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In classroom assessments, examinees can often answer test items multiple times, resulting in sequential multiple-attempt data. Sequential diagnostic classification models (DCMs) have been developed for such data. As student learning processes may be aligned with a hierarchy of measured traits, this study aimed to develop a sequential hierarchical DCM (sequential HDCM), which combines a sequential DCM with the HDCM, and investigate classification accuracy of the model in the presence of hierarchies when multiple attempts are allowed in dynamic assessment. We investigated the model's impact on classification accuracy when hierarchical structures are correctly specified, misspecified, or overspecified. The results indicate that (1) a sequential HDCM accurately classified students as masters and nonmasters when the data had a hierarchical structure; (2) a sequential HDCM produced similar or slightly higher classification accuracy than nonhierarchical sequential LCDM when the data had hierarchical structures; and (3) the misspecification of the hierarchical structure of the data resulted in lower classification accuracy when the misspecified model had fewer attribute profiles than the true model. We discuss limitations and make recommendations on using the proposed model in practice. This study provides practitioners with information about the possibilities for psychometric modeling of dynamic classroom assessment data.

Abstract A hypertensive response to exercise is a precursor leading to hypertension, which is a major risk factor for the development of heart failure and diastolic dysfunction. Herein, we aimed to assess blood pressure (BP) in patients with a hypertensive response to exercise and different degrees of diastolic dysfunction. Between January 2009 and December 2014, 373 patients with a hypertensive response to exercise (HRE) and echocardiographic data assessing diastolic function were enrolled at the University Hospital of Zurich. ANCOVA was used to assess the changes in BP response during exercise testing in individuals with different degrees of diastolic dysfunction. Normalization of systolic BP was blunted in patients with grade II and III diastolic dysfunction after 3 min of recovery in univariable [β (95%) ‐ 9.2 (‐13.8 to ‐ 4.8) p

Abstract The rapid expansion of new technologies necessitates the adaptation of educational programs to meet the evolving demands of the labor market. This study focuses on students in technical fields, investigating their understanding of XR 3D visualization and proposing a unified training approach to improve both theoretical knowledge and practical skills. The research also evaluates how this training influences students’ attitudes towards XR technologies in various applications. Key findings reveal significant improvements in technical competencies and a more positive perception of XR technologies after the training. These results suggest that targeted XR education can better prepare students for the technological challenges in their respective industries.

Abstract Background Schizophrenia (SCZ) is a severe psychiatric disorder associated with alterations in early brain development. Details of underlying pathomechanisms remain unclear, despite genome and transcriptome studies providing evidence for aberrant cellular phenotypes and pathway deregulation in developing neuronal cells. However, mechanistic insight at the protein level is limited. Methods Here, we investigate SCZ-specific protein expression signatures of neuronal progenitor cells (NPC) derived from patient iPSC in comparison to healthy controls using high-throughput Western Blotting (DigiWest) in a targeted proteomics approach. Results SCZ neural progenitors displayed altered expression and phosphorylation patterns related to Wnt and MAPK signaling, protein synthesis, cell cycle regulation and DNA damage response. Consistent with impaired cell cycle control, SCZ NPCs also showed accumulation in the G2/M cell phase and reduced differentiation capacity. Furthermore, we correlated these findings with elevated p53 expression and phosphorylation levels in SCZ patient-derived cells, indicating a potential implication of p53 in hampering cell cycle progression and efficient neurodevelopment in SCZ. Conclusions Through targeted proteomics we demonstrate that SCZ NPC display coherent mechanistic alterations in regulation of DNA damage response, cell cycle control and p53 expression. These findings highlight the suitability of iPSC-based approaches for modeling psychiatric disorders and contribute to a better understanding of the disease mechanisms underlying SCZ, particularly during early development.

Introduction3D Markerless motion capture technologies have advanced significantly over the last few decades to overcome limitations of marker-based systems, which require significant cost, time, and specialization. As markerless motion capture technologies develop and mature, there is increasing demand from the biomechanics community to provide kinematic and kinetic data with similar levels of reliability and accuracy as current reference standard marker-based 3D motion capture methods. The purpose of this study was to evaluate how a novel markerless system trained with both hand-labeled and synthetic data compares to lower extremity kinematic and kinetic measurements from a reference marker-based system during the drop vertical jump (DVJ) task.MethodsSynchronized video data from multiple camera views and marker-based data were simultaneously collected from 127 participants performing three repetitions of the DVJ. Lower limb joint angles and joint moments were calculated and compared between the markerless and marker-based systems. Root mean squared error values and Pearson correlation coefficients were used to quantify agreement between the systems.ResultsRoot mean squared error values of lower limb joint angles and joint moments were ≤ 9.61 degrees and ≤ 0.23 N×m/kg, respectively. Pearson correlation values between markered and markerless systems were 0.67-0.98 hip, 0.45-0.99 knee and 0.06-0.99 ankle for joint kinematics. Likewise, Pearson correlation values were 0.73-0.90 hip, 0.61-0.95 knee and 0.74-0.95 ankle for joint kinetics.DiscussionThese results highlight the promising potential of markerless motion capture, particularly for measures of hip, knee and ankle rotations. Further research is needed to evaluate the viability of markerless ankle measures in the frontal plane to determine if differences in joint solvers are inducing unanticipated error.

Abstract Promising synaptic behaviour has been exhibited by memristors based on natural organic materials. Such memristor‐based neuromorphic systems offer notable benefits, including environmental sustainability, low production and disposal costs, non‐volatile storage capability, and bio/Complementary Metal‐Oxide‐Semiconductor (CMOS) compatibility. Here, a 256‐level honey memristor‐based neuromorphic system is experimentally evaluated for image recognition. In detail, first, 256‐level honey memristors are manufactured and tested based on in‐house technology; next, the non‐linear characteristics and inherent variation of honey memristor devices, which lead to imprecise weight updates and limit the inference accuracy, are investigated. Experimental results indicate that the inference accuracy of the 256‐level honey memristor‐based neuromorphic system is greater than 88% without cycle‐to‐cycle variations and 87% with cycle‐to‐cycle variations for different optimization algorithms. The overall performance of optimization algorithms with and without variation is compared in terms of energy and latency, where the momentum algorithm consistently outperforms the rest of the algorithms. This 256‐level honey memristor is a promising alternative enabling sustainable neuromorphic systems, encouraging further research into natural organic materials for neuromorphic computing.

Abstract Background The DNA damage response (DDR) is a physiological network preventing malignant transformation, e.g. by halting cell cycle progression upon DNA damage detection and promoting DNA repair. Glioblastoma are incurable primary tumors of the nervous system and DDR dysregulation contributes to acquired treatment resistance. Therefore, DDR targeting is a promising therapeutic anti-glioma strategy. Here, we investigated Ataxia telangiectasia and Rad3 related (ATR) inhibition (ATRi) and functionally-instructed combination therapies involving ATRi in experimental glioma. Methods We used acute cytotoxicity to identify treatment efficacy as well as RNAseq and DigiWest protein profiling to characterize ATRi-induced modulations within the molecular network in glioma cells. Genome-wide CRISPR/Cas9 functional genomic screens and subsequent validation with functionally-instructed compounds and selected shRNA-based silencing were employed to discover and investigate molecular targets modifying response to ATRi in glioma cell lines in vitro, in primary cultures ex vivo and in zebrafish and murine models in vivo. Results ATRi monotherapy displays anti-glioma efficacy in vitro and ex vivo and modulates the molecular network. We discovered molecular targets by genome-wide CRISPR/Cas9 loss-of-function and activation screens that enhance therapeutic ATRi effects. We validated selected druggable targets by a customized drug library and functional assays in vitro, ex vivo and in vivo. Conclusion In conclusion, our study leads to the identification of novel combination therapies involving ATRi that could inform future preclinical studies and early phase clinical trials.

Abstract Background Mutations in the gene DISC1 are associated with increased risk for schizophrenia, bipolar disorder and major depression. The study of mutated DISC1 represents a well-known and comprehensively characterized approach to understand neuropsychiatric disease mechanisms. However, previous studies have mainly used animal models or rather heterogeneous populations of iPSC-derived neurons, generated by undirected differentiation, to study the effects of DISC1 disruption. Since major hypotheses to explain neurodevelopmental, psychiatric disorders rely on altered neuronal connectivity observed in patients, an ideal iPSC-based model requires accurate representation of the structure and complexity of neuronal circuitries. In this study, we made use of an isogenic cell line with a mutation in DISC1 to study neuronal synaptic phenotypes in a culture system comprising a defined ratio of NGN2 and ASCL1/DLX2 (AD2)-transduced neurons, enriched for glutamatergic and GABAergic neurons, respectively, to mimic properties of the cortical microcircuitry. Results In heterozygous DISC1 mutant neurons, we replicated the expected phenotypes including altered neural progenitor proliferation as well as neurite outgrowth, deregulated DISC1-associated signaling pathways, and reduced synaptic densities in cultures composed of glutamatergic neurons. Cultures comprising a defined ratio of NGN2 and AD2 neurons then revealed considerably increased GABAergic synapse densities, which have not been observed in any iPSC-derived model so far. Increased inhibitory synapse densities could be associated with an increased efficiency of GABAergic differentiation, which we observed in AD2-transduced cultures of mutant neurons. Additionally, we found increased neuronal activity in GABAergic neurons through calcium imaging while the activity pattern of glutamatergic neurons remained unchanged. Conclusions In conclusion, our results demonstrate phenotypic differences in a co-culture comprising a defined ratio of DISC1 mutant NGN2 and AD2 neurons, as compared to culture models comprising only one neuronal cell type. Altered synapse numbers and neuronal activity imply that DISC1 impacts the excitatory/inhibitory balance in NGN2/AD2 co-cultures, mainly through increased GABAergic input.

Hatcheries are vital to many salmon fisheries, with inherent risks and rewards. While hatcheries can increase the returns of adult fish, the demographic and evolutionary consequences for natural populations interacting with hatchery fish on spawning grounds remain unclear. This study examined the impacts of stray hatchery-origin pink salmon on natural population productivity and resilience. We explored temporal assortative mating dynamics using a quantitative genetic model that assumed the only difference between hatchery- and natural-origin adults was their return timing to natural spawning grounds. This model was parameterized with empirical data from an intensive multi-generational study of hatchery–wild interactions in the world’s largest pink salmon fisheries enhancement program located in Prince William Sound, Alaska. Across scenarios of increasing hatchery fish presence on spawning grounds, our findings underscore a trade-off between demographic enhancement and preservation of natural population diversity. While enhancement bolstered natural population sizes towards local carrying capacities, hatchery introgression reduced variation in adult return timing by up to 20%. Results indicated that hatchery-origin alleles can rapidly assimilate into natural populations, despite the reduced fitness of hatchery fish attributable to phenotypic mismatches. These findings elucidate the potential for long-term demographic and evolutionary consequences arising from specific hatchery–wild interactions, emphasizing the need for management strategies that balance demographic enhancement with the conservation of natural diversity.

Abstract Objective We aimed to assess the effect of SGLT2i on arrhythmias by conducting a meta-analysis using data from randomized controlled trials(RCTs). Background Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have shown cardioprotective effects via multiple mechanisms that may also contribute to decrease arrhythmias risk. Methods We searched in databases (PubMed, Embase, Cochrane Library, and clinicaltrials.gov) up to April 2023. RCTs comparing SGLT2i with placebo were included. The effects of SGLT2i on atrial fibrillation(AF), atrial flutter(AFL), composite AF/AFL, ventricular fibrillation(VF), ventricular tachycardia(VT), ventricular extrasystoles(VES), sudden cardiac death(SCD) and composite VF/VT/SCD were evaluated. Results 33 placebo-controlled RCTs were included, comprising 88,098 patients (48,585 in SGLT2i vs. 39,513 in placebo). The mean age was 64.9 ± 9.4 years, 63.0% were male. The mean follow-up was 1.4 ± 1.1 years. The pooled-results showed that SGLT2i was associated with a significantly lower risk of AF [risk ratio(RR): 0.88, 95% confidence interval(CI) 0.78–1.00, P = 0.04] and composite AF/AFL (RR: 0.86, 95%CI 0.77–0.96, P = 0.01). This favorable effect appeared to be substantially pronounced in patients with HFrEF, male gender, dapagliflozin, and > 1 year follow-up. For SCD, only in heart failure patients, SGLT2i were found to be associated with a borderline lower risk of SCD (RR: 0.67, P = 0.05). No significant effects of SGLT2i on other ventricular arrhythmic outcomes were found. Conclusions SGLT2i lowers the risks of AF and AF/AFL, and this favorable effect appeared to be particularly pronounced in patients with HFrEF, male gender, dapagliflozin, and longer follow-up (> 1 year). SGLT2i lowers the risk of SCD only in heart failure patients. Graphical Abstract

Abstract Fibroblast growth factor receptor (FGFR)−2 can be inhibited by FGFR-selective or non-selective tyrosine kinase inhibitors (TKIs). Selective TKIs are approved for cholangiocarcinoma (CCA) with FGFR2 fusions; however, their application is limited by a characteristic pattern of adverse events or evocation of kinase domain mutations. A comprehensive characterization of a patient cohort treated with the non-selective TKI lenvatinib reveals promising efficacy in FGFR2-driven CCA. In a bed-to-bench approach, we investigate FGFR2 fusion proteins bearing critical tumor-relevant point mutations. These mutations confer growth advantage of tumor cells and increased resistance to selective TKIs but remain intriguingly sensitive to lenvatinib. In line with clinical observations, in-silico analyses reveal a more favorable interaction pattern of lenvatinib with FGFR2, including an increased flexibility and ligand efficacy, compared to FGFR-selective TKIs. Finally, the treatment of a patient with progressive disease and a newly developed kinase mutation during therapy with a selective inhibitor results in a striking response to lenvatinib. Our in vitro, in silico, and clinical data suggest that lenvatinib is a promising treatment option for FGFR2-driven CCA, especially when insurmountable adverse reactions of selective TKIs or acquired kinase mutations occur.

Generative artificial intelligence (AI) can exhibit biases, compromise data privacy, misinterpret prompts that are adversarial attacks, and produce hallucinations. Despite the potential of generative AI for many applications in digital health, practitioners must understand these tools and their limitations. This scoping review pays particular attention to the challenges with generative AI technologies in medical settings and surveys potential solutions. Using PubMed, we identified a total of 120 articles published by March 2024, which reference and evaluate generative AI in medicine, from which we synthesized themes and suggestions for future work. After first discussing general background on generative AI, we focus on collecting and presenting 6 challenges key for digital health practitioners and specific measures that can be taken to mitigate these challenges. Overall, bias, privacy, hallucination, and regulatory compliance were frequently considered, while other concerns around generative AI, such as overreliance on text models, adversarial misprompting, and jailbreaking, are not commonly evaluated in the current literature.

BackgroundBlack adolescents with type 1 diabetes (T1D) are at increased risk for suboptimal diabetes health outcomes; however, evidence-based interventions for this population are lacking. Depression affects a high percentage of youth with T1D and increases the likelihood of health problems associated with diabetes. ObjectiveOur aim was to test whether baseline levels of depression moderate the effects of a brief eHealth parenting intervention delivered to caregivers of young Black adolescents with T1D on youths’ glycemic control. MethodsWe conducted a multicenter randomized controlled trial at 7 pediatric diabetes clinics located in 2 large US cities. Participants (N=149) were allocated to either the intervention group or a standard medical care control group. Up to 3 intervention sessions were delivered on a tablet computer during diabetes clinic visits over a 12-month period. ResultsIn a linear mixed effects regression model, planned contrasts did not show significant reductions in hemoglobin A1c (HbA1c) for intervention adolescents compared to controls. However, adolescents with higher baseline levels of depressive symptoms who received the intervention had significantly greater improvements in HbA1c levels at 6-month follow-up (0.94%; P=.01) and 18-month follow-up (1.42%; P=.002) than those with lower levels of depression. Within the intervention group, adolescents had a statistically significant reduction in HbA1c levels from baseline at 6-month and 18-month follow-up. ConclusionsA brief, culturally tailored eHealth parenting intervention improved health outcomes among Black adolescents with T1D and depressive symptoms. Trial RegistrationClinicalTrials.gov NCT03168867; https://clinicaltrials.gov/study/NCT03168867

In the context of multimodal treatments for abdominal cancer, including procedures such as cytoreductive surgery and intraperitoneal chemotherapy, recurrence rates remain high, and long-term survival benefits are uncertain due to post-operative complications. Notably, treatment-limiting side effects often arise from an uncontrolled activation of the immune system, particularly peritoneally localized macrophages, leading to massive cytokine secretion and phenotype changes. Exploring alternatives, an increasing number of studies investigated the potential of plasma-activated liquids (PAL) for adjuvant peritoneal cancer treatment, aiming to mitigate side effects, preserve healthy tissue, and reduce cytotoxicity towards non-cancer cells. To assess the non-toxicity of PAL, we isolated primary human macrophages from the peritoneum and subjected them to PAL exposure. Employing an extensive methodological spectrum, including flow cytometry, Raman microspectroscopy, and DigiWest protein analysis, we observed a pronounced resistance of macrophages towards PAL. This resistance was characterized by an upregulation of proliferation and anti-oxidative pathways, countering PAL-derived oxidative stress-induced cell death. The observed cellular effects of PAL treatment on human tissue-resident peritoneal macrophages unveil a potential avenue for PAL-derived immunomodulatory effects within the human peritoneal cavity. Our findings contribute to understanding the intricate interplay between PAL and macrophages, shedding light on the promising prospects for PAL in the adjuvant treatment of peritoneal cancer.

ABSTRACT Wolbachia are a genus of insect endosymbiotic bacteria which includes strains wMel and wAlbB that are being utilized as a biocontrol tool to reduce the incidence of Aedes aegypti-transmitted viral diseases like dengue. However, the precise mechanisms underpinning the antiviral activity of these Wolbachia strains are not well defined. Here, we generated a panel of Ae. aegypti-derived cell lines infected with antiviral strains wMel and wAlbB or the non-antiviral Wolbachia strain wPip to understand host cell morphological changes specifically induced by antiviral strains. Antiviral strains were frequently found to be entirely wrapped by the host endoplasmic reticulum (ER) membrane, while wPip bacteria clustered separately in the host cell cytoplasm. ER-derived lipid droplets (LDs) increased in volume in wMel- and wAlbB-infected cell lines and mosquito tissues compared to cells infected with wPip or Wolbachia-free controls. Inhibition of fatty acid synthase (required for triacylglycerol biosynthesis) reduced LD formation and significantly restored ER-associated dengue virus replication in cells occupied by wMel. Together, this suggests that antiviral Wolbachia strains may specifically alter the lipid composition of the ER to preclude the establishment of dengue virus (DENV) replication complexes. Defining Wolbachia’s antiviral mechanisms will support the application and longevity of this effective biocontrol tool that is already being used at scale.IMPORTANCEAedes aegypti transmits a range of important human pathogenic viruses like dengue. However, infection of Ae. aegypti with the insect endosymbiotic bacterium, Wolbachia, reduces the risk of mosquito to human viral transmission. Wolbachia is being utilized at field sites across more than 13 countries to reduce the incidence of viruses like dengue, but it is not well understood how Wolbachia induces its antiviral effects. To examine this at the subcellular level, we compared how different strains of Wolbachia with varying antiviral strengths associate with and modify host cell structures. Strongly antiviral strains were found to specifically associate with the host endoplasmic reticulum and induce striking impacts on host cell lipid droplets. Inhibiting Wolbachia-induced lipid redistribution partially restored dengue virus replication demonstrating this is a contributing role for Wolbachia's antiviral activity. These findings provide new insights into how antiviral Wolbachia strains associate with and modify Ae. aegypti host cells.

Summary: Understanding the emergence of human notochordal cells (NC) is essential for the development of regenerative approaches. We present a comprehensive investigation into the specification and generation of bona fide NC using a straightforward pluripotent stem cell (PSC)-based system benchmarked with human fetal notochord. By integrating in vitro and in vivo transcriptomic data at single-cell resolution, we establish an extended molecular signature and overcome the limitations associated with studying human notochordal lineage at early developmental stages. We show that TGF-β inhibition enhances the yield and homogeneity of notochordal lineage commitment in vitro. Furthermore, this study characterizes regulators of cell-fate decision and matrisome enriched in the notochordal niche. Importantly, we identify specific cell-surface markers opening avenues for differentiation refinement, NC purification, and functional studies. Altogether, this study provides a human notochord transcriptomic reference that will serve as a resource for notochord identification in human systems, diseased-tissues modeling, and facilitating future biomedical research.

Objective: Aggregation of human islet amyloid polypeptide (hIAPP), a β-cell secretory product, leads to islet amyloid deposition, islet inflammation and β-cell loss in type 2 diabetes (T2D), but the mechanisms that underlie this process are incompletely understood. Receptor interacting protein kinase 3 (RIPK3) is a pro-death signaling molecule that has recently been implicated in amyloid-associated brain pathology and β-cell cytotoxicity. Here, we evaluated the role of RIPK3 in amyloid-induced β-cell loss using a humanized mouse model of T2D that expresses hIAPP and is prone to islet amyloid formation. Methods: We quantified amyloid deposition, cell death and caspase 3/7 activity in islets isolated from WT, Ripk3−/−, hIAPP and hIAPP; Ripk3−/− mice in real time, and evaluated hIAPP-stimulated inflammation in WT and Ripk3−/− bone marrow derived macrophages (BMDMs) in vitro. We also characterized the role of RIPK3 in glucose stimulated insulin secretion (GSIS) in vitro and in vivo. Finally, we examined the role of RIPK3 in high fat diet (HFD)-induced islet amyloid deposition, β-cell loss and glucose homeostasis in vivo. Results: We found that amyloid-prone hIAPP mouse islets exhibited increased cell death and caspase 3/7 activity compared to amyloid-free WT islets in vitro, and this was associated with increased RIPK3 expression. hIAPP; Ripk3−/− islets were protected from amyloid-induced cell death compared to hIAPP islets in vitro, although amyloid deposition and caspase 3/7 activity were not different between genotypes. We observed that macrophages are a source of Ripk3 expression in isolated islets, and that Ripk3−/− BMDMs were protected from hIAPP-stimulated inflammatory gene expression (Tnf, Il1b, Nos2). Following 52 weeks of HFD feeding, islet amyloid-prone hIAPP mice exhibited impaired glucose tolerance and decreased β-cell area compared to WT mice in vivo, whereas hIAPP; Ripk3−/− mice were protected from these impairments. Conclusions: In conclusion, loss of RIPK3 protects from amyloid-induced inflammation and islet cell death in vitro and amyloid-induced β-cell loss and glucose intolerance in vivo. We propose that therapies targeting RIPK3 may reduce islet inflammation and β-cell loss and improve glucose homeostasis in the pathogenesis of T2D.

Acute chest pain and dyspnea often raise coronary disease suspicion. When echocardiography and cardiac computed tomography findings appear normal, alternative diagnoses should be explored. We present a case initially suggestive of myocarditis but later revealed as coronary dissection by cardiac magnetic resonance. This case emphasizes the role of advanced imaging in atypical cardiac presentations.

Poor oral health is an important concern for athletes, as it can affect both general health and athletic performance. The aim of this study is to investigate the effects of activity in chlorinated water on oral health in elite swimmers compared to non-swimming athletes. This cross-sectional study included 101 swimmers and 100 other athletes aged 13–26 years with a minimum training intensity of five hours per week (for at least the preceding two years). Oral health was assessed using the approximal plaque index (API) and the decayed/missing/filled teeth (DMFT) index. A DIAGNOcam was used to detect caries. Results show that swimmers were younger (15 years vs. 18 years), were more likely to be female (54% vs. 17%), and had a lower body mass index (20.1 kg/m2 vs. 21.9 kg/m2) and a lower juice consumption (9% vs. 24%). Non-swimmers had significantly more decayed, missing, or filled teeth due to caries and plaque. In conclusion, by comparing elite swimmers and athletes competing in different sports, we have shown that competitive swimmers have a lower incidence of dental caries and plaque. Further research is needed to test our findings and to understand this relationship in greater detail.

Background and Aims Cardiogenic shock (CS) remains the primary cause of in-hospital death after acute coronary syndromes (ACS), with its plateauing mortality rates approaching 50%. To test novel interventions, personalized risk prediction is essential. The ORBI (Observatoire Régional Breton sur l'Infarctus) score represents the first-of-its-kind risk score to predict in-hospital CS in ACS patients undergoing percutaneous coronary intervention (PCI). However, its sex-specific performance remains unknown, and refined risk prediction strategies are warranted. Methods This multinational study included a total of 53 537 ACS patients without CS on admission undergoing PCI. Following sex-specific evaluation of ORBI, regression and machine-learning models were used for variable selection and risk prediction. By combining best-performing models with highest-ranked predictors, SEX-SHOCK was developed, and internally and externally validated. Results The ORBI score showed lower discriminative performance for the prediction of CS in females than males in Swiss (area under the receiver operating characteristic curve [95% confidence interval]: 0.78 [0.76–0.81] vs. 0.81 [0.79–0.83]; P =.048) and French ACS patients (0.77 [0.74–0.81] vs. 0.84 [0.81–0.86]; P =.002). The newly developed SEX-SHOCK score, now incorporating ST-segment elevation, creatinine, C-reactive protein, and left ventricular ejection fraction, outperformed ORBI in both sexes (females: 0.81 [0.78–0.83]; males: 0.83 [0.82–0.85]; P <.001), which prevailed following internal and external validation in RICO (females: 0.82 [0.79–0.85]; males: 0.88 [0.86–0.89]; P <.001) and SPUM-ACS (females: 0.83 [0.77–0.90], P =.004; males: 0.83 [0.80–0.87], P =.001). Conclusions The ORBI score showed modest sex-specific performance. The novel SEX-SHOCK score provides superior performance in females and males across the entire spectrum of ACS, thus providing a basis for future interventional trials and contemporary ACS management. [ABSTRACT FROM AUTHOR]

The rapid expansion of new technologies necessitates the adaptation of educational programs to meet the evolving demands of the labor market. This study focuses on students in technical fields, investigating their understanding of XR 3D visualization and proposing a unified training approach to improve both theoretical knowledge and practical skills. The research also evaluates how this training influences students' attitudes towards XR technologies in various applications. Key findings reveal significant improvements in technical competencies and a more positive perception of XR technologies after the training. These results suggest that targeted XR education can better prepare students for the technological challenges in their respective industries. [ABSTRACT FROM AUTHOR]

A hypertensive response to exercise is a precursor leading to hypertension, which is a major risk factor for the development of heart failure and diastolic dysfunction. Herein, we aimed to assess blood pressure (BP) in patients with a hypertensive response to exercise and different degrees of diastolic dysfunction. Between January 2009 and December 2014, 373 patients with a hypertensive response to exercise (HRE) and echocardiographic data assessing diastolic function were enrolled at the University Hospital of Zurich. ANCOVA was used to assess the changes in BP response during exercise testing in individuals with different degrees of diastolic dysfunction. Normalization of systolic BP was blunted in patients with grade II and III diastolic dysfunction after 3 min of recovery in univariable [β (95%) ‐ 9.2 (‐13.8 to ‐ 4.8) p <.001, ‐16.0 (‐23.0 to 9.0) p <.001, respectively] and adjusted models. In fully adjusted models, when taking maximal effort into account, there were no differences with regard to systolic BP during exercise. Patients without diastolic dysfunction achieved higher heart rates (HRs) [both in absolute terms (p <.001) and as a percentage of the calculated maximum (p =.003)] and greater wattage (p <.001) at maximum exertion. The findings of this cross‐sectional study suggest that exercise capacity is compromised in patients with diastolic dysfunction. A hypertensive response to exercise and the finding of a blunted BP recovery may help identify patients at risk of developing heart failure. [ABSTRACT FROM AUTHOR]

Ventricular arrhythmias originating from the papillary muscle of the ventricles are complex clinical problems. Catheter ablation has the potential to cure these arrhythmias. However, the procedure is usually challenging due to the specific anatomy, catheter instability and difficulty in localization of the origin of the arrhythmias. Intracardiac echocardiography (ICE) has been reported to be the suitable imaging method for assessing the location of focus in papillary muscles. We used transthoracic echocardiography (TTE), as a noninvasive cost-effective imaging supporting modality, in combination with 3D mapping to guide the exact localization and successful ablation of papillary muscle-originating premature ventricular contractions (PVCs). [ABSTRACT FROM AUTHOR]

Promising synaptic behaviour has been exhibited by memristors based on natural organic materials. Such memristor‐based neuromorphic systems offer notable benefits, including environmental sustainability, low production and disposal costs, non‐volatile storage capability, and bio/Complementary Metal‐Oxide‐Semiconductor (CMOS) compatibility. Here, a 256‐level honey memristor‐based neuromorphic system is experimentally evaluated for image recognition. In detail, first, 256‐level honey memristors are manufactured and tested based on in‐house technology; next, the non‐linear characteristics and inherent variation of honey memristor devices, which lead to imprecise weight updates and limit the inference accuracy, are investigated. Experimental results indicate that the inference accuracy of the 256‐level honey memristor‐based neuromorphic system is greater than 88% without cycle‐to‐cycle variations and 87% with cycle‐to‐cycle variations for different optimization algorithms. The overall performance of optimization algorithms with and without variation is compared in terms of energy and latency, where the momentum algorithm consistently outperforms the rest of the algorithms. This 256‐level honey memristor is a promising alternative enabling sustainable neuromorphic systems, encouraging further research into natural organic materials for neuromorphic computing. [ABSTRACT FROM AUTHOR]

Background Spontaneous coronary artery dissection (SCAD) is the most important cause of acute coronary syndromes during pregnancy and in the post-partum period and involves a spontaneous intimal tear or intramural haematoma of a coronary artery. Pregnancy-associated SCAD accounts for a minority of SCAD cases but is associated with a high rate of adverse events. Case summary We present a series of three cases with pregnancy-associated SCAD. All patients presented with acute coronary syndromes in the post-partum period, between 12 days and 5 months after delivery. They all had additional conditions that are associated with SCAD, such as fibromuscular dysplasia and migraine. The management of one patient was uncomplicated, however, the courses of the other two were characterized by adverse events. One presented after an out-of-hospital cardiac arrest, the other presented with multivessel SCAD and developed progression and recurrence of SCAD during follow-up. In conclusion, the patients could be successfully treated conservatively and were in good condition at their latest follow-ups. Discussion This case series highlights the wide range of clinical courses that could exist in pregnancy-associated SCAD, from a benign manifestation to a life-threatening condition. Importantly, those patients are at an increased risk for acute and late adverse events. [ABSTRACT FROM AUTHOR]