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Background: Marine sediments represent one of the planet's largest carbon stores. Bottom trawl fisheries constitute the most widespread physical disturbance to seabed habitats, which exert a large influence over the oceanic carbon dioxide (CO 2 ) sink. Recent research has sparked concern that seabed disturbance from trawling can therefore turn marine sediments into a large source of CO 2 , but the calculations involved carry a high degree of uncertainty. This is primarily due to a lack of quantitative understanding of how trawling mixes and resuspends sediments, how it alters bioturbation, bioirrigation, and oxygenation rates, and how these processes translate into carbon fluxes into or out of sediments., Methods: The primary question addressed by this review protocol is: how does mobile bottom fishing affect benthic carbon processing and storage? This question will be split into the following secondary questions: what is the effect of mobile bottom fishing on: (i) the amount and type of carbon found in benthic sediments; (ii) the magnitude and direction of benthic-pelagic carbon fluxes; (iii) the biogeochemical, biological, and physical parameters that control the fate of benthic carbon; and (iv) the biogeochemical, biological, and physical parameters that control the fate of resuspended carbon. Literature searches will be conducted in Web of Science, SCOPUS, PROQUEST, and a range of grey and specialist sources. An initial scoping search in Web of Science informed the final search string, which has been formulated according to Population Intervention Comparator Outcome (PICO) principles. Eligible studies must contain data concerning a change in a population of interest caused by mobile bottom fishing. Eligible study designs are Before and After, Control and Impact, and Gradient studies. Studies included at full-text screening will be critically appraised, and study findings will be extracted.Extracted data will be stored in an Excel spreadsheet. Results will be reported in narrative and quantitative syntheses using a variety of visual tools including forest plots. Meta-analysis will be conducted where sufficient data exists., (© 2024. The Author(s).)

Digital pathology has become increasingly popular for research and clinical applications. Using high-quality microscopes to produce Whole Slide Images of tumor tissue enables the discovery of insights into biological aspects invisible to the human eye. These are acquired through downstream analyses using spatial statistics and artificial intelligence. Determination of the quality and consistency of these images is needed to ensure accurate outcomes when identifying clinical and subclinical image features. Additionally, the time-intensive process of generating high-volume images results in a trade-off that needs to be carefully balanced. This study aims to determine optimal instrument settings to generate representative images of pathological tissue using digital microscopy. Using various settings, an H&E stained sample was scanned using the ZEISS Axio Scan.Z1. Next, nucleus segmentation was performed on resulting images using StarDist. Subsequently, detections were compared between scans using a matching algorithm. Finally, nucleus-level information was compared between scans. Results indicated that while general matching percentages were high, similarity between information from replicates was relatively low. Additionally, settings resulting in longer scanning times and increased data volume did not increase similarity between replicates. In conclusion, the scan setting ultimately deemed optimal combined consistent and qualitative performance with low throughput time., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Geubbelmans 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.)

Nowadays cardiorespiratory fitness (CRF) is assessed using summary indexes of cardiopulmonary exercise tests (CPETs). Yet, raw time-series CPET recordings may hold additional information with clinical relevance. Therefore, we investigated whether analysis of raw CPET data using dynamic time warping combined with k-medoids could identify distinct CRF phenogroups and improve cardiovascular (CV) risk stratification. CPET recordings from 1,399 participants (mean age, 56.4 years; 37.7% women) were separated into 5 groups with distinct patterns. Cluster 5 was associated with the worst CV profile with higher use of antihypertensive medication and a history of CV disease, while cluster 1 represented the most favorable CV profile. Clusters 4 (hazard ratio: 1.30; p  = 0.033) and 5 (hazard ratio: 1.36; p  = 0.0088) had a significantly higher risk of incident adverse events compared to clusters 1 and 2. The model evaluation in the external validation cohort revealed similar patterns. Therefore, an integrative CRF profiling might facilitate CV risk stratification and management., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Objective: To conceptualize a composite primary endpoint for parallel-group RCTs of exercise-based cardiac rehabilitation (CR) interventions and to explore its application and statistical efficiency., Design: We conducted a statistical exploration of sample size requirements. We combined exercise capacity and physical activity for the composite endpoint (CE), both being directly related to reduced premature mortality in patients with cardiac diseases. Based on smallest detectable and minimal clinically important changes (change in exercise capacity of 15 W and change in physical activity of 10 min/day), the CE combines 2 dichotomous endpoints (achieved/not achieved). To examine statistical efficiency, we compared sample size requirements based on the CE to single endpoints using data from 2 completed CR trials., Setting: Cardiac rehabilitation phase III., Participants: Patients in cardiac rehabilitation., Interventions: Not applicable., Main Outcome Measure(s): Exercise capacity (P max assessed by incremental cycle ergometry) and physical activity (daily minutes of moderate to vigorous physical activity assessed by accelerometry)., Results: Expecting, for example, a 10% between-group difference and improvement in the clinical outcome, the CE would increase sample size by up to 21% or 61%, depending on the dataset. When expecting a 10% difference and designing an intervention with the aim of non-deterioration, the CE would allow to reduce the sample size by up to 55% or 70%., Conclusions: Trialists may consider the utility of the CE for future studies in exercise-based CR to reduce sample size requirements. However, perhaps surprisingly at first, the CE could also lead to an increased sample size needed, depending on the observed baseline proportions in the trial population and the aim of the intervention., (Copyright © 2024 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: There is a need for valid and reliable clinical assessment tools to assess cardiorespiratory fitness (CRF) levels in adolescents with autism. Therefore, this study aimed to examine the concurrent validity and test-retest reliability of the Astrand-Rhyming Test (ART) in this population., Materials and Methods: 45 adolescents with autism aged 12-18 years ( n  = 32 males, 14.47 ± 1.79 years) performed the ART twice (test-retest reliability) and completed a maximal cardiopulmonary exercise test (CPET) (concurrent validity). Reliability parameters included Pearson correlations, intraclass correlation coefficients (ICCs), standard error of measurements (SEM), minimal detectable changes (MDC), coefficients of variation, paired sample t-tests, linear regressions and Bland-Altman plots. The concurrent validity was evaluated with Pearson correlations, ICCs, paired sample t-tests, linear regressions and Bland-Altman plots., Results: Strong test-retest reliability ( r  = 0.84-0.85, ICC = 0.84-0.85) was found for the ART, but the wide limits of agreement intervals suggest the presence of substantial variability. The large SEM (4.73-5.08 mL/kg/min) and MDC (13.20-14.07 mL/kg/min) values suggest lower absolute reliability. Moderate to strong levels of association ( r  = 0.74-0.75) and agreement (ICC = 0.59-0.66) were found between estimated (ART1) and measured (CPET) VO 2 max levels, but significant systematic differences (5.71-8.82 mL/kg/min) were observed., Conclusion: The ART is an accessible and promising method to monitor submaximal CRF levels over time but is less appropriate to estimate maximal CRF levels in this population.

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Spatial heterogeneity of cells in liver biopsies can be used as biomarker for disease severity of patients. This heterogeneity can be quantified by non-parametric statistics of point pattern data, which make use of an aggregation of the point locations. The method and scale of aggregation are usually chosen ad hoc, despite values of the aforementioned statistics being heavily dependent on them. Moreover, in the context of measuring heterogeneity, increasing spatial resolution will not endlessly provide more accuracy. The question then becomes how changes in resolution influence heterogeneity indicators, and subsequently how they influence their predictive abilities. In this paper, cell level data of liver biopsy tissue taken from chronic Hepatitis B patients is used to analyze this issue. Firstly, Morisita-Horn indices, Shannon indices and Getis-Ord statistics were evaluated as heterogeneity indicators of different types of cells, using multiple resolutions. Secondly, the effect of resolution on the predictive performance of the indices in an ordinal regression model was investigated, as well as their importance in the model. A simulation study was subsequently performed to validate the aforementioned methods. In general, for specific heterogeneity indicators, a downward trend in predictive performance could be observed. While for local measures of heterogeneity a smaller grid-size is outperforming, global measures have a better performance with medium-sized grids. In addition, the use of both local and global measures of heterogeneity is recommended to improve the predictive performance., Competing Interests: Declaration of competing interest None Declared, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Growing crops on marginal lands is a promising solution to alleviate the increasing pressure on agricultural land in Europe. Such crops will however be at the same time exposed to increased drought and pathogen prevalence, on already challenging soil conditions. Some sustainable practices, such as Silicon (Si) foliar fertilization, have been proposed to alleviate these two stress factors, but have not been tested under controlled, future climate conditions. We hypothesized that Si foliar fertilization would be beneficial for crops under future climate, and would have cascading beneficial effects on ecosystem processes, as many of them are directly dependent on plant health. We tested this hypothesis by exposing spring barley growing on marginal soil macrocosms (three with, three without Si treatment) to 2070 climate projections in an ecotron facility. Using the high-capacity monitoring of the ecotron, we estimated C, water, and N budgets of every macrocosm. Additionally, we measured crop yield, the biomass of each plant organ, and characterized bacterial communities using metabarcoding. Despite being exposed to water stress conditions, plants did not produce more biomass with the foliar Si fertilization, whatever the organ considered. Evapotranspiration (ET) was unaffected, as well as water quality and bacterial communities. However, in the 10-day period following two of the three Si applications, we measured a significant increase in C sequestration, when climate conditions where significantly drier, while ET remained the same. We interpreted these results as a less significant effect of Si treatment than expected as compared with literature, which could be explained by the high CO 2 levels under future climate, that reduces need for stomata opening, and therefore sensitivity to drought. We conclude that making marginal soils climate proof using foliar Si treatments may not be a sufficient strategy, at least in this type of nutrient-poor, dry, sandy soil., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

For cookie batters, there is a strong interaction between ingredient formulation and processing. Changing the amounts and types of sugar and fat in a recipe to change taste or healthiness influences the type of product formation in a production plant. In this study, the applicability of three measurement methods, a rheometer, a forward extrusion cell, and the Foodtexture Puff Device (FPD), was evaluated to measure the extrudability of cookie batters. When looking at the sugar and fat content, both the rheometer and the FPD proved to be consistent and reliable methods to describe the impact of those ingredients on extrudability. A further optimization of the measurement settings of the FPD may improve the performance of this new method. Although the forward extrusion cell performed well for recipes with an increasing sugar content, it did not yield proper results for recipes with a higher fat content due to a separating fat layer. This also limited the applicability of the forward extrusion cell for different fat types, while the other two methods performed well in that case. The small differences in consistency due to different sugar grain sizes were properly described by the forward extrusion cell and the FPD. Overall, it can be concluded that the rheometer performed best to analyze the extrudability of cookie batters, closely followed by the FPD, of which the measurement settings can be optimized. These methods can also be used in the product development phase., (© 2023 Wiley Periodicals LLC.)

Background: Interpretation of cardiopulmonary exercise testing (CPET) results requires thorough understanding of test confounders such as anthropometrics, comorbidities and medication. Here, we comprehensively assessed the clinical determinants of cardiorespiratory fitness and its components in a heterogeneous patient sample., Methods: We retrospectively collected medical and CPET data from 2320 patients (48.2% females) referred for cycle ergometry at the University Hospital Leuven, Belgium. We assessed clinical determinants of peak CPET indexes of cardiorespiratory fitness (CRF) and its hemodynamic and ventilatory components using stepwise regression and quantified multivariable-adjusted differences in indexes between cases and references., Results: Lower peak load and peak O 2 uptake were related to: higher age, female sex, lower body height and weight, and higher heart rate; to the intake of beta blockers, analgesics, thyroid hormone replacement and benzodiazepines; and to diabetes mellitus, chronic kidney disease, non-ST elevation myocardial infarction and atrial fibrillation (p < 0.05 for all). Lower peak load also correlated with obstructive pulmonary diseases. Stepwise regression revealed associations of hemodynamic and ventilatory indexes (including heart rate, O 2 pulse, systolic blood pressure and ventilation at peak exercise and ventilatory efficiency) with age, sex, body composition and aforementioned diseases and medications. Multivariable-adjusted differences in CPET metrics between cases and controls confirmed the associations observed., Conclusion: We described known and novel associations of CRF components with demographics, anthropometrics, cardiometabolic and pulmonary diseases and medication intake in a large patient sample. The clinical implications of long-term noncardiovascular drug intake for CPET results require further investigation., (© 2023 Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

The design of quantum hardware that reduces and mitigates errors is essential for practical quantum error correction (QEC) and useful quantum computation. To this end, we introduce the circuit-Quantum Electrodynamics (QED) dual-rail qubit in which our physical qubit is encoded in the single-photon subspace, [Formula: see text], of two superconducting microwave cavities. The dominant photon loss errors can be detected and converted into erasure errors, which are in general much easier to correct. In contrast to linear optics, a circuit-QED implementation of the dual-rail code offers unique capabilities. Using just one additional transmon ancilla per dual-rail qubit, we describe how to perform a gate-based set of universal operations that includes state preparation, logical readout, and parametrizable single and two-qubit gates. Moreover, first-order hardware errors in the cavities and the transmon can be detected and converted to erasure errors in all operations, leaving background Pauli errors that are orders of magnitude smaller. Hence, the dual-rail cavity qubit exhibits a favorable hierarchy of error rates and is expected to perform well below the relevant QEC thresholds with today's coherence times.

The organization and interaction between hepatocytes and other hepatic non-parenchymal cells plays a pivotal role in maintaining normal liver function and structure. Although spatial heterogeneity within the tumor micro-environment has been proven to be a fundamental feature in cancer progression, the role of liver tissue topology and micro-environmental factors in the context of liver damage in chronic infection has not been widely studied yet. We obtained images from 110 core needle biopsies from a cohort of chronic hepatitis B patients with different fibrosis stages according to METAVIR score. The tissue sections were immunofluorescently stained and imaged to determine the locations of CD45 positive immune cells and HBsAg-negative and HBsAg-positive hepatocytes within the tissue. We applied several descriptive techniques adopted from ecology, including Getis-Ord, the Shannon Index and the Morisita-Horn Index, to quantify the extent to which immune cells and different types of liver cells co-localize in the tissue biopsies. Additionally, we modeled the spatial distribution of the different cell types using a joint log-Gaussian Cox process and proposed several features to quantify spatial heterogeneity. We then related these measures to the patient fibrosis stage by using a linear discriminant analysis approach. Our analysis revealed that the co-localization of HBsAg-negative hepatocytes with immune cells and the co-localization of HBsAg-positive hepatocytes with immune cells are equally important factors for explaining the METAVIR score in chronic hepatitis B patients. Moreover, we found that if we allow for an error of 1 on the METAVIR score, we are able to reach an accuracy of around 80%. With this study we demonstrate how methods adopted from ecology and applied to the liver tissue micro-environment can be used to quantify heterogeneity and how these approaches can be valuable in biomarker analyses for liver topology., Competing Interests: Declaration of competing interest None Declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The development of scalable, high-fidelity qubits is a key challenge in quantum information science. Neutral atom qubits have progressed rapidly in recent years, demonstrating programmable processors 1,2 and quantum simulators with scaling to hundreds of atoms 3,4 . Exploring new atomic species, such as alkaline earth atoms 5-7 , or combining multiple species 8 can provide new paths to improving coherence, control and scalability. For example, for eventual application in quantum error correction, it is advantageous to realize qubits with structured error models, such as biased Pauli errors 9 or conversion of errors into detectable erasures 10 . Here we demonstrate a new neutral atom qubit using the nuclear spin of a long-lived metastable state in 171 Yb. The long coherence time and fast excitation to the Rydberg state allow one- and two-qubit gates with fidelities of 0.9990(1) and 0.980(1), respectively. Importantly, a large fraction of all gate errors result in decays out of the qubit subspace to the ground state. By performing fast, mid-circuit detection of these errors, we convert them into erasure errors; during detection, the induced error probability on qubits remaining in the computational space is less than 10 -5 . This work establishes metastable 171 Yb as a promising platform for realizing fault-tolerant quantum computing., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

We introduce fault-tolerant (FT) architectures for error correction with the XZZX cluster state based on performing measurements of two-qubit Pauli operators Z⊗Z and X⊗X, or fusions, on a collection of few-body entangled resource states. Our construction is tailored to effectively correct noise that predominantly causes faulty X⊗X measurements during fusions. This feature offers a practical advantage in linear optical quantum computing with dual-rail photonic qubits, where failed fusions only erase X⊗X measurement outcomes. By applying our construction to this platform, we find a record-high threshold to fusion failures exceeding 25% in the experimentally relevant regime of nonzero loss rate per photon, considerably simplifying hardware requirements.

Fast, high-fidelity operations between microwave resonators are an important tool for bosonic quantum computation and simulation with superconducting circuits. An attractive approach for implementing these operations is to couple these resonators via a nonlinear converter and actuate parametric processes with RF drives. It can be challenging to make these processes simultaneously fast and high fidelity, since this requires introducing strong drives without activating parasitic processes or introducing additional decoherence channels. We show that in addition to a careful management of drive frequencies and the spectrum of environmental noise, leveraging the inbuilt symmetries of the converter Hamiltonian can suppress unwanted nonlinear interactions, preventing converter-induced decoherence. We demonstrate these principles using a differentially-driven DC-SQUID as our converter, coupled to two high-Q microwave cavities. Using this architecture, we engineer a highly-coherent beamsplitter and fast (~100 ns) swaps between the cavities, limited primarily by their intrinsic single-photon loss. We characterize this beamsplitter in the cavities' joint single-photon subspace, and show that we can detect and post-select photon loss events to achieve a beamsplitter gate fidelity exceeding 99.98%, which to our knowledge far surpasses the current state of the art., (© 2023. Springer Nature Limited.)

Aims: A key treatment for patients with varying stages of heart failure with preserved ejection fraction (HFpEF) is exercise. Yet, despite a Class 1A recommendation, only one-third of patients exercise sufficiently. A huge treatment gap exists between guidelines and clinical practice. PRIORITY aims to establish the feasibility, clinical effectiveness and cost-effectiveness of a hybrid centre and home-based personalized exercise and physical activity intervention for patients along the HFpEF continuum., Methods: An assessor-blinded, multicenter randomized controlled trial will be conducted among 312 patients along the HFpEF continuum. Participants will be randomized (1:1) to the PRIORITY intervention or a comparator group receiving only a written exercise prescription. Participants in the PRIORITY group will receive 18 supervised centre-based exercise sessions during one year, supplemented with a remotely guided home-based physical activity program. Outcomes will be assessed at baseline, 4 months, one and two years. The primary outcome is the peak oxygen uptake (pVO2) at 1-year. Secondary outcomes include physical activity, other physical fitness parameters, cardiovascular health, echocardiographic parameters, health-related quality of life and costs at 1-year FU. Machine learning algorithms will analyse big data on physical activity collected during the 1-year intervention to develop models that can predict physical activity uptake and adherence as well as changes in fitness and health. A cost-utility analysis will be performed to evaluate the cost-effectiveness of the PRIORITY intervention compared to the control condition., Discussion: We anticipate that participants in the supervised home-based exercise intervention group will have a greater increase in pVO2 compared to those receiving a written exercise prescription., Trial Registration Number: This trial is registered at ClinicalTrials.gov (NCT04745013) and is currently in the recruitment stage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 De Wilde, Bekhuis, Kuznetsova, Claes, Claessen, Coninx, Decorte, De Smedt, Hansen, Lannoo, Van Craenenbroeck, Verhaeghe and Cornelissen.)

Integrative interpretation of cardiopulmonary exercise tests (CPETs) may improve assessment of cardiovascular (CV) risk. Here, we identified patient phenogroups based on CPET summary metrics and evaluated their predictive value for CV events. We included 2280 patients with diverse CV risk who underwent maximal CPET by cycle ergometry. Key CPET indices and information on incident CV events (median follow-up time: 5.3 years) were derived. Next, we applied unsupervised clustering by Gaussian Mixture modeling to subdivide the cohort into four male and four female phenogroups solely based on differences in CPET metrics. Ten of 18 CPET metrics were used for clustering as eight were removed due to high collinearity. In males and females, the phenogroups differed significantly in age, BMI, blood pressure, disease prevalence, medication intake and spirometry. In males, phenogroups 3 and 4 presented a significantly higher risk for incident CV events than phenogroup 1 (multivariable-adjusted hazard ratio: 1.51 and 2.19; p ≤ 0.048). In females, differences in the risk for future CV events between the phenogroups were not significant after adjustment for clinical covariables. Integrative CPET-based phenogrouping, thus, adequately stratified male patients according to CV risk. CPET phenomapping may facilitate comprehensive evaluation of CPET results and steer CV risk stratification and management.

The fortification of food with edible insect flour can improve its nutrition profile, but also affect its techno-functional characteristics. In this study, an I-optimal design was applied to improve the rheological and textural properties of wheat flour chapatti containing 10% cricket ( Acheta domesticus ) flour. More specifically, the impact and optimal addition of hydrocolloids (carboxymethyl cellulose, hydroxypropyl methylcellulose, guar gum and xanthan gum) and water content were studied. For all the responses, the model and model terms were highly significant and showed the different impact of the hydrocolloids on the rheological properties. To evaluate the predictive power of the models, two sets of optimal process settings were chosen: one based on dough properties, and another on baked chapatti. For both sets, the actual responses were in the range of predicted responses for almost all properties. In addition, it was shown that using the settings based on dough properties, the actual responses were not significantly different from the control chapatti, whereas for the settings based on baked chapatti, there were differences in terms of the extensibility of both dough and chapatti. Thus, the I-optimal design is suitable to optimize the dough properties and the baked chapatti when enriching chapatti with cricket flour.

Intermittent claudication (IC) is characterized by decreased blood flow and oxygen delivery to the lower-limb muscles, resulting in pain and impaired functional capacity. This study evaluated the effects of a 12-week hybrid walking intervention on muscle oxygenation and functional capacity in 38 patients with IC (Rutherford I-III). Functional capacity was evaluated by means of two different treadmill test protocols and a six-minute walk test (6MWT). Muscle oxygenation was assessed during the treadmill tests using near-infrared spectroscopy. After the intervention, maximal walking distance was significantly increased (p < 0.001) during the progressive maximal treadmill test (mean (SD): +155 (SD 177) metres) and 6MWT (+18 (SD 29) metres) metres, with concomitant improvements in muscle oxygenation measures. Deoxygenation was slower during the progressive maximal test (p < 0.001) and reoxygenation was faster during recovery (p = 0.045). During the more submaximal test, oxygenated haemoglobin was better preserved (p = 0.040). Slower deoxygenation was more pronounced in the high responders of the progressive maximal treadmill test (p = 0.002). The findings suggest that preserved oxygen availability and slower deoxygenation during exercise could partly explain the improvements in functional capacity.

Addition of edible insects to food products may improve the nutritional status but can also influence their techno-functional properties. This study investigates the impact of supplementing wheat flour by cricket flour or paste at different levels (5-15%) on the rheological and textural properties of flour, dough, and baked chapatti. Addition of freeze-dried cricket flour resulted in the highest water absorption. The storage modulus increased at higher level (10-15%) of supplementation to wheat flour indicating an increased dough consistency. Similarly, biaxial extension of the dough showed an increased resistance to extension and decreased extensibility at higher level of supplementation due to a reduced strength of the gluten network. Uniaxial extension of baked chapatti showed less extensible and harder chapatti with the addition of a higher amount of cricket flour or paste. At lower level (5%), incorporation of cricket flour resulted in chapatti with textural properties comparable to the reference. Oven dried cricket powder is suggested as the best option for incorporating in chapatti dough to improve food security in Asian Countries.