an ultrashort echo-time (UTE) MRI method. Chemical modifications did not reduce pharmacological or biological activity as shown in the in vitro dihydroorotate dehydrogenase enzyme and T cell proliferation assays. Instead, SF 5 -substituted TF showed an improved capacity to inhibit T cell proliferation, indicating better anti-inflammatory activity and its suitability as a viable bioisostere in this context. This study proposes SF 5 as a novel superior 19 F MR reporter group for the MS drug teriflunomide.

Cannabidiol supplements (CBD) are increasingly consumed by athletes to improve regeneration. However, the evidence for the pro-regenerative effects of CBD in sports is quite limited. Therefore, our aim was to investigate the effects of a single CBD supplementation in a six-arm placebo-controlled crossover study after resistance training on performance and muscle damage. Before and after the resistance training, one-repetition maximum in the back squat (1RM BS), countermovement jump (CMJ), and blood serum concentrations of creatine kinase (CK) and myoglobin (Myo) were measured in healthy, well-trained participants. 16 out of 21 participants completed the study and were included in the analysis. In 1RM BS, a significant decrease was observed after 24 h ( p < 0.01) but not after 48 and 72 h. A significant group difference was detected after 72 h ( p < 0.05; ES = 0.371). In CMJ, no significant changes were observed. The CK and Myo concentrations increased significantly after 24 h (CK: p < 0.001; Myo: p < 0.01), 48 h (CK: p < 0.001; Myo: p < 0.01) and 72 h (CK: p < 0.001; Myo: p < 0.001). After 72 h, significant group differences were observed for both muscle damage biomarkers (CK: p < 0.05 ES = 0.24; Myo: p < 0.05; ES = 0.21). The results show small but significant effects on muscle damage and recovery of squat performance after 72 h. However, more data are required for clearer statements concerning potential pro-regenerative effects of CBD supplementation after resistance training.

Renal hypoxia is generally accepted as a key pathophysiologic event in acute kidney injury of various origins and has also been suggested to play a role in the development of chronic kidney disease. Here we describe step-by-step data analysis protocols for MRI monitoring of renal oxygenation in rodents via the deoxyhemoglobin concentration sensitive MR parameters T 2 * and T 2 -a contrast mechanism known as the blood oxygenation level dependent (BOLD) effect.This chapter describes how to use the analysis tools provided by vendors of animal and clinical MR systems, as well as how to develop an analysis software. Aspects covered are: data quality checks, data exclusion, model fitting, fitting algorithm, starting values, effects of multiecho imaging, and result validation.This chapter is based upon work from the PARENCHIMA COST Action, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This experimental protocol chapter is complemented by two separate chapters describing the basic concept and data analysis.

Kidney-associated pathologies would greatly benefit from noninvasive and robust methods that can objectively quantify changes in renal function. In the past years there has been a growing incentive to develop new applications for fluorine ( 19 F) MRI in biomedical research to study functional changes during disease states. 19 F MRI represents an instrumental tool for the quantification of exogenous 19 F substances in vivo. One of the major benefits of 19 F MRI is that fluorine in its organic form is absent in eukaryotic cells. Therefore, the introduction of exogenous 19 F signals in vivo will yield background-free images, thus providing highly selective detection with absolute specificity in vivo. Here we introduce the concept of 19 F MRI, describe existing challenges, especially those pertaining to signal sensitivity, and give an overview of preclinical applications to illustrate the utility and applicability of this technique for measuring renal function in animal models.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction chapter is complemented by two separate chapters describing the experimental procedure and data analysis.