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Numerical predictions of nearshore waves and shoreline runup are usually initialized on the inner shelf, seaward of the surfzone, with sea‐swell (SS) waves from local wave buoys or regional wave models. Lower frequency infragravity (IG) waves are not reliably measured by buoys or included in regional models. Here, co‐located pressure and velocity observations are used to characterize IG waves in 10–15 m depth in southern California. Shoreward propagating IG waves are often dominated by free waves, with the boundwave energy fraction <30% for moderate and low energy incident SS waves. Only 5% of records, with energetic long swell, show primarily bound waves. The shoreline slope of concave beaches increases by ∼3 between spring high and low tides, and free seaward and shoreward IG energy in 10–15 m vary tidally. The observed linear dependency of free IG energy on SS energy and period is consistent with Ardhuin et al. (2014, https://doi.org/10.1016/j.ocemod.2014.02.006)'s parameterization (R2 = 0.71). Including the tide level as a proxy for beach slope and modifying the SS frequency dependency increases R2 to 0.91. The ratio of free seaward to shoreward propagating IG energy suggests between 50 and 100% of the energy radiated seaward in depths of 10–15 m is trapped offshore and redirected shoreward. Free (random phase) and bound (phase‐coupled) IG waves are combined to initialize the SWASH numerical model. SWASH predicted runup is only weakly influenced by waves at the offshore boundary. Nonlinear IG generation and dissipation in the shoaling and surfzone overwhelm the effects of shoreward propagating waves observed at the offshore boundary. Plain Language Summary: Infragravity (IG) waves are long‐period (25 s–2.5 min) waves that contribute to coastal flooding and beach erosion. IG waves, generated near the shoreline by short‐period sea‐swell (SS) wave groups (known by surfers as "sets"), have long wavelengths (100s of m) and do not typically curl and break like ordinary sea and swell waves. Instead, they can be reflected off the beach face and propagate seaward. Our study concerns IG waves on the inner shelf (10–15 m depth, ∼500–700 m offshore), seaward of the main region of IG generation. Similar to previous observations in Hawai'i and North Carolina, we find most of the reflected, seaward‐going IG energy cannot reach deep water and is trapped on the continental shelf. We develop an observation‐based estimate of IG wave energy on the inner shelf as a function of SS wave energy and tide level. Finally, we show with a numerical model that IG wave runup at the shoreline is influenced only weakly by IG waves on the inner shelf. Key Points: Infragravity (IG) waves on the inner shelf (10–15 m depth) in San Diego, USA are often dominated by refractively trapped free wavesFree IG energies are parameterized as a function of local sea‐swell conditions and tide levelNumerically modeled wave runup is only weakly influenced by the shoreward propagating IG waves observed at the offshore boundary [ABSTRACT FROM AUTHOR]

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Copyright of Česká a Slovenská Neurologie a Neurochirurgie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Affect is known to be predictive of and enhanced by higher physical activity (PA) levels in the general population. This secondary analysis aimed to increase the understanding of the bi-directional relationship between PA and core affect (i.e. valence, energetic arousal, and calmness) among adults with higher body weight. Affect and PA were assessed in naturalistic settings via ecological momentary assessment using a mixed sampling scheme from 157 participants (body mass index: 32.99 ± 3.78 kg/m 2 ). Multilevel models revealed that being more physically active in the 15 minutes prior to the assessment predicted an increase in energetic arousal and a decrease in calmness. Subsequently, feeling more energetic and agitated was associated with increased PA within the following 15 minutes. Valence (i.e. pleasure-displeasure) was not associated with PA nor predictive of subsequent PA. Digital PA interventions may target the enhancement of feelings of energy and present psychoeducation about these distinct psychological benefits., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Previous studies indicate an implication of the terminal complement complex (TCC) in disc degeneration (DD). To investigate the functional role of TCC in trauma-induced DD in vivo, the model of endplate (EP) drilling was first applied in rabbits using a C6-deficient rabbit strain in which no TCC formation was possible. In parallel the model of needle puncture was investigated. Using a minimally invasive surgical intervention, lumbar rabbit intervertebral discs (IVDs) were treated with EP drilling or needle puncture. Degenerative effects of both surgical interventions were assessed by Pfirrmann grading and T2 quantification of the IVDs based on high-resolution MRI (11.7 T), as well as radiographic determination of disc height index. Pfirrmann grading indicated significant degenerative effects after EP drilling. Contrary to our assumption, no evidence was found that the absence of TCC formation in C6-deficient rabbits reduces the development of DD compared to C6-sufficient animals. EP drilling was proven to be suitable for application in rabbits. However, results of the present study do not provide clear evidence of a central functional role of TCC within DD and suggest that TCC deposition in DD patients may be primarily considered as a marker of complement activation during DD progression.

Various nonribosomal peptide synthetases (NRPSs) create structural and functional diversity by incorporating α-hydroxy acids into peptide backbones. Trigonic acid, an unusual cyclopropanol-substituted hydroxy acid, is the source of the molecular warhead of malleicyprol, a critical virulence factor of human and animal pathogens of the Burkholderia pseudomallei (BP) group. The process of selecting and loading this building block remained enigmatic as the NRPS module designated for this task is incomplete. Using a combination of bioinformatics, mutational analyses, targeted metabolomics, and in vitro biochemical assays, we show that two trans-acting enzymes are required to load this central building block onto the modular assembly line. An adenylation-thiolation didomain enzyme (BurJ) activates trigonic acid, followed by the translocation of the enzyme-bound α-hydroxy acid thioester by an FkbH-like protein with a mutated phosphatase domain (BurH). This specialized gateway is the first reported direct loading of an α-hydroxy acid onto a bona fide NRPS module in bacteria and expands the synthetic biology toolbox for the site-specific incorporation of non-canonical building blocks. Moreover, insight into the biochemical basis of virulence factor biosynthesis can provide a foundation for developing enzyme inhibitors as anti-virulence therapeutics against BP pathogen infections., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Beneficial effects of sodium glucose co-transporter 2 inhibitors (SGLT2is) in cardiovascular diseases have been extensively reported leading to the inclusion of these drugs in the treatment guidelines for heart failure. However, molecular actions especially on non-myocyte cells remain uncertain. We observed dose-dependent inhibitory effects of two SGLT2is, dapagliflozin (DAPA) and empagliflozin (EMPA), on inflammatory signaling in human umbilical vein endothelial cells. Proteomic analyses and subsequent enrichment analyses discovered profound effects of these SGLT2is on proteins involved in mitochondrial respiration and actin cytoskeleton. Validation in functional oxygen consumption measurements as well as tube formation and migration assays revealed strong impacts of DAPA. Considering that most influenced parameters played central roles in endothelial to mesenchymal transition (EndMT), we performed in vitro EndMT assays and identified substantial reduction of mesenchymal and fibrosis marker expression as well as changes in cellular morphology upon treatment with SGLT2is. In line, human cardiac fibroblasts exposed to DAPA showed less proliferation, reduced ATP production, and decelerated migration capacity while less extensive impacts were observed upon EMPA. Mechanistically, sodium proton exchanger 1 (NHE1) as well as sodium-myoinositol cotransporter (SMIT) and sodium-multivitamin cotransporter (SMVT) could be identified as relevant targets of SGLT2is in non-myocyte cardiovascular cells as validated by individual siRNA-knockdown experiments. In summary, we found comprehensive beneficial effects of SGLT2is on human endothelial cells and cardiac fibroblasts. The results of this study therefore support a distinct effect of selected SGLT2i on non-myocyte cardiovascular cells and grant further insights into potential molecular mode of action of these drugs., (© 2024. The Author(s).)

Background and Objectives: Endovascular treatment of cerebral aneurysms has tremendously advanced over the past decades. Nevertheless, aneurysm residual and recurrence remain challenges after embolization. The objective of this study was to elucidate the portion of embolized aneurysms requiring open surgery and evaluate whether newer endovascular treatments have changed the need for open surgery after failed embolization., Methods: All 15 cerebrovascular centers in Austria and the Czech Republic provided overall aneurysm treatment frequency data and retrospectively reviewed consecutive cerebral aneurysms treated with open surgical treatment after failure of embolization from 2000 to 2022. All endovascular modalities were included., Results: On average, 1362 aneurysms were treated annually in the 2 countries. The incidence increased from 0.006% in 2005 to 0.008% in 2020 in the overall population. Open surgery after failed endovascular intervention was necessary in 128 aneurysms (0.8%), a proportion that remained constant over time. Subarachnoid hemorrhage was the initial presentation in 70.3% of aneurysms. The most common location was the anterior communicating artery region (40.6%), followed by the middle cerebral artery (25.0%). The median diameter was 6 mm (2-32). Initial endovascular treatment included coiling (107 aneurysms), balloon-assist (10), stent-assist (4), intrasaccular device (3), flow diversion (2), and others (2). Complete occlusion after initial embolization was recorded in 40.6%. Seventy-one percent of aneurysms were operated within 3 years after embolization. In 7%, the indication for surgery was (re-)rupture and, in 88.3%, reperfusion. Device removal was performed in 16.4%. Symptomatic intraoperative and postoperative complications occurred in 10.2%. Complete aneurysm occlusion after open surgery was achieved in 94%., Conclusion: Open surgery remains a rare indication for cerebral aneurysms after failed endovascular embolization even in the age of novel endovascular technology, such as flow diverters and intrasaccular devices. Regardless, it is mostly performed for ruptured aneurysms initially treated with primary coiling that are in the anterior circulation., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Carbon quantum dots have become attractive in various applications, such as drug delivery, biological sensing, photocatalysis, and solar cells. Among these, pH sensing via luminescence lifetime measurements of surface-functionalized carbon dots is one application currently investigated for their long lifetime and autonomous operation. In this article, we explore the theoretical connection between excitation lifetimes and the pH value of the surrounding liquid via the protonation and deprotonation of functional groups. Example calculations applied to m-phenylenediamine, phloroglucinol, and tethered disperse blue 1 are shown by applying a separation approach treating the electronic wave function of functional groups separately from the internal electronic structure of the (large) carbon dot. The bulk of the carbon dot is treated as an environment characterized by its optical spectrum that shifts the transition rates of the functional group. A simple relationship between pH, pKa, and mixed fluorescence lifetime is derived from the transition rates of the protonated and deprotonated states. pH sensitivity improves when the difference in the transition rates is greatest between protonated and deprotonated species, with the greatest sensitivity found where the pKa is close to the pH region of interest. The introduced model can directly be extended to consider multicomponent liquids and multiple protonation states., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Oats (Avena sativa L.) provide unique nutritional benefits and contribute to sustainable agricultural systems. Breeding high-value oat varieties that meet milling industry standards is crucial for satisfying the demand for oat-based food products. Test weight, thins, and groat percentage are primary traits that define oat milling quality and the final price of food-grade oats. Conventional selection for milling quality is costly and burdensome. Multi-trait genomic selection (MTGS) combines information from genome-wide markers and secondary traits genetically correlated with primary traits to predict breeding values of primary traits on candidate breeding lines. MTGS can improve prediction accuracy and significantly accelerate the rate of genetic gain. In this study, we evaluated different MTGS models that used morphometric grain traits to improve prediction accuracy for primary grain quality traits within the constraints of a breeding program. We evaluated 558 breeding lines from the University of Illinois Oat Breeding Program across 2 years for primary milling traits, test weight, thins, and groat percentage, and secondary grain morphometric traits derived from kernel and groat images. Kernel morphometric traits were genetically correlated with test weight and thins percentage but were uncorrelated with groat percentage. For test weight and thins percentage, the MTGS model that included the kernel morphometric traits in both training and candidate sets outperformed single-trait models by 52% and 59%, respectively. In contrast, MTGS models for groat percentage were not significantly better than the single-trait model. We found that incorporating kernel morphometric traits can improve the genomic selection for test weight and thins percentage., (© 2024 The Authors. The Plant Genome published by Wiley Periodicals LLC on behalf of Crop Science Society of America.)

Background: Numerous smartphone apps are targeting physical activity (PA) and healthy eating (HE), but empirical evidence on their effectiveness for the initialization and maintenance of behavior change, especially in children and adolescents, is still limited. Social settings influence individual behavior; therefore, core settings such as the family need to be considered when designing mobile health (mHealth) apps., Objective: The purpose of this study was to evaluate the effectiveness of a theory- and evidence-based mHealth intervention (called SMARTFAMILY [SF]) targeting PA and HE in a collective family-based setting., Methods: A smartphone app based on behavior change theories and techniques was developed, implemented, and evaluated with a cluster randomized controlled trial in a collective family setting. Baseline (t 0 ) and postintervention (t 1 ) measurements included PA (self-reported and accelerometry) and HE measurements (self-reported fruit and vegetable intake) as primary outcomes. Secondary outcomes (self-reported) were intrinsic motivation, behavior-specific self-efficacy, and the family health climate. Between t 0 and t 1 , families of the intervention group (IG) used the SF app individually and collaboratively for 3 consecutive weeks, whereas families in the control group (CG) received no treatment. Four weeks following t 1 , a follow-up assessment (t 2 ) was completed by participants, consisting of all questionnaire items to assess the stability of the intervention effects. Multilevel analyses were implemented in R (R Foundation for Statistical Computing) to acknowledge the hierarchical structure of persons (level 1) clustered in families (level 2)., Results: Overall, 48 families (CG: n=22, 46%, with 68 participants and IG: n=26, 54%, with 88 participants) were recruited for the study. Two families (CG: n=1, 2%, with 4 participants and IG: n=1, 2%, with 4 participants) chose to drop out of the study owing to personal reasons before t 0 . Overall, no evidence for meaningful and statistically significant increases in PA and HE levels of the intervention were observed in our physically active study participants (all P>.30)., Conclusions: Despite incorporating behavior change techniques rooted in family life and psychological theories, the SF intervention did not yield significant increases in PA and HE levels among the participants. The results of the study were mainly limited by the physically active participants and the large age range of children and adolescents. Enhancing intervention effectiveness may involve incorporating health literacy, just-in-time adaptive interventions, and more advanced features in future app development. Further research is needed to better understand intervention engagement and tailor mHealth interventions to individuals for enhanced effectiveness in primary prevention efforts., Trial Registration: German Clinical Trials Register DRKS00010415; https://drks.de/search/en/trial/DRKS00010415., International Registered Report Identifier (irrid): RR2-10.2196/20534., (©Kathrin Wunsch, Janis Fiedler, Sebastian Hubenschmid, Harald Reiterer, Britta Renner, Alexander Woll. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 26.04.2024.)

Cardiomyopathies encompass a spectrum of heart disorders with diverse causes and presentations. Fibrosis stands out as a shared hallmark among various cardiomyopathies, reflecting a common thread in their pathogenesis. This prevalent fibrotic response is intricately linked to the consequences of dysregulated extracellular matrix (ECM) remodeling, emphasizing its significance in the development and progression the disease. This review explores the ECM involvement in various cardiomyopathies and its impact on myocardial stiffness and fibrosis. Additionally, we discuss the potential of ECM fragments as early diagnosis, prognosis, and risk stratification. Biomarkers deriving from turnover of collagens and other ECM proteins hold promise in clinical applications. We outline current clinical management, future directions, and the potential for personalized ECM-targeted therapies with specific focus on microRNAs. In summary, this review examines the role of the fibrosis in cardiomyopathies, highlighting the potential of ECM-derived biomarkers in improving disease management with implications for precision medicine., Competing Interests: Declaration of Competing Interest EA was funded by the Danish Research Foundation and has a shared affiliation with the University of Copenhagen and Nordic Bioscience, Herlev, Denmark, as a PhD fellow. MJ, MO, and JF were funded by the Bundesamt für Strahlenschutz, Z4/AG-R-08313/3621S32210 and supported by Fraunhofer Cluster of Excellence for Immune Mediated Diseases (CIMD). MJ kindly acknowledges support by Hannover Biomedical Research School (HBRS). FG and MK are full-time employees and shareholders at Nordic Bioscience, Herlev, Denmark. SDS participated in PRACTIS, a Clinician Scientist Program supported and funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – 3696/3 and Hannover Medical School. SDS was supported by internal project funding (HiLF) of the Hannover Medical School (MHH) and was funded by the German Cardiac Society Research Stipend (Deutsche Gesellschaft für Kardiologie, DGK, no. DGK06/2023). TT is founder and shareholder of Cardior Pharmaceuticals. TT has filed and licensed multiple patents about diagnostic and therapeutic use of noncoding RNAs. We acknowledge funding by the ERC Advanced Grant REVERSE (to TT)., (Copyright © 2024. Published by Elsevier B.V.)

Optical whispering gallery mode biosensors are able to detect single molecules through effects of their polarizability. We address the factors that affect the polarizability of amino acids, which are the building blocks of life, via electronic structure theory. Amino acids are detected in aqueous environments, where their polarizability is different compared to the gasphase due to solvent effects. Solvent effects include structural changes, protonation and the local field enhancement through the solvent (water). We analyse the impact of these effects and find that all contribute to an increased effective polarizability in the solvent. We also address the excess polarizability relative to the displaced water cavity and develop a hybrid quantum-classical model that is in good agreement with self-consistent calculations. We apply our model to calculate the excess polarizability of 20 proteinogenic amino acids and determine the minimum resolution required to distinguish the different molecules and their ionised conformers based on their polarizability.

Background : The effectiveness of knee orthoses as part of conservative treatment for patients with medial knee osteoarthritis has not been fully explored. The purpose of this study was to evaluate the effects of a novel semi-rigid knee orthosis on pain, physical activity, and functional capacity. Methods : Pain levels, physical activity, and functional capacity were assessed in 24 participants experiencing symptomatic medial knee osteoarthritis one week before (i.e., pretest) initiating a six-week orthosis intervention and again during the final week of the intervention (i.e., post-test). Results : Night pain, pain during walking, pain during stair climbing, and pain during sitting consistently decreased by 41% to 48% while wearing the knee orthosis. Device-based measured physical activity showed a 20.2-min increase in vigorous physical activity during the post-test, while light and moderate physical activity did not show significant changes. After six weeks of orthosis application, there was a 5% increased distance for the six-minute walk test, and participants reported fewer limitations both in everyday and athletic activities, as well as an enhanced quality of life. Conclusions : These findings highlight the potential effectiveness of a semi-rigid knee orthosis to enhancing functional capacity and quality of life. More extensive and longer clinical trials are needed to improve confidence in these findings and understand their impact on disease progression.

Modular polyketide synthases (PKSs) are giant assembly lines that produce an impressive range of biologically active compounds. However, our understanding of the structural dynamics of these megasynthases, specifically the delivery of acyl carrier protein (ACP)-bound building blocks to the catalytic site of the ketosynthase (KS) domain, remains severely limited. Using a multipronged structural approach, we report details of the inter-domain interactions after C-C bond formation in a chain-branching module of the rhizoxin PKS. Mechanism-based crosslinking of an engineered module was achieved using a synthetic substrate surrogate that serves as a Michael acceptor. The crosslinked protein allowed us to identify an asymmetric state of the dimeric protein complex upon C-C bond formation by cryo-electron microscopy (cryo-EM). The possible existence of two ACP binding sites, one of them a potential "parking position" for substrate loading, was also indicated by AlphaFold2 predictions. NMR spectroscopy showed that a transient complex is formed in solution, independent of the linker domains, and photochemical crosslinking/mass spectrometry of the standalone domains allowed us to pinpoint the interdomain interaction sites. The structural insights into a branching PKS module arrested after C-C bond formation allows a better understanding of domain dynamics and provides valuable information for the rational design of modular assembly lines., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Introduction: Emotions consist of different components such as the emotional experience, physiological reactions, action tendencies, or emotional expressions. Assessing the relation of these components may help to better understand the role of emotions in sport competitions. Based on the component process model of emotions, the goal of the present study was to assess the relation between emotional experiences and emotional expressions., Methods: Twenty tennis players (7 female) with an average age of 23.10 (SD = 4.88) were taped during competitive tennis matches. Thereafter, in individual meetings, after having watched themselves on the footage at pre-selected points, the players had to indicate whether, immediately after the end of a rally, they had a positive or a negative emotional experience and, in case they had one, rate its intensity. Moreover, based on their observable behavior, the players were also asked to state whether they could recognize a positive or a negative emotional expression and, in case they recognized one, rate its intensity. The occurrence of emotional expressions was additionally rated by two external coders. Using multilevel models, separate analyses were conducted for positive emotions after won points and negative emotions after lost points., Results and Discussion: For both positive and negative emotions, the results indicated a positive correlation between emotional experiences and emotional expressions. Moreover, the intensity of emotional experiences could predict the occurrence of an emotional expression rated by both the players or external coders. These insights into the relation between emotional experiences and emotional expressions may help players to more effectively regulate their emotions., 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 © 2024 Fritsch, Fiedler, Hatzigeorgiadis and Jekauc.)