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Abstract Extracellularly released molecular inflammasome assemblies -ASC specks- cross-seed Aβ amyloid in Alzheimer’s disease. Here we show that ASC governs the extent of inflammation-induced amyloid A (AA) amyloidosis, a systemic disease caused by the aggregation and peripheral deposition of the acute-phase reactant serum amyloid A (SAA) in chronic inflammatory conditions. Using super-resolution microscopy, we found that ASC colocalized tightly with SAA in human AA amyloidosis. Recombinant ASC specks accelerated SAA fibril formation and mass spectrometry after limited proteolysis showed that ASC interacts with SAA via its pyrin domain (PYD). In a murine model of inflammatory AA amyloidosis, splenic amyloid load was conspicuously decreased in Pycard −/− mice which lack ASC. Treatment with anti-ASCPYD antibodies decreased amyloid loads in wild-type mice suffering from AA amyloidosis. The prevalence of natural anti-ASC IgG (−logEC50 ≥ 2) in 19,334 hospital patients was

Atmospheric new particle formation (NPF) is a naturally occurring phenomenon, during which high concentrations of sub-10 nm particles are created through gas to particle conversion. The NPF is observed in multiple environments around the world. Although it has observable influence onto annual total and ultrafine particle number concentrations (PNC and UFP, respectively), only limited epidemiological studies have investigated whether these particles are associated with adverse health effects. One plausible reason for this limitation may be related to the absence of NPF identifiers available in UFP and PNC data sets. Until recently, the regional NPF events were usually identified manually from particle number size distribution contour plots. Identification of NPF across multi-annual and multiple station data sets remained a tedious task. In this work, we introduce a regional NPF identifier, created using an automated, machine learning based algorithm. The regional NPF event tag was created for 65 measurement sites globally, covering the period from 1996 to 2023. The discussed data set can be used in future studies related to regional NPF. [ABSTRACT FROM AUTHOR]

The dangerous chemical hydrogen fluoride sits at the apex of the fluorochemical industry, but the substantial hazards linked to its production under harsh conditions (above 300 degrees Celsius) and transport are typically contracted to specialists. All fluorochemicals for applications, including refrigeration, electric transportation, agrochemicals and pharmaceuticals, are prepared from fluorspar (CaF2) through a procedure that generates highly dangerous hydrogen fluoride1–5. Here we report a mild method to obtain fluorochemicals directly from fluorspar, bypassing the necessity to manufacture hydrogen fluoride. Acid-grade fluorspar (more than 97 per cent CaF2) is treated with the fluorophilic Lewis acid boric acid (B(OH)3) or silicon dioxide (SiO2), in the presence of oxalic acid, a Brønsted acid that is highly effective for Ca2+ sequestration. This scalable process carried out in water at low temperature (below 50 degrees Celsius) enables access to widely used fluorochemicals, including tetrafluoroboric acid, alkali metal fluorides, tetraalkylammonium fluorides and fluoro(hetero)arenes. The replacement of oxalic acid with sulfuric acid gave comparable results for B(OH)3, but was not as effective when the fluorophilic Lewis acid was SiO2. A similar process also works with the lower-purity metspar. The production of fluorochemicals directly from fluorspar offers the possibility of decentralized manufacturing—an attractive model for the fluorochemical industry. With the renewed interest in innovative methods to synthesize oxalic acid via carbon dioxide capture and biomass6,7, and the challenges posed by our dependence on fossil fuels for sulfur and therefore sulfuric acid supply8,9, our technology may represent a departure towards a sustainable fluorochemical industry. Fluorochemicals are obtained directly from fluorspar activated in water at low temperature, without the requirement to manufacture hydrogen fluoride, a toxic and hazardous gas that is central to the current industrial process. [ABSTRACT FROM AUTHOR]

Aim: To compare three-dimensional changes of aporcine derived collagen matrix (CM) and free gingival grafts (FGG) for increasing keratinized tissue (KT) at dental implants over a 24-month follow-up period. Materials and methods: This retrospective study enrolled 25 patients exhibiting 41 implants with deficient KT width (i.e., < 2 mm) who underwent soft tissue augmentation using either CM (11 patients/15 implants) or FGG (14 patients/26 implants). The primary outcome was tissue thickness change (mm) at treated implant sites between 1- (S0), 12- (S1), and 24-months (S2). Secondary outcome was the changes of KT width over a 24-month follow-up period. Results: Dimensional analyses from S0 to S1 and from S0 to S2 revealed a mean decrease in tissue thickness of -0.05 ± 0.35 mm and − 0.31 ± 0.41 mm in the CM group, and − 0.23 ± 0.38 mm and − 0.22 ± 0.81 mm in the FGG group, with no significant differences found between the groups (S0-S1: p = 0.14, S0-S2: p = 0.58). Within S1 and S2, the CM and FGG groups displayed comparable tissue thickness reduction (CM: -0.32 ± 0.53 mm, FGG: -0.02 ± 0.21 mm; p = 0.07). The FGG group exhibited a significantly greater KT gain 24-months compared to the CM group (CM: 1.50 ± 1.14 mm, FGG: 4.04 ± 1.65 mm; p < 0.001). Conclusions: CM and FGG were associated with comparable three-dimensional thickness changes over a period of 24 months. A significantly wider KT band could be established in the FGG group. [ABSTRACT FROM AUTHOR]

Introduction: Bernese periacetabular osteotomy (PAO) is an effective procedure for treating acetabular dysplasia. However, limited visual control of the acetabular position during surgery may result in under- or overcorrection or changes in acetabular version resulting in residual dysplasia or femoroacetabular impingement. Thus, we wanted to develop a simple and straightforward navigation method that provides information about acetabular correction in all three planes during surgery. Method: Intraoperatively, acetabular coordinates are shown in coronal, sagittal, and transverse plane by two perpendicular tubes of an external fixator mounted onto a third tube that is fixed to the mobilized acetabular fragment with two Schanz screws. The application and fixation of the external fixator on the pelvis are demonstrated in this article. We used this analog navigation method on 27 PAOs, where we mainly performed a lateral rotational correction. The pre- and postoperative radiographs of these 27 hips were analyzed regarding the radiological hip parameters, taking into account the pelvic tilt. Results: The mean preoperative lateral center edge angle (LCEA) of the 27 PAOs improved from 16° (+-6) to a mean of 34° (+-6°) and the mean acetabular index (AI) was corrected from 15° (+-4) to 2° (+-4). This implements highly physiologic postoperative values for lateral coverage in this population. In this case series, no postoperative acetabular retroversion was measured in any of the 27 PAOs. Conclusion: Three-dimensional control of the acetabular orientation during periacetabular osteotomy is important to avoid over- and undercorrection. Using a fixateur externe as an analog navigation method this three-dimensional control can be implemented intraoperatively for PAOs. [ABSTRACT FROM AUTHOR]

Background: Recommendations for breast surveillance following breast plastic surgery are frequently changing. Establishing guidelines for long-term monitoring protocols may help identify treatable conditions and prevent untoward sequelae. We sought to evaluate the current state of evidence-based long-term monitoring protocols for patients following breast augmentation, reduction, and breast reconstruction. Methods: Official guidelines from various American societies and international societies were analyzed for alignment in evidence-based recommendations regarding breast surveillance. Results: The most recent US FDA update recommends magnetic resonance imaging or ultrasound starting 5–6 years after surgery and every 2–3 years thereafter. Discrepancies exist among professional societies: the American Society of Plastic Surgeons (ASPS) aligns with the FDA, while the American Society of Breast Surgeons and American College of Radiology (ACR) find no role for imaging for asymptomatic cases. Ultrasound is first-line for any implant concerns, with MRI if necessary. European societies oppose routine breast implant imaging. Breast reduction patients lack unique screening protocols; monitoring aligns with age and cancer risk factors. Following mastectomy and breast reconstruction, most organizations advocate for annual clinical examinations, with more frequent examinations initially. Evidence suggests that physical examination is sufficient to detect local cancer recurrence, with imaging only indicated if there is concern for recurrence. No surveillance imaging is recommended by the American Society of Clinical Oncology, National Comprehensive Cancer Network, or ASPS; however, ACR recommends mammography for autologous reconstruction only. Conclusion: Multispecialty and regulatory body alignment may promote provider and patient adherence. Ongoing studies of long-term outcomes are needed to strengthen the level of evidence for monitoring guidelines. [ABSTRACT FROM AUTHOR]

The current limitations in utilizing metal-organic frameworks for (photo)electrochemical applications stem from their diminished electrochemical stability. In our study, we illustrate a method to bolster the activity and stability of (photo)electrocatalytically active metal-organic frameworks through ligand engineering. We synthesize four distinct mixed-ligand versions of zeolitic imidazolate framework-67, and conduct a comprehensive investigation into the structural evolution and self-reconstruction during electrocatalytic oxygen evolution reactions. In contrast to the conventional single-ligand ZIF, where the framework undergoes a complete transformation into CoOOH via a stepwise oxidation, the ligand-engineered zeolitic imidazolate frameworks manage to preserve the fundamental framework structure by in-situ forming a protective cobalt (oxy)hydroxide layer on the surface. This surface reconstruction facilitates both conductivity and catalytic activity by one order of magnitude and considerably enhances the (photo)electrochemical stability. This work highlights the vital role of ligand engineering for designing advanced and stable metal-organic frameworks for photo- and electrocatalysis. The application of metal-organic frameworks in (photo)electrocatalysis is constrained by their structural stability. Here, the authors report mixed-ligand zeolitic imidazolate frameworks that can in-situ form a protective (oxy)hydroxide layer through surface reconstruction, enhancing both catalytic activity and stability during (photo)electrocatalytic oxygen evolution reactions. [ABSTRACT FROM AUTHOR]

Pharmaceutical formulations are increasingly based on drug nanoparticles or carrier nanoparticles encapsulating drugs or mRNA molecules. Sizes and monodispersity of the nanoparticles regulate bioavailability, pharmacokinetics and pharmacology. Microfluidic mixers promise unique conditions for their continuous preparation. A novel microfluidic antisolvent precipitation device was realized by two-photon-polymerization with a mixing channel in which the organic phase formed a sheet with a homogeneous thickness of down to 7 μm completely wrapped in the aqueous phase. Homogeneous diffusion through the sheet accelerates mixing. Optical access was implemented to allow in-situ dynamic light scattering. By centering the thin sheet in the microchannel cross-section, two important requirements are met. On the one hand, the organic phase never reaches the channel walls, avoiding fouling and unstable flow conditions. On the other hand, in the sheet positioned at the maximum of the parabolic flow profile the nanoparticle velocities are homogenized which enables flow-compensated Dynamic Light Scattering (flowDLS). These unique features allowed in-situ particle size determination for the first time. Monitoring of lipid nanoparticle precipitation was demonstrated for different rates of solvent and antisolvent flows. This breakthrough innovation will not only enable feedback control of nanoparticle production but also will provide new insights into the dynamics of nanoparticle precipitation. [ABSTRACT FROM AUTHOR]

The effect of hydrogen diffusion and trapping was studied in a high-Cr ferrous alloy using an inverted scanning Kelvin probe and thermal desorption spectroscopy in correlation with microstructure and residual stress study. In addition, different processing of ferritic/martensitic 9Cr1WTaV alloy (EUROFER97) was tested in correlation with observed selected properties to observe induced changes in material degradation and surface. The activation energies for hydrogen traps were shown to have distinct peaks corresponding to different trapping mechanisms, including matrix dislocations and grain boundaries. For the cryogenically treated sample, an additional peak was also identified and correlated with increased carbide precipitation. [ABSTRACT FROM AUTHOR]

The C programming language offers setjmp/ longjmp as a mechanism for nonlocal control flow. This mechanism has complicated semantics. As most developers do not encounter it day-to-day, they may be unfamiliar with all its intricacies – leading to subtle programming errors. At the same time, most static analyzers lack proper support, implying that otherwise sound tools miss whole classes of program deficiencies. We propose a concrete semantics of a subset of C with setjmp/ longjmp, where interprocedural longjmps are performed directly, as well as an equivalent formulation where such jumps are implemented via stack-unwinding at the call-sites. Reflecting this semantic equivalence, we propose an approach for lifting existing interprocedural analyses to support setjmp/ longjmp and to flag their misuse. To deal with the nonlocal semantics, our approach leverages side-effecting transfer functions, which, when executed, may additionally trigger contributions for program points that are not static control-flow successors. We showcase our analysis on a real-world example and propose a set of litmus tests for other analyzers. [ABSTRACT FROM AUTHOR]

Sweetpotato, Ipomoea batatas (L.) Lam. (2n = 6x = 90), is among the world’s most important food crops and is North Carolina’s most important vegetable crop. The recent introduction of Meloidogyne enterolobii poses a significant economic threat to North Carolina’s sweetpotato industry and breeding resistance into new varieties has become a high priority for the US sweetpotato industry. Previous studies have shown that ‘Tanzania’, a released African landrace, is resistant to M. enterolobii. We screened the biparental sweetpotato mapping population, ‘Tanzania’ x ‘Beauregard’, for resistance to M. enterolobii by inoculating 246 full-sibs with 10,000 eggs each under greenhouse conditions. ‘Tanzania’, the female parent, was highly resistant, while ‘Beauregard’ was highly susceptible. Our bioassays exhibited strong skewing toward resistance for three measures of resistance: reproductive factor, eggs per gram of root tissue, and root gall severity ratings. A 1:1 segregation for resistance suggested a major gene conferred M. enterolobii resistance. Using a random-effect multiple interval mapping model, we identified a single major QTL, herein designated as qIbMe-4.1, on linkage group 4 that explained 70% of variation in resistance to M. enterolobii. This study provides a new understanding of the genetic basis of M. enterolobii resistance in sweetpotato and represents a major step towards the identification of selectable markers for nematode resistance breeding. [ABSTRACT FROM AUTHOR]

The effective lifetime of the B s 0 meson in the decay B s 0 → J / ψK S 0 is measured using data collected during 2016–2018 with the CMS detector in s = 13 TeV proton-proton collisions at the LHC, corresponding to an integrated luminosity of 140 fb−1. The effective lifetime is determined by performing a two-dimensional unbinned maximum likelihood fit to the B s 0 meson invariant mass and proper decay time distributions. The resulting value of 1.59 ± 0.07(stat) ± 0.03(syst) ps is the most precise measurement to date and is in good agreement with the expected value. [ABSTRACT FROM AUTHOR]

Summary: Background: The Broström procedure is an established procedure in cases of primary lateral ankle ligament repair (LALR). To improve postoperative stability an augmentation device, InternalBrace™ (Arthrex, Naples, FL) has been introduced. This study evaluates remodelling of the anterior talofibular ligament (ATFL) in patients undergoing a tape augmented Broström technique as well as clinical outcomes. Methods: In this study 32 patients with chronic lateral ankle instability (CLAI) receiving augmented LALR were included. Clinical outcomes were evaluated at a one-time postoperative visit between 12 and 18 months. A 3 T magnetic resonance imaging (MRI) was done to evaluate the morphology of the ATFL. Statistical analysis was completed with the free software and environment R version 3.6.3 (Bell Laboratories, Murray Hill, NJ, USA) and P-values < 0.05 were considered statistically significant. Results: The mean follow-up time was 15.3 ± 1.8 months with a return to sport time of 4.0 ± 2.4 months. The average AOFAS (American Orthopaedic Foot and Ankle Society Score) score was 94.4 ± 7.2, the FAOS (Foot and Ankle Outcome Score) demonstrated 87.3 ± 10.4 points and the FFI (Foot Function Index – 2 scores (pain and function score)) was 22.9 ± 20.1 and 15.4 ± 10.4, respectively. The MRI findings demonstrated an average length of the ATFL of 18.6 ± 4.3 mm and the width was 3.6 ± 0.9 mm. A clear differentiation between the ATFL and the augmentation device could be shown in 28 cases. The Fisher's exact test could not depict a significant correlation between the presence of a bone marrow edema and the tension of the augmentation device with a level of significance of α = 0.05. Conclusion: An anatomical healing tendency of the ligament repair and good integrity of the augmentation device could be shown based on MRI findings. The lateral ligament repair augmented with suture tape is an effective and safe procedure regarding surgical treatment in chronic lateral ankle instability producing good clinical outcome. [ABSTRACT FROM AUTHOR]

Volunteers are frequently assigned illegitimate tasks that exceed what can be reasonably required from them. In this study, we used affective events theory to investigate the impact of illegitimate tasks on volunteer engagement. We developed a moderated mediation model and analyzed the mediating role of emotional labor and moderating role of power distance. Based on data from a three-wave survey of 1,948 volunteers, we found that illegitimate tasks negatively affected volunteers' subsequent work engagement. Our results show that emotional labor is the mechanism through which illegitimate tasks affect engagement. By identifying a dual pathway, we demonstrate that illegitimate tasks affected the two strategies for dealing with emotional labor differently, causing volunteers to increase surface acting and decrease deep acting. The volunteers' power distance has a moderating role, weakening the positive effect of illegitimate tasks on volunteers' surface acting while enhancing the negative effect of illegitimate tasks on volunteers' deep acting, reducing subsequent engagement. [ABSTRACT FROM AUTHOR]

The Shake-The-Box technique was applied to experimentally quantify the time-resolved volumetric flow field around a free-flying quadcopter UAV with an overall span of about 0.5 m. State-of-the-art LED illumination and high-speed camera equipment was combined with modern Lagrangian tracer particle tracking and data assimilation techniques, facilitating a measurement volume larger than 1.5 m 3 . The setup allowed for both hover and limited maneuvering of the quadcopter, while resolving even small details of the complex interactional aerodynamics. In hover out of ground effect, the four individual rotor wakes merged into a single jet within a few rotor radii below the rotor planes. Evaluating the mass and momentum fluxes over suitable control volumes yields accurate estimates for the quadcopter's total thrust, the asymmetric thrust distribution between front and back rotors, and the entrainment of external flow through turbulent mixing. Hover in ground effect decreases the power requirement and induces recirculating flow in the center of the four rotors. The outwash pattern is non-uniform with jets developing between the rotors and pointing in radially outward directions. Forward flight cases result in a skewed, rapidly merging wake flanked by the roll-up of two "supervortices" similar to the wingtip vortices of fixed-wing vehicles. [ABSTRACT FROM AUTHOR]

Background: Understanding the relationship between psychopathology and major domains of human neurobehavioral functioning may identify new transdiagnostic treatment targets. However, studies examining the interrelationship between psychopathological symptoms, sensorimotor, cognitive, and global functioning in a transdiagnostic sample are lacking. We hypothesized a close relationship between sensorimotor and cognitive functioning in a transdiagnostic patient sample. Methods: We applied network analysis and community detection methods to examine the interplay and centrality [expected influence (EI) and strength] between psychopathological symptoms, sensorimotor, cognitive, and global functioning in a transdiagnostic sample consisting of 174 schizophrenia spectrum (SSD) and 38 mood disorder (MOD) patients. All patients (n = 212) were examined with the Positive and Negative Syndrome Scale (PANSS), the Heidelberg Neurological Soft Signs Scale (NSS), the Global Assessment of Functioning (GAF), and the Brief Cognitive Assessment Tool for Schizophrenia consisted of trail making test B (TMT-B), category fluency (CF) and digit symbol substitution test (DSST). Results: NSS showed closer connections with TMT-B, CF, and DSST than with GAF and PANSS. DSST, PANSS general, and NSS motor coordination scores showed the highest EI. Sensory integration, DSST, and CF showed the highest strength. Conclusions: The close connection between sensorimotor and cognitive impairment as well as the high centrality of sensorimotor symptoms suggests that both domains share aspects of SSD and MOD pathophysiology. But, because the majority of the study population was diagnosed with SSD, the question as to whether sensorimotor symptoms are really a transdiagnostic therapeutic target needs to be examined in future studies including more balanced diagnostic groups. [ABSTRACT FROM AUTHOR]

Diboson production in association with jets is studied in the fully leptonic final states, pp → (Z/γ*)(Z/γ*) + jets → 2ℓ2ℓ′ + jets, (ℓ, ℓ′ = e or μ) in proton-proton collisions at a center-of-mass energy of 13 TeV. The data sample corresponds to an integrated luminosity of 138 fb−1 collected with the CMS detector at the LHC. Differential distributions and normalized differential cross sections are measured as a function of jet multiplicity, transverse momentum pT, pseudorapidity η, invariant mass and ∆η of the highest-pT and second-highest-pT jets, and as a function of invariant mass of the four-lepton system for events with various jet multiplicities. These differential cross sections are compared with theoretical predictions that mostly agree with the experimental data. However, in a few regions we observe discrepancies between the predicted and measured values. Further improvement of the predictions is required to describe the ZZ+jets production in the whole phase space. [ABSTRACT FROM AUTHOR]

Advanced Parkinson´s disease (PD) is often complicated by fluctuations of disability depending on plasma levels of levodopa. For most patients OFF phases with worsening of tremor and immobility, but also pain, depression, autonomic symptoms are troublesome. While adjustments of levodopa administrations can relief such fluctuations for some time, "on demand" therapies become more and more important. These "on demand" therapies should provide fast and efficacious relief. During the past years, new options for on demand therapies in PD-associated OFF episodes have been developed, including new formulations of levodopa and apomorphine to provide fast and readily accessible on demand treatment. In this narrative review, the challenges of the treatment of PD-associated fluctuations and OFF states are addressed, with a special focus on sublingual apomorphine (SL-APO) including the results from recent clinical trials. [ABSTRACT FROM AUTHOR]

Copyright of Rechtsmedizin 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.)

Copyright of Rechtsmedizin 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.)

Copyright of Rechtsmedizin 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.)

Downbeat nystagmus (DBN) is the most common form of acquired central vestibular nystagmus. Gravity perception in patients with DBN has previously been investigated by means of subjective visual straight ahead (SVA) and subjective visual vertical (SVV) in the pitch and roll planes only during whole-body tilts. To our knowledge, the effect of head tilt in the roll plane on the SVV and on DBN has not yet been systematically studied in patients. In this study, we investigated static and dynamic graviceptive function in the roll-plane in patients with DBN (patients) and healthy-controls (controls) by assessment of the Subjective Visual Vertical (SVV) and the modulation of slow-phase-velocity (SPV) of DBN. SPV of DBN and SVV were tested at different head-on trunk-tilt positions in the roll-plane (0°,30° clockwise (cw) and 30° counterclockwise (ccw)) in 26 patients suffering from DBN and 13 controls. In patients, SPV of DBN did not show significant modulations at different head-tilt angles in the roll-plane. SVV ratings did not differ significantly between DBN patients vs. controls, however patients with DBN exhibited a higher variability in mean SVV estimates than controls. Our results show that the DBN does not exhibit any modulation in the roll-plane, in contrast to the pitch-plane. Furthermore, patients with DBN show a higher uncertainty in the perception of verticality in the roll-plane in form of a higher variability of responses. [ABSTRACT FROM AUTHOR]

Background: Posthepatectomy liver failure (PHLF), complications of portal hypertension, and disease recurrence determine the outcome for hepatocellular carcinoma (HCC) patients undergoing liver resection. This study aimed to evaluate the von Willebrand factor antigen (vWF-Ag) as a non-invasive test for clinically significant portal hypertension (CSPH) and a predictive biomarker for time to recurrence (TTR) and overall survival (OS). Methods: The study recruited 72 HCC patients with detailed preoperative workup from a prospective trial (NCT02118545) and followed for complications, TTR, and OS. Additionally, 163 compensated patients with resectable HCC were recruited to evaluate vWF-Ag cutoffs for ruling out or ruling in CSPH. Finally, vWF-Ag cutoffs were prospectively evaluated in an external validation cohort of 34 HCC patients undergoing liver resection. Results: In receiver operating characteristic (ROC) analyses, vWF-Ag (area under the curve [AUC], 0.828) was similarly predictive of PHLF as indocyanine green clearance (disappearance rate: AUC, 0.880; retention rate: AUC, 0.894), whereas computation of future liver remnant was inferior (AUC, 0.756). Cox-regression showed an association of vWF-Ag with TTR (per 10%: hazard ratio [HR], 1.056; 95% confidence interval [CI] 1.017–1.097) and OS (per 10%: HR, 1.067; 95% CI 1.022–1.113). In the analyses, VWF-Ag yielded an AUC of 0.824 for diagnosing CSPH, with a vWF-Ag of 182% or lower ruling out and higher than 291% ruling in CSPH. Therefore, a highest-risk group (> 291%, 9.7% of patients) with a 57.1% incidence of PHLF was identified, whereas no patient with a vWF-Ag of 182% or lower (52.7%) experienced PHLF. The predictive value of vWF-Ag for PHLF and OS was externally validated. Conclusion: For patients with resectable HCC, VWF-Ag allows for simplified preoperative risk stratification. Patients with vWF-Ag levels higher than 291% might be considered for alternative treatments, whereas vWF-Ag levels of 182% or lower identify patients best suited for surgery. [ABSTRACT FROM AUTHOR]

Copyright of Monatsschrift Kinderheilkunde 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.)

A precise quantification of mitral regurgitation (MR) severity is essential for treatment and outcome of patients with MR. 3D echocardiography facilitates estimation of MR but selection of patients with necessity of invasive treatment remains challenging. We investigate effective regurgitation orifice area (EROA) quantification by 3D compared to 2D echocardiography in patients with MR and highlight the improved discrimination of MR severity. We consecutively enrolled fifty patients with primary or secondary and at least moderate MR undergoing 2D and 3D colour Doppler echocardiography prior to transcatheter edge-to-edge repair (TEER). Improved accuracy of MR grading using 3D vena contracta area (VCA) as an estimate of EROA was compared to 2D proximal isovelocity surface area (PISA) quantification method and a multiparameter reference standard. Quantification of EROA remarkably varies between 2D and 3D echocardiography and the discrimination between moderate and severe MR was significantly (p = 0.001) different using 2D PISA or 3D VCA, respectively. 3D VCA correlated significantly (r = 0.501, p < 0.001) better with the pre-defined MR severity. We detected crucial differences in the correct identification of severe MR between 2D and 3D techniques, thus 2D PISA significantly (p < 0.0001) underestimates EROA due to clinical and morphological parameters. The assessment of 3D VCA resulted in improved diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Translating vascular aging research from bench to bedside presents both significant opportunities and challenges. This paper summarizes insights from a roundtable discussion at the Artery 23 conference, featuring perspectives from basic science, clinical trials, regulation, and industry. The main conclusions of the discussion are as follows: basic science research must align with clinical relevance, using appropriate animal models and standardized measurement techniques. Pragmatic and registry-based clinical trials offer viable alternatives to traditional randomized controlled trials, facilitating real-world applicability. The regulatory landscape, particularly for software medical devices, must evolve to keep pace with technological advancements like artificial intelligence. Industry efforts focus on developing devices or solutions for vascular aging assessment and treatment strategies, yet face hurdles in large-scale adoption and reimbursement. Despite significant progress, the development of pharmacological interventions to mitigate vascular aging remains a critical need. This discussion underscores the importance of interdisciplinary collaboration to overcome barriers and translate scientific discoveries into clinical practice effectively. [ABSTRACT FROM AUTHOR]

Therapy-related acute myeloid leukemia (t-AML) often exhibits adverse (genetic) features. There is ongoing discussion on the impact of t-AML on long-term outcome in AML. Therefore, we retrospectively analyzed clinical and biological characteristics of 1133 AML patients (225 t-AML patients and 908 de novo AML patients) with a median follow-up of 81.8 months. T-AML patients showed more adverse genetic alterations, higher age and more comorbidities as compared to de novo AML. Median OS in intensively treated t-AML patients was 13.7 months as compared to 39.4 months in de novo AML (p < 0.001). With non-intensive therapy, OS did not differ significantly (p = 0.394). With intensive therapy, significant differences in favor of de novo AML were observed in the ELN intermediate I/II (p = 0.009) and adverse (p = 0.016) risk groups but not within favorable risk groups (APL p = 0.927, ELN favorable p = 0.714). However, t-AML was no independent risk factor for OS (p = 0.103), RR (p = 0.982) and NRM (p = 0.320) in the multivariate analysis. A limitation of our study is an ELN 2010 risk stratification due to a lack of more comprehensive molecular data according to ELN 2022. We conclude that therapeutic algorithms in t-AML, in particular with regard to allo-HSCT, should be guided by ELN genetic risk rather than classification as t-AML alone. Our data support the WHO and ICC 2022 classifications, which include t-AML as diagnostic qualifier rather than a separate subcategory. [ABSTRACT FROM AUTHOR]

Butyl octyl magnesium solutions are important raw materials in various chemical processes but suffer from their high reactivity with even traces of water, protic solvents or oxygen and an increased viscosity in hydrocarbon solution due to the formation of polymeric structures. N1,N2-diphenylacenaphthylene-1,2-diimines (BIANs) have already been identified as potential candidates to reduce the viscosity of alkyl magnesium solutions and this study provides a systematic insight into the dependence of this ability on the position and structures of substituents on the BIAN. Besides the various BIANs, ZnCl2 complexes and hydrogenated derivatives were characterized and tested for their ability to reduce the viscosity. HPLC-high resolution mass spectrometry, MALDI-ToF mass spectrometry, but most important FTIR and NMR experiments under inert conditions have been used to shine light on the interaction of the different BIAN derivatives with alkyl magnesium solutions. Hydrogenated BIANs, especially those with bulky alkyl groups in the ortho position(s) have been identified as the most promising candidates. An additional benefit of the hydrogenated species is that in contrast to BIANs and BIAN-Zn complexes they do not undergo permanent chemical modification and can be reused after extraction. [ABSTRACT FROM AUTHOR]

We report on a study bearing implications for ethical learning in schoolchildren during social interaction. The study was conducted as part of a project aimed at promoting ethical learning of socially-oriented values within the context of dialogic education. 172 fourth graders from 7 classes participated in an 8-session series designed to foster empathy, inclusion, and tolerance. Two of these sessions (3 and 8) were pre-selected for analysis. We investigated (1) whether students' discussion of ethical issues and the ethical aspects of their actual in-class interaction with each other can be reliably measured, and (2) what relation holds between students' ethical thinking during classroom discussions and the ethical aspects of their behavior. We thus developed an analytical framework comprising two tools for appraising ethical thinking and behavior in in-class interaction: dialogue on ethics (DoE) and ethics of dialogue (EoD). This framework was applied to the dialogues taken from the two sessions. The DoE and EoD tools proved reliable, as inter-rater agreement was substantial. Moreover, the relation between children's DoE and their EoD was positive where the topic posed for discussion presented a dilemma and students' interaction proceeded under moderate teacher guidance. In contrast, it was negative when the discussion was conceptual, and the teacher was dominant. We conclude that (1) DoE/EoD is a suitable framework for studying children's ethical learning and development in social interaction, and (2) ethical learning, in its epistemological and behavioral dimensions, can be boosted or inhibited in a context of dialogic education, depending on design principles. [ABSTRACT FROM AUTHOR]

Health sciences students face many challenges in regard to clinical practical learning. A better understanding of student learning is required to address student needs in this crucial phase. The theory of self-regulated learning provides a comprehensive view of learning and could serve as a basis for further research. There are instruments to assess self-regulated learning in preclinical academic learning. However, there are no such instruments for workplace learning. The aim of the present study is to provide a comprehensive inventory from which researchers can select those scales that are relevant to their research questions in the investigation of workplace learning. Hence, the aim is to develop and validate a set of scales to assess undergraduates' workplace learning in health sciences education in four areas (cognition, motivation, emotion, and context) on two levels (the learning process level and the metalevel). Study 1 is a qualitative multimethod study to identify indicators and develop items. It integrates the perspectives of students, teachers, and researchers and includes six steps: literature review, interviews, synthesis, item development, expert review, and cognitive pretesting. This study yields a set of scales for each area on both levels. Study 2 is a quantitative study to assess the psychometric properties. The results show acceptable values in terms of unidimensionality, reliability and validity for each of the 31 scales. The newly developed Workplace Learning Inventory is comprehensive; the scales are relevant to workplace learning and short enough that their administration is feasible in the workplace setting. The rigorous process of questionnaire development contributes to the validity of scales. By providing the Workplace Learning Inventory, we hope to encourage research on workplace learning in health sciences education from an educational psychology perspective. [ABSTRACT FROM AUTHOR]

Background: Caustic ingestions are relatively uncommon, but remain a significant source of morbidity. Patients with caustic injury often undergo an urgent EGD, although it is not clear if an EGD is routinely needed in an asymptomatic patient. The study has two primary objectives; 1) to determine the utility of routine EGD in asymptomatic suicidal caustic ingestions; 2) to determine if asymptomatic unintentional acidic ingestions can be managed with observation alone, similar to basic ingestions. Methods: This retrospective study, which took place at 14 hospitals in three countries evaluated all patients who presented with a caustic ingestion between 2014–2020. The presence of symptoms and esophageal injury, demographic information, pH of ingested substance, reason for the ingestion, and outcome were recorded. Results: 409 patients were identified; 203 (46.9%) were male. The median (IQR) age was 18 (4–31) years; overall range 10 months to 78 years. Suicidal ingestions accounted for 155 (37.9%) of cases. Dysphagia or dysphonia were more likely in those with significant esophageal injury compared to those without (59.3% vs. 12.6% respectively; OR 10.1; 95% CI 4.43–23.1). Among 27 patients with significant esophageal injury, 48% were found in suicidal patients, compared with 51.9% in non-suicidal patients (p = NS). On multivariate regression, there was no difference in the rate of significant esophageal injury among suicidal vs. non suicidal patients (aOR 1.55; p = 0.45, 95% CI 0.45–5.33). Most ingestions involved basic substances (332/409; 81.2%). Unknown or mixed ingestions accounted for 25 (6.11%) of the ingestions. Significant esophageal burns were found in 6/52 (11.5%) of acid ingestions, compared with 21/332 (6.3%) of basic ingestions. Of the 42 cases of acidic ingestions without dysphagia or odynophagia, 2 (4.8%; 0.58–16.1%) had significant esophageal burns, compared with 9 (3.2%; 95% CI 1.4–5.9%) of the 284 basic ingestions; p = 0.64). On multivariate logistic regression, patients with acidic ingestions were not more likely to experience a significant burn (aOR 1.7; p = 0.11, 95% CI 0.9–3.1) compared to those with basic ingestions. No patient with significant esophageal burns was asymptomatic. Conclusion: In this study, there was no statistical differences in the rates of significant burns between acidic and basic caustic ingestions. There were no significant esophageal injuries noted among asymptomatic patients. [ABSTRACT FROM AUTHOR]

Introduction: The growth of surgeon burnout is of significant concern. As we work to reimagine the practice of surgery, an accurate understanding of the extent of surgeon burnout is essential. Our goal was to define the current prevalence of burnout and quality of life (QOL) among SAGES surgeons. Methodology: An electronic survey was administered to SAGES members to establish a current baseline for QOL, burnout, depression, and career satisfaction. To assess outcomes, we utilized the validated Maslach Burnout Inventory for Medical Personnel, the Medical Outcomes Study Short Form, and the Primary Care Evaluation of Mental Disorders. All scoring followed validated norm-based methods. Results: Of 4194 active members, 604 responded (14.40%). 69% met burnout threshold, with high levels of emotional exhaustion and depersonalization, and low personal accomplishment. 81% reported "being at the end of their rope", 74% felt emotionally drained, and 65% felt used up daily. Nearly all maintained caring about what happened to their patients (96%), easily understanding how their patients feel (84.3%) and being capable of dealing effectively with their patient's problems (87.6%). However, respondents never, rarely, or occasionally felt energetic (77.5%) or experienced a sense of professional accomplishment (57.8%). The overall QOL score was 69/100, with lower Mental than Physical scores (62.69 (SD 10.20) vs.77.27 (SD 22.24)). More than half of respondents met depression criteria. While 77% supported they would become a physician again, less than half would choose surgery again or recommend surgery to their children. Furthermore, less than a third felt work allowed sufficient time for their personal lives. Conclusions: Participating SAGES surgeons reported alarmingly high rates of burnout and depression. Despite experiencing emotional exhaustion and depersonalization, they maintained a strong commitment to patient care. These findings likely reflect the broader state of surgeons, underscoring the urgent need for action to address this critical issue. [ABSTRACT FROM AUTHOR]

Objectives: Aim of this study was to assess the value of virtual non-contrast (VNC) reconstructions in differentiating between adrenal adenomas and metastases on a photon-counting detector CT (PCD-CT). Material and methods: Patients with adrenal masses and contrast-enhanced CT scans in portal venous phase were included. Image reconstructions were performed, including conventional VNC (VNCConv) and PureCalcium VNC (VNCPC), as well as virtual monochromatic images (VMI, 40–90 keV) and iodine maps. We analyzed images using semi-automatic segmentation of adrenal lesions and extracted quantitative data. Logistic regression models, non-parametric tests, Bland–Altman plots, and a random forest classifier were used for statistical analyses. Results: The final study cohort consisted of 90 patients (36 female, mean age 67.8 years [range 39–87]) with adrenal lesions (45 adenomas, 45 metastases). Compared to metastases, adrenal adenomas showed significantly lower CT-values in VNCConv and VNCPC (p = 0.007). Mean difference between VNC and true non-contrast (TNC) was 17.67 for VNCConv and 14.85 for VNCPC. Random forest classifier and logistic regression models both identified VNCConv and VNCPC as the best discriminators. When using 26 HU as the threshold in VNCConv reconstructions, adenomas could be discriminated from metastases with a sensitivity of 86.7% and a specificity of 75.6%. Conclusion: VNC algorithms overestimate CT values compared to TNC in the assessment of adrenal lesions. However, they allow a reliable discrimination between adrenal adenomas and metastases and could be used in clinical routine in near future with an increased threshold (e.g., 26 HU). Further (multi-center) studies with larger patient cohorts and standardized protocols are required. Clinical relevance statement: VNC reconstructions overestimate CT values compared to TNC. Using a different threshold (e.g., 26 HU compared to the established 10 HU), VNC has a high diagnostic accuracy for the discrimination between adrenal adenomas and metastases. Key Points: • Virtual non-contrast reconstructions may be promising tools to differentiate adrenal lesions and might save further diagnostic tests. • The conventional and a new calcium-preserving virtual non-contrast algorithm tend to systematically overestimate CT-values compared to true non-contrast images. • Therefore, increasing the established threshold for true non-contrast images (e.g., 10HU) may help to differentiate between adrenal adenomas and metastases on contrast-enhanced CT. [ABSTRACT FROM AUTHOR]

Estimating sex ratios is important for understanding population demographics. Here, we present a direct comparison of paired sex ratio estimates from visual field surveys and molecular sex identification using scat in sexually dimorphic Steller sea lions (Eumetopias jubatus). For this purpose, we designed novel qPCR Taqman gene expression assays to determine sex from scat of both Steller and California (Zalophus californianus) sea lions targeting the zinc-finger X-linked gene (ZFX) and sex-determining region Y gene (SRY). The assay pair was validated using scat samples from California sea lions of known sex with 100% success rate of signal amplification. Our assays yielded a 94.1% success rate in identifying sea lion sex from field-collected scats. In addition, the sex ratio determined via molecular analysis was closely correlated to the adult male and adult female proportions observed at the haul-out site for each month scat samples and demographic counts were collected in tandem. While visual counts cannot determine the sex of juvenile sea lions, scat collections are assumed to represent all age classes present at the haulout, suggesting that the juvenile sex ratios likely mirrored the adult sex ratio. The protocol described here could be implemented to identify the sex of Steller and California sea lions from their feces in free-ranging populations in other non-invasive, scat-based studies. Further, the concordance with visual observations suggests that molecular sex identification from scat collected at haul-outs is a robust methodology in sea lions and possibly in other pinniped species that lack distinctive sexual dimorphism. [ABSTRACT FROM AUTHOR]

Abstract Autoinflammatory diseases are a heterogenous group of disorders defined by fever and systemic inflammation suggesting involvement of genes regulating innate immune responses. Patients with homozygous loss‐of‐function variants in the OTU‐deubiquitinase OTULIN suffer from neonatal‐onset OTULIN‐related autoinflammatory syndrome (ORAS) characterized by fever, panniculitis, diarrhea, and arthritis. Here, we describe an atypical form of ORAS with distinct clinical manifestation of the disease caused by two new compound heterozygous variants (c.258G>A (p.M86I)/c.500G>C (p.W167S)) in the OTULIN gene in a 7‐year‐old affected by a life‐threatening autoinflammatory episode with sterile abscess formation. On the molecular level, we find binding of OTULIN to linear ubiquitin to be compromised by both variants; however, protein stability and catalytic activity is most affected by OTULIN variant p.W167S. These molecular changes together lead to increased levels of linear ubiquitin linkages in patient‐derived cells triggering the disease. Our data indicate that the spectrum of ORAS patients is more diverse than previously thought and, thus, supposedly asymptomatic individuals might also be affected. Based on our results, we propose to subdivide the ORAS into classical and atypical entities.

Summary: Background and aims: Micro-elimination projects targeted to specific hepatitis C virus (HCV) risk populations have been successful. Systematic identification of persons with HCV viremia, regardless of risk group, based on already available laboratory records may represent an effective macroelimination approach to achieve global HCV elimination. Methods: Persons with a last positive HCV-RNA PCR result between 2008–2020 in the reference virology laboratories in eastern Austria were identified. First, (i) we described their demographic characteristics, (ii) we systematically recalled persons to the respective centers and (iii) started antiviral treatment if HCV-RNA viremia was confirmed, and (iv) recorded sustained virologic response (SVR). This interim report includes the preliminary results from 8 participating centers. Results: During the study period 22,682 persons underwent HCV-RNA PCR testing, 11,216 (49.4%) were positive at any point in time, and 6006 (26.5%) showed detectable HCV-RNA at the last PCR test, suggesting ongoing HCV viremia. At the time of this interim report, 2546/6006 HCV-RNA PCR(+) persons were evaluated: 443/2546 (17.4%) had died, 852/2546 (33.5%) had invalid contact data, and 547/2546 (21.5%) had achieved SVR between data retrieval and recall. Contact could be established in 236/704 (33.5%) of the remaining target population with 97/236 (41.1%) presenting at the clinic for treatment evaluation. Ultimately, 71/236 (30.1%) started antiviral treatment and SVR was documented in 47/71 (66.2%). Conclusion: This ELIMINATE project based on systematic assessment of HCV-RNA PCR-records, identified 6006 persons with potential persisting HCV viremia. Invalid contact data and missed visits for treatment evaluation were the main barriers towards HCV elimination within this project. Importantly, many subjects with HCV viremia lost to follow-up were successfully linked to care and started antiviral treatment. [ABSTRACT FROM AUTHOR]

Abstract In colorectal cancer, oncogenic mutations transform a hierarchically organized and homeostatic epithelium into invasive cancer tissue lacking visible organization. We sought to define transcriptional states of colorectal cancer cells and signals controlling their development by performing single‐cell transcriptome analysis of tumors and matched non‐cancerous tissues of twelve colorectal cancer patients. We defined patient‐overarching colorectal cancer cell clusters characterized by differential activities of oncogenic signaling pathways such as mitogen‐activated protein kinase and oncogenic traits such as replication stress. RNA metabolic labeling and assessment of RNA velocity in patient‐derived organoids revealed developmental trajectories of colorectal cancer cells organized along a mitogen‐activated protein kinase activity gradient. This was in contrast to normal colon organoid cells developing along graded Wnt activity. Experimental targeting of EGFR‐BRAF‐MEK in cancer organoids affected signaling and gene expression contingent on predictive KRAS/BRAF mutations and induced cell plasticity overriding default developmental trajectories. Our results highlight directional cancer cell development as a driver of non‐genetic cancer cell heterogeneity and re‐routing of trajectories as a response to targeted therapy.

This study investigated the influence of visual and chemical stimuli from live prey on juvenile Florida pompano (Trachinotus carolinus) growth. Twelve tanks within four independent recirculating systems housed fish of similar weight (obtained from a commercial fish farm) in groups of ten. Prior to their morning feeding (they were fed twice daily at 10 h and 16 h with commercial pellets), fish were exposed to one of four stimuli: visual and chemical cues from Artemia, mole crab, feed pellets (control for stimuli), or seawater (control for procedures). Key growth parameters were monitored weekly for seven weeks, including feed intake, weight gain, and specific growth rate (SGR). Fish exposed to Artemia and mole crab stimuli exhibited significantly higher feed intake (23.11 ± 1.37 and 23.45 ± 1.38 g/fish), weight gain (169.28 ± 7.59 and 172.75 ± 12.57%), and SGR (2.02 ± 0.05 and 2.04 ± 0.09% day−1) compared to those exposed to feed pellets (stimuli control) and seawater (procedures control): feed intake (20.81 ± 0.684 and 19.30 ± 0.39 g/fish), weight gain (136.25 ± 4.51 and 140.23 ± 6.36%), and SGR (1.75 ± 0.03 and 1.78 ± 0.05%.day−1). These findings highlight the importance of visual and chemical cues from live prey as feeding incitants and stimulants. By enhancing feeding motivation and intake, these stimuli promote growth and potentially improve the welfare of juvenile Florida pompano. [ABSTRACT FROM AUTHOR]

In this paper sharp lower error bounds for numerical methods for jump-diffusion stochastic differential equations (SDEs) with discontinuous drift are proven. The approximation of jump-diffusion SDEs with non-adaptive as well as jump-adapted approximation schemes is studied and lower error bounds of order 3/4 for both classes of approximation schemes are provided. This yields optimality of the transformation-based jump-adapted quasi-Milstein scheme. [ABSTRACT FROM AUTHOR]