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This quality improvement initiative aimed to reduce the no-show rate at a hospital-based tertiary sickle cell ophthalmology clinic. Missed appointments place a significant burden on the healthcare system, resulting in prolonged waiting times and underutilized clinical resources that impact the quality of care provided. Individuals with sickle cell disease commonly require multiple appointments to address the myriads of comorbidities associated with their disease. Nevertheless, the sickle cell ophthalmology clinic experienced an alarmingly high no-show rate of 49% from June to September of 2021 despite offering same-day appointments with the hematology clinic. To address this issue, we conducted a study in which we compared the baseline no-show rate with the rate after relocating both clinics to the same floor, aiming to overcome patient-related barriers. Following 3.5 months of the clinics sharing the same floor, the no-show rate decreased to 39%, reflecting a 10% improvement from the baseline rate. In summary, co-locating two related clinics can alleviate patient burdens, foster communication between multidisciplinary specialties, and contribute to an overall improvement in the quality of care and treatment provided.

By applying a dynamic approach to field‐level institutional complexity, we explore how growing institutional complexity affects fields over time. We examine field transition processes, which are shaped by the number of logics, the nature of their relationships and the shifts in dominance. Focusing on Germany's energy field, our analysis identifies a variety of conflicts that arose among up to seven institutional logics in the context of the German energy transition, i.e., the transition towards a low carbon energy market. The paper makes two theoretical contributions to the institutional complexity and field literature. First, we develop a process model explaining the field‐level consequences of two different types of growing complexity, namely increasing and accelerating complexity. Second, we identify conflicting logic constellations as a distinct form of complexity that we term constellation complexity. We discuss our contributions in light of the literature on institutional logics and fields and show how applying a dynamic perspective to institutional complexity supports scholars in conceptualizing field transition processes.

Chaperonins are large barrel-shaped complexes that mediate ATP-dependent protein folding1–3. The bacterial chaperonin GroEL forms juxtaposed rings that bind unfolded protein and the lid-shaped cofactor GroES at their apertures. In vitro analyses of the chaperonin reaction have shown that substrate protein folds, unimpaired by aggregation, while transiently encapsulated in the GroEL central cavity by GroES4–6. To determine the functional stoichiometry of GroEL, GroES and client protein in situ, here we visualized chaperonin complexes in their natural cellular environment using cryo-electron tomography. We find that, under various growth conditions, around 55–70% of GroEL binds GroES asymmetrically on one ring, with the remainder populating symmetrical complexes. Bound substrate protein is detected on the free ring of the asymmetrical complex, defining the substrate acceptor state. In situ analysis of GroEL–GroES chambers, validated by high-resolution structures obtained in vitro, showed the presence of encapsulated substrate protein in a folded state before release into the cytosol. Based on a comprehensive quantification and conformational analysis of chaperonin complexes, we propose a GroEL–GroES reaction cycle that consists of linked asymmetrical and symmetrical subreactions mediating protein folding. Our findings illuminate the native conformational and functional chaperonin cycle directly within cells.

Hypoxia is more and more perceived as pivotal physiological driving force, allowing cells in the brain and elsewhere to acclimate to lowered oxygen (O2), and abridged metabolism. The mediating transcription program is induced by inspiratory hypoxia but also by intensive motor‐cognitive tasks, provoking a relative decrease in O2in relation to the acutely augmented requirement. We termed this fundamental, demand‐dependent drop in O2availability “functional hypoxia.” Major players in the hypoxia response are hypoxia‐inducible factors (HIFs) and associated prolyl‐hydroxylases. HIFs are transcription factors, stabilized by low O2accessibility, and control expression of a multitude of genes. Changes in oxygen, however, can also be sensed via other pathways, among them the thiol‐oxidase (2‐aminoethanethiol) dioxygenase. Considering the far‐reaching biological response to hypoxia, hitherto mostly observed in rodents, we initiated a translational project, combining mild to moderate inspiratory with functional hypoxia. We had identified this combination earlier to benefit motor‐cognitive attainment in mice. A total of 20 subjects were included: 13 healthy individuals and 7 patients with depression and/or autism spectrum disorder. Here, we show that motor‐cognitive training under inspiratory hypoxia (12% O2) for 3.5 h daily over 3 weeks is optimally tolerated. We present first signals of beneficial effects on general well‐being, cognitive performance, physical fitness and psychopathology. Erythropoietin in serum increases under hypoxia and flow cytometry analysis of blood reveals several immune cell types to be mildly modulated by hypoxia. To obtain reliable information regarding the “add‐on” value of inspiratory on top of functional hypoxia, induced by motor‐cognitive training, a single‐blind study—with versus without inspiratory hypoxia—is essential and outlined here. Motor‐cognitive training under inspiratory hypoxia (12% O2) for 3.5 h daily over 3 weeks is very well tolerated by healthy individuals as well as by patients with depression and/or autism spectrum disorder.We find first promising signals of beneficial effects on general well‐being, cognitive performance, physical fitness, and psychopathology.Our protocol of motor‐cognitive training under inspiratory hypoxia does not adversely affect the mononuclear cell composition in the blood of adults.To obtain reliable information regarding the “add‐on” value of mild to moderate inspiratory on top of functional hypoxia, induced by motor‐cognitive training, the planned single‐blind study—with versus without inspiratory hypoxia—is required. Motor‐cognitive training under inspiratory hypoxia (12% O2) for 3.5 h daily over 3 weeks is very well tolerated by healthy individuals as well as by patients with depression and/or autism spectrum disorder. We find first promising signals of beneficial effects on general well‐being, cognitive performance, physical fitness, and psychopathology. Our protocol of motor‐cognitive training under inspiratory hypoxia does not adversely affect the mononuclear cell composition in the blood of adults. To obtain reliable information regarding the “add‐on” value of mild to moderate inspiratory on top of functional hypoxia, induced by motor‐cognitive training, the planned single‐blind study—with versus without inspiratory hypoxia—is required.

ABSTRACTSchools are ideal settings to promote adolescent physical activity (PA), yet school-based interventions have shown limited long-term impact. This position paper presents key issues surrounding school-based PA interventions. Collaborative conceptual thinking drawing on multi-author expertise and available evidence advanced our understanding and opinion. Key arguments: 1) the adoption of a systems approach, which maximizes partnership action and leverages policy, is crucial for understanding the complexities of implementing whole-school programs; 2) a reorientation to an assets perspective optimizes existing strengths and resources allowing greater emphasis on the full range of physical, cognitive, emotional and social benefits that PA provides, and 3) a move beyond traditional positivist research designs to advance our knowledge of what works better, for whom and in what context is needed for greater progress We provide suggestions, specifically advocating for systems approaches, as a realistic way to improve how we support PA in schools in the future.

Carbon-supported silver catalysts have proven high activity and durability in the electrochemical reduction of CO2to CO. This work investigates the impact of cathode catalyst layer composition on performance by varying the ionomer content and Ag/C catalysts with differing BET surface areas (33–455 m2g–1). For optimal performance, there is a positive correlation between optimal ionomer binder content and catalyst surface area: 5 wt % PiperION for Ag/CSuper P, 15 wt % PiperION for Ag/CVulcan, and 25 wt % PiperION for Ag/CKetjen. The top-performing cells exhibited remarkably high CO faradaic efficiencies of 93% for 15 wt % Ag/CVulcan, 91% for 5 wt % Piperion Ag/CSuper P, and 90% for 25 wt % Piperion Ag/CKetjen(all at 400 mA cm–2with 0.01 M CsOH as anolyte). Long-term measurements at 300 mA cm–2over 100 h revealed the lowest FECOloss for Ag/CVulcan, decreasing from 93 to 87%, followed by Ag/CSuper P(91–79%) and Ag/CKetjen(90–63%).

Individuals with minor ischaemic stroke and intracranial occlusion are at increased risk of poor outcomes. Intravenous thrombolysis with tenecteplase might improve outcomes in this population. We aimed to test the superiority of intravenous tenecteplase over non-thrombolytic standard of care in patients with minor ischaemic stroke and intracranial occlusion or focal perfusion abnormality.

Generalized pustular psoriasis (GPP) is a rare skin disease characterized by episodes of widespread sterile pustules.

Plants exposed to incidences of excessive temperatures activate heat-stress responses to cope with the physiological challenge and stimulate long-term acclimation1,2. The mechanism that senses cellular temperature for inducing thermotolerance is still unclear3. Here we show that TWA1 is a temperature-sensing transcriptional co-regulator that is needed for basal and acquired thermotolerance in Arabidopsis thaliana. At elevated temperatures, TWA1 changes its conformation and allows physical interaction with JASMONATE-ASSOCIATED MYC-LIKE (JAM) transcription factors and TOPLESS (TPL) and TOPLESS-RELATED (TPR) proteins for repressor complex assembly. TWA1 is a predicted intrinsically disordered protein that has a key thermosensory role functioning through an amino-terminal highly variable region. At elevated temperatures, TWA1 accumulates in nuclear subdomains, and physical interactions with JAM2 and TPL appear to be restricted to these nuclear subdomains. The transcriptional upregulation of the heat shock transcription factor A2 (HSFA2) and heat shock proteins depended on TWA1, and TWA1 orthologues provided different temperature thresholds, consistent with the sensor function in early signalling of heat stress. The identification of the plant thermosensors offers a molecular tool for adjusting thermal acclimation responses of crops by breeding and biotechnology, and a sensitive temperature switch for thermogenetics.

Fractals are patterns that are self-similar across multiple length-scales1. Macroscopic fractals are common in nature2–4; however, so far, molecular assembly into fractals is restricted to synthetic systems5–12. Here we report the discovery of a natural protein, citrate synthase from the cyanobacterium Synechococcus elongatus, which self-assembles into Sierpiński triangles. Using cryo-electron microscopy, we reveal how the fractal assembles from a hexameric building block. Although different stimuli modulate the formation of fractal complexes and these complexes can regulate the enzymatic activity of citrate synthase in vitro, the fractal may not serve a physiological function in vivo. We use ancestral sequence reconstruction to retrace how the citrate synthase fractal evolved from non-fractal precursors, and the results suggest it may have emerged as a harmless evolutionary accident. Our findings expand the space of possible protein complexes and demonstrate that intricate and regulatable assemblies can evolve in a single substitution.

In this study, Mamontova et al. investigated the mechanism that links lncRNA NEAT1 to the DNA damage response (DDR) and describe a protective role against DNA damage that sustains genomic stability. DNA damage controls NEAT1 expression and structure through METTL3-driven m6A methylation, resulting in NEAT1's accumulation at promoter-associated DNA double-strand breaks and its regulation of CHD4-mediated histone acetylation.

Abstract.Carotenoid dietary intake, especially within fruits/vegetables and their plasma levels have been associated in many epidemiological studies with a reduced risk of several chronic diseases, including type-2 diabetes, cardiovascular diseases, several types of cancer, and agerelated macular degeneration. However, intervention trials with isolated carotenoids (as supplements) have fallen short of fulfi lling the hopes that were placed in these lipophilic pigments, often producing no positive or even adverse effects, such as increased lung cancer rate or total mortality. More recent studies have suggested that certain metabolites, and not necessarily the native compounds may be (the most) biologically active ones, such as certain apocarotenals (originating following enzymatic cleavage) and other more polar compounds, acting as more suitable electrophiles to react with transcription factors such as nuclear factor kappa-B (NF-KB) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). In addition, it appears that questions of dosing are likewise crucial, as may be interactions of non-provitamin A carotenoids and their derivatives with retinoic acid receptors (RAR) or retinoid X receptors (RXR). Furthermore, our picture on carotenoid metabolism may be incomplete, as our knowledge on e. g. the interaction with the microbiota is virtually nil. In this position article, it is aimed to highlight some of the discrepancies that appear to trouble carotenoid-related research, and point out some of the existing gaps in our knowledge.

Background: Neuropsychiatric symptoms (NPS) are highly prevalent among individuals with major neurocognitive disorders (MNCD). Objective: Here, we characterized blood biomarkers (metabolic, inflammatory, neurotrophic profiles and total antioxidant), body composition, physical fitness and quality of life (QoL) in individuals with MNCD according to NPS.Methods: The sample comprised 34 older adults (71.4% women; 74.06±6.03 yrs, with MNCD diagnosis) categorized according to 50th percentile [Low (≤12) or High (≥13)] for NPS (Neuropsychiatric Inventory Questionnaire). Sociodemographic, clinical data, body composition, anthropometric, cognitive assessment (ADAS-Cog), physical fitness (Senior Fitness Test), QoL (QoL-Alzheimer’s Disease scale) were evaluated, and blood samples were collected for biochemical analysis.Results: Low compared to high NPS group showed higher levels of IL-6, IGF-1and neurotrophic zscore (composite of IGF-1, VEGF-1, BDNF). Additionally, low compared to high NPS group have higher QoL, aerobic fitness and upper body and lower body strength.Conclusion: The severity of NPS seems to be related to modified neurotrophic and inflammatory outcomes, lower physical fitness, and poor QoL. Strategies to counteract NPS development may preserve the physical and mental health of individuals with MNCD.

Background: It is plausible that depression symptoms and disrupting sleep quality were differently affected according to the rigidity of social distancing during the COVID-19 outbreak.Objective: To describe and compare depression symptoms and sleep quality amongst older Brazilian and Chinese women who were submitted to different social distancing measures (less rigid (Brazil) versus more rigid (China)).Methods: This observational cross-sectional study assessed urban older women who underwent home confinement with less (Brazil; n=1015) or more (China; n=644) rigidity. Socio-demographic correlates, general health information, depression symptoms [Geriatric Depression Scale (GDS- 15)], and sleep quality [Pittsburgh Sleep Quality Index (PSQI)] were assessed through interviews.Results: 1659 older women (66.74 ± 5.48 years old; 38.8% Chinese; 61.2% Brazilian) were included for analysis. 22% of Brazilians and 19.6% of Chinese women presented depression symptoms. The frequency of bad sleepers was 56.4% and 37.7% amongst Brazilian and Chinese older women, respectively. After adjusting for socio-demographic variables, general health status, and PSQI global score, Chinese women had a significantly higher score of depression symptoms (3.88 ± 0.13) compared to the Brazilians (3.26 ± 0.10; p < 0.001).Conclusion: The frequency of poor sleep quality was very high regardless of the country. After adjusting for confounders and sleep quality, older Chinese women had a significantly superior score of depression symptoms exacerbating psychological distress by confinement rigidness.

The present study focused on optimizing the biosorbent production through chemical modification of natural coconut fibers (NCFs) using a biorefinery process combined with nanoparticle impregnation and its adsorptive performance for removing Rhodamine B (Rh-B) and methylene blue. NCF was chemically modified via the formosolv process using formic acid (85% wt.) and 2% v/v HCl as catalyst at 100 °C for 1 h under atmospheric pressure, yielding formosolv coconut fiber (FCF). Nanomagnetic composites (NCF/Fe3O4and FCF/Fe3O4) were produced through wet co-precipitation by mixing FeSO4·7H2O and FeCl3·6H2O salts (1:2 mol/mol) in an alkaline medium at different concentrations. This process generated four biosorbents, such as NCF, FCF, NCF/Fe3O4, and FCF/Fe3O4, which were characterized by chemical composition, XRD, FTIR, and magnetic properties. (1) The biorefinery process caused a chemical modification in the fibers, increasing the cellulose content and the crystallinity indexes. (2) The formosolv process enhanced the iron incorporation. (3) FCF exhibited the highest Rh-B removal efficiencies (REs), approximately 98% for FCF and 74% for FCF/Fe3O4. (4) For MB, RE values were 98% for FCF and 93% for FCF/Fe3O4. (5) These biosorbents were produced via a simple, fast, and cost-effective methodology and showed great potential for adsorption purposes. (6) Isotherms revealed distinct behaviors for the dyes, indicating different interactions with adsorbents. (7) Rh-B fitted better to the Freundlich model, suggesting a physisorption mechanism, while MB showed better fitting to the Langmuir model, suggesting the occurrence of chemisorption. (8) Thermodynamic parameters indicated that the adsorption of both dyes was endothermic and spontaneous for all biosorbents. (10) Biorefinery-processed fibers exhibited higher enthalpy values, indicating stronger interaction with MB and Rh-B. (11) Regeneration studies suggested that a higher NaOH concentration enhanced the desorption efficiency. Overall, the proposed modification routes have demonstrated the capability to produce eco-friendly magnetic biosorbents with high adsorption potential through a simple, fast, and low-cost approach.

RNA structure determination is essential to understand how RNA carries out its diverse biological functions. In cells, RNA isoforms are readily expressed with partial variations within their sequences due, for example, to alternative splicing, heterogeneity in the transcription start site, RNA processing or differential termination/polyadenylation. Nanopore dimethyl sulfate mutational profiling (Nano-DMS-MaP) is a method for in situ isoform-specific RNA structure determination. Unlike similar methods that rely on short sequencing reads, Nano-DMS-MaP employs nanopore sequencing to resolve the structures of long and highly similar RNA molecules to reveal their previously hidden structural differences. This Protocol describes the development and applications of Nano-DMS-MaP and outlines the main considerations for designing and implementing a successful experiment: from bench to data analysis. In cell probing experiments can be carried out by an experienced molecular biologist in 3–4 d. Data analysis requires good knowledge of command line tools and Python scripts and requires a further 3–5 d.

Abstract:Carotenoids are C-30, C-40 or C-50 terpenoids produced by a number of bacteria, fungi, and plants. In addition to acting as vitamin A precursors such as β-carotene, their dietary intake and blood plasma/serum and tissue levels have been associated in several epidemiological studies to the reduced incidence of chronic diseases, including the reduction of type 2 diabetes and other cardiometabolic diseases, as well as some types of cancer. Lutein and zeaxanthin also appear to play a role in the amelioration of age-related macular degeneration (AMD), the main cause of blindness in the elderly, and may be regarded as conditionally essential nutrients for the elderly. Furthermore, some studies have proposed that carotenoids may improve cognitive functions. Though the underlying mechanisms remain to be fully elucidated, it is perceived that direct antioxidant effects and protection from UV-light, as well as rather indirect effects, acting on transcription factors such as NF-κB, Nrf-2, and nuclear receptors such as RAR/RXR (retinoic acid receptor/retinoid X receptor), altering gene expression, all can play a role. Despite individual intervention trials suggesting negative effects of high doses of β-carotene on smokers, perhaps due to effects related to cytochrome enzyme activation, there is accumulating evidence that these colourful pigments indeed contribute to a healthy life and well-being. However, further research is warranted to better understand factors influencing variable inter-individual responses following carotenoid consumption and to establish more detailed recommendations regarding their dietary intake and toward establishing health claims.

Attitude control of fixed-wing unmanned aerial vehicles (UAVs) is a difficult control problem in part due to uncertain nonlinear dynamics, actuator constraints, and coupled longitudinal and lateral motions. Current state-of-the-art autopilots are based on linear control and are thus limited in their effectiveness and performance. Gls drl is a machine learning method to automatically discover optimal control laws through interaction with the controlled system that can handle complex nonlinear dynamics. We show in this article that deep reinforcement learning (DRL) can successfully learn to perform attitude control of a fixed-wing UAV operating directly on the original nonlinear dynamics, requiring as little as 3 min of flight data. We initially train our model in a simulation environment and then deploy the learned controller on the UAV in flight tests, demonstrating comparable performance to the state-of-the-art ArduPlane proportional-integral-derivative (PID) attitude controller with no further online learning required. Learning with significant actuation delay and diversified simulated dynamics were found to be crucial for successful transfer to control of the real UAV. In addition to a qualitative comparison with the ArduPlane autopilot, we present a quantitative assessment based on linear analysis to better understand the learning controller’s behavior.

Ni-based superalloys, including Alloy 625, are known for their high strength and excellent resistance to corrosion at high temperatures. Alloy 625 is widely used in geothermal, petrochemical, and power generation industries due to its exceptional performance in harsh environments. It is an austenitic alloy composed of Ni, Cr, Mo, and Nb, with high Cr content (~20 wt%) contributing to its superior corrosion resistance, and solid solution strengthening is attributed to the presence of other alloying elements such as Mo, Nb, and Fe. However, during welding with Alloy 625, Mo and Nb tend to segregate aggressively towards the liquid. This study will investigate the effect of reducing the level of Nb in commercial alloy 625 for weld overlay cladding on carbon-manganese steel. The CALPHAD method will be used to obtain the phase equilibria by thermodynamic simulations of compositions ranging from 0% to 100% dilution. This study is crucial to the weld overlay cladding sector as it aims to identify the best properties of CRA material suitable for highly corrosive environments.

In sustainability governance, the reliance on deliberative participatory processes has greatly increased over the last decades due to expectations that such processes can mobilize additional creative potential, foster better understanding of problems and acceptance of the costs of relevant solutions, and mediate the decline in traditional forms of participation. However, in complex technological contexts such as bioeconomics and, especially, biotechnology, participatory processes are still rare, at least partly because of concerns that citizens might lack the necessary information and skills. Yet bioeconomic innovation trajectories often imply societal, political, and economic changes that also affect citizens’ lifestyles and budgets and may cohere or conflict with individual and collective norms. Thus, citizen participation in relevant deliberations and decisions would seem opportune. In this paper, we therefore inquire into the potential and challenges for participatory processes in bioeconomic contexts. Specifically, we identify pivotal criteria for the democratic quality of relevant participatory processes on the basis of the rich literature on citizen participation in sustainability governance. We then explore how (well) these criteria can be achieved in participatory processes on the bioeconomy and biotechnological innovation strategies, drawing on two such processes we carried out in 2021 and 2022. On this basis, we propose further questions and implications for research and practice.