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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]

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.)

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.)

Effiziente Produktionen in der kosmetischen Industrie haben weitreichende Auswirkungen auf CO2-Emissionen, Kostenstrukturen, Produktionszeiten und letztendlich die Wirtschaftlichkeit der Branche. Dieser Artikel liefert Ansätze und Empfehlungen zur Optimierung der Herstellung von Emulsionen in der kosmetischen Produktion. Dabei wird die Auswahl der Rohstoffe, die Phasenkonstruktion, das Produktionsverfahren und der Maschinenpark betrachtet, um die Emissionen zu reduzieren und die Effizienz zu steigern. Obwohl der Fokus auf Emulsionen liegt, sind auch andere Aspekte der Produktionsoptimierung relevant. Eine enge Zusammenarbeit zwischen Entwicklung und Produktion sowie gezielte Maßnahmen können zu signifikanten Verbesserungen führen. [ABSTRACT FROM AUTHOR]

Efficient production in the cosmetic industry has far-reaching effects on CO2 emissions, cost structures, production times, and ultimately the industry’s profitability. This article provides approaches and recommendations for optimizing the production of emulsions in cosmetic manufacturing. The selection of raw materials, phase construction, production processes, and machinery are considered to reduce emissions and enhance efficiency. Although the focus is on emulsions, other aspects of production optimization are also relevant. Close collaboration between development and production, along with targeted measures, can lead to significant improvements. [ABSTRACT FROM AUTHOR]

This article discusses the case of a pregnant patient with von Hippel-Lindau syndrome (VHL) who presented with multiple hemangioblastomas in the central nervous system (CNS). Hemangioblastomas are common tumors associated with VHL and can significantly increase morbidity and mortality. The possible influence of pregnancy on the growth of these tumors remains unclear. The article presents the case of a 28-year-old pregnant patient with VHL who underwent microsurgical resection of three dominant lesions. The patient had a successful pregnancy and delivered a healthy baby. The article also discusses the progression of hemangioblastomas during pregnancy and the recommended treatment approaches. [Extracted from the article]

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.)

Objective: This study aims to evaluate the usage and implementation of video remote (VR) interpreting and telephone remote (TR) interpreting in primary healthcare settings., Design: This publication forms part of a larger three-pronged study in which we compared both remote interpreting modalities to each other and to a control group. This paper conveys the findings of the qualitative evaluation of the implementation and usage of both remote interpreting solutions. The quantitative evaluation of the 6-month intervention period (September 2018-February 2019) has been reported previously. After this period, we conducted focus groups with the healthcare professionals involved. The focus groups were recorded, transcribed verbatim and analysed using the structured qualitative content analysis., Setting: We provided either VR or TR tools to 10 different primary healthcare practices (general medicine, gynaecology and paediatrics) in the city of Hamburg, Germany., Participants: Three physicians and two physician's assistants took part in the TR focus group. The VR focus group consisted of four physicians., Results: The main topics identified were the importance of communication for diagnostic and therapeutic processes, previous solutions to language barriers, as well as advantages and disadvantages of the two remote interpreting solutions. Advantages included the possibility to adequately communicate with language discordant patients and the high quality of the interpreting. Disadvantages included the habituation time required for new technology as well as time constraints., Conclusion: Our evaluation found that these solutions were highly appreciated, if not considered indispensable, for the delivery of appropriate medical care to language-discordant patients. Differences between the two modalities were named and concrete suggestions for improvement were made. Policy-makers should consider providing VR or TR as an adequate and safe interpreting service alternative when professional in-person interpreters are not available or too expensive., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This study aimed to demonstrate the behavior of different complexes using IR spectroelectrochemistry (SEC), a technique that combines IR spectroscopy with electrochemistry. Four different Mn and Re catalysts for electrochemical CO 2 reduction were studied in dry acetonitrile. In the case of Mn(apbpy)(CO) 3 Br (apbpy = 4(4-aminophenyl)-2,2'-bipyridine), SEC suggested that a very slow catalytic reduction of CO 2 also occurs in acetonitrile in the absence of proton donors, but at rather negative potentials. In contrast, the corresponding Re(apbpy)(CO) 3 Br clearly demonstrated slow catalytic conversion at the first reduction potential. Switching to saturated CO 2 solutions in a mixture of acetonitrile and 5% water as a proton donor, the SEC of Mn(apbpy)(CO) 3 Br displayed a faster catalytic behavior.

Background & Aims: Body composition (BC) changes with age and is associated with morbidity and mortality. A physically active lifestyle influences BC and represents an important predictor of successful aging. To emphasize this, the World Health Organization established activity recommendations for all age groups. We describe BC during adulthood using a cross-sectional sample from a German community and investigate the associations between physical activity (PA), physical fitness (PF), and BC., Methods: Data from 329 men and women aged 35 to 86 years were analyzed. PA was measured by questionnaire and classified into sport activity and habitual activity. PF was measured through physical performance tests and BC by bioelectrical impedance analysis. Fat mass index (FMI) and fat-free mass index (FFMI) were calculated to represent height-adjusted BC. Associations between PA, PF, and BC were analyzed using linear regression models., Results: For both sexes, strength was positively associated with FFMI (♂: ß = 0.313; ♀: ß = 0.213) and phase angle (♂: ß = 0.357; ♀: ß = 0.409). For FMI, a significant negative association with strength was found only in women (ß = -0.189). Cardiorespiratory fitness showed a negative association with FMI (ß = -0.312) and FFMI (ß = -0.201) for men, while in women a positive association was found for FFMI (ß = 0.186). For coordination, a significant association with FMI was observed only in women (ß = -0.190). Regarding PA only one significant relationship between sport activity and FMI among women (ß = -0.170) was found., Conclusions: In our sample, PF was closer related to BC than PA. Strength and cardiorespiratory fitness were the strongest predictors for BC. This supports the World Health Organization's activity recommendations to include both resistance and endurance training in the weekly sports program to maintain a healthy BC., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Schilling 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.)

The conserved multiple PDZ-domain containing protein PATJ stabilizes the Crumbs-Pals1 complex to regulate apical-basal polarity and tight junction formation in epithelial cells. However, the molecular mechanism of PATJ's function in these processes is still unclear. In this study, we demonstrate that knockout of PATJ in epithelial cells results in tight junction defects as well as in a disturbed apical-basal polarity and impaired lumen formation in three-dimensional cyst assays. Mechanistically, we found PATJ to associate with and inhibit histone deacetylase 7 (HDAC7). Inhibition or downregulation of HDAC7 restores polarity and lumen formation. Gene expression analysis of PATJ-deficient cells revealed an impaired expression of genes involved in cell junction assembly and membrane organization, which is rescued by the downregulation of HDAC7. Notably, the function of PATJ regulating HDAC7-dependent cilia formation does not depend on its canonical interaction partner, Pals1, indicating a new role of PATJ, which is distinct from its function in the Crumbs complex. By contrast, polarity and lumen phenotypes observed in Pals1- and PATJ-deficient epithelial cells can be rescued by inhibition of HDAC7, suggesting that the main function of this polarity complex in this process is to modulate the transcriptional profile of epithelial cells by inhibiting HDAC7., (© 2023. The Author(s).)

Background and Aim: In-stent restenosis (ISR) belongs to an infrequent but potentially serious complication after carotid angioplasty and stenting in patients with severe carotid stenosis. Some of these patients might be contraindicated to repeat percutaneous transluminal angioplasty with or without stenting (rePTA/S). The purpose of the study is to compare the safety and effectiveness of carotid endarterectomy with stent removal (CEASR) and rePTA/S in patients with carotid ISR., Methods: Consecutive patients with carotid ISR (≥80%) were randomly allocated to the CEASR or rePTA/S group. The incidence of restenosis after intervention, stroke, transient ischaemic attack myocardial infarction and death 30 days and 1 year after intervention and restenosis 1 year after intervention between patients in CEASR and rePTA/S groups were statistically evaluated., Results: A total of 31 patients were included in the study; 14 patients (9 males; mean age 66.3±6.6 years) were allocated to CEASR and 17 patients (10 males; mean age 68.8±5.6 years) to the rePTA/S group. The implanted stent in carotid restenosis was successfully removed in all patients in the CEASR group. No clinical vascular event was recorded periproceduraly, 30 days and 1 year after intervention in both groups. Only one patient in the CEASR group had asymptomatic occlusion of the intervened carotid artery within 30 days and one patient died in the rePTA/S group within 1 year after intervention. Restenosis after intervention was significantly greater in the rePTA/S group (mean 20.9%) than in the CEASR group (mean 0%, p=0.04), but all stenoses were <50%. Incidence of 1-year restenosis that was ≥70% did not differ between the rePTA/S and CEASR groups (4 vs 1 patient; p=0.233)., Conclusion: CEASR seems to be effective and save procedures for patients with carotid ISR and might be considered as a treatment option., Trial Registration Number: NCT05390983., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Cutaneous lupus erythematosus (CLE) is a disfiguring autoimmune skin disease characterized by an inflammatory infiltrate rich in T cells, which are strongly implicated in tissue damage. How these cells adapt to the skin environment and promote tissue inflammation and damage is not known. In lupus nephritis, we previously identified an inflammatory gene program in kidney-infiltrating T cells that is dependent on HIF-1, a transcription factor critical for the cellular and developmental response to hypoxia as well as inflammation-associated signals. In our present studies using a mouse model of lupus skin disease, we find that skin-infiltrating CD4+ and CD8+ T cells also express high levels of HIF-1. Skin-infiltrating T cells demonstrated a strong cytotoxic signature at the transcript and protein levels, and HIF-1 inhibition abrogated skin and systemic diseases in association with decreased T cell cytotoxic activity. We also demonstrate in human CLE tissue that the T cell-rich inflammatory infiltrate exhibited increased amounts of HIF-1 and a cytotoxic signature. Granzyme B-expressing T cells were concentrated at sites of skin tissue damage in CLE, suggesting relevance of this pathway to human disease.

Bacterial pathogens of the Burkholderia pseudomallei (BP) group cause life-threatening infections in both humans and animals. Critical for the virulence of these often antibiotic-resistant pathogens is the polyketide hybrid metabolite malleicyprol, which features two chains, a short cyclopropanol-substituted chain and a long hydrophobic alkyl chain. The biosynthetic origin of the latter has remained unknown. Here, we report the discovery of novel overlooked malleicyprol congeners with varied chain lengths and identify medium-sized fatty acids as polyketide synthase (PKS) starter units that constitute the hydrophobic carbon tails. Mutational and biochemical analyses show that a designated coenzyme A-independent fatty acyl-adenylate ligase (FAAL, BurM) is essential for recruiting and activating fatty acids in malleicyprol biosynthesis. In vitro reconstitution of the BurM-catalyzed PKS priming reaction and analysis of ACP-bound building blocks reveal a key role of BurM in the toxin assembly. Insights into the function and role of BurM hold promise for the development of enzyme inhibitors as novel antivirulence therapeutics to combat infections with BP pathogens.

Despite the importance of functional outcome, only a few scoring systems exist to predict neurologic outcome in meningioma surgery. Therefore, our study aims to identify preoperative risk factors and develop the receiver operating characteristics (ROC) models estimating the risk of a new postoperative neurologic deficit and a decrease in Karnofsky performance status (KPS). A multicentric study was conducted in a cohort of 552 consecutive patients with skull base meningiomas who underwent surgical resection from 2014 to 2019. Data were gathered from clinical, surgical, and pathology records as well as radiological diagnostics. The preoperative predictive factors of functional outcome (neurologic deficit, decrease in KPS) were analyzed in univariate and multivariate stepwise selection analyses. Permanent neurologic deficits were present in 73 (13.2%) patients and a postoperative decrease in KPS in 84 (15.2%). Surgery-related mortality was 1.3%. A ROC model was developed to estimate the probability of a new neurologic deficit (area 0.74; SE 0.0284; 95% Wald confidence limits (0.69; 0.80)) based on meningioma location and diameter. Consequently, a ROC model was developed to predict the probability of a postoperative decrease in KPS (area 0.80; SE 0.0289; 95% Wald confidence limits (0.74; 0.85)) based on the patient's age, meningioma location, diameter, presence of hyperostosis, and dural tail. To ensure an evidence-based therapeutic approach, treatment should be founded on known risk factors, scoring systems, and predictive models. We propose ROC models predicting the functional outcome of skull base meningioma resection based on the age of the patient, meningioma size, and location and the presence of hyperostosis and dural tail., (© 2023. The Author(s).)

Background: Despite all the gains that have been achieved with endovascular mechanical thrombectomy revascularization and intravenous thrombolysis logistics since 2015, there is still a subgroup of patients with salvageable brain tissue for whom persistent emergent large vessel occlusion portends a catastrophic outcome., Objective: To test the safety and efficacy of emergent microsurgical intervention in patients with acute ischemic stroke and symptomatic middle cerebral artery occlusion after failure of mechanical thrombectomy., Methods: A prospective two-center cohort study was conducted. Patients with acute ischemic stroke and middle cerebral artery occlusion for whom recanalization failed at center 1 were randomly allocated to the microsurgical intervention group (MSIG) or control group 1 (CG1). All similar patients at center 2 were included in the control group 2 (CG2) with no surgical intervention. Microsurgical embolectomy and/or extracranial-intracranial bypass was performed in all MSIG patients at center 1., Results: A total of 47 patients were enrolled in the study: 22 at center 1 (12 allocated to the MSIG and 10 to the CG1) and 25 patients at center 2 (CG2). MSIG group patients showed a better clinical outcome on day 90 after the stroke, where a modified Rankin Scale score of 0-2 was reached in 7 (58.3%) of 12 patients compared with 1/10 (10.0%) patients in the CG1 and 3/12 (12.0%) in the CG2., Conclusions: This study demonstrated the potential for existing microsurgical techniques to provide good outcomes in 58% of microsurgically treated patients as a third-tier option., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Gas hydrates (GHs) in water close to freezing temperatures can be stabilised via the formation of ice layers. In a recent work [Boström et al. , Astron. Astrophys. , A54 , 650, 2021], it was found that a surface region with partial gas dilution could be essential for obtaining nano- to micron-sized anomalously stabilizing ice layers. In this paper, it is demonstrated that the Casimir-Lifshitz free energy in multi-layer systems could induce thinner, but more stable, ice layers in cavities than those found for gas hydrates in a large reservoir of cold water. The thickness and stability of such ice layers in a pore filled with cold water could influence the leakage of gas molecules. Additional contributions, e.g. from salt-induced stresses, can also be of importance, and are briefly discussed.

Key Message: We identified and integrated the novel FHB-resistant Fhb7 The2 allele into wheat B genome and made it usable in both common and durum wheat breeding programs without yellow flour linkage drag. A novel tall wheatgrass-derived (Thinopyrum elongatum, genome EE) Fhb7 allele, designated Fhb7 The2 , was identified and integrated into the wheat B genome through a small 7B-7E translocation (7BS·7BL-7EL) involving the terminal regions of the long arms. Fhb7 The2 conditions significant Type II resistance to Fusarium head blight (FHB) in wheat. Integration of Fhb7 The2 into the wheat B genome makes this wild species-derived FHB resistance gene usable for breeding in both common and durum wheat. By contrast, other Fhb7 introgression lines involving wheat chromosome 7D can be utilized only in common wheat breeding programs, not in durum wheat. Additionally, we found that Fhb7 The2 does not have the linkage drag of the yellow flour pigment gene that is tightly linked to the decaploid Th. ponticum-derived Fhb7 allele Fhb7 Thp . This will further improve the utility of Fhb7 The2 in wheat breeding. DNA sequence analysis identified 12 single nucleotide polymorphisms (SNPs) in Fhb7 The2 , Fhb7 Thp , and another Th. elongatum-derived Fhb7 allele Fhb7 The1 , which led to seven amino acid conversions in Fhb7 The2 , Fhb7 Thp , and Fhb7 The1 , respectively. However, no significant variation was observed in their predicted protein configuration as a glutathione transferase. Diagnostic DNA markers were developed specifically for Fhb7 The2 . The 7EL segment containing Fhb7 The2 in the translocation chromosome 7BS·7BL-7EL exhibited a monogenic inheritance pattern in the wheat genetic background. This will enhance the efficacy of marker-assisted selection for Fhb7 The2 introgression, pyramiding, and deployment in wheat germplasm and varieties., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: Major depressive disorder (MDD) constitutes a main risk factor for suicide. Suicide risk in psychiatric patients is primarily determined by often unreliable, self-reported information. We assessed serum levels of three microRNAs (miRNAs), previously demonstrated to be dysregulated in post-mortem brain samples of suicide victims, as potential peripheral biomarkers for suicidality., Methods: All study participants were diagnosed with MDD according to Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria. Suicidality, defined as acute suicide risk or suicide attempt within one week prior to study entry, was assessed by clinical interview. Relative serum levels of miR-30a, miR-30e, and miR-200a, normalized to U6, were measured by quantitative real-time PCR in MDD inpatients with (MDD/SI, N = 19) and without (MDD, N = 31) acute suicide risk. Median age and gender distribution were comparable in both groups., Results: Levels of miR-30a, miR-30e, and miR-200a were significantly elevated in MDD/SI compared to MDD. Subgroup analysis of the MDD/SI group showed that levels of miR-30e and miR-200a were significantly higher and miR-30a was increased by trend in patients admitted following a suicide attempt ( N = 7) compared to patients with acute suicide risk but without recent suicide attempt ( N = 12). Additionally, use of two databases for in silico transcription factor-miRNA interaction prediction indicated early growth response protein (EGR) 1 as potential transcriptional regulator for all three miRNAs., Conclusion: This study demonstrates suicide risk in MDD patients to be associated with increased levels of miR-30a, miR-30e, and miR-200a. Thus, these miRNAs might constitute potential biomarkers to predict suicidal behavior in MDD patients., Competing Interests: KK received speaker honoraria by Janssen, Otsuka, Neuraxpharm, EliLilly, Schwabe, Servier, and Trommsdorff/Ferrer; he received an unrestricted grant by Ferrer, ADDISCA. TT was founder and shareholder of Cardior Pharmaceuticals GmbH. TT filed and licensed patents regarding noncoding RNAs. TT received speaker honoraria and/or was in advisory boards by/of Takeda, Boehringer Ingelheim, Novo Nordisk, Sanofi-Genzyme, Amicus Therapeutics, Ksilink. The remaining 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 Stapel, Xiao, Gorinski, Schmidt, Pfanne, Fiedler, Richter, Vollbrecht, Thum, Kahl and Ponimaskin.)

Objectives: Fluctuations of physical performance and biological responses during a repetitive daily 24-h cycle are known as circadian rhythms. These circadian rhythms can influence the optimal time of day for endurance performance and related parameters which can be crucial in a variety of sports disciplines. The current study aimed to evaluate the daytime variations in endurance running performance in a 3.000-m field run and endurance running performance, blood lactate levels, and heart rate in an incremental treadmill test in adolescent soccer players., Results: In this study, 15 adolescent male soccer players (age: 18.0 ± 0.6 years) performed a 3.000-m run and an incremental treadmill test at 7:00-8:00 a.m. and 7:00-8:00 p.m. in a randomized cross-over manner. No significant variations after a Bonferroni correction were evident in endurance running performance, perceived exertion, blood lactate levels, and heart rates between the morning and the evening. Here, the largest effect size was observed for maximal blood lactate concentration (9.15 ± 2.18 mmol/l vs. 10.64 ± 2.30 mmol/l, p = .110, ES = 0.67). Therefore, endurance running performance and physiological responses during a field-based 3.000-m run and a laboratory-based test in young male soccer players indicated no evidence for daytime variations., (© 2022. The Author(s).)

We study the impact of an environment on the electromagnetic responses of a molecule in the presence of a dielectric medium. By applying the dipole-dipole coupling between the molecule's and the environment's degrees of freedom, we can reduce the complex system into its components and predict excitation lifetimes of single and few molecules attached to a dielectric surface by knowing the entire quantum-mechanical properties of the molecules, such as transition energies and dipole moments. The derived theory allows for the description of superradiance between two molecules depending on the geometric arrangement between both concerning their separation and orientation with respect to each other. We analyze the possibility of superradiance between two molecules bound to a dielectric sphere and determine a change in the relevant length scale where the usually considered wavelength in free space is replaced with the binding distance, drastically reducing the length scales at which collective effects can take place.

Background: During the COVID-19 pandemic there has been a strong interest in forecasts of the short-term development of epidemiological indicators to inform decision makers. In this study we evaluate probabilistic real-time predictions of confirmed cases and deaths from COVID-19 in Germany and Poland for the period from January through April 2021., Methods: We evaluate probabilistic real-time predictions of confirmed cases and deaths from COVID-19 in Germany and Poland. These were issued by 15 different forecasting models, run by independent research teams. Moreover, we study the performance of combined ensemble forecasts. Evaluation of probabilistic forecasts is based on proper scoring rules, along with interval coverage proportions to assess calibration. The presented work is part of a pre-registered evaluation study., Results: We find that many, though not all, models outperform a simple baseline model up to four weeks ahead for the considered targets. Ensemble methods show very good relative performance. The addressed time period is characterized by rather stable non-pharmaceutical interventions in both countries, making short-term predictions more straightforward than in previous periods. However, major trend changes in reported cases, like the rebound in cases due to the rise of the B.1.1.7 (Alpha) variant in March 2021, prove challenging to predict., Conclusions: Multi-model approaches can help to improve the performance of epidemiological forecasts. However, while death numbers can be predicted with some success based on current case and hospitalization data, predictability of case numbers remains low beyond quite short time horizons. Additional data sources including sequencing and mobility data, which were not extensively used in the present study, may help to improve performance., (© 2022. The Author(s).)

Key Message: We mapped three adult plant resistance (APR) loci on oat chromosomes 4D and 6C and developed flanking KASP/PACE markers for marker-assisted selection and gene pyramiding. Using sequence orthology search and the available oat genomic and transcriptomic data, we surveyed these genomic regions for genes that may control disease resistance. Sources of durable disease resistance are needed to minimize yield losses in cultivated oat caused by crown rust (Puccinia coronata f. sp. avenae). In this study, we developed five oat recombinant inbred line mapping populations to identify sources of adult plant resistance from crosses between five APR donors and Otana, a susceptible variety. The preliminary bulk segregant mapping based on allele frequencies showed two regions in linkage group Mrg21 (Chr4D) that are associated with the APR phenotype in all five populations. Six markers from these regions in Chr4D were converted to high-throughput allele specific PCR assays and were used to genotype all individuals in each population. Simple interval mapping showed two peaks in Chr4D, named QPc.APR-4D.1 and QPc.APR-4D.2, which were detected in the OtanaA/CI4706-2 and OtanaA/CI9416-2 and in the Otana/PI189733, OtanaD/PI260616, and OtanaA/CI8000-4 populations, respectively. These results were validated by mapping two entire populations, Otana/PI189733 and OtanaA/CI9416, genotyped using Illumina HiSeq, in which polymorphisms were called against the OT3098 oat reference genome. Composite interval mapping results confirmed the presence of the two quantitative trait loci (QTL) located on oat chromosome 4D and an additional QTL with a smaller effect located on chromosome 6C. This mapping approach also narrowed down the physical intervals to between 5 and 19 Mb, and indicated that QPc.APR-4D.1, QPc.APR-4D.2, and QPc.APR-6C explained 43.4%, 38.5%, and 21.5% of the phenotypic variation, respectively. In a survey of the gene content of each QTL, several clusters of disease resistance genes that may contribute to APR were found. The allele specific PCR markers developed for these QTL regions would be beneficial for marker-assisted breeding, gene pyramiding, and future cloning of resistance genes from oat., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Loss of MHC I expression is a tumoral escape mechanism, part of the process of immunoediting. MHC expression patterns and their prognostic and predictive value have not been studied in urothelial carcinoma of the bladder (UC) so far., Objective: To correlate the expression of MHC I and MHC II with prognosis after curative treatment, response to chemotherapy and checkpoint inhibition., Patients and Methods: We analyzed different patient cohorts for their expression of MHC I(HLA-A/B/C) and II (HLA-DR/DP/DQ) and examined potential correlations with prognosis and response to cisplatin-based chemotherapy or PD-1/PD-L1 directed immunotherapy., Results and Limitations: Overall, MHC expression was analyzed in 246 patients, and complete MHC I loss was seen in 29.7% of patients. In 35% of patients aberrant tumoral expression of MHC II was observed. In a homogeneous cohort of 149 patients with cystectomy with curative intent there were no significant differences in survival between the MHC expression groups. MHC I+ and MHC II+ patients had higher infiltration densities with CD8+ T effector cells.An analysis of 77 additional patients (cohort II) with neoadjuvant chemotherapy revealed no associations of MHC status with response defined as < pT2 pN0 in the cystectomy specimen. Lastly, we analyzed 26 patients with metastatic disease treated with PD-1/PD-L1 directed immunotherapy (cohort III, best response: 11 PD, 5 SD, 10 OR) and observed responses exclusively in MHC I+ patients (10/19 patients, 52.6). All four MHC I+ /MHC II+ /PD-L1+ patients had a progression-free interval of at least 12 months., Conclusions: Tumoral MHC I expression is frequently lost in UC. We found no association with prognosis or response to cisplatin-based chemotherapy but response to checkpoint inhibitors was limited to MHC I+ patients., Competing Interests: Nawroth R. is an Editorial Board member of this journal, but was not involved in the peer-review process nor had access to any information regarding its peer-review. Slotta-Huspenina J.: none Schwamborn K.: lecture honoraria and advisory board participation for Roche, BMS, MSD, Merck Steiger K.: none Simon R.: none Kirchhoff F.: none Büchler J.: none Fiedler J.: none Retz M.: lecture honoraria from BMS Ritschel C.: none Gschwend J.: lecture honoraria from Amgen, Astellas, Bayer, Janssen, Merck, Roche, consultant for AAA, Amgen, Bayer, BMS, Janssen, MSD, Merck, Pfizer, Roche Horn T.: lecture honoraria from Merck, medac GmbH and Pfizer, advisory board participation Merck and Bayer, (© 2022 – The authors. Published by IOS Press.)