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Keywords: benchmarking; NEC SX-8; HPC Challenge; CFD; ab initio molecular dynamics 131 Teraflops Sustained Performance With Real World Applications SAGE Publications, Inc.200810.1177/1094342007085017 S.R.Tiyyagura HOCHSTLEISTUNGSRECHENZENTRUM STUTTGART, GERMANY P.Adamidis HOCHSTLEISTUNGSRECHENZENTRUM STUTTGART, GERMANY […]

Purpose/objective: To investigate associations between illness appraisals, dyadic coping, and illness adjustment in individuals with stroke and their healthy partners., Method/design: This longitudinal observational study examined dyadic data in 17 couples (patient and partner) after stroke. Patients and partners completed self-report measures on event centrality of the stroke (appraisal) at 2 months ( t ₁), common dyadic coping (CDC) at 5 months ( t ₂), and quality of life (adjustment) at 8 months ( t ₃) after the stroke. Dyadic data were analyzed using actor-partner interdependence models., Results: Higher event centrality at t ₁ predicted more CDC at t ₂ in patients ( b = 0.38, p < .05). For partners, the effect of event centrality on dyadic coping differed significantly from the patients' effect but was not significant itself ( b = -0.17, p = .601). More CDC at t2 predicted higher physical ( b = 3.21 , p < .05) and psychological quality of life at t ₃ ( b = 3.66, p < .05) for partners but not for patients., Conclusions/implications: Preliminary evidence suggests that patients and their healthy partners may endorse event centrality of the stroke differentially. Perceiving dyadic coping processes seems to be especially important to the healthy partners' illness adjustment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Microalgal solutions to clean waste streams and produce biomass were evaluated in Nordic conditions during winter, spring, and autumn in Southeast Sweden. The study investigated nitrogen (N) removal, biomass quality, and safety by treating industrial leachate water with a polyculture of local microalgae and bacteria in open raceway ponds, supplied with industrial CO 2 effluent. Total N (TN) removal was higher in spring (1.5 g -2 d -1 ), due to beneficial light conditions compared to winter and autumn (0.1 and 0.09 g -2 d -1 ). Light, TN, and N species influenced the microalgal community (dominated by Chlorophyta), while the bacterial community remained stable throughout seasons with a large proportion of cyanobacteria. Winter conditions promoted biomass protein (19.6-26.7%) whereas lipids and carbohydrates were highest during spring (11.4-18.4 and 15.4-19.8%). Biomass toxin and metal content were below safety levels for fodder, but due to the potential presence of toxic strains, biofuels or fertilizer could be suitable applications for the algal biomass. PRACTITIONER POINTS: Microalgal removal of nitrogen from leachate water was evaluated in Nordic conditions during winter, spring, and autumn. Total nitrogen removal was highest in spring (1.5 g -2 d -1 ), due to beneficial light conditions for autotrophic growth. Use of local polyculture made the cultivation more stable on a seasonal (light) and short-term (N-species changes) scale. Toxic elements in produced algal biomass were below legal thresholds for upcycling., (© 2024 The Author(s). Water Environment Research published by Wiley Periodicals LLC on behalf of Water Environment Federation.)

Background: A valid and reliable tool is crucial for municipal registered nurses (RNs) to make quick decisions in older adults who show rapid signs of health deterioration. The aim of this study was to investigate the psychometric properties of the Decision Support System (DSS) among older adults in the municipal healthcare system., Methods: Firstly, we utilized the Rasch dichotomous model to analyze the DSS assessments (n=281) that were collected from municipal RNs working with older adults in the municipal healthcare system. We examined the properties of the DSS in terms of its unidimensionality, item fit, and separation indices. Secondly, to investigate inter-rater agreement in using the DSS, four experienced municipal RNs used the DSS to assess 60 health deterioration scenarios presented by one human patient simulators. The 60 DSS assessments were then analyzed using the ICC (2,1), percentage agreement, and Cohen κ statistics., Results: The sample of older adults had a mean age of 82.8 (SD 11.7). The DSS met the criteria for unidimensionality, although two items did not meet the item fit statistics when all the DSS items were analyzed together. The person separation index was 0.47, indicating a limited level of separation among the sample. The item separation index was 11.43, suggesting that the DSS has good ability to discriminate between and separate the items. At the overall DSS level, inter-rater agreements were good according to the ICC. At the individual DSS item level, the percentage agreements were 75% or above, while the Cohen κ statistics ranged from 0.46 to 1.00., Conclusions: The Rasch analysis revealed that the psychometric properties of the instrument were acceptable, although further research with a larger sample size and more items is needed. The DSS has the potential to assist municipal RNs in making clinical decisions regarding health deterioration in older adults, thereby avoiding unnecessary emergency admistion and helping., (© 2024. The Author(s).)

N-Acyl indolines 4 are potent, non-covalent Notum inhibitors developed from a covalent virtual screening hit 2a. The lead compounds were simple to synthesise, achieved excellent potency in a biochemical Notum-OPTS assay and restored Wnt signalling in a cell-based TCF/LEF reporter assay. Multiple high resolution X-ray structures established a common binding mode of these inhibitors with the indoline bound centred in the palmiteolate pocket with key interactions being aromatic stacking and a water mediated hydrogen bond to the oxyanion hole. These N-acyl indolines 4 will be useful tools for use in vitro studies to investigate the role of Notum in disease models, especially when paired with a structurally related covalent inhibitor (e.g. 4w and 2a). Overall, this study highlights the designed switch from covalent to non-covalent Notum inhibitors and so illustrates a complementary approach for hit generation and target inhibition., Competing Interests: Declaration of competing interest B.N.A., N.J.W, Y.Z., E.Y.J. and P.V.F. are co-inventors of patent application #WO 2020043866 issued to UCL Business Ltd, which describes inhibitors of Notum., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Acquired brain injury (ABI) is often associated with personality changes. Pre- as well as post-injury personality traits are related to rehabilitation outcomes. However, it largely remains unclear whether post-injury personality shows any associations with rehabilitation outcomes over and above pre-injury personality. Using a case-control design, this study investigated (1) personality changes after ABI from patients' and significant others' perspective, and (2) relations of pre- and post-ABI personality traits to rehabilitation outcomes in the short- and long-term. 40 patients with ABI (85% stroke, 15% traumatic brain injury), 46 healthy controls and their significant others participated. Personality was assessed with NEO-FFI, rehabilitation outcomes (activities, participation, depression) were measured at two and ten months after ABI. Patient-ratings indicated decreases in extraversion and a trend towards reduced conscientiousness. Significant others reported increases in patients' neuroticism. Pre- as well as post-injury personality traits were associated with depression and activities at both short- and long-term timepoints after ABI. The association was strongest for long-term depressive symptoms where personality trait variables accounted for 49% of variance ( R a d j u s t e d 2 ). Our results confirm that ABI patients and significant others perceive personality changes, albeit in different dimensions. Pre- and post-ABI personality traits showed associations with rehabilitation outcomes, especially with emotional adjustment after the injury.

The present eye-tracking study investigates whether individuals with different levels of contamination fear are more likely to focus their attention on disgusting stimuli to explore them or to pull their attention away to avoid them. Ninety-two nonclinical participants with varying degrees of contamination fear performed a dot probe task. Eye-tracking methodology was employed to record gaze patterns during the task. In each trial participants looked at two pictures (disgust-neutral, fear-neutral, or neutral-neutral). Participants were further asked about the contents of the picture and the confidence of their answer. The results show that reaction times were slower and fixations were longer and more frequent for disgust targets compared with fear and neutral targets, which was further amplified in individuals with high contamination fear. However, image details of disgusting pictures were remembered less correctly than details of fearful pictures. These findings confirm the idea that attention on disgusting stimuli is maintained. Further, the findings indicate that disgust is processed more superficially and might also be related to disgust-associated uncertainty and ambiguity. The results may help to understand the difficult-to-change nature of disgust, which could be relevant to habituation and extinction processes in exposure therapy. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Background: Population-based register data could be used to improve our knowledge of patients surgically treated for foot and ankle disorders. The quality register Swefoot was recently created to collect surgical and patient-reported data of foot and ankle surgery. This manuscript aims to describe the development and current use of the register., Methods: The development of Swefoot started in 2014 and currently, data on 16 different diagnoses are collected in 49 units performing foot and ankle surgery. Registrations are performed by the surgeon and the patient., Results: Between 2014 and 2020 approximately 20,000 surgical procedures have been registered. 75.1% of the registered patients were women, 9.3% were smokers, 9.3% had a concomitant rheumatoid disease, and 18.4% a BMI larger than 30 kg/m 2 . CONCLUSIONS: The Swefoot is a unique national register for foot and ankle surgery. It is by now possible to present demographic, surgical, and outcome parameters based on Swefoot., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Traditional recordings of muscle activation often involve time-consuming application of surface electrodes affixed to the skin in laboratory environments. The development of textile electromyography (EMG) electrodes now allows fast and unobtrusive assessment of muscle activation in ecologically valid environments. In this study, textile EMG shorts were used to assess whether performing squats with the barbell resting freely on the shoulders or using a Smith machine for a fixed barbell movement path is preferable for maximizing lower limb muscle activation., Methods: Sixteen athletes performed free and fixed barbell squats in a gym with external loads equivalent to their body mass. Quadriceps, hamstrings and gluteus maximus activation was measured bilaterally with textile EMG electrodes embedded in shorts., Results: Mean quadriceps activation was greater for the free compared with the fixed movement path for the right (mean difference [MD] 14μV, p = 0.04, η p 2 = 0.28) and left leg (MD 15μV, p = 0.01, η p 2 = 0.39) over the entire squat and specifically during the first half of the eccentric phase for the left leg (MD 7μV, p = 0.04, d = 0.56), second half of the eccentric phase for both legs (right leg MD 21μV, p = 0.05, d = 0.54; left leg MD 23μV, p = 0.04, d = 0.52) and the first half of the concentric phase for both legs (right leg MD 24μV, p = 0.04, d = 0.56; left leg MD 15μV, p = 0.01, d = 0.72). Greater hamstrings activation for the free path was seen for the second half of the eccentric phase (left leg MD 4μV, p = 0.03, d = 0.58) and first half of the concentric phase (right leg MD 5μV, p = 0.02, d = 0.72). No significant differences were found for gluteus maximus., Discussion: Textile EMG electrodes embedded in shorts revealed that to maximize thigh muscle activity during loaded squats, a free barbell movement path is preferable to a fixed barbell movement path., 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., (Copyright © 2022 Svensson, Aasa and Strong.)

Notum is a carboxylesterase that suppresses Wnt signaling through deacylation of an essential palmitoleate group on Wnt proteins. There is a growing understanding of the role Notum plays in human diseases such as colorectal cancer and Alzheimer's disease, supporting the need to discover improved inhibitors, especially for use in models of neurodegeneration. Here, we have described the discovery and profile of 8l (ARUK3001185) as a potent, selective, and brain-penetrant inhibitor of Notum activity suitable for oral dosing in rodent models of disease. Crystallographic fragment screening of the Diamond-SGC Poised Library for binding to Notum, supported by a biochemical enzyme assay to rank inhibition activity, identified 6a and 6b as a pair of outstanding hits. Fragment development of 6 delivered 8l that restored Wnt signaling in the presence of Notum in a cell-based reporter assay. Assessment in pharmacology screens showed 8l to be selective against serine hydrolases, kinases, and drug targets.

Machine learning models are widely applied to predict molecular properties or the biological activity of small molecules on a specific protein. Models can be integrated in a conformal prediction (CP) framework which adds a calibration step to estimate the confidence of the predictions. CP models present the advantage of ensuring a predefined error rate under the assumption that test and calibration set are exchangeable. In cases where the test data have drifted away from the descriptor space of the training data, or where assay setups have changed, this assumption might not be fulfilled and the models are not guaranteed to be valid. In this study, the performance of internally valid CP models when applied to either newer time-split data or to external data was evaluated. In detail, temporal data drifts were analysed based on twelve datasets from the ChEMBL database. In addition, discrepancies between models trained on publicly-available data and applied to proprietary data for the liver toxicity and MNT in vivo endpoints were investigated. In most cases, a drastic decrease in the validity of the models was observed when applied to the time-split or external (holdout) test sets. To overcome the decrease in model validity, a strategy for updating the calibration set with data more similar to the holdout set was investigated. Updating the calibration set generally improved the validity, restoring it completely to its expected value in many cases. The restored validity is the first requisite for applying the CP models with confidence. However, the increased validity comes at the cost of a decrease in model efficiency, as more predictions are identified as inconclusive. This study presents a strategy to recalibrate CP models to mitigate the effects of data drifts. Updating the calibration sets without having to retrain the model has proven to be a useful approach to restore the validity of most models., (© 2022. The Author(s).)

After the accident at the Fukushima Daiichi Nuclear Power Plant (FDNPP), Japan, in March 2011, 137 Cs in demersal fish had, between 2011 and 2015, a prolonged ecological half-life when compared to pelagic fish. Using stable isotope mixing models combined with gut content analysis and 137 Cs activity concentrations, this study investigated the hypothesis that an unexplored food web structure could be a contributing factor explaining the ecological half-life of 137 Cs in benthic flatfish. Benthic invertebrates and demersal fish species sampled in 2015 still showed 137 Cs activity concentrations higher than pre-accident. The mixing models of stable N and C isotopes and gut content analysis identified deposit, suspension and filter feeders to be the main flatfish food items in the benthos. There was a significant correlation between 137 Cs activity concentrations in specific flatfish species and benthos, and between 137 Cs activity concentrations in benthos and surface sediment. The results of this study partially explained the 137 Cs activity concentrations found in the analysed demersal fish, suggesting that the benthos can be a continuous source of 137 Cs for the demersal fish during this period of time. Extending monitoring programmes to include invertebrates that are not food species for humans would greatly improve our ability to understand the role of trophic transfer pathways and take appropriate management actions., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims: Accurate and reliable diagnosis is essential for lung cancer treatment. The study aim was to investigate interpathologist diagnostic concordance for pulmonary tumours according to WHO diagnostic criteria., Methods: Fifty-two unselected lung and bronchial biopsies were diagnosed by a thoracic pathologist based on a broad spectrum of immunohistochemical (IHC) stainings, molecular data and clinical/radiological information. Slides stained with H&E, thyroid transcription factor-1 (TTF-1) clone SPT24 and p40 were scanned and provided digitally to 20 pathologists unaware of reference diagnoses. The pathologists independently diagnosed the cases and stated if further diagnostic markers were deemed necessary., Results: In 31 (60%) of the cases, ≥80% of the pathologists agreed with each other and with the reference diagnosis. Lower agreement was seen in non-small cell neuroendocrine tumours and in squamous cell carcinoma with diffuse TTF-1 positivity. Agreement with the reference diagnosis ranged from 26 to 45 (50%-87%) for the individual pathologists. The pathologists requested additional IHC staining in 15-44 (29%-85%) of the 52 cases. In nearly half (17 of 36) of the malignant cases, one or more pathologist advocated for a different final diagnosis than the reference without need of additional IHC markers, potentially leading to different clinical treatment., Conclusions: Interpathologist diagnostic agreement is moderate for small unselected bronchial and lung biopsies based on a minimal panel of markers. Neuroendocrine morphology is sometimes missed and TTF-1 clone SPT24 should be interpreted with caution. Our results suggest an intensified education need for thoracic pathologists and a more generous use of diagnostic IHC markers., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Notum is a negative regulator of Wnt signaling acting through the hydrolysis of a palmitoleoylate ester, which is required for Wnt activity. Inhibitors of Notum could be of use in diseases where dysfunctional Notum activity is an underlying cause. A docking-based virtual screen (VS) of a large commercial library was used to shortlist 952 compounds for experimental validation as inhibitors of Notum. The VS was successful with 31 compounds having an IC 50 < 500 nM. A critical selection process was then applied with two clusters and two singletons ( 1 - 4d ) selected for hit validation. Optimization of 4d guided by structural biology identified potent inhibitors of Notum activity that restored Wnt/β-catenin signaling in cell-based models. The [1,2,4]triazolo[4,3- b ]pyradizin-3(2 H )-one series 4 represent a new chemical class of Notum inhibitors and the first to be discovered by a VS campaign. These results demonstrate the value of VS with well-designed docking models based on X-ray structures.

Confidence predictors can deliver predictions with the associated confidence required for decision making and can play an important role in drug discovery and toxicity predictions. In this work we investigate a recently introduced version of conformal prediction, synergy conformal prediction, focusing on the predictive performance when applied to bioactivity data. We compare the performance to other variants of conformal predictors for multiple partitioned datasets and demonstrate the utility of synergy conformal predictors for federated learning where data cannot be pooled in one location. Our results show that synergy conformal predictors based on training data randomly sampled with replacement can compete with other conformal setups, while using completely separate training sets often results in worse performance. However, in a federated setup where no method has access to all the data, synergy conformal prediction is shown to give promising results. Based on our study, we conclude that synergy conformal predictors are a valuable addition to the conformal prediction toolbox., (© 2021. The Author(s).)