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Summary: Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to cause very high morbidity and mortality throughout Latin American countries. However, few population-based seroprevalence surveys have been conducted to quantify attack rates and characterize drivers of transmission. Methods: We conducted a population-based cross-sectional study to assess the seroprevalence of antibodies against SARS-CoV-2 in ten cities in Colombia between September and December 2020. The study involved multi-stage cluster sampling at each city. Participants provided a serum sample and answered a demographic and risk factor questionnaire. Prior infection by SARS-CoV-2 was ascertained using the ''SARS-CoV-2 Total (COV2T) Advia Centaur - Siemens'' chemiluminescence assay. Findings: A total of 17863 participants from 7320 households participated in the study. Seroprevalence varied substantially between cities, ranging from 26% (95%CI 23–29 %) in Medellín to 68% (95%CI 62–74 %) in Guapi. There were no differences in seroprevalence by sex, but seropositivity was higher in certain ethnic groups. There was substantial heterogeneity in seroprevalence within cities, driven to a large extent by a strong association between socioeconomic stratum and seropositivity. Interpretation: Colombia has been one of the Latin American countries most affected by the COVID-19 pandemic. This study documented very high attack rates in several Colombian cities by the end of 2020 and identified key drivers of heterogeneities including ethnicity and socioeconomic stratum. Few studies of seroprevalence of SARS-CoV-2 have been conducted in Latin America, and therefore this study contributes to the fundamental understanding of the pandemic in the region. Funding: The study was sponsored by, Ministerio de Ciencia y Tecnología e Innovación –CT361/2020, Ministerio de Salud y Protección Social, Fundación Universitaria del Norte, Imperial College of London, Universidad Nacional de Colombia (Sede Medellín), Universidad de Córdoba, California University, Unidad Nacional de Gestión del Riesgo, Centro de Atención y Diagnóstico de Enfermedades Infecciosas -CDI-, Centro Internacional de Entrenamiento e Investigaciones Médicas -CIDEIM-, Departamento Administrativo Nacional de Estadística - DANE, Fondo Nacional de Turismo -FONTUR-, Secretarías de Salud Departamentales, Distritales y Municipales and Instituto Nacional de Salud.

The origin, extent, and timing of intraplate contraction in Patagonia are among the least understood geological processes of southern South America. Particularly, the intraplate Deseado fold‐thrust belt (FTB), located in the Patagonian broken foreland (47°–48°30′S), is one of the most enigmatic areas. In this belt, time constraints on tectonic events are limited and synorogenic deposits have not been documented so far. Furthermore, the driving mechanism for intraplate contraction remains unknown. In this study, we carried out a structural and sedimentological analysis. We report the first syntectonic deposits in this area in the Baqueró (Aptian) and Chubut (Cenomanian/Campanian) groups and a newly found unit referred to as the Albian beds (109.9 ± 1.5 Ma). Thus, several contractional stages in late Aptian, Albian, and Cenomanian‐Campanian are then inferred. We suggest that the Deseado FTB constituted the southernmost expression of the early Patagonian broken foreland in Cretaceous times. Additionally, we analyzed the spatiotemporal magmatic arc behavior as a proxy of dynamic changes in the Andean subduction during determined stages of intraplate contraction. We observe a significant arc broadening from ~121 to 82 Myr and magmatic quiescence after ~67 Ma. This is interpreted as a slab shallowing to flattening process. Far‐field tectonic forces would have been produced by increased plate coupling linked to the slab flattening as indirectly indicated by the correlation between Cretaceous arc expansion and intraplate contraction. Finally, the tectonic evolution of the Deseado FTB favors studies supporting inception of Andean shortening since Cretaceous times. Key Points: We document Cretaceous syntectonic deposits linked to intraplate contraction in Southern PatagoniaThis process took place in concert with a significant magmatic arc expansionIntraplate contraction in southern Patagonia could be the aftermath of an ancient flat subduction event [ABSTRACT FROM AUTHOR]

The Central Patagonia is characterized by prominent continental deposits that belong to the Cretaceous Chubut Group Basin, whose tectonic setting remains controversial. It has been interpreted as a foreland basin, an extensional basin and even as a sag stage of a rift event. Related deposits outcrop as part of the Patagonian broken foreland, east of the Patagonian Andes. Particulary, the San Bernardo fold and thrust belt, between 42° and 48°S, as the main sector of the broken foreland, constitutes a NNW-trending intraplate belt located 450 km away from the trench. Coincidentally, at these latitudes, 1200 km east of the trench, intraplate deformation has caused tectonic inversion of Mesozoic basins presently located at the Atlantic offshore area. Additionally, at the San Jorge Gulf area this orogenic system interferes with a conspicuous E–W extensional system, transversally disposed to the Andean strike, mainly active between the late Early Cretaceous and late Paleocene. We carried out an integrated analysis from structural, 2-D and 3-D seismic data at the San Bernardo FTB and the adjacent Río Mayo Basin, studying sections of the Chubut Group Basin to unravel the different evolutionary stages. Thus, surface and subsurface evidence of syn-compressional deposition indicate the development of a broken foreland basin related to the formation of the San Bernardo FTB, suggesting an initial growth during the late Early Cretaceous and probably up to the late Paleocene. Our results imply that the Cretaceous compression acted in concert with transversal foreland extension. Hence, we propose a syncontractional rift reactivation of a potential lithospheric anisotropy, triggered by regional contraction. Finally, the origin of compression during this time is discussed in relation to multiple processes that go from high convergence between plates and trenchward motion of South America, collision of mid-ocean ridges, to potential dip changes in the subducted slab, as suggested by arc expansion. [ABSTRACT FROM AUTHOR]

The article presents information on a study which investigated the role of the main components of a polyvinylacetate (PVAc)-based wood adhesive formulation in the formation and performance of the adhesive joint. A review of the related literature is given. An analytical methodology was utilized for the chemical separation and characterization of the adhesive components present in the bond line. The insoluble parts present in the adhesive films were also characterized.

In the paper, the classic contour dynamics method for the study of inviscid two-dimensional flow in an infinite domain is extended to systems with a circular boundary. A suitable use of the image-charge technique allows one to express the velocity on the contour of each vortex in terms of line integrals on the contours. Results are presented in the framework of the dynamics of non-neutral plasmas in a Penning trap (the problem is isomorphic to the classic fluid-dynamics problem for a Euler fluid), showing the high accuracy attainable with the method. [Copyright &y& Elsevier]

Background: The availability of pacing configurations offered by quadripolar left ventricular leads could improve patients' response to cardiac resynchronization therapy; however, the selection of an optimal setting remains a challenge. Echo-particle imaging velocimetry has shown that regional anomalies of synchrony/synergy of the left ventricle are related to the alteration, reduction, or suppression of the physiological intracavitary pressure gradients. These observations are also supported by several numerical models of the left ventricle that have shown the close relationship between wall motion abnormalities, change of intraventricular flow dynamics, and abnormal distribution of forces operating on the ventricular endocardium.Case Presentation: A 73-year-old white man in New York Heart Association III functional class with an ejection fraction of 27.5 % did not improve after 1 month of cardiac resynchronization therapy. Five configurations were tested and settings were defined by optimizing intraventricular flow. After 6 months, he became New York Heart Association II class with left ventricular ejection fraction of 53.2 %.Conclusions: The abnormal dynamic of pressure gradients during the cardiac cycle, through biohumoral endocrine, autocrine, and paracrine transduction, may lead to structural changes of the myocardial walls with subsequent left ventricular remodeling. The echo-particle imaging velocimetry technique may be useful for elucidating the favorable effects of cardiac resynchronization therapy on intraventricular fluid dynamics and it could be used to identify appropriate pacing setting during acute echocardiographic optimization of left pacing vector. [ABSTRACT FROM AUTHOR]

The North Patagonian fold-thrust belt (41°–44° S) is characterized by a low topography, reduced crustal thickness and a broad lateral development determined by a broken foreland system in the retroarc zone. This particular structural system has not been fully addressed in terms of the age and mechanisms that built this orogenic segment. Here, new field and seismic evidence of syntectonic strata constrain the timing of the main deformational stages, evaluating the prevailing crustal regime for the different mountain domains through time. Growth strata and progressive unconformities, controlled by extensional or compressive structures, were recognized in volcanic and sedimentary rocks from the cordilleran to the extra-Andean domain. These data were used to construct a balanced cross section, whose deep structure was investigated through a thermomechanical model that characterizes the upper plate rheology. Our results indicate two main compressive stages, interrupted by an extensional relaxation period. The first contractional stage in the mid-Cretaceous inverted Jurassic–Lower Cretaceous half graben systems, reactivating the western Cañadón Asfalto rift border ~ 500 km away from the trench, at a time of arc foreland expansion. For this stage, available thermochronological data reveal forearc cooling episodes, and global tectonic reconstructions indicate mid-ocean ridge collisions against the western edge of an upper plate with rapid trenchward displacement. Widespread synextensional volcanism is recognized throughout the Paleogene during plate reorganization; retroarc Paleocene-–Eocene flare up activity is interpreted as product of a slab rollback, and fore-to-retroarc Oligocene slab/asthenospheric derived products as an expression of enhanced extension. The second stage of mountain growth occurred in Miocene time associated with Nazca Plate subduction, reaching nearly the same amplitude than the first compressive stage. Extensional weakening of the upper plate predating the described contractional stages appears as a necessary condition for abnormal lateral propagation of deformation. [ABSTRACT FROM AUTHOR]

The retroarc region of central Patagonia recorded three contractional stages (Late Triassic, Late Cretaceous, and Miocene) coincident with eastward broadening of arc magmatism. Inboard arc migration may be linked to shallowing of the subducted slab, subduction erosion of forearc regions, or a combination of both. Contractional episodes were followed by slab rollback, producing a series of extensional depocenters and magmatic belts across Patagonia at ~170-130 Ma, ~55-22 Ma and ~5 Ma. These rollback events weakened Patagonian crust through fracturing, mantle upwelling, and magmatic injection, favoring inception and propagation of subsequent contractional episodes. Phases of slab rollback and retroarc extension are reflected in εHf and εNd isotopic trends, with more juvenile trajectories corresponding to mantle upwelling into a broad asthenospheric wedge during slab retreat. Periods of crustal shortening are recorded by evolved εHf and εNd isotopic trajectories, demonstrating modified mantle sources. Mesozoic-Cenozoic extensional basins of Patagonia, such as the Chubut Basin, Cañadón Asfalto Basin, Río Mayo-Aysén Basin, Pilcaniyeu and Auca Pan-El Maitén magmatic belts/volcanogenic basins, and the Traiguén Basin were generated during episodes of slab rollback. In contrast, the extension-related San Jorge Gulf Basin constitutes an east-west-trending anomaly developed in an interval of the Cretaceous when the rest of western Patagonia experienced shortening. During this time, crustal evolution trends shifted from juvenile to more evolved and the arc expanded toward the continental interior most likely under a flat-slab regime. The San Jorge Gulf Basin is linked to Neocomian extensional structures in an intracratonic basin later influenced by compressional stresses linked to subduction zone in the west and incipient opening of the south Atlantic to east. • The evolution of the Northern Patagonian Andes comprises shallow slab subduction, slab-rollback and flare-up events. • Eastward arc broadening and flare-ups coincided with modification of the asthenospheric source during slab shallowing. • Westward arc retreat coincided with asthenospheric rejuvenation as indicated by more juvenile isotopic trajectories. • San Jorge Gulf Basin is an extensional basin in Patagonia that is not associated with extension during slab resteepening. [ABSTRACT FROM AUTHOR]

Background: Parameningeal (PM) site is an unfavorable characteristic in rhabdomyosarcoma (RMS). We described the treatment and outcome for patients with PM RMS and investigated the prognostic value of risk factors. We scored PM site by originating site and by highest risk extension., Methods: Patients with PM RMS were treated within the European pediatric Soft tissue sarcoma Study Group (EpSSG) RMS 2005 study with risk-adapted, multi-modal treatment., Results: Three-hundred-eighty-one patients with PM RMS were included. Radiotherapy was administered in 359 patients (77 with surgery). After a median follow-up of 75 months, 5-year event-free survival was 60% (95% confidence interval (CI) 55%-65%), 5-year overall survival was 65% (95% CI 60%-70%)., Conclusions: The outcome for patients with PM RMS has not improved in comparison to previous historical studies, despite the more rigorous application of radiotherapy (94% of patients). Signs of meningeal involvement, PM site, and age at diagnosis remained prognostic risk factors., Trial Registration: EudraCT number 2005-000217-35., (© 2024 The Author(s). Head & Neck published by Wiley Periodicals LLC.)

Background: Detecting cognitive impairment in Parkinson's disease (PD) is challenging due to diverse manifestations and outdated diagnostic criteria. Cognitive screening tools, as Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), are adopted worldwide, but despite several cutoffs has been proposed for PD, no consensus has been reached, hindered by limited sample sizes, lack of validation, and inconsistent age- and education-adjustments., Objectives: Determine the optimal MMSE and MoCA cutoffs in a large PD cohort, spanning from normal cognition (PD-NC), mild cognitive impairment (PD-MCI) to dementia (PDD), and develop a decision tree model to assist physicians in cognitive workups., Methods: Our retrospective Italian multicenter study involves 1780 PD, cognitively diagnosed with a level-II assessment: PD-NC(n = 700), PD-MCI(n = 706), and PDD(n = 374). Optimal cutoffs (for raw scores) were determined through ROC analysis. Then, a machine learning approach-decision trees-was adopted to validate and analyze the possible inclusion of other relevant clinical features., Results: The decision tree model selected as primary feature a MMSE cutoff ≤24 to predict dementia, and a score ≤ 27 for PD-MCI. To enhance PD-MCIvs.PD-NC accuracy, it also recommends including a MoCA score ≤ 22 for PD-MCI, and > 22 for PD-NC. Age and education were not selected as relevant features for the cognitive workup. Both MoCA and MMSE cutoffs exhibited high sensitivity and specificity in detecting PD cognitive statues., Conclusions: For the first time, a clinical decision tree model based on robust MMSE and MoCA cutoffs has been developed, allowing to diagnose PD-MCI and/or PDD with a high accuracy and short administration time., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Some oligopeptides can impart kokumi flavor to foods and beverages, a topic still not addressed in wine. A targeted ultra-high performance liquid-chromatography-mass spectrometry (UHPLC-MS/MS) metabolomics method capable of quantifying both amino acids and oligopeptides in wines was therefore developed and validated, confirming the presence of 50 oligopeptides in wine, most of which had been previously unexplored. In silico screening of the affinity of these oligopeptides to interact with CaSR, the protein necessary to activate kokumi sensations, highlighted 8 dipeptides and 3 tripeptides as putative kokumi compounds. These compounds were ubiquitous in a representative set of Trentodoc classic method sparkling wines, with an average concentration of kokumi oligopeptides of 19.8 mg/L, ranging between 9.1 and 33.3 mg/L. Half of the sparkling wine samples also contained glutamic acid at concentrations equal to or greater than the threshold for the umami taste in wine, namely, 48 mg/L. Sensory tests on the dipeptide Gly-Val confirmed the ability of this novel kokumi compound to significantly modify the perception of complex real wine matrices but not of the simple model one. Preliminary laboratory-scale fermentation tests showed that the oligopeptide profile in wines is linked to the starting grape matrix and that the patterns change by fermenting barley or apple juice with the same yeast.

Repeat expansions in the C9orf72 gene are the most common genetic cause of (ALS) and frontotemporal dementia (FTD). Like other genetic forms of neurodegeneration, pinpointing the precise mechanism(s) by which this mutation leads to neuronal death remains elusive, and this lack of knowledge hampers the development of therapy for C9orf72-related disease. We used an agnostic approach based on genomic data (n = 41,273 ALS and healthy samples, and n = 1,516 C9orf72 carriers) to overcome these bottlenecks. Our drug-repurposing screen, based on gene- and expression-pattern matching and information about the genetic variants influencing onset age among C9orf72 carriers, identified acamprosate, a γ-aminobutyric acid analog, as a potentially repurposable treatment for patients carrying C9orf72 repeat expansions. We validated its neuroprotective effect in cell models and showed comparable efficacy to riluzole, the current standard of care. Our work highlights the potential value of genomics in repurposing drugs in situations where the underlying pathomechanisms are inherently complex. VIDEO ABSTRACT., Competing Interests: Declaration of interests B.J.T. holds patents on clinical testing and therapeutic intervention for the hexanucleotide repeat expansion of C9orf72., (Published by Elsevier Inc.)

This large multicenter study of 37 magnetic resonance imaging scanners aimed at characterizing, for the first time, spatial profiles of inaccuracy (namely, Δ-profiles) in apparent diffusion coefficient (ADC) values with varying acquisition plan orientation and diffusion weighting gradient direction, using a statistical approach exploiting unsupervised clustering analysis.&#xD;A diffusion-weighted imaging (DWI) protocol (b-value: 0-200-400-600-800-1000 s/mm 2 ) with different combinations of acquisition plan orientation (axial/sagittal/coronal) and diffusion weighting gradient direction (anterior-posterior/left-right/feet-head) was acquired on a standard water phantom. For each acquisition setup, Δ-profiles along the 3 main orthogonal directions were characterized by fitting data with a second order polynomial function ( ar 2 + br + c ) . Moreover, for each Δ-profile, the maximum minus minimum of the fitting function ( δ max ) was calculated. &#xD;The parameters a , b , c , and δ max showed some significant variations between scanner systems by different manufacturers or with different static magnetic field strengths, as well as between different acquisition/estimation setups. Unsupervised clustering analysis showed two evident clusters with significantly different values of parameter a ( p < 0.0001), which can be grouped by acquisition protocol/Δ-profile direction but not scanner system.&#xD;The results of ∆-profiles confirm an appreciable inter-scanner variability in ADC measurement and corroborate the importance of guarantying the reliability of ADC estimations in clinical or research studies, considering for each scanner system the specific acquisition sequence in terms of acquisition plan orientation and diffusion weighting gradient direction., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Aim: Although there has been a significant amount of research on nurse workloads in hospital environments, there has been a lack of comprehensive investigation of the workload of triage nurses. This study assesses the workload fluctuations of triage nurses in various emergency departments in the same region and examines how workload varies based on emergency department visit volumes and seasonal fluctuations., Design: The study is a retrospective, multicentre, observational study from January 1, 2019, to December 31, 2023, in seven Italian emergency departments, gathering information on all patients who went through the triage process., Methods: We documented the number of nurses present throughout each shift and adjusted the data to account for the number of patients attended to by each triage nurse per shift. The EDs were classified into high-inflow, medium-inflow and low-inflow categories according to the annual number of patients they served., Results: The study included 1,223,331 emergency department triage assessments. During daytime shifts, triage nurses in high-inflow emergency departments assessed a median of 74 patients, while those in medium-inflow and low-inflow emergency departments assessed 63 and 32 patients, respectively. During nighttime shifts, triage nurses in high-inflow emergency departments assessed 26 patients, compared to 14 in medium-inflow and 5 in low-inflow emergency departments. Significant seasonal fluctuations in the workload of triage nurses were observed., Conclusions: This study reveals substantial disparities in the number of patients triage nurses assess, which vary according to emergency department patient inflow volumes and seasonal factors. The findings emphasise the need for more standardised and equitable workload distribution among triage nurses. Future research should aim to establish a systematic nurse staffing model for triage to ensure manageable workloads and maintain patient safety., Reporting Method: The Strengthening the Reporting of Observational Studies in Epidemiology was used., Patient and Public Contribution: No patient or public contribution., (© 2024 John Wiley & Sons Ltd.)

Background: The effectiveness of complete revascularization is well established in patients with ST-segment elevation myocardial infarction (STEMI), but it is less investigated in those with non-ST-segment elevation myocardial infarction (NSTEMI)., Objectives: This study aimed to assess whether complete revascularization, compared with culprit-only revascularization, was associated with consistent outcomes in older patients with STEMI and NSTEMI., Methods: In the FIRE (Functional Assessment in Elderly MI Patients with Multivessel Disease) trial, 1,445 older patients with myocardial infarction (MI) were randomized to culprit-only or physiology-guided complete revascularization, stratified by STEMI (n = 256 culprit-only vs n = 253 complete) and NSTEMI (n = 469 culprit-only vs n = 467 complete). The primary outcome comprised a composite of death, MI, stroke, or revascularization at 1 year. The key secondary outcome included a composite of cardiovascular death or MI at 1 year., Results: In the overall study population, physiology-guided complete revascularization reduced both primary and key secondary outcomes. The primary outcome occurred in 54 (21.1%) STEMI patients randomized to culprit-only vs 41 (16.2%) STEMI patients of the complete group (HR: 0.75; 95% CI: 0.50-1.13) and in 98 (20.9%) NSTEMI patients randomized to culprit-only vs 72 (15.4%) NSTEMI patients of the complete group (HR: 0.71; 95% CI: 0.53-0.97), with negative interaction testing (P for interaction, 0.846). Similarly, no signal of heterogeneity with respect to the initial clinical presentation was observed for the key secondary endpoint (P for interaction, 0.654)., Conclusions: Physiology-guided complete revascularization, compared with culprit-only revascularization, provided consistent benefit across the whole spectrum of patients with MI. (FIRE [Functional Assessment in Elderly MI Patients With Multivessel Disease]; NCT03772743)., Competing Interests: Funding Support and Author Disclosures Sahajanand Medical Technologies Ltd (SMT), Medis Medical Imaging Systems, Eukon S.r.l., Siemens Healthineers, General Electric (GE) Healthcare, and Insight Lifetech provided unrestricted funding to the study sponsor for the conduction of the trial. These companies had no involvement in the trial design, data collection, analysis, interpretation, or writing of the manuscript. Dr Campo has received research grants and personal fees from Abbott Vascular, GADA, Menarini, Amgen, Daichi-Sankyo, and Sanofi, outside the submitted work. Dr Moreno has received speaker/consulting fees from Abbott Vascular, AMGEN, AstraZeneca, Biosensors, Biotronik, Boston Scientific, Daiichi-Sankyo, Edwards, Medtronic, and Philips, outside the submitted work. Dr Biscaglia has received funding from the Italian Health Minister (Ricerca Finalizzata 2021, GR-2021-12372516) for the conduction of the Functional Coronary Angiography Guided Revascularization in STEMI trial; and has received personal fees from Abbott Vascular and Siemens Healthcare, outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Investigating the role of individual differences in Environmental Sensitivity for well-being and stress at work is an emerging area of research with significant potential for practical implications in organizational management and human resources. Recent studies have begun to explore how individuals with high sensory-processing sensitivity (SPS) may be more vulnerable to work-related stress than their less sensitive peers, but may also derive greater benefits from positive job resources when available. The present study aims to investigate the role of leadership style in the complex interplay between individual differences in sensitivity, stress at work, and general well-being. A questionnaire was administered through Qualtrics to a total of 317 workers from two medium-large-sized Italian companies, across two waves between May and July 2022. Findings provided support for a three-way interaction effect, with job stressors exerting an adverse effect on participants' well-being, mitigated by democratic and let-it-be leadership styles at the team level, particularly among highly sensitive individuals. Thus, our findings suggest a vantage sensitivity effect and underscore the importance of cultivating positive work climates to enhance workers' ability to cope with stressors and improve their global well-being, with particular relevance for highly sensitive individuals., (© 2024. The Author(s).)

Background: Fractional flow reserve (FFR) or non-hyperaemic pressure ratios are recommended to assess functional relevance of intermediate coronary stenosis. Both diagnostic methods require the placement of a pressure wire in the coronary artery during invasive coronary angiography. Quantitative flow ratio (QFR) is an angiography-based computational method for the estimation of FFR that does not require the use of pressure wires. We aimed to investigate whether a QFR-based diagnostic strategy yields a non-inferior 12-month clinical outcome compared with an FFR-based strategy., Methods: FAVOR III Europe was a multicentre, randomised, open-label, non-inferiority trial comparing a QFR-based with an FFR-based diagnostic strategy for patients with intermediate coronary stenosis. Enrolment was performed in 34 centres across 11 European countries. Patients aged 18 years or older with either chronic coronary syndrome or stabilised acute coronary syndrome, and with at least one intermediate non-culprit stenosis (40-90% diameter stenosis by visual estimate; referred to here as a study lesion), were randomly assigned (1:1) to the QFR-guided or the FFR-guided group. Randomisation was done using a concealed web-based system and was stratified by diabetes and presence of a left anterior descending coronary artery study lesion. The primary endpoint was a composite of death, myocardial infarction, and unplanned revascularisation at 12 months. The predefined non-inferiority margin was 3·4% and the primary analysis was performed in the intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT03729739) and long-term follow-up is ongoing., Findings: Between Nov 6, 2018, and July 21, 2023, 2000 patients were enrolled and randomly assigned to the QFR-guided strategy (1008 patients) or the FFR-guided strategy (992 patients). The median age was 67·3 years (IQR 59·9-74·7); 1538 (76·9%) patients were male and 462 (23·1%) were female. Median follow-up time was 365 days (IQR 365-365). At 12 months, a primary endpoint event had occurred in 67 (6·7%) patients in the QFR group, and in 41 (4·2%) patients in the FFR group (hazard ratio 1·63 [95% CI 1·11-2·41]). The event proportion difference was 2·5% (90% two-sided CI 0·9-4·2). The upper limit of the 90% CI exceeded the prespecified non-inferiority margin of 3·4%. Therefore, QFR did not meet non-inferiority to FFR. A total of 18 (1·8%) patients in each group experienced an adverse procedural event, the most frequent being procedure-related myocardial infarction, which occurred in ten (1·0%) patients in the QFR group and seven (0·7%) in the FFR group. One patient in the QFR group died in relation to the index procedure., Interpretation: The results of the FAVOR III Europe trial do not support the use of QFR if FFR is available to guide revascularisation decisions in patients with intermediate coronary stenosis. This finding could have implications for current clinical guidelines recommending QFR for this purpose., Funding: Medis Medical Imaging Systems and Aarhus University., Competing Interests: Declaration of interests BKA reports an institutional research grant from Medis Medical Imaging and free licences for the QFR application from Medis Medical Imaging during the trial. GCam reports institutional research grants from SMT, Medis Medical Imaging, Abbott Vascular, GADA, Siemens, and GE Healthcare outside the present work. TR reports consultant and proctoring honoraria from Boston Scientific, EPS Vascular, and Cardirad. BES is supported by the H H Sheikh Khalifa bin Hamad Al-Thani Research Programme; has received research grants to the institution from Boston Scientific, the B Braun Foundation, the German Center for Cardiovascular Research (DZHK), the German Heart Research Foundation, Edwards Lifesciences, the Iten-Kohaut Foundation, and the OPO Foundation; has received consulting and speaker fees from Abbott Vascular, Abiomed, and Boston Scientific; and received free licences for the QFR application from Medis Medical Imaging during the trial. LDS reports consulting fees from Abbott Vascular, Boston Scientific, and Philips outside the submitted work. JE reports serving as a speaker or advisory board member for Abbott, Boston Scientific, Medis Medical Imaging, and Philips. RL-P received a free licence for the QFR software from Medis Medical Imaging during the trial. UL reports research grants to the institution from Abbott, Amgen, Bayer, and Novartis. RSD reports an institutional research grant from Medis Medical Imaging and free licences for the QFR application from Medis Medical Imaging during the trial. HM-R reports consultancy fees from Medis Medical Imaging and speaker fees from Philips and Abbott. LK received free licences for the QFR application from Medis Medical Imaging during the trial. JA reports teaching grants from Biotronik and Medis Medical Imaging. YSA reports consulting fees from Boston Scientific and Shockwave. TL served as a Medis technical and research support consultant in Haga Hospital (The Hague, Netherlands) and performed beta testing of software from Medis Medical Imaging, neither of which was study related, and received a free licence for the QFR application from Medis Medical Imaging during the trial. KL received free licences for the QFR application from Medis Medical Imaging during the trial; speaker fees and travel support from BMS and Boston Scientific; speaker fees from DGK; and served as an advisory board member for BMS. GCas received a free licence for the QFR application from Medis Medical Imaging during the trial. SB reports institutional research grants from Medis Medical Imaging, SMT, Abbott, Siemens, Insight Lifetech, and Amgen; free licences for the QFR application from Medis Medical Imaging during the trial; speaker's fee from SMT, Medis Medical Imaging, Abbott, and Siemens; and advisory board activities for Siemens. NTO reports institutional research grants from Abbott and from Shockwave. RS reports an institutional research grant from Abbott; institutional research contract with Medis Medical Imaging; and speaker and consultation fees from Abbott and Fondazione Menarini. EHC reports institutional research grants from Abbott, Biosensors, Meril, and Medis Medical Imaging; and speaker fees from Abbott and EPS. NRH reports Institutional research grants from Abbott, B Braun, Biosensors, Boston Scientific, and Medis Medical Imaging; and speaker fees from Abbott and EPS. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

All-atom molecular simulations offer detailed insights into macromolecular phenomena, but their substantial computational cost hinders the exploration of complex biological processes. We introduce Advanced Machine-learning Atomic Representation Omni-force-field (AMARO), a new neural network potential (NNP) that combines an O(3)-equivariant message-passing neural network architecture, TensorNet, with a coarse-graining map that excludes hydrogen atoms. AMARO demonstrates the feasibility of training coarser NNP, without prior energy terms, to run stable protein dynamics with scalability and generalization capabilities.

Introduction: Identifying cancer earlier can help save lives. An increasingly popular approach to diagnosing cancer earlier is in the development of risk prediction models to be applied to the electronic healthcare record of patients. Development of these models requires systematic and thorough identification of the risk factors that might increase an individual's propensity to develop the disease. This protocol sets out the methods for an umbrella review to identify risk factors that might be included in these models. The example used is pancreatic cancer, a disease with a high percentage of late-stage diagnoses and consequent high mortality., Methods and Analysis: Relevant systematic reviews will be identified through searching of MEDLINE and EMBASE via Ovid and the Science Citation Index Expanded of the Web of Science Core Collection. Screening will be performed by two independent reviewers using Covidence software and the results reported as a Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram. Data from eligible studies will be extracted independently by two reviewers and each systematic review will be graded using defined credibility assessment criteria and the ROBIS (Risk of Bias in Systematic Reviews) tool. Results will be presented in detail for each paper. Summary results for each risk factor will be discussed in the narrative and summarised using a table, graphical summary and an infographic., Ethics and Dissemination: Ethical approval is not required for this review. Results of the review will be disseminated by publication in a peer-reviewed journal and presented at conferences., Prospero Registration Number: CRD42024526338., Competing Interests: Competing interests: FMW is a member of the BMJ Open Editorial Board., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Currently, there is uncertainty about which frailty scale is most appropriate and valid for use in the emergency department. The objective of this study was to compare the most commonly used frailty scales in triage and evaluate their performance., Methods: This prospective, single-center observational study was conducted from June to December 2023. Data collection spanned 80 days, during which the triage nurse recorded frailty scales using the Clinical Frailty Scale, Identification of Seniors at Risk, Program of Research to Integrate the Service for the Maintenance of Autonomy 7 (PRISMA-7), and the Triage Frailty and Comorbidity tool. The Clinical Frailty Scale, Identification of Seniors at Risk, and PRISMA-7 were used for patients aged >65 years, whereas the Triage Frailty and Comorbidity tool was applied to all patients presenting to the emergency department. The scales were compared using the area under the receiver operating characteristic curve for 90-day mortality, 30-day mortality, and hospitalization., Results: A total of 1270 patients were enrolled during the study period. In comparing the receiver operating characteristic curves, the Triage Frailty and Comorbidity tool demonstrated a receiver operating characteristic curve of 0.894 (95% CI: 0.858-0.929), whereas the Clinical Frailty Scale had 0.826 (95% CI: 0.762-0.890), PRISMA-7 had 0.814 (95% CI: 0.751-0.876), and Identification of Seniors at Risk had 0.821 (95% CI: 0.759-0.882), with a comparison P value of 0.03. The Triage Frailty and Comorbidity tool also significantly outperformed the other scales for 90-day mortality, 30-day mortality, and hospitalization across the overall population. Considering only the population aged >65 years, it identifies frail patients equally well as the other tools., Discussion: The findings of this study suggest that the Triage Frailty and Comorbidity tool is a valid instrument for assessing frailty in the emergency department. Moreover, among the scales used, it is the only 1 that considers the entire adult population, not just those aged >65 years, making it more inclusive for a setting such as the emergency department., (Copyright © 2024 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.)

A significant challenge in the treatment of central nervous system (CNS) disorders is represented by the presence of the blood-brain barrier (BBB), a highly selective membrane that regulates molecular transport and restricts the passage of pathogens and therapeutic compounds. Traditional in vivo models are constrained by high costs, lengthy experimental timelines, ethical concerns, and interspecies variations. In vitro models, particularly microfluidic BBB-on-a-chip devices, have been developed to address these limitations. These advanced models aim to more accurately replicate human BBB conditions by incorporating human cells and physiological flow dynamics. In this framework, here we developed an innovative microfluidic system that integrates thin-film electrodes for non-invasive, real-time monitoring of BBB integrity using electrochemical impedance spectroscopy (EIS). EIS measurements showed frequency-dependent impedance changes, indicating BBB integrity and distinguishing well-formed from non-mature barriers. The data from EIS monitoring was confirmed by permeability assays performed with a fluorescence tracer. The model incorporates human endothelial cells in a vessel-like arrangement to mimic the vascular component and three-dimensional cell distribution of human astrocytes and microglia to simulate the parenchymal compartment. By modeling the BBB-on-a-chip with an equivalent circuit, a more accurate trans-endothelial electrical resistance (TEER) value was extracted. The device demonstrated successful BBB formation and maturation, confirmed through live/dead assays, immunofluorescence and permeability assays. Computational fluid dynamics (CFD) simulations confirmed that the device mimics in vivo shear stress conditions. Drug crossing assessment was performed with two chemotherapy drugs: doxorubicin, with a known poor BBB penetration, and temozolomide, conversely a specific drug for CNS disorders and able to cross the BBB, to validate the model predictive capability for drug crossing behavior. The proposed sensorized microfluidic device represents a significant advancement in BBB modeling, offering a versatile platform for CNS drug development, disease modeling, and personalized medicine.