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The technological requirements of low-power and high-fidelity color displays have been instrumental in driving research into advanced coloration technologies. At the forefront of these developments is the implementation of dye-free approaches, which overcome previous constraints related to color resolution and fading. Resonant dielectric nanostructures have emerged as a promising paradigm, showing great potential for high efficiency, high color saturation, wide gamut palette, and image reproduction. However, they still face limitations related to color accuracy, purity, and simultaneous brightness tunability. Here, we demonstrate an all-dielectric metasurface empowered by photonic bound states in the continuum (BICs), which supports sharp resonances throughout the visible spectral range, ideally suited for producing a wide range of structural colors. The metasurface design consists of TiO2 ellipses with carefully controlled sizes and geometrical asymmetry, allowing versatile and on-demand variation of the brightness and hue of the output colors, respectively. [ABSTRACT FROM AUTHOR]

Summary: Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease that is characterized by left ventricular hypertrophy unexplained by secondary causes. Based on international epidemiological data, around 20,000–40,000 patients are expected to be affected in Austria. Due to the wide variety of clinical and morphological manifestations the diagnosis can be difficult and the disease therefore often goes unrecognized. HCM is associated with a substantial reduction in quality of life and can lead to sudden cardiac death, especially in younger patients. Early and correct diagnosis, including genetic testing, is essential for comprehensive counselling of patients and their families and for effective treatment. The latter is especially true as an effective treatment of outflow tract obstruction has recently become available in the form of a first in class cardiac myosin ATPase inhibitor, as a noninvasive alternative to established septal reduction therapies. The aim of this Austrian consensus statement is to summarize the recommendations of international guidelines with respect to the genetic background, pathophysiology, diagnostics and management in the context of the Austrian healthcare system and resources, and to present them in easy to understand algorithms. [ABSTRACT FROM AUTHOR]

Rationale: Preserved ratio impaired spirometry (PRISm) is a recently recognized spirometric pattern defined by a ratio of forced expiratory volume in 1 second to forced vital capacity of at least 0.70 and a forced expiratory volume in 1 second  <80% of reference. For unclear reasons, PRISm is associated with increased cardiovascular (CV) morbidity and mortality. Arterial stiffness is a major mechanism of CV disease, which can be measured by carotid-femoral pulse-wave velocity (cfPWV). Objectives: We explored the hypothesis that cfPWV would be increased in individuals with PRISm and airflow limitation (AL). Methods: We measured forced spirometry, lung volumes by body plethysmography, and cfPWV in 9,466 subjects recruited from the general population in the Austrian cross-sectional LEAD (Lung, Heart, Social, Body) study and tested the association of arterial stiffness with PRISm and AL by multivariable linear regression analysis. Individuals younger than 18 years were excluded from the study. Results: Individuals with PRISm (n = 431; 4.6%) were of similar age to those with normal spirometry (n = 8,136; 85.9%) and significantly younger than those with AL (n = 899; 9.5%). Arterial hypertension, diabetes mellitus, coronary artery disease, heart failure, and peripheral arterial occlusive disease were significantly more common in individuals with PRISm than in those with normal lung function and similar to those with AL. There was a significant association between PRISm and arterial stiffness on bivariate linear regression analysis (crude model, β = 0.038; 95% confidence interval [CI], 0.016–0.058), which persisted after robust adjustment for clinical confounders upon multivariable analysis (final model, β = 0.017; 95% CI, 0.001–0.032). cfPWV was significantly higher in individuals with PRISm irrespective of the presence of established CV disease or pulmonary restriction. AL also showed a significant association with arterial stiffness on multivariable linear regression analysis (final model, β = 0.025; 95% CI, 0.009–0.042). Conclusions: Arterial stiffness measured by cfPWV is increased in individuals with PRISm independent of CV disease and risk factors. The pathobiological mechanisms underlying this association deserve further research. [ABSTRACT FROM AUTHOR]

To date, apart from moderate hypothermia, there are almost no adequate interventions available for neuroprotection in cases of brain damage due to cardiac arrest. Affected persons often have severe limitations in their quality of life. The aim of this study was to investigate protective properties of the active compound of dimethyl fumarate, monomethyl fumarate (MMF), on distinct regions of the central nervous system after ischemic events. Dimethyl fumarate is an already established drug in neurology with known anti-inflammatory and antioxidant properties. In this study, we chose organotypic slice cultures of rat cerebellum and hippocampus as an ex vivo model. To simulate cardiac arrest and return of spontaneous circulation we performed oxygen-glucose-deprivation (OGD) followed by treatments with different concentrations of MMF (1–30 μM in cerebellum and 5–30 μM in hippocampus). Immunofluorescence staining with propidium iodide (PI) and 4′,6-diamidine-2-phenylindole (DAPI) was performed to analyze PI/DAPI ratio after imaging with a spinning disc confocal microscope. In the statistical analysis, the relative cell death of the different groups was compared. In both, the cerebellum and hippocampus, the MMF-treated group showed a significantly lower PI/DAPI ratio compared to the non-treated group after OGD. Thus, we showed for the first time that both cerebellar and hippocampal slice cultures treated with MMF after OGD are significantly less affected by cell death. [ABSTRACT FROM AUTHOR]

Dielectric metasurfaces supporting quasi-bound states in the continuum (qBICs) enable high field enhancement with narrow-linewidth resonances in the visible and near-infrared ranges. The resonance emerges when distorting the meta-atom's geometry away from a symmetry-protected BIC condition and, usually, a given design can sustain one or two of these states. In this work, we introduce a silicon-on-silica metasurface that simultaneously supports up to four qBIC resonances in the near-infrared region. This is achieved by combining multiple symmetry-breaking distortions on an elliptical cylinder array. By pumping two of these resonances, the nonlinear process of degenerate four-wave mixing is experimentally realized. By comparing the nonlinear response with that of an unpatterned silicon film, the near-field enhancement inside the nanostructured dielectric is revealed. The presented results demonstrate independent geometric control of multiple qBICs and their interaction through wave mixing processes, opening new research pathways in nanophotonics, with potential applications in information multiplexing, multi-wavelength sensing and nonlinear imaging. [ABSTRACT FROM AUTHOR]

Healthcare entrepreneurs (HCEs) develop and implement solutions to improve processes, structures, and practices. Unfortunately, they also operate in environments with multiple levels of uncertainty because of their industry's unpredictable, nonlinear, and risk-averse features. Moreover, entrepreneurial uncertainty has been underexplored in the healthcare context. This empirical study examines HCEs' uncertainty management processes throughout the entrepreneurial process. In-depth interviews were conducted with 25 for-profit and social HCEs across nine sectors in nineteen different states within the United States. We used a mixed methods qualitative approach to analyze, interpret and visualize data, including constant comparative and lexical analyses. Interview data reveals HCEs experience five major uncertainties and utilize distinct strategies to manage those uncertainties. Findings highlight the effect of external environmental conditions on HCEs' uncertainty, the complexity and interconnectedness of HCEs' uncertainties, their willingness to utilize a wide repertoire of strategies to cope with uncertainty, and communication's central role in the management process. We provide practical advice to improve educational, training and professional development initiatives for aspiring, novice and experienced HCEs. [ABSTRACT FROM AUTHOR]

Public transportation systems, including trams and buses, play a crucial role in urban traffic. However, these traditional modes of transport have some well-known drawbacks, such as long distances between stops, lengthy waiting times, and a lack of privacy. In response to these challenges, an innovative mobility concept called "FLAIT-train" offers potential solutions. The FLAIT-train operates on regular roads and aims to provide DOOR-2-DOOR transport, addressing the issues associated with fixed stops and offering increased accessibility and convenience. In its initial phase, the FLAIT-train operates on exclusive lanes, but it is designed to integrate with other traffic eventually. The vehicle technology of FLAIT-trains closely resembles that of battery electric autonomous vehicles. To assess whether FLAIT-trains can be used as a suitable alternative to conventional public transportation systems, this paper employs traffic simulations that consider key performance indicators, including the average waiting time per passenger, maximum waiting time of a single passenger, average in-vehicle time per passenger, and average occupancy rate of the vehicles. Using SUMO software ("Simulation of Urban Mobility", version 1.12.0), a night bus service scenario is meticulously designed and generated. Within this scenario, both FLAIT-trains and conventional buses are simulated under identical conditions and based on statistical data. [ABSTRACT FROM AUTHOR]

Ocean biogeochemical models have become critical tools for interpreting trace element and isotope (TEI) distributions observed during the GEOTRACES program and understanding their driving processes. Models stimulate new research questions that cannot be addressed with observations alone, for instance, concerning processes that occur over vast spatial scales and linkages between TEIs and other elemental cycles. A spectrum of modeling approaches has been applied to date, including (1) fully prognostic models that couple TEIs to broader biogeochemical frameworks, (2) simpler element-specific mechanistic models that allow for assimilation of observations, and (3) machine learning models that have no mechanistic underpinning but allow for skillful extrapolation of sparse data. Here, we evaluate the strengths and weaknesses of these approaches and review three sets of novel insights they have facilitated. First, models have advanced our understanding of global-scale micronutrient distributions, and their deviations from macronutrients, in terms of a "ventilation-regeneration-scavenging" balance. Second, models have yielded global-scale estimates of TEI inputs to and losses from the ocean, revealing, for instance, a rapid iron (Fe) cycle with an oceanic residence time on the order of decades. Third, models have identified novel links among various TEI cycling processes and the global ocean carbon cycle, such as tracing the supply of hydrothermally sourced Fe to iron-starved microbial communities in the Southern Ocean. We foresee additional important roles for modeling work in the next stages of trace element research, including synthesizing understanding from the GEOTRACES program in the form of TEI state estimates, and projecting the responses of TEI cycles to global climate change. [ABSTRACT FROM AUTHOR]

Semiconductor‐based surface‐enhanced Raman spectroscopy (SERS) substrates, as a new frontier in the field of SERS, are hindered by their poor electromagnetic field confinement and weak light‐matter interaction. Metasurfaces, a class of 2D artificial materials based on the electromagnetic design of nanophotonic resonators, enable strong electromagnetic field enhancement and optical absorption engineering for a wide range of semiconductors. However, the engineering of semiconductor substrates into metasurfaces for improving SERS activity remains underexplored. Here, an improved SERS metasurface platform is developed that leverages the combination of titanium oxide (TiO2) and the emerging physical concept of optical bound states in the continuum (BICs) to boost the Raman emission. Moreover, fine‐tuning of BIC‐assisted resonant absorption offers a pathway for maximizing the photoinduced charge transfer effect (PICT) in SERS. High values of BIC‐assisted electric field enhancement (|E/E0|2 ≈103) are achieved, challenging the preconception of weak electromagnetic (EM) field enhancement on semiconductor SERS substrates. The BIC‐assisted TiO2 metasurface platform offers a new dimension in spectrally‐tunable SERS with earth‐abundant and bio‐compatible semiconductor materials, beyond the traditional plasmonic ones. [ABSTRACT FROM AUTHOR]

Dissolved gas concentrations in surface waters can have sharp gradients across marine and freshwater environments, which often prove challenging to capture with analytical measurement. Collecting discrete samples for laboratory analysis provides accurate results, but suffers from poor spatial resolution. To overcome this limitation, water equilibrators and gas membrane contactors (GMCs) have been used for the automated underway measurement of dissolved gas concentrations in surface water. However, while water equilibrators can provide continuous measurements, their analytical response times to changes in surface water concentration can be slow, lasting tens of minutes. This leads to spatial imprecisions in the dissolved gas concentration data. Conversely, while GMCs have proven to have much faster analytical response times, often lasting only a few minutes or less, they suffer from poor accuracy and thus require routine calibration. Here we present an analytical system for the high accuracy and high precision spatial mapping of dissolved methane concentration in surface waters. The system integrates a GMC with a cavity ringdown spectrometer for fast analytical response times, with a calibration method involving two Weiss‐style equilibrators and discrete measurements in vials. Data from both the GMC and equilibrators are collected simultaneously, with discrete vial samples collected periodically throughout data collection. We also present a mathematical algorithm integrating all data collected for the routine calibration of the GMC dataset. The algorithm facilitates comparison between the GMC and equilibrator datasets despite the substantial differences in response times (0.7–2.1 and 4.1–17.6 min, respectively). This measurement system was tested with both systematic laboratory experiments and field data collected on a research cruise along the US Atlantic margin. Once calibrated, this system identified numerous sharp peaks of dissolved methane concentration in the US Atlantic margin dataset that would be poorly resolved, or outright missed with previous measurement techniques. Overall, the precision and accuracy for the technique presented here were determined to be 11.2% and 10.4%, respectively, the operating range was 0–1000 ppm methane, and the e‐folding response time to changes in dissolved methane concentration was 0.7–2.1 min. [ABSTRACT FROM AUTHOR]

Today, adeno-associated virus (AAV)-based vectors are arguably the most promising in vivo gene delivery vehicles for durable therapeutic gene expression. Advances in molecular engineering, high-throughput screening platforms, and computational techniques have resulted in a toolbox of capsid variants with enhanced performance over parental serotypes. Despite their considerable promise and emerging clinical success, there are still obstacles hindering their broader use, including limited transduction capabilities, tissue/cell type-specific tropism and penetration into tissues through anatomical barriers, off-target tissue biodistribution, intracellular degradation, immune recognition, and a lack of translatability from preclinical models to clinical settings. Here, we first describe the transduction mechanisms of natural AAV serotypes and explore the current understanding of the systemic and cellular hurdles to efficient transduction. We then outline progress in developing designer AAV capsid variants, highlighting the seminal discoveries of variants which can transduce the central nervous system upon systemic administration, and, to a lesser extent, discuss the targeting of the peripheral nervous system, eye, ear, lung, liver, heart, and skeletal muscle, emphasizing their tissue and cell specificity and translational promise. In particular, we dive deeper into the molecular mechanisms behind their enhanced properties, with a focus on their engagement with host cell receptors previously inaccessible to natural AAV serotypes. Finally, we summarize the main findings of our review and discuss future directions. [ABSTRACT FROM AUTHOR]

Background: Dual‐energy (DE) detection of bone marrow edema (BME) would be a valuable new diagnostic capability for the emerging orthopedic cone‐beam computed tomography (CBCT) systems. However, this imaging task is inherently challenging because of the narrow energy separation between water (edematous fluid) and fat (health yellow marrow), requiring precise artifact correction and dedicated material decomposition approaches. Purpose: We investigate the feasibility of BME assessment using kV‐switching DE CBCT with a comprehensive CBCT artifact correction framework and a two‐stage projection‐ and image‐domain three‐material decomposition algorithm. Methods: DE CBCT projections of quantitative BME phantoms (water containers 100–165 mm in size with inserts presenting various degrees of edema) and an animal cadaver model of BME were acquired on a CBCT test bench emulating the standard wrist imaging configuration of a Multitom Rax twin robotic x‐ray system. The slow kV‐switching scan protocol involved a 60 kV low energy (LE) beam and a 120 kV high energy (HE) beam switched every 0.5° over a 200° angular span. The DE CBCT data preprocessing and artifact correction framework consisted of (i) projection interpolation onto matched LE and HE projections views, (ii) lag and glare deconvolutions, and (iii) efficient Monte Carlo (MC)‐based scatter correction. Virtual non‐calcium (VNCa) images for BME detection were then generated by projection‐domain decomposition into an Aluminium (Al) and polyethylene basis set (to remove beam hardening) followed by three‐material image‐domain decomposition into water, Ca, and fat. Feasibility of BME detection was quantified in terms of VNCa image contrast and receiver operating characteristic (ROC) curves. Robustness to object size, position in the field of view (FOV) and beam collimation (varied 20–160 mm) was investigated. Results: The MC‐based scatter correction delivered > 69% reduction of cupping artifacts for moderate to wide collimations (> 80 mm beam width), which was essential to achieve accurate DE material decomposition. In a forearm‐sized object, a 20% increase in water concentration (edema) of a trabecular bone‐mimicking mixture presented as ∼15 HU VNCa contrast using 80–160 mm beam collimations. The variability with respect to object position in the FOV was modest (< 15% coefficient of variation). The areas under the ROC curve were > 0.9. A femur‐sized object presented a somewhat more challenging task, resulting in increased sensitivity to object positioning at 160 mm collimation. In animal cadaver specimens, areas of VNCa enhancement consistent with BME were observed in DE CBCT images in regions of MRI‐confirmed edema. Conclusion: Our results indicate that the proposed artifact correction and material decomposition pipeline can overcome the challenges of scatter and limited spectral separation to achieve relatively accurate and sensitive BME detection in DE CBCT. This study provides an important baseline for clinical translation of musculoskeletal DE CBCT to quantitative, point‐of‐care bone health assessment. [ABSTRACT FROM AUTHOR]

The second article in this Special Section reflects the actions of not one AI firm, but instead 1,387 publicly-traded companies in the People's Republic of China from 2007 to 2018. An interesting, empirically testable implication of the authors' theoretical analysis is whether different enforcement regimes, which result in differences of piracy cost, do result in the nuanced prevalence (or not) of product bundles on the local markets for information goods as it would be predicted by the model. The authors report that they found evidence for a causal link in the presence of higher-intensity AI investments proxied by the estimated AI applications of individual firms with their overall employment as well as higher employment of nonacademically-trained workers. The authors' results are developed as a function of product similarity (amounting to a valuation discount factor between 0 and 1) and (expected per-product) piracy cost, which provides a somewhat new perspective, as the set of parameters where bundling dominates becomes nonconvex - due to the newly discovered "wedge" of intermediate piracy costs and sufficiently high product similarity. [Extracted from the article]

Introduction: Severe acute global cerebral hypoxia can lead to significant disability in humans. Although different animal models have been described to study hypoxia, there is no endogenous model that considers hypoxia and its effect on the brain as an independent factor. Thus, we developed a minimally invasive rat model, which is based on the non-depolarizing muscle blocking agent rocuronium in anesthetized animals. This drug causes respiratory insufficiency by paralysis of the striated muscles. Methods: In this study, 14 rats underwent 12 min of hypoxemia with an oxygen saturation of approximately 60% measured by pulse oximetry; thereafter, animals obtained sugammadex to antagonize rocuronium immediately. Results: Compared to controls (14 rats, anesthesia only), hypoxic animals demonstrated significant morphological alterations in the hippocampus (cell decrease in the CA 1 region) and the cerebellum (Purkinje cell decrease), as well as significant changes in hypoxia markers in blood (Hif2α, Il1β, Tgf1β, Tnfα, S100b, cspg2, neuron-specific enolase), hippocampus (Il1β, Tnfα, S100b, cspg2, NSE), and cerebellum (Hif1α, Tnfα, S100b, cspg2, NSE). Effects were more pronounced in females than in males. Discussion: Consequently, this model is suitable to induce hypoxemia with consecutive global cerebral hypoxia. As significant morphological and biochemical changes were proven, it can be used to investigate therapeutic and preventive drugs for global cerebral hypoxia. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES Chylothorax is a complex condition and many different pharmacological agents have been tried as treatment. Octreotide is used off-label to treat chylothorax, but the efficacy of octreotide remains unclear. A decrease in lymph production is suggested as the mechanism. In this cross-over study, we explore the direct effect of octreotide on human lymphatic drainage. METHODS Pre-clinical: the effect of octreotide on force generation was assessed during acute and prolonged drug incubation on human lymphatic vessels mounted in a myograph. Clinical: in a double-blinded, randomized, cross-over trial including 16 healthy adults, we administered either octreotide or saline as an intravenous infusion for 2.5 h. Near-infrared fluorescence imaging was used to examine spontaneous lymphatic contractions and lymph pressure in peripheral lymphatic vessels and plethysmography was performed to assess the capillary filtration rate, capillary filtration coefficient and isovolumetric pressures of the lower leg. RESULTS Pre-clinical: human thoracic duct (n  = 12) contraction rate was concentration-dependently stimulated by octreotide with a maximum effect at 10 and 100 nmol/l in the myograph chamber. Clinical: spontaneous lymphatic contractions and lymph pressure evaluated by near-infrared fluorescence did not differ between octreotide or placebo (P  = 0.36). Plethysmography revealed similar capillary filtration coefficients (P  = 0.057), but almost a doubling of the isovolumetric pressures (P  = 0.005) during octreotide infusion. CONCLUSIONS Octreotide stimulated lymphatic contractility in the pre-clinical setup but did not affect the spontaneous lymphatic contractions or lymph pressure in healthy individuals. Plethysmography revealed a doubling in the isovolumetric pressure. These results suggest that octreotide increases lymphatic drainage capacity in situations with high lymphatic afterload. [ABSTRACT FROM AUTHOR]

Broadband acoustic analysis of scattering from sharp density gradients in the water column generally treat the interfaces as smooth surfaces. However, these interfaces may exhibit roughness owing to external water column forcing and local convective processes. In this work we extend broadband backscatter analysis methods to consider interface roughness by drawing upon methods developed for sea surface and seabed acoustic backscattering. The one-dimensional acoustic model from Weidner and Weber [J. Acoust. Soc. Am. 150(6), 4353–4361 (2021)], which predicts a decay in the reflected wave amplitude from stratification interfaces with increasing frequency, was expanded for surface applications. The expanded model was used to analyze the scattered pressure field from interfaces over a range of surface roughness magnitudes. Analysis of model results indicate that stratification interface roughness, quantified by the root-mean-squared interface slope angle and root-mean-squared height of the interface, modifies the model-predicted frequency-dependent backscattering. A broadband acoustic inversion procedure to remotely measure the magnitude of the vertical extent of stratification gradients and the corresponding sound speed perturbation was defined. The broadband inversion method was tested on data collected in the Baltic Sea with well-documented, strong salinity-driven stratification. [ABSTRACT FROM AUTHOR]

This study empirically investigates the direct and interactive effects of firm‐level ethics policies and country‐level investor protection on firm corporate governance transparency. Using data on 9298 firms collected from the Bloomberg Terminal, we find that there is a positive relationship between country‐level investor protection and firm corporate governance transparency. The results also support the argument that firms with existing ethics policies exhibit greater corporate governance transparency. We also find that in countries with weaker investor protection, the impact of firm‐level ethics policies on corporate governance transparency is stronger. This study advances our understanding of the corporate governance transparency determinants, and the empirical evidence supports the notion that firm‐level factors such as ethics policies may compensate for the lack of formal national investor protection regulations. [ABSTRACT FROM AUTHOR]

We demonstrate the application of fluorescence optical fiber coupled to a telecom grade fiber as a sensor for alpha particles using alpha-specific ZnS(Ag) scintillation materials whose wavelength is down-shifted into a low-loss region of the telecom grade fiber transmission band. Telecom-grade fiber optics offer a solution for sensing alpha radiation in deep repositories and cask storage for radioactive materials due to the stability of SiO2 under normal environmental conditions and its relative radiation hardness at low radiation doses. Long-term nuclear waste storage facilities require sensors for the detection of leakage of radioactive materials that are maintenance-free, do not require power and can survive with no 'wear out' mechanisms for decades. By accomplishing the wavelength transformation, we maximize efficiencies in the detection of α -particles and signal transport and can detect alpha scintillation at distances on the order of >1 km with a sensor that is ~3% efficient and can be easily scaled as a sensor array. This paper describes the construction and testing of the sensor including manufacture of the controlled thickness films, verification of the wavelength shift from 450 to 620 nm and optimization of the sensitivity as a function of thickness. We also model the relative sensitivity of the film as a function of film thickness, and we demonstrate a signal-to-noise ratio of 10 at a range of greater than 1 km. [ABSTRACT FROM AUTHOR]

To describe the history of the Excellence Centre (EC) programme of the European Society of Hypertension (ESH) since the beginning in 2006, its achievements, and its future developments. We list the number of ECs per country, the research projects performed so far, and the organisational steps needed to reshape the EC programme for the future. In August 2023, the ESH EC programme includes 118 registered ECs in 21 European and 7 non-European countries. Updates about the formal steps for application, re-application, transfer of EC and retirement of EC heads are given. The EC programme of the ESH has been a success from the beginning. Further refinements will make it fit for the next decades. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic and the subsequent lockdown profoundly affected almost all aspects of daily life including health services worldwide. The established risk factors for increased blood pressure (BP) and hypertension may also demonstrate significant changes during the pandemic. This study aims to determine the impact of the COVID-19 pandemic on BP control and BP phenotypes as assessed with 24-hour ambulatory BP monitoring (ABPM). This is a multi-centre, observational, retrospective and comparative study involving Excellence Centres of the European Society of Hypertension across Europe. Along with clinical data and office BP, ABPM recordings will be collected in adult patients with treated arterial hypertension. There will be two groups in the study: Group 1 will consist of participants who have undergone two ABPM recordings - the second one occurring during the COVID-19 pandemic, i.e. after March 2020, and the first one 9–15 months prior to the second. Participants in Group 2 will have two repeated ABPM recordings - both performed before the pandemic within a similar 9–15 month interval between the recordings. Within each group, we will analyse and compare BP variables and phenotypes (including averaged daytime and night-time BP, BP variability, dipper and non-dipper status, white-coat and masked hypertension) between the two respective ABPM recordings and compare these changes between the two groups. The target sample size will amount to least 590 participants in each of the study groups, which means a total of at least 2360 ABPM recordings overall. As a result, we expect to identify the impact of a COVID-19 pandemic on blood pressure control and the quality of medical care in order to develop the strategy to control cardiovascular risk factors during unpredictable global events. What is the context? A wide range of daily activities, including health care worldwide, were deeply affected by the Coronavirus disease 2019 pandemic and the subsequent lockdown. What is new? Our multicenter study will examine the impact of the COVID-19 pandemic on blood pressure control in hypertensive patients across Europe by analysing results of 24-hour ambulatory blood pressure monitoring. What is the impact? Optimising strategies for dealing with future unpredictable global situations will depend on understanding how the pandemic affected blood pressure control. [ABSTRACT FROM AUTHOR]

Effective market mechanisms are important for supporting the high performance and profitability of digital commerce firms, just as they have been for traditional buyer-seller exchange networks that maximize overall welfare and optimize the distribution of goods and services so firms can sustain viable businesses [[5], [12]]. Interestingly however, there is no evidence that more post-campaign comments (suggesting ongoing creator-backer alignment) led to higher backer satisfaction, nor were experienced campaign creators likely to moderate the effects of low funding targets on backer satisfaction. [Extracted from the article]

Tailoring critical light‐matter coupling is a fundamental challenge of nanophotonics, impacting fields from higher harmonic generation and energy conversion to surface‐enhanced spectroscopy. Plasmonic perfect absorbers (PAs), where resonant antennas couple to their mirror images in adjacent metal films, excel at obtaining different coupling regimes by tuning the antenna‐film gap size. However, practical PA applications require constant gap size, making it impossible to maintain critical coupling beyond singular wavelengths. Here, a new approach for plasmonic PAs is introduced by combining mirror‐coupled resonances with the unique loss engineering capabilities of plasmonic quasi‐bound states in the continuum. This novel combination allows to tailor the light–matter interaction within the under‐coupling, over‐coupling, and critical coupling regimes using flexible tuning knobs including asymmetry parameter, dielectric gap, and geometrical scaling factor. The study demonstrates a pixelated PA metasurface with optimal absorption over a broad range of mid‐infrared wavenumbers (950–2000 cm−1) using only a single gap size and applies it for multispectral surface‐enhanced molecular spectroscopy. Moreover, the asymmetry parameter enables convenient adjustment of the quality factor and resonance amplitude. This concept expands the capabilities and flexibility of traditional gap‐tuned PAs, opening new perspectives for miniaturized sensing platforms towards on‐chip and in situ detection. [ABSTRACT FROM AUTHOR]

Summary Single-cell DNA template strand sequencing (Strand-seq) allows a range of various genomic analysis including chromosome length haplotype phasing and structural variation (SV) calling in individual cells. Here, we present MosaiCatcher v2, a standardized workflow and reference framework for single-cell SV detection using Strand-seq. This framework introduces a range of functionalities, including: an automated upstream Quality Control (QC) and assembly sub-workflow that relies on multiple genome assemblies and incorporates a multistep normalization module, integration of the single-cell nucleosome occupancy and genetic variation analysis SV functional characterization and of the ArbiGent SV genotyping modules, platform portability, as well as a user-friendly and shareable web report. These new features of MosaiCatcher v2 enable reproducible computational processing of Strand-seq data, which are increasingly used in human genetics and single-cell genomics, toward production environments. MosaiCatcher v2 is compatible with both container and conda environments, ensuring reproducibility and robustness and positioning the framework as a cornerstone in computational processing of Strand-seq data. Availability and implementation MosaiCatcher v2 is a standardized workflow, implemented using the Snakemake workflow management system. The pipeline is available on GitHub: https://github.com/friendsofstrandseq/mosaicatcher-pipeline/ and on the snakemake-workflow-catalog: https://snakemake.github.io/snakemake-workflow-catalog/?usage=friendsofstrandseq/mosaicatcher-pipeline. Strand-seq example input data used in the publication can be found in the Data availability statement. Additionally, a lightweight dataset for test purposes can be found on the GitHub repository. [ABSTRACT FROM AUTHOR]

We investigate in-plane ferroelectricity in an epitaxial ferroelectric | dielectric PbTiO 3 | SrTiO 3 (PTO | STO) superlattice under tensile strain. Using a combination of x-ray diffraction and piezoresponse force microscopy, we identify a strain-induced periodic in-plane nanoscale domain architecture with polarization along the base diagonals of the PTO unit cell. We scrutinize its switching behavior using local in-plane trailing fields from the scanning-probe tip. For an electric field pointing in the polarization direction of a specific domain state, we create stable single-domain areas of in-plane polarization at the scale of tens of micrometers. Our findings on controlling robust in-plane ferroelectricity in ultrathin ferroelectric layers can help one to develop device concepts unaffected by the detrimental effects of the depolarizing field. [ABSTRACT FROM AUTHOR]

This correction notice provides updates and corrections to a publication titled "Natural Adeno-Associated Virus Serotypes and Engineered Adeno-Associated Virus Capsid Variants: Tropism Differences and Mechanistic Insights." The updates include a correction to the affiliation of Kyle Chamberlain and the correction of errors in the naming and reporting of certain variants. The correction also includes revised information on the tropism and cell targeting of AAV9-X1 in mouse CNS compared to macaques. The authors state that these corrections do not affect the scientific conclusions of the publication. [Extracted from the article]

This paper introduces joint product design and non-linear pricing in the context of sharing markets. Product ecosystems enable user sensing, setting the stage for the control of post-purchase consumption patterns. By varying the degree to which products can be reused and transferred among peers, a company can engineer their shareability, which together with a capacity of aftermarket control, allows for flexible non-linear pricing that involves charging for the initial purchase and for subsequent collaborative transfers separately. Using a dynamic model with heterogeneous consumers and asymmetric information, we analyze a firm's economic strategy, including ecosystem design and flexible pricing, for long-term profitability. We show that an optimal product design balances durability-driven demand and price effects. Furthermore, for any given product design a profit-maximizing non-linear pricing schedule features retail price and sharing tariff in a robustly quadratic relationship, independent of the specifics of the consumer distribution. Various extensions, relating to the interaction of the firm's policy with a sharing market and the possibility of time-varying sales distributions, are also considered. [ABSTRACT FROM AUTHOR]

As the moving parts of a given economy, all individual agents are sitting in the same boat. They cover: sharing economy product pricing and consumer choice of buying goods versus accessing them on a sharing market - paired with firms' incentives to provide product durability; and the value of insurance contracts for sharing intermediaries to decouple their rent-extraction problem from the underlying inter-agent moral-hazard problem. His optimization model, which includes the use of optimal control, implies that good product designs balance the trade-off between the respective demands for product reusability and aftermarket transferability. [Extracted from the article]

The purine derivative fludarabine is part of frontline therapy for chronic lymphocytic leukaemia (CLL). It has shown positive effects on solid tumours such as melanoma, breast, and colon carcinoma in clinical phase I studies. As the treatment of CLL cells with combinations of fludarabine and metal complexes of antitumoural natural products, e.g., illudin M ferrocene, has led to synergistically enhanced apoptosis, in this research study different complexes of fludarabine itself. Four complexes bearing a trans-[Br(PPh3)2]Pt/Pd fragment attached to atom C-8 via formal η1-sigma or η2-carbene bonds were synthesised in two or three steps without protecting polar groups on the arabinose or adenine. The platinum complexes were more cytotoxic than their palladium analogues, with low single-digit micromolar IC50 values against cells of various solid tumour entities, including cisplatin-resistant ones and certain B-cell lymphoma and CLL, presumably due to the ten-fold higher cellular uptake of the platinum complexes. However, the palladium complexes interacted more readily with isolated Calf thymus DNA. Interestingly, the platinum complexes showed vastly greater selectivity for cancer over non-malignant cells when compared with fludarabine. [ABSTRACT FROM AUTHOR]

Arterial hypertension is a leading cause of death globally. Due to ageing, the rising incidence of obesity, and socioeconomic and environmental changes, its incidence increases worldwide. Hypertension commonly coexists with Type 2 diabetes, obesity, dyslipidaemia, sedentary lifestyle, and smoking leading to risk amplification. Blood pressure lowering by lifestyle modifications and antihypertensive drugs reduce cardiovascular (CV) morbidity and mortality. Guidelines recommend dual- and triple-combination therapies using renin–angiotensin system blockers, calcium channel blockers, and/or a diuretic. Comorbidities often complicate management. New drugs such as angiotensin receptor-neprilysin inhibitors, sodium–glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and non-steroidal mineralocorticoid receptor antagonists improve CV and renal outcomes. Catheter-based renal denervation could offer an alternative treatment option in comorbid hypertension associated with increased sympathetic nerve activity. This review summarises the latest clinical evidence for managing hypertension with CV comorbidities. [ABSTRACT FROM AUTHOR]

A post‐mortem analysis is conducted after potential‐induced degradation (PID) of a commercial copper‐indium‐gallium‐selenide (CIGS) photovoltaic module. After PID, the conversion efficiency of the total module decreased by 62%. Electroluminescence images of the module show that the edges of the modules were much more affected by the PID than the middle part of the module. Coring samples were prepared of the different areas and chemical compositional information of the various areas was combined with electrical characterisation, cell modelling and luminescence data to obtain an overall perspective on the root cause of degradation in these modules during high voltage stress. Consistent with earlier studies on cell level, the module analysis shows the occurrence of alkali migration. From current–voltage modelling, it was concluded that the degradation of the most affected areas is due to an increase in bulk and CdS/CIGS interface defects, likely induced by ion migration. Further degradation on the same samples occurred when they are taken out of the argon‐filled glovebox and stored under ambient conditions. Remarkably, the PID‐degraded areas show stronger degradation when left in ambient atmosphere, as well as a stronger Na redistribution. These new results show that ion migration not only causes the immediate degradation but also strongly affects the longer‐term stability of the cells in ambient atmosphere. This indicates that PID degradation makes CIGS devices more vulnerable to hermeticity problems, which are most prominent at the module edges. [ABSTRACT FROM AUTHOR]

Simple Summary: The histone lysine methyltransferase EZH2 is frequently altered in lymphoid tumors. Its overexpression or mutation is associated with tumor progression and resistance to chemotherapy. This makes it an attractive target for inhibition especially in combination treatments with established chemotherapeutics with the goal of overcoming chemotherapy resistance. However, the impact of antagonistic effects in rationally designed drug combinations remains poorly understood necessitating thorough investigation. In the current study, we show that the combinational treatment with SAM-competitive EZH2 inhibitors leads to platinum resistance due to increased platinum efflux. On a molecular level, we have discovered off-target effects leading to the upregulation of proteins that are associated with chemotherapy resistance. Our findings underline the need for detailed studies of combination therapies in order to rule out adverse effects of rational therapeutic approaches. T-cell lymphomas are heterogeneous and rare lymphatic malignancies with unfavorable prognosis. Consequently, new therapeutic strategies are needed. The enhancer of zeste homologue 2 (EZH2) is the catalytic subunit of the polycomb repressive complex 2 and responsible for lysine 27 trimethylation of histone 3. EZH2 is overexpressed in several tumor entities including T-cell neoplasms leading to epigenetic and consecutive oncogenic dysregulation. Thus, pharmacological EZH2 inhibition is a promising target and its clinical evaluation in T-cell lymphomas shows favorable results. We have investigated EZH2 expression in two cohorts of T-cell lymphomas by mRNA-profiling and immunohistochemistry, both revealing overexpression to have a negative impact on patients' prognosis. Furthermore, we have evaluated EZH2 inhibition in a panel of leukemia and lymphoma cell lines with a focus on T-cell lymphomas characterized for canonical EZH2 signaling components. The cell lines were treated with the inhibitors GSK126 or EPZ6438 that inhibit EZH2 specifically by competitive binding at the S-adenosylmethionine (SAM) binding site in combination with the common second-line chemotherapeutic oxaliplatin. The change in cytotoxic effects under pharmacological EZH2 inhibition was evaluated revealing a drastic increase in oxaliplatin resistance after 72 h and longer periods of combinational incubation. This outcome was independent of cell type but associated to reduced intracellular platinum. Pharmacological EZH2 inhibition revealed increased expression in SRE binding proteins, SREBP1/2 and ATP binding cassette subfamily G transporters ABCG1/2. The latter are associated with chemotherapy resistance due to increased platinum efflux. Knockdown experiments revealed that this was independent of the EZH2 functional state. The EZH2 inhibition effect on oxaliplatin resistance and efflux was reduced by additional inhibition of the regulated target proteins. In conclusion, pharmacological EZH2 inhibition is not suitable in combination with the common chemotherapeutic oxaliplatin in T-cell lymphomas revealing an EZH2-independent off-target effect. [ABSTRACT FROM AUTHOR]

Purpose: SARS‐CoV‐2 vaccines cause acute ipsilateral lymph node swelling in an important proportion of vaccines. Thus far, no malignant lymphadenopathies have been reported in temporal context to vaccination in the ipsilateral draining lymph node areas. Experimental design: Prompted by two cases with unilateral axillary lymphomas that occurred ipsilaterally to prior SARS‐CoV‐2 vaccination, we systematically retrieved all B‐cell non‐Hodgkin lymphomas at two German University Medical Centers diagnosed before and after introduction of SARS‐CoV‐2 vaccines in Germany. Available lymphoma tissue (n=19) was subjected to next‐generation immunosequencing of the IGH locus. Malignant clonotypes were mined in the CoVabDab database and published data sets from 342 uninfected individuals, 55 individuals 28 days after anti‐SARS‐CoV‐2 vaccination and 139 individuals with acute COVID‐19 together encompassing over 1 million CDR3 sequences in total. Results: Of 313 newly diagnosed cases in the two centers and observation periods, 27 unilateral manifestations in the defined deltoid draining regions were identified. The majority thereof were diffuse large B‐cell lymphomas (18 of 27 cases). Eleven unilateral cases were diagnosed in the era of SARS‐CoV‐2 vaccination and 16 in the control period before introduction of such vaccines. Of the 11 unilateral lymphomas that occurred during the vaccination period, ten had received a SARS‐CoV‐2 vaccine prior to lymphoma diagnosis. These cases were further evaluated. While left‐sided were more frequent than right‐sided lymphomas (19 vs 8 cases), no statistically significant association of vaccination site and laterality of the lymphoma manifestation was found. The unilateral lymphomas showed a normal range of B‐cell receptors typically found in these lymphoma subtypes with no evidence for anti‐SARS‐CoV‐2 sequences in the malignant clonotype. Conclusions: Together, we found no evidence that the current SARS‐CoV‐2 vaccines could serve as a trigger for lymphomagenesis in the draining lymph node areas of the deltoid region used for vaccination. [ABSTRACT FROM AUTHOR]

This article presents the utilitarian functional drive behind Adolf Hitler's antisemitism. It argues that Hitler's political and proto-genocidal antisemitism was a function of the existential anxiety he felt about what he perceived to be the greatest polycrisis in centuries and his ensuing quest for sustainable security. Regaining security lay at the centre of his politicization and radicalization as well as of all his actions once in power. As the article contends, three ingredients had to come together to produce Hitler's genocidal antisemitism: 1) an awareness of, belief in, and anxiety about, the existence of an existential national and international all-encompassing crisis; 2) a linking of Jews to that crisis; and 3) a translation of that link into a programme of total solutions and a quest for sustainable security. The goal of his antisemitism was to overcome a life-or-death mega-crisis to be able to return subsequently to a conventional pursuit of security. It was not to produce permanent security for eternity. [ABSTRACT FROM AUTHOR]