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This paper constitutes a comparative assessment of the impact of robots on local labor markets across eight European countries. Doing so, we find that robots generally reduce employment in the manufacturing sector, while their impacts on total employment are more ambiguous. Though local markets experienced significant employment losses in Italy, Norway, and the United Kingdom, we find no statistically significant impact of robots on employment in Germany, Sweden, Denmark, Finland, and Spain. Job losses were seemingly offset by employment gains in other sectors of the economy. We explore two mechanisms that might explain these patterns: differences in investment in complementary job-creating technologies and robot-induced reshoring. Our analysis provides some support for both mechanisms in elucidating the differential impacts of robots on jobs across space. [ABSTRACT FROM AUTHOR]

Clinical Scenario: Ankle sprains are one of the most common injuries in athletics, and many lead to recurrent sprains, chronic ankle instability, and persistent symptoms. Treatment improvements are needed. Platelet-rich plasma (PRP) involves formulating autologous plasma with higher platelet concentration to be injected in the desired tissue. There is currently high-quality evidence supporting the use of PRP with lateral epicondylitis and knee osteoarthritis to accelerate the healing process and decrease pain. Clinical Question: Does the injection of PRP relieve pain faster and improve function compared with no injection or placebo in patients with a lateral ankle sprain? Summary of Key Findings: A computerized search yielded 191 studies; of these, 3 studies fit the inclusion and exclusion criteria. PRP injection reduces pain and increases function after lateral ankle sprain 5 to 8 weeks after intervention. Clinical Bottom Line: The use of PRP after lateral ankle sprain to decrease pain and increase function is supported with moderate evidence. Strength of Recommendation: Based on the Strength of Recommendation Taxonomy, evidence from the included studies is considered as level B, reflecting limited quality patient-oriented evidence. [ABSTRACT FROM AUTHOR]

Indium oxide and doped indium oxide films were successfully grown utilizing a plasma-enhanced atomic layer deposition supercycling process, which was found to be an effective means of controlling films' composition and, hence, their properties. Using trimethylindium and oxygen plasma as an indium precursor and a co-reactant, respectively, a growth rate of approximately 1.26 Å per cycle was obtained based on thickness measurements by spectroscopic ellipsometry. Three distinct dopants, Sn, Ti, and Mo, have been incorporated into indium oxide. The effects of dopant type, cycle ratio of dopant to indium oxide, and thermal annealing on the structural, electrical, and optical properties were studied. The deposited films consisted of polycrystalline columnar grains perpendicular to the substrate with a cubic bixbyite structure and [111] as the favored growth direction. Thermal annealing had a significant effect on the film characteristics, resulting in an order of magnitude reduction in resistivity, as well as changes in transmittance in the near-infrared (NIR) and ultraviolet (UV) regions. The lowest resistivities achieved for Sn-doped, Ti-doped, and Mo-doped were 2.8 × 10−4, 4.2 × 10−4, and 6.1 × 10−4 Ω cm, respectively. The changes are attributed to dopant activation, as the UV shift between the differently doped samples may be linked to the Moss–Burstein effect and the NIR behavior can be explained by an increase in charge carrier density, as predicted by the Drude model. The three dopants primarily provide a trade-off between electrical resistance and NIR transparency. Mo-doped films exhibited the highest near-infrared transparency, while Sn-doped films offered the lowest sheet resistance. [ABSTRACT FROM AUTHOR]

Negative experiences are pervasive and consequential in entrepreneurship: on the one hand, they have the potential to unlock higher-order learning; on the other, they can lead an entrepreneur to retreat. This presents a tension for experiential entrepreneurship education: how to expose students to negative experiences to promote their learning while mitigating the risks of this exposure. We investigate this puzzle through a longitudinal, inductive field study of undergraduate students in a yearlong experiential entrepreneurship course. We find that students experienced an array of circumstances that triggered negative emotions—or critical incidents—related to developing their venture idea and to the interpersonal dynamics associated with this process. Planned elements of the course pedagogy—planned pedagogical scaffolds—as well as elements that emerged from students' engagement in the learning process—emergent individual buffers—facilitated students' ongoing sensemaking of critical incidents. In the moment, such sensemaking contributed to the de-escalation of negative emotions and to the cognitive reframing of given critical incidents. Over time, ongoing sensemaking promoted the development of an entrepreneurial mindset and of resilient behaviors. By explaining how students learn from critical incidents in an experiential entrepreneurship course, we contribute to research on experiential learning, experiential entrepreneurship education, and entrepreneurial mindset. [ABSTRACT FROM AUTHOR]

Measurement of the ventricular action potential (AP) via whole-cell patch clamp is an important contributor to cardiac electrophysiological research. Neonatal rat ventricular cardiomyocytes (NRVCM) are a commonly used model, in particular for stressor- or drug-related questions. High variability of APs and individual methodological settings hinder comparison both in individual studies and, to an even greater degree, between different projects. This study aims to describe sources of AP heterogeneity in NRVCM related to patch clamp measurement with a focus on resolvable causes. Therefore, AP of NRVCM were induced in whole-cell configuration and measured in current-clamp mode. The effects of varying setup temperature, electrode resistance, resting- (RMP), respectively holding membrane potential (HMP), induction approach, current pulse duration and amplitude plus total assay duration were studied and compared to systematically analyzed literature. We analyzed the impact on different output parameters, namely, maximal upstroke velocity (dV/dt), maximal AP amplitude (APA) and AP duration at different percentages (XX%) of repolarization, APDXX. In a comparative literature research, we found that mean APD90 in between 27.0 and 560.7 ms (own data 59.7 ± 5.8 ms) were described, with high variability and likely non-Gaussian distribution. In this study, APD90, APD50 and APD30, are decreased at more negative RMP (respectively HMP) values. E.g., APD90 is shortened by ∼60% after lowering HMP from −70 mV to −90 mV) while dV/dt and APA are increased at a more negative HMP. Pulse duration in induction did not affect main AP parameters itself, but induction energy levels above 1.5-fold the threshold energy level increased APA, while APD50 and APD90 were shortened. During series of APs at 1 Hz, spike duration (APD90) decreased by ∼27%, with stable AP after the third repetitive AP. Spike duration did also decreased by ∼40% after prolongated measurements for 21 min, indicating degradation of electrophysiological properties. To improve data quality in NRVCM-APs, we suggest using a constant HMP, adjustment of current pulse amplitude to the individual cells' threshold and the use of repetitive AP-inductions. Finally, we suggest the use of nonparametric statistical methods for statistical analysis. These aspects could reduce variability and lead to more reliable and comparable data. [ABSTRACT FROM AUTHOR]

Background: Evidence suggests a benefit of a rhythm control approach in patients with a recent diagnosis of atrial fibrillation (AF). This study sought to evaluate clinical characteristics, treatment strategies and outcomes in patients with first diagnosed AF (FDAF) undergoing a non-invasive rhythm control strategy in an emergency department (ED). Methods: This analysis uses data from the Heidelberg Registry of Atrial Fibrillation (HERA-FIB). HERA-FIB is a retrospective single-centre observational study which consecutively included patients presenting to the ED of the University Hospital of Heidelberg between June 2009 and March 2020 with a sequential follow-up for all-cause mortality, stroke, major bleeding events and myocardial infarction (MI). Outcomes of patients with FDAF were related to treatment strategy (non-invasive rhythm vs. rate control). Results: Among the 2,758 (27%) patients who presented with FDAF, a non-implementation of a non-invasive rhythm control strategy at admission was observed in 75.4% and associated with an excess of all-cause mortality hazard ratio (HR): 1.61 (95%CI 1.30–1.99), p < 0.0001 and incident MI HR: 1.88 (95% CI 1.22–2.90), p = 0.0043 during follow-up. The non-implementation of a non-invasive rhythm control remained an independent predictor for all-cause mortality and MI even after adjustment for significant univariate variables with an adjusted HR of 1.52 (95%CI: 1.14–2.04, p = 0.0043) and 1.89 (95%CI: 1.03–3.45, p = 0.0392), respectively. Conclusion: Real-world data from FDAF patients presenting to an ED showed a benefit regarding all-cause mortality and MI favouring a non-invasive rhythm control strategy. Further prospective research is needed to validate this hypothesis. Trial registration: The trial was registered at ClinicalTrials.gov Identifier: NCT05995561. [ABSTRACT FROM AUTHOR]

Background: The success of competitive alpine skiers with respective to their world ranking (WR) positions might be associated with prominent gene polymorphisms. Methods: Twenty-six competitive alpine skiers were followed from 2015 to 2019 for their WR positions (FIS-ranking). Using PCR, the genotypes of ACE-I/D, TNC, ACTN3, and PTK2 were identified. The correlations between the discipline-specific WR position (slalom—SL, giant slalom—GS, super G—SG, downhill—DH, and alpine combined—AC) and gene polymorphisms were analyzed concerning an influence with multivariate regression models. Results: The WR position and the ACE gene as well as the copy number of the ACE I-allele exhibited reciprocal relationships for speed specialists (SG and DH) but not for technical specialists (SL and GS). Similarly, the gene polymorphisms ACTN3 and (partly) PTK2 were associated with the WR position in disciplines characterized by a high number of turns (technical specialists—SL and GS) and speed (speed-specialists—SG and DH), respectively. Conclusions: Our findings emphasize the contributions of aerobic and cardiovascular metabolism in fueling muscle work and recovering from muscle fatigue for competitive success in slalom-driven skiing disciplines and highlight the contributions of sequence variants in the genes ACE, TNC, and ACTN3. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the feasibility of a novel intervention of health literacy-informed, telemedicine-enhanced asthma education and home management support for hospitalized children and caregivers, and assess caregiver perspectives of the intervention. Methods: We conducted a pilot randomized trial of the Telehealth Education for Asthma Connecting Hospital and Home (TEACHH) intervention vs. standardized care (SC) for children (5–13 yrs) hospitalized with asthma. Participants in TEACHH received health literacy-informed teaching prior to discharge, including pictorial materials (e.g. flipchart, action plan), color- and shape-coded medication labels, and medication demonstration. Two Zoom-based follow-up teaching visits were completed within 1-month of discharge. Feasibility was assessed by tracking visit completion, and we measured preliminary outcomes using health records (i.e. total asthma-related acute healthcare visits) and blinded surveys of caregivers 2-, 4-, and 6-months post-discharge (i.e. symptom-free days, quality of life). We interviewed caregivers about their perceptions of TEACHH. Transcripts were coded inductively. Results: We enrolled 26 children and interviewed 14 caregivers (9 TEACHH, 5 SC). All inpatient sessions were completed, as were 77% of virtual visits. Both groups experienced improved symptoms and quality of life over time. Caregivers valued the teaching, involvement of children, visual tools, and color-coded information of TEACHH. They described child-specific benefits, greater support after discharge, and improved asthma-related communication, and indicated that other families would benefit from similar teaching. Conclusions: A novel program of patient-centered asthma education was feasible in both hospital and home settings and well received by caregivers. A larger study is needed to assess the impact of TEACHH on childhood asthma morbidity. Clinicaltrials.gov identifier: NCT04995692 (Registration date 8/9/2021) [ABSTRACT FROM AUTHOR]

Background: Promptable foundation auto-segmentation models like Segment Anything (SA, Meta AI, New York, USA) represent a novel class of universal deep learning auto-segmentation models that could be employed for interactive tumor auto-contouring in RT treatment planning. Methods: Segment Anything was evaluated in an interactive point-to-mask auto-segmentation task for glioma brain tumor auto-contouring in 16,744 transverse slices from 369 MRI datasets (BraTS 2020 dataset). Up to nine interactive point prompts were automatically placed per slice. Tumor boundaries were auto-segmented on contrast-enhanced T1w sequences. Out of the three auto-contours predicted by SA, accuracy was evaluated for the contour with the highest calculated IoU (Intersection over Union, "oracle mask," simulating interactive model use with selection of the best tumor contour) and for the tumor contour with the highest model confidence ("suggested mask"). Results: Mean best IoU (mbIoU) using the best predicted tumor contour (oracle mask) in full MRI slices was 0.762 (IQR 0.713–0.917). The best 2D mask was achieved after a mean of 6.6 interactive point prompts (IQR 5–9). Segmentation accuracy was significantly better for high- compared to low-grade glioma cases (mbIoU 0.789 vs. 0.668). Accuracy was worse using the suggested mask (0.572). Stacking best tumor segmentations from transverse MRI slices, mean 3D Dice score for tumor auto-contouring was 0.872, which was improved to 0.919 by combining axial, sagittal, and coronal contours. Conclusion: The Segment Anything foundation segmentation model can achieve high accuracy for glioma brain tumor segmentation in MRI datasets. The results suggest that foundation segmentation models could facilitate RT treatment planning when properly integrated in a clinical application. [ABSTRACT FROM AUTHOR]

Purpose: In the rapidly expanding field of artificial intelligence (AI) there is a wealth of literature detailing the myriad applications of AI, particularly in the realm of deep learning. However, a review that elucidates the technical principles of deep learning as relevant to radiation oncology in an easily understandable manner is still notably lacking. This paper aims to fill this gap by providing a comprehensive guide to the principles of deep learning that is specifically tailored toward radiation oncology. Methods: In light of the extensive variety of AI methodologies, this review selectively concentrates on the specific domain of deep learning. It emphasizes the principal categories of deep learning models and delineates the methodologies for training these models effectively. Results: This review initially delineates the distinctions between AI and deep learning as well as between supervised and unsupervised learning. Subsequently, it elucidates the fundamental principles of major deep learning models, encompassing multilayer perceptrons (MLPs), convolutional neural networks (CNNs), recurrent neural networks (RNNs), transformers, generative adversarial networks (GANs), diffusion-based generative models, and reinforcement learning. For each category, it presents representative networks alongside their specific applications in radiation oncology. Moreover, the review outlines critical factors essential for training deep learning models, such as data preprocessing, loss functions, optimizers, and other pivotal training parameters including learning rate and batch size. Conclusion: This review provides a comprehensive overview of deep learning principles tailored toward radiation oncology. It aims to enhance the understanding of AI-based research and software applications, thereby bridging the gap between complex technological concepts and clinical practice in radiation oncology. [ABSTRACT FROM AUTHOR]

Copyright of Notfall & Rettungsmedizin is the property of Springer Nature 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.)

Background: Phosphorus (P) availability in soils regulates forest productivity. However, the drivers of soil P dynamics following forest management remain poorly understood, particularly in P-deficient forests in tropical and subtropical regions. Method: Soil samples of 0–10 cm were collected from the plots after 9 years of thinning and understory removal (UR) in Pinus massoniana plantations in subtropical China. Soil physicochemical properties, microbial biomass and community composition, and Hedley P fractions were measured to assess the underlying mechanisms for the dynamics of soil P fractions. Results: Compared to undisturbed plots, total soil inorganic P (Pi; + 24%) within the dominant species thinning (DST) plots showed a significant increase, which was associated with the accrual in resin-Pi (+ 30%), NaHCO3-Pi (+ 21%), and C.CHl-Pi (+ 45%). These Pi fractions were primarily correlated with increased relative abundance of Ascomycota, Rozellomycota, and Proteobacteria. Conversely, post-management (thinning and UR) assessments revealed no significant changes in total P, total organic P (Po), and residual P. The observed decrease in total Po (– 9%) in DST plots was linked to reductions in NaHO-Po (– 7%) and C.CHl-Po (– 24%). Notably, these Po fractions were negatively affected by the relative abundance of Glomeromycota. Furthermore, variations in soil fungal and bacterial community structures accounted for 44.3% and 26.3% of the variances in soil Pi fractions, respectively, similarly explaining 20.4% and 33.3% for soil Po fractions, respectively. Conclusions: These results indicate that P availability following forest management interventions within subtropical pine plantations is intricately connected to microbial community composition that enhances the transformation from Po into Pi forms. [ABSTRACT FROM AUTHOR]

Aerosols play a critical role in the Arctic's radiative balance, influencing solar radiation and cloud formation. Limited observations in the central Arctic leave gaps in understanding aerosol dynamics year-round, affecting model predictions of climate-relevant aerosol properties. Here, we present the first annual high-time-resolution observations of submicron aerosol chemical composition in the central Arctic during the Arctic Ocean 2018 (AO2018) and the 2019–2020 Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) expeditions. Seasonal variations in the aerosol mass concentrations and chemical composition in the central Arctic were found to be driven by typical Arctic seasonal regimes and resemble those of pan-Arctic land-based stations. Organic aerosols dominated the pristine summer, while anthropogenic sulfate prevailed in autumn and spring under haze conditions. Ammonium, which impacts aerosol acidity, was consistently less abundant, relative to sulfate, in the central Arctic compared to lower latitudes of the Arctic. Cyclonic (storm) activity was found to have a significant influence on aerosol variability by enhancing emissions from local sources and the transport of remote aerosol. Local wind-generated particles contributed up to 80 % (20 %) of the cloud condensation nuclei population in autumn (spring). While the analysis presented herein provides the current central Arctic aerosol baseline, which will serve to improve climate model predictions in the region, it also underscores the importance of integrating short-timescale processes, such as seasonal wind-driven aerosol sources from blowing snow and open leads/ocean in model simulations. This is particularly important, given the decline in mid-latitude anthropogenic emissions and the increase in local ones. [ABSTRACT FROM AUTHOR]

Background: Despite durable responses achieved with Immune Checkpoint Inhibitors (ICIs), data about optimal duration of treatment, especially in the context of adverse events, remain scarce. Objective: To systematically review the evidence concerning the impact of treatment discontinuation with ICIs for reasons other than progressive disease (PD) on relapse rates and survival of melanoma patients. Methods: A systematic literature search was conducted in three electronic databases until July 2024. Studies referring to melanoma patients who ceased ICIs electively (i.e. due to complete response (CR), protocol completion or patient/physician's wish) or due to treatment-limiting toxicities (TLTs) were selected. Relapse rates (RRs) post cessation, time to PD, rechallenge and disease control rate (DCR) after 2nd course were the main outcomes. Random-effects models were preferred, and subgroup and sensitivity analyses were conducted to investigate possible sources of heterogeneity. Results: 38 and 35 studies were included in qualitative and quantitative synthesis, respectively. From 2542 patients discontinued treatment with ICIs electively or due to TLTs, 495 experienced progression [number of studies (n)=34, RR 20.9%, 95%CI 17.1 – 24.7%, I2 85%) and higher rates were detected in patients with TLTs compared to elective discontinuation. Mean time to PD was 14.26 months (n=18, mean time 14.26, 95%CI 11.54 – 16.98, I2 93%) and was numerically higher in patients who ceased for CR compared to patients with TLTs. Treatment duration before cessation was not associated with risk and time to relapse, while mucosal melanomas and non-CR as BOR during treatment led to increased risk for relapse and shorter time to PD compared to other histologic subtypes or CR. Rechallenge with ICI resulted in 57.3% DCR and 28.6% pooled CR rates (n=22, CR rate 28.6%, 95%CI 17.1 – 40.2, I2 68%). Heterogeneity among studies was high, but subgroup analysis based on type of ICI used (anti-CTL4 and anti-PD1 inhibitor or anti-PD1 monotherapy) and type of study (RCTs or observational studies), along with sensitivity analyses did not reveal significant alterations in results. Conclusion: Discontinuation of ICIs in patients without progression is possible. Outcomes to rechallenge with ICIs may differ depending on the reason for discontinuation, but remains a considerable option. Systematic review registration: https://www.crd.york.ac.uk/prospero/ , identifier CRD42024547792. [ABSTRACT FROM AUTHOR]

Near-infrared light (NIR)-responsive metal-based nanoparticles (NPs) could be used for tumour therapy. We examined how platinum (Pt), gold (Au), and core-shell Pt-Au NPs affect the viability of human hepatocellular carcinoma (HCC) cell lines (Hep3B, HepG2, and Huh7D-12) alone and in combination with NIR exposure. In addition, the expression of immune checkpoint molecules (ICMs) on the tumour cells was analysed. We revealed that the cytotoxicity and programmed cell death induction of Au and Pt-Au NPs toward HCC cells could be enhanced by NIR with 960 nm in a different way. Pt-Au NPs were the only particles that resulted in an additional temperature increase of up to 2 °C after NIR. Regarding the tumour cell immune phenotype, not all of the cells experienced changes in immune phenotype. NIR itself was the trigger of the alterations, while the NPs did not significantly affect the expression of most of the examined ICMs, such as PD-L1, PD-L1, HVEM, CD70, ICOS-L, Ox40-L, and TNFRSF9. The combination of Pt-Au NPs with NIR resulted in the most prominent increase of ICMs in HepG2 cells. We conclude that the thermotherapeutic effect of Pt-Au NP application and NIR could be beneficial in multimodal therapy settings in liver cancer for selected patients. [ABSTRACT FROM AUTHOR]

For electric propulsion (EP) systems, measurement of plume ion currents and densities is a core diagnostic tool. The state of the art, Faraday-Cups (FCs), terminate the beam, since the ions must impinge on a collector plate. Chief among the issues associated with this approach are the emission of secondary electrons, the unknown transmission function of the screening grid used, and backscattering, thus requiring calibration. Direct-Current Current Transformers (DCCT) provide, in principle, an absolute and contactless option for inductively measuring any direct current. For application in typical EP systems, the concept needs to be adapted for small currents < 1 μ A compared to the established use case in particle accelerators ( ≫ 1 μ A ). A modular prototype was developed and investigated for possible optimizations as well as error sources. The system was tested in the far field of the ion beam of a gridded ion source. However, the measurement does not align with the theoretically expected value. Susceptibility to electromagnetic interference (EMI) and non-periodic drifts in the measurement signal across various timescales were found to introduce noise. Wire-bound test currents down to < 10 μ A could be reliably measured. The wire-bound tests show promise for DCCTs to complement FCs as a calibration device and alternative for use cases in which FCs show limitations, i.e. for extended, integral, near field, or combined diagnostics. [ABSTRACT FROM AUTHOR]

Federated learning is a renowned technique for utilizing decentralized data while preserving privacy. However, real-world applications often face challenges like partially labeled datasets, where only a few locations have certain expert annotations, leaving large portions of unlabeled data unused. Leveraging these could enhance transformer architectures' ability in regimes with small and diversely annotated sets. We conduct the largest federated cardiac CT analysis to date (n = 8, 104) in a real-world setting across eight hospitals. Our two-step semi-supervised strategy distills knowledge from task-specific CNNs into a transformer. First, CNNs predict on unlabeled data per label type and then the transformer learns from these predictions with label-specific heads. This improves predictive accuracy and enables simultaneous learning of all partial labels across the federation, and outperforms UNet-based models in generalizability on downstream tasks. Code and model weights are made openly available for leveraging future cardiac CT analysis. [ABSTRACT FROM AUTHOR]

The radio source J0028+0035 is a recently discovered double–double radio galaxy at redshift z = 0.398 . Its relic outer lobes are separated by about 3 ′ in the sky, corresponding to ∼1 Mpc projected linear size. Inside this large-scale structure, the inner pair of collinear lobes span about 100 kpc. In the arcsec-resolution radio images of J0028+0035, there is a central radio feature that offers the intriguing possibility of being resolved into a pc-scale, third pair of innermost lobes. This would make this radio galaxy a rare triple–double source where traces of three distinct episodes of radio activity could be observed. To reveal the compact radio structure of the central component, we conducted observation with the European Very Long Baseline Interferometer Network and the enhanced Multi Element Remotely Linked Interferometer Network. Our 1.66 GHz image with high (∼5 milliarcsec) resolution shows a compact central radio core with no indication of a third, innermost double feature. The observation performed in multi-phase-centre mode also revealed that the physically unrelated but in projection closely separated background source 5BZU J0028+0035 has a single weak, somewhat resolved radio feature, at odds with its blazar classification. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune disease marked by systemic inflammation. While RA primarily affects the joints, its systemic effects may lead to an increased cerebro- and cardiovascular risk. Atherosclerosis of the carotid arteries is a significant risk factor for cerebrovascular events and serves as a surrogate marker for cardiovascular risk. This study explores the link between RA and carotid artery atherosclerosis with data from the Paracelsus 10,000 Study. Baseline assessments were conducted on individuals randomly selected from Salzburg and its surrounding regions. Participants diagnosed with RA based on ACR-EULAR classification criteria and who underwent carotid artery ultrasound were included. Data were gathered from a total of 9729 participants, among whom 299 were diagnosed with RA. Carotid arteries were examined using ultrasound imaging. The primary endpoint was the difference in the prevalence of plaque presence between the RA and non-RA groups. One univariate (Model I) and three multivariate analyses were conducted, with adjustments in Model II incorporating SCORE 2, while Model III accounted for metabolic syndrome, age and sex. Additionally, Model IV included further adjustments for high-sensitivity C-reactive protein (hs-CRP). Plaque presence was defined as the ultrasound detection of plaque formation larger than 0 mm2, regardless of whether it was unilateral or bilateral. Additional assessments included carotid stenosis, intima-media thickness (IMT) and total plaque area (TPA). RA patients had a higher prevalence of plaque (50%) compared to non-RA individuals (38%). The odds ratio (OR) for plaque presence in RA patients versus non-RA individuals was 1.64 (95% CI 1.30–2.06). This association persisted after adjusting for SCORE2, with an adjusted odds ratio (aOR) of 1.65 (95% CI 1.26–2.15). The association remained significant when adjusting for metabolic syndrome, age and sex (aOR = 1.32, 95% CI 1.02–1.72) and also in Model IV, which included further adjustment for hs-CRP (OR = 1.33, 95% CI 1.02–1.74). The findings underscore an increased risk of cerebrovascular disease associated with RA. This study highlights the importance of thorough cerebrovascular and cardiovascular risk assessments, along with proactive management, for RA patients to reduce this risk. Recognizing the substantial impact of RA on stroke and cerebrovascular disease is important for enhancing patient care strategies. Carotid ultrasound appears to be an effective method for atherosclerosis screening in RA patients. [ABSTRACT FROM AUTHOR]

Background: Partial anterior cruciate ligament (ACL) tears, particularly injuries detected with magnetic resonance imaging (MRI) but stable on ligamentous examination, appear to be recognized more frequently; however, there remains no consensus management for this complex pathology. Purpose: To present the results of a survey of a group of international ACL experts on the management of partial ACL injuries. Study Design: Survey study; Level of evidence, 5. Methods: The ACL Study Group is an international group of orthopaedic surgeons with a special interest in the ACL. There are 169 members overall, with 135 clinically active surgeons. A branching logic survey was developed and circulated to members of the ACL Study Group via electronic mail. Categories included member demographics as well as recommended management strategies of partial ACL injuries, including recommendations on return to play. Results: Of the 135 clinically active surgeon members, 113 responded to the survey (84%). Nonoperative management of partial ACL injuries was selected by 92% of respondents. Of those who managed nonoperatively, 75% indicated they would not restrict weightbearing and 59% would not recommend a knee brace. When those who managed the patient nonoperatively determined criteria for return to sports (RTS), 33% would use differential knee laxity, 87% would assess functional testing, 26% would utilize imaging, and 40% selected time from injury. When using time as a guide for RTS, 13% chose RTS between 7 and 11 weeks postinjury, 56% selected no sport before 3 months, and 22% favored waiting 4 to 6 months before allowing an athlete with a partial ACL injury to RTS. With regard to function as a tool to determine RTS, painless Lachman, strength, swelling, and functional performance tests were all chosen by a majority of respondents. Conclusion: This study presented the results of a survey on partial ACL injury management administered to ACL Study Group active surgical members. The majority favored nonoperative management for partial ACL injuries (stable ligament examination but MRI changes in the ligament). Nonoperative treatment and RTS protocols varied and must be customized to the patient. [ABSTRACT FROM AUTHOR]

Background/Objectives: The COVID-19 pandemic has adversely impacted the mental health of nurses worldwide. Nurse burnout results from chronic workplace stress and is characterized by exhaustion, negative or cynical feelings about work, and a diminished sense of accomplishment. This can lead to turnover intention. Therefore, psychological capacities, such as psychological flexibility, that could help nurses regulate and minimize the impact should be studied. This study aimed to compare burnout, insomnia and turnover intention among nurses from an Eastern and Western cultural context and to investigate the role of psychological flexibility as a protective factor against mental health and related problems such as insomnia and turnover intention. Methods: Nurses from Hong Kong (n = 158) and Switzerland (n = 294) involved in patient care during the COVID-19 pandemic participated in an online mental health survey. Results: We observed high levels of burnout, subthreshold insomnia and turnover intention in nurses from both Switzerland and Hong Kong, with higher burnout rates among Hong Kong nurses and higher turnover intentions among nurses from Switzerland, and that psychological flexibility is a crucial factor that may protect nurses from burnout and insomnia. Conclusions: The nurses from both regions involved in patient care one year after the onset of the pandemic suffered from poor mental health. Psychological flexibility was identified as a critical factor in improving nurses' mental health. The results of this study should be incorporated into health promotions for nursing professionals and help develop specific and effective interventions for practical nursing application. [ABSTRACT FROM AUTHOR]

Background Bipolar disorder (BD) has been associated with impaired cellular resilience. Recent studies have shown abnormalities in the unfolded protein response (UPR) in BD. The UPR is the cellular response to endoplasmic reticulum (ER) stress. Mesencephalic astrocyte-derived neurotrophic factor (MANF), a trophic factor, decreases ER stress by modulating the UPR. The objective of this study is to investigate the MANF-ER stress pathway in BD and major depressive disorder (MDD) compared to healthy controls (HC). Methods MANF protein concentration and MANF and GRP78 gene expression were assessed in peripheral blood from individuals with BD, MDD, and HC (protein: 40 BD, 55 MDD, 55 HC; gene expression: 52 BD, 61 MDD, 69 HC). MANF protein and gene expression along with GRP78 gene expression were also analyzed in postmortem brain tissue (20 BD, 20 MDD, 19 HC). MANF protein was quantified using an ELISA assay while quantitative polymerase chain reaction was used for MANF and GRP78 gene expression. Results Peripheral MANF protein levels were reduced in individuals with BD in a depressive state compared to controls (P  = .031) and euthymic BD participants (P  = .013). No significant differences in MANF or GRP78 gene expression were observed in BD irrespective of mood state, or MDD compared to HC (all P  > .05). No differences were observed regarding MANF/GRP78 protein or gene expression levels in postmortem tissue (P  > .05). Conclusions Individuals with BD who were in an acute depressive phase were found to have reduced peripheral MANF levels potentially signifying abnormal UPR and supporting the notion that BD is associated with increased ER stress. [ABSTRACT FROM AUTHOR]

Copyright of Automatisierungstechnik is the property of De Gruyter 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.)

Two common mechanisms contributing to multiple neurological disorders, including Alzheimer's disease, are brain glucose hypometabolism (BGHM) and brain iron accumulation (BIA). Currently, BGHM and BIA are both widely acknowledged as biomarkers that aid in diagnosing CNS disorders, distinguishing between disorders with similar symptoms, and tracking disease progression. Therapeutics targeting BGHM and BIA in Alzheimer's disease can be beneficial in treating neurocognitive symptoms. This review addresses the evidence for the therapeutic potential of targeting BGHM and BIA in multiple CNS disorders. Intranasal insulin, which is anti-inflammatory and increases brain cell energy, and intranasal deferoxamine, which reduces oxidative damage and inflammation, represent promising treatments targeting these mechanisms. Both BGHM and BIA are promising therapeutic targets for AD and other CNS disorders. [ABSTRACT FROM AUTHOR]

Grafting is a horticultural technique that involves a healing process that requires grafted plants to develop physiological responses to overcome oxidative stress. In this study, oxidative damage, total antioxidant capacity and antioxidant enzymatic activities were analysed in functional and non-functional tomato autografts for eight days after grafting, considering scion and rootstock tissues separately. The results showed that oxidative damage, measured as lipid peroxidation, was controlled, especially in functional grafts. Scion tissues showed significant increases in total antioxidant capacity and activities of key antioxidant enzymes, including superoxide dismutase and catalase. Non-functional grafts showed elevated levels of class III peroxidase, potentially related to defensive suberisation and lignification. Principal component analysis revealed that antioxidant activities correlated dynamically with grafting stages, highlighting their critical role in stress mitigation. These results suggest that an efficient and asymmetric antioxidant response is essential for successful graft healing in tomato plants. Furthermore, different patterns in non-functional grafts underline the importance of redox balance in determining graft success. [ABSTRACT FROM AUTHOR]

Background: Roux-en-Y gastric bypass may present long-term complications that require revisional surgery or even reversal to normal anatomy. Data on the indications, surgical technique, and outcomes of RYGB reversal remain scarce. Methods: We identified 48 cases of RYGB reversals with complete 90-day follow-up within a multi-centric international retrospective database of elective secondary bariatric surgery. The operations were performed between 2010 and 2024 in high-volume referral centers in Europe and USA. Data were collected on body weight, associated diseases, and on surgical outcomes up to 1-year postoperatively. Results: Patients were mainly female (81.3%) with a median age of 50 years (IQR 39–56). RYGB reversal was performed 7 years (median) after primary RYGB in patients with a BMI of 23.9 kg/m2 (IQR 20–27). Half of the patients underwent at least 1 bariatric revision before the reversal. Main indications for reversal were dumping syndrome (33.3%), excessive weight loss (29.2%), marginal ulcer (14.6%), malabsorption (12.5%), and abdominal pain (10.4%). Rate of conversion to open surgery was 8.3%, and the postoperative complications during the first year reached 50%, including 31.3% Clavien-Dindo grade I–II, 16.7% grade III–IV complications, and one death. At 1 year, the mean BMI of the cohort increased by 18% to 28.25 kg/m2; only 1 patient reached pre-RYGB BMI. Conclusion: Although RYGB is a theoretically reversible procedure, normal anatomy is re-established only in selected cases which are refractory to medical therapy and often also to revisional bariatric surgery. RYGB reversals entail high morbidity, while the extent of recurrent weight gain at 1-year post-reversal seems to allow patients to remain below the threshold of severe obesity. [ABSTRACT FROM AUTHOR]

Influenza has been a global health concern for the past century. Current seasonal influenza vaccines primarily elicit an antibody response that targets the immunodominant head domain of the viral glycoprotein hemagglutinin (HA), which consistently mutates due to selective pressure. To circumvent this problem, we introduce a "tethered antigenic suppression" strategy to shield the HA head domain and refocus the immune response towards the conserved but immunosubdominant stalk domain of HA. Specifically, we tethered an antibody fragment (Fab) that recognizes the Sb antigenic site in the HA head domain to the HA protein with a linker. We immunized separate groups of female mice with the Fab-tethered HA or regular HA and characterized the elicited antibody response. We demonstrate that shielding the HA head domain with a tethered Fab suppresses the antibody titers towards all five key antigenic sites in the HA head domain while eliciting a robust anti-stalk antibody response. Our work highlights the potential of tethered antigenic suppression as a strategy to refocus the antibody response towards conserved epitopes on protein antigens. [ABSTRACT FROM AUTHOR]

Background: The gradual extrusion of water-soluble intracellular components (such as proteins) from microalgae after pulsed electric field (PEF) treatment is a well-documented phenomenon. This could be utilized in biorefinery applications with lipid extraction taking place after such an 'incubation' period, i.e., a post-PEF-treatment step during which the biomass is left undisturbed before any further processing. The goal of this work was to further explore how this incubation could improve lipid extraction. Results: Experiments were conducted on wet, freshly harvested Auxenochlorella protothecoides, treated with 0.25 or 1.5 MJ/kgDW and incubated for 24 h. Lipid extraction took place with a monophasic ethanol:hexane:water, 1:0.41:0.04 vol/vol/vol mixture with a 75.6 mL solvent per 1 g of dry biomass ratio. The kinetics of the extraction were studied with samples taken between 10 and 1080 min from fresh and incubated biomass. The yields at 10 min were significantly increased with incubation compared to without (31.2% dry weight compared to 1.81%, respectively). The experimental data were fitted with the Patricelli model where extraction occurs in two steps, a rapid washing of immediate available lipids and a slower diffusion one. During Nile-Red staining of microalgae and microscopy imaging, a shift of emission from both GFP and RFP channels to mostly RFP was observed indicating an increase in the polarity of the environment of Nile-Red. These led to an adaption of a biphasic ethanol:hexane:water 1:6:0.4 vol/vol/vol solvent with 37 mL solvent per 1 g of dry biomass ratio which while ineffective on fresh biomass, achieved a 27% dry weight yield from incubated microalgae. The extraction efficiency in the biphasic route was lower compared to the monophasic (i.e., 69% and 95%, respectively). It was compensated however, by the significant solvent reduction (37 mL to 75.6 mL respectively), in particular the ethanol minimization. For the extraction of 1 L lipids, it was estimated that the energy consumption ratio for the biphasic process was 1.6 compared to 9.9 for monophasic, making clearly the most preferential one. Conclusions: This biphasic approach significantly reduces solvent consumption and the respective energy requirement for solvent recovery. Incubation thus could majorly improve the commercialization prospects of the process. [ABSTRACT FROM AUTHOR]

Introduction: Intranasal (IN) deferoxamine (DFO) has emerged over the past decade as a promising therapeutic in preclinical experiments across neurodegenerative and neurovascular diseases. As an antioxidant iron chelator, its mechanisms are multimodal, involving the binding of brain iron and the consequent engagement of several pathways to counter pathogenesis across multiple diseases. We and other research groups have shown that IN DFO rescues cognitive impairment in several rodent models of Alzheimer Disease (AD). Methods: This study was designed to probe dosing regimens to inform future clinical trials, while exploring mechanisms within the intracerebroventricular (ICV) streptozotocin (STZ) model. Results: Five weeks of daily IN dosing of Long Evans rats with 15 μL of a 1% (0.3 mg), but not 0.1% (0.03 mg), solution of DFO rescued cognitive impairment caused by ICV STZ administration as assessed with the Morris Water Maze (MWM) test of spatial memory and learning. Furthermore, IN DFO modulated several aspects of the neuroinflammatory milieu of the ICV STZ model, which was assessed through a novel panel of brain cytokines and immunohistochemistry. Using RNA-sequencing and pathway analysis, STZ was shown to induce several pathways of cell death and neuroinflammation, and IN DFO engaged multiple transcriptomic pathways involved in hippocampal neuronal survival. Discussion: To our knowledge this study is the first to assess the transcriptomic pathways and mechanisms associated with either the ICV STZ model or DFO treatment, and the first to demonstrate efficacy at this low dose. [ABSTRACT FROM AUTHOR]

The rapid advancements in additive manufacturing (AM) across different scales and material classes have enabled the creation of architected materials with highly tailored properties. Beyond geometric flexibility, multi-material AM further expands design possibilities by combining materials with distinct characteristics. While machine learning has recently shown great potential for the fast inverse design of lattice structures, its application has largely been limited to single-material systems. In this work, we propose a novel approach that incorporates material properties as edge features within the graph representation of multi-material truss lattices, utilizing graph neural networks (GNNs) to develop a fast and efficient inverse design framework. We validate this framework by designing lattices with tunable thermal expansion and stiffness properties, showcasing its ability to explore a broad and flexible design space. We showcase the framework's inverse design capabilities for both single and multi-objective optimization tasks and assess its limitations. Additionally, we demonstrate the superior capacity of GNNs in capturing structure-property relationships for multi-material systems. We anticipate that the continued advancement of GNN-assisted inverse design will play a key role in unlocking the full potential of multi-material truss lattices. [ABSTRACT FROM AUTHOR]

Agatston score, the degree of lumen narrowing categorized by CAD-RADS, high-risk atherosclerotic plaque features and pericoronary adipose tissue attenuation (PCAT) are parameters, which can be assessed non-invasively by coronary computed tomography angiography (CCTA) and aid risk stratification in patients with chronic coronary syndromes (CCS). However, few studies have so far compared the prognostic value of all those parameters together. To develop and test the prognostic value of a composite CCTA score, derived from Agatston score, CAD-RADS, high-risk plaques and PCAT in patients undergoing CCTA due to CCS. Consecutive patients with clinical indication for CCTA and available clinical follow-up of ≥ 6 months after the CCTA examination were included. (i) Agatston score, (ii) CAD-RADS, (iii) the number of plaques with at least one high-risk feature and (iv) PCAT in the proximal 4 cm of the right coronary artery (RCA) were measured, and a composite CCTA score was generated considering all four parameters. The primary endpoint encompassed all-cause mortality, myocardial infarction, and coronary revascularization (> 60 days after the CCTA scan) during follow-up. In total, 759 patients (median age 68.0 (IQR 59.0–76.0) years, 352 (46.4%) female) were included. During a median follow-up of 591.5 (IQR 505.5-686.8) days, 39 (5.1%) patients reached the primary endpoint. Cox-proportional regression demonstrated that the Agatston score, the number of high-risk plaques and CAD-RADS predicted the primary endpoint, independent of age and conventional cardiovascular risk factors. The number of high-risk plaques per patient provided the most robust prediction of the primary endpoint (HR = 2.74, 95%CI = 1.56–4.80, p < 0.001), whereas the composite CCTA score outperformed all other parameters (HR = 1.54, 95%CI = 1.19–1.98, p < 0.001). The Agatston score, CAD-RADS and high-risk plaque features may provide complementary prognostic information in patients with CCS. A composite CCTA score, derived by these imaging markers may identify high-risk individuals, who may benefit from more intensified treatment and clinical follow-up in future studies. [ABSTRACT FROM AUTHOR]

Metagenomes present a source for novel enzymes, but under 1% of environmental microbes are cultivatable. Because of its useful properties, Escherichia coli has been used as a host organism in functional genomic screens. However, due to differing expression machineries in the expression host compared to the source organism of the DNA sequences, screening outcomes can be biased. Here, we focused on one of the limiting processes—translation initiation. To that end, we created an operon-like screening system in E. coli to select mutants of the ribosomal protein S1 with more relaxed sequence requirements for 5'-untranslated regions of mRNAs. We created two mutation libraries of the ribosomal protein S1, one covering domains 3 and 4 (D3-D4) and the second covering domains 3 to 5 (D3-D5). Most mutants from library D3-D4 proofed to be specific for a particular UTR sequence and improved only expression from a single construct. Only mutant 3 from library D3-D4 led to increased expression of four different reporters improving fluorescence levels by up to 21%. Mutants isolated from D3-D5 library led up to 90% higher expression compared to the control, though the mutants with highest improvements exhibited a specialist phenotype. The most promising mutant, mutant 4, exhibited a generalist phenotype and showed increased expression in all six reporter strains compared to the control. This could indicate the potential for a more promiscuous translation initiation of metagenomic sequences in E. coli although at the price of smaller increases compared to specialist mutants. Key points: • An operon-like selection system allowed to isolate generalist and specialist S1 mutants. • S1 mutants improved translation of mRNAs with 5'-UTRs from metagenomic sequences. • Use of S1 mutants could increase coverage from metagenomic libraries in functional screens. [ABSTRACT FROM AUTHOR]

The Japanese Global Observing SATellite for Greenhouse gases and Water cycle (GOSAT-GW) will be an Earth-observing satellite to conduct global observations of atmospheric carbon dioxide (CO2), methane (CH4), and nitrogen dioxide (NO2) simultaneously from a single platform. GOSAT-GW is the third satellite in the series of the currently operating Greenhouse gases Observing SATellite (GOSAT) and GOSAT-2. It will carry two sensors, the Total Anthropogenic and Natural emissions mapping SpectrOmeter-3 (TANSO-3) and the Advanced Microwave Scanning Radiometer 3 (AMSR3), with the latter dedicated to the observation of physical parameters related to the water cycle. TANSO-3 is a high-resolution grating spectrometer designed to measure reflected sunlight in the visible to short-wave infrared spectral ranges. It aims to retrieve the column-averaged dry-air mole fractions of CO2 and CH4 (denoted as XCO2 and XCH4, respectively), as well as the vertical column density of tropospheric NO2. The TANSO-3 sensor onboard GOSAT-GW will utilize the wavelength bands of 0.45, 0.76, and 1.61 µm for NO2, O2, and CO2 and CH4 retrievals, respectively. GOSAT-GW will fly in a sun-synchronous orbit with a local overpass time of approximately 13:30 and a 3-day ground-track repeat cycle. The TANSO-3 sensor has two observation modes in the push-broom operation: Wide Mode, which provides globally covered maps with a 10-km spatial resolution within 3 days, and Focus Mode, which provides snapshot maps over targeted areas with a high spatial resolution of 1–3 km. The objectives of the GOSAT-GW mission include (1) monitoring atmospheric global-mean concentrations of greenhouse gasses (GHGs), (2) verifying national anthropogenic GHG emissions inventories, and (3) detecting GHG emissions from large sources, such as megacities and power plants. A comprehensive validation exercise will be conducted to ensure that the sensor products' quality meets the required precision to achieve the above objectives. With a projected operational lifetime of seven years, GOSAT-GW will provide vital space-based constraints on both anthropogenic and natural GHG emissions. These measurements will contribute significantly to climate change mitigation efforts, particularly by supporting the Global Stocktake (GST) mechanism, a key element of the Paris Agreement. [ABSTRACT FROM AUTHOR]

Competitive alpine skiing requires a high level of physical fitness to perform sport-specific manoeuvres and to minimise the risk of injury. The aim of this study was to establish reference values for the maximal anatomical cross-sectional area (ACSAmax) of the individual hamstrings (HAM) and quadriceps (QUAD) muscles as well as for the maximal voluntary torque (MVT) during knee flexion (KF) and knee extension (KE) of female and male elite competitive alpine skiers. Ultrasound and dynamometer data were obtained from a largely overlapping but not identical dataset. The ultrasound data were collected from 33 elite alpine skiers (20 women and 13 men), and the dynamometer data were collected from 35 elite alpine skiers (20 women and 15 men). Compared with female skiers, male skiers presented a significantly greater ACSAmax in the biceps femoris short head (BFsh), biceps femoris long head (BFlh), and semitendinosus (ST) muscles, as well as in the entire HAM muscle group. The ACSAmax of the semimembranosus (SM) did not differ significantly between the two sexes. Compared with female skiers, male skiers presented significantly greater ACSAmax values in the vastus lateralis (VL), rectus femoris (RF), vastus medialis (VM) and entire QUAD muscle groups. At VI, there was no significant difference in the ACSAmax between the two sexes. Compared with male skiers, female skiers had a significantly greater proportional SM ACSAmax. In terms of MVT, male skiers presented greater absolute and relative values than females did. There were no differences in the MVT/ACSAmax between the sexes. Neither the HAM/QUAD ACSAmax ratio nor the KF/KE MVT ratio differed between the sexes. The present study provides normative values for the muscle size and strength of the HAM and QUAD muscles of elite competitive alpine skiers. These values can be used as benchmarks for youth alpine skiers striving for the elite level. An interesting finding of the present study was that female skiers had a greater proportional ACSAmax of the SM, as this may be relevant in anterior cruciate ligament injury prevention given the function of tibia internal rotation. [ABSTRACT FROM AUTHOR]

In order to reduce the uncertainty of aerosol radiative forcing in global climate models, we need to better understand natural aerosol sources which are important to constrain the current and pre-industrial climate. Here, we analyse particle number size distributions (PNSDs) collected during a year (2015) across four coastal and inland Antarctic research bases (Halley, Marambio, Dome C and King Sejong). We utilise k -means cluster analysis to separate the PNSD data into six main categories. "Nucleation" and "bursting" PNSDs occur 28 %–48 % of the time between sites, most commonly at the coastal sites of Marambio and King Sejong where air masses mostly come from the west and travel over extensive regions of sea ice, marginal ice and open ocean and likely arise from new particle formation. "Aitken high", "Aitken low" and "bimodal" PNSDs occur 37 %–68 % of the time, most commonly at Dome C on the Antarctic Plateau, and likely arise from atmospheric transport and ageing from aerosol originating likely in both the coastal boundary layer and free troposphere. "Pristine" PNSDs with low aerosol concentrations occur 12 %–45 % of the time, most commonly at Halley, located at low altitudes and far from the coastal melting ice and influenced by air masses from the west. Not only the sea spray primary aerosols and gas to particle secondary aerosol sources, but also the different air masses impacting the research stations should be kept in mind when deliberating upon different aerosol precursor sources across research stations. We infer that both primary and secondary components from pelagic and sympagic regions strongly contribute to the annual seasonal cycle of Antarctic aerosols. Our simultaneous aerosol measurements stress the importance of the variation in atmospheric biogeochemistry across the Antarctic region. [ABSTRACT FROM AUTHOR]

An efficient urease-catalyzed approach for the synthesis of highly substituted 6-amino-4 H -pyran-3-carbonitriles based on the formation of three bonds in one step is developed. This unprecedented three-component reaction between one molecule of an aromatic aldehyde and two molecules of an aroylacetonitrile proceeds by employing commercially available urease from jack bean (Canavalia ensiformis) as the catalyst in water at 65 °C to deliver the desired 4 H -pyrans in yields of up to 92%. The transformation is proposed to occur via a domino Knoevenagel condensation/1,4-addition/ O -cyclization/tautomerization sequence, providing a practical and sustainable approach to 6-amino-4 H -pyran-3-carbonitriles from commercially available substrates. Full and unambiguous structural elucidation of all the products is achieved by means of NMR spectroscopy and X-ray crystal structure analysis. [ABSTRACT FROM AUTHOR]

The integration of increasing shares of intermittent renewable energy necessitates flexibility in both energy generation and consumption. Typically, the operation of flexible energy resources is orchestrated through optimization models. However, the manual creation of these models is a complex and error-prone task, often requiring the expertise of domain specialists. This work introduces a methodology for the automatic generation of optimization models for systems of flexible energy resources to simplify the modeling process and increase the use of energy flexibility. This methodology utilizes a modular, generic model structure designed to depict systems of flexible energy resources. It incorporates algorithms for model parameter derivation from operational data and an information model that represents the system's structure and dependencies of resources. The efficacy of this methodology is demonstrated in two case studies, highlighting its relevance and ability to significantly streamline the optimization modeling process by minimizing the need for manual intervention. [ABSTRACT FROM AUTHOR]

This contribution investigates whether the use of the MATLAB Optimization Toolbox on a parameter identification problem for a TRNSYS model provides better performance in iteration time. It presents the development of a framework connecting the MATLAB Optimization Toolbox with TRNSYS on the one hand and coordinating the optimization process of a TRNSYS model by GenOpt through MATLAB on the other hand. A benchmark framework in MATLAB was created to link TRNSYS and MATLAB and to configure the optimization process of GenOpt and the MATLAB Optimization Toolbox. Using this framework, a comprehensive comparison of the optimization solvers in GenOpt and the MATLAB Optimization Toolbox for the identification of the overall heat transfer coefficient of a TRNSYS heat exchanger model regarding the optimization time and number of iterations is presented as a use case. The results for the given problem show that GenOpt gives slightly better results in optimization time, whereas MATLAB has more potential and flexibility. [ABSTRACT FROM AUTHOR]

Ataxia-telangiectasia (A-T) is a pleiotropic genome instability syndrome resulting from the loss of the homeostatic protein kinase ATM. The complex phenotype of A-T includes progressive cerebellar degeneration, immunodeficiency, gonadal atrophy, interstitial lung disease, cancer predisposition, endocrine abnormalities, chromosomal instability, radiosensitivity, and segmental premature aging. Cultured skin fibroblasts from A-T patients exhibit premature senescence, highlighting the association between genome instability, cellular senescence, and aging. We found that lung fibroblasts derived from ATM-deficient mice provide a versatile experimental system to explore the mechanisms driving the premature senescence of primary fibroblasts lacking ATM. Atm-/- fibroblasts failed to proliferate under ambient oxygen conditions (21%). Although they initially proliferated under physiological oxygen levels (3%), they rapidly entered senescence. In contrast, wild-type (WT) lung fibroblasts did not senesce under 3% oxygen and eventually underwent immortalization and neoplastic transformation. However, rapid senescence could be induced in WT cells either by Atm gene ablation or persistent chemical inhibition of ATM kinase activity, with senescence induced by ATM inhibition being reversible upon inhibitor removal. Moreover, the concomitant loss of ATM and p53 led to senescence evasion, vigorous growth, rampant genome instability, and subsequent immortalization and transformation. Our findings reveal that the rapid senescence of Atm-/- lung fibroblasts is driven by the collaborative action of the cGAS-STING, p38 MAPK, and p53 pathways in response to persistent DNA damage, ultimately leading to the induction of interferon-a1 and downstream interferon-stimulated genes. We propose that accelerated cellular senescence may exacerbate specific A-T symptoms, particularly contributing to the progressive, life-threatening interstitial lung disease often observed in A-T patients during adulthood. [ABSTRACT FROM AUTHOR]

Background: Hypomorphic mutations in the phosphoacetylglucosamine mutase 3 (PGM3) gene cause a glycosylation disorder that leads to immunodeficiency. It is often associated with recurrent infections and atopy. The exact etiology of this condition remains unclear. Objective: This study aimed to characterize the phenotypes and immunological features associated with PGM3 insufficiency and investigate potential disease mechanisms. Methods: A systematic review of 44 published cases of PGM3 variants was performed, followed by T-cell phenotyping of two patients with PGM3 variants. A genotype-phenotypic severity study was conducted by comparing the residual PGM3 expression of the 12 reconstituted variants in human B cells. A PGM3 inhibitor was used to assess its effect on CD4+ T cell proliferation and differentiation. Results: Patients with PGM3 variants frequently presented with recurrent infections and atopy, accompanied by reduced naïve CD4+ T cell counts. A genotype–phenotype study showed that low levels of residual PGM3 expression are correlated with disease severity. Notably, inhibition of PGM3 activity impaired TCR-mediated CD4+ T cell proliferation and the synthesis of UDP-GlcNAc, complex N-glycans, O-GlcNAc, glycolytic stress, and mitochondrial respiration during proliferation in a dose-dependent manner. Partial loss of PGM3 activity was observed to preferentially enhance Th1 and Th2 differentiation, while attenuating Th17 and Treg differentiation, consistent with clinical observations. Conclusion: PGM3 is a critical regulator of CD4+ T-cell proliferation and differentiation. These findings provide new insights into the diverse clinical manifestations and therapeutic development of PGM3 deficiency. [ABSTRACT FROM AUTHOR]