University Children's Hospital Zurich

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    Can ChatGPT reduce human financial analysts’ optimistic biases?

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    This paper examines the potential of ChatGPT, a large language model, as a financial advisor for listed firm performance forecasts. We focus on the constituent stocks of the China Securities Index 300 and compare ChatGPT’s forecasts for major financial performance measures with human analysts’ forecasts and the realised values. Our findings suggest that ChatGPT can correct the optimistic biases of human analysts. This study contributes to the literature by exploring the potential of ChatGPT as a financial advisor and demonstrating its role in reducing human biases in financial decision-making

    Concentration-effect relationships of plasma caffeine on EEG delta power and cardiac autonomic activity during human sleep

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    Acute caffeine intake affects brain and cardiovascular physiology, yet the concentration-effect relationships on the electroencephalogram and cardiac autonomic activity during sleep are poorly understood. To tackle this question, we simultaneously quantified the plasma caffeine concentration with ultra-high-performance liquid chromatography, as well as the electroencephalogram, heart rate and high-frequency (0.15-0.4 Hz) spectral power in heart rate variability, representing parasympathetic activity, with standard polysomnography during undisturbed human sleep. Twenty-one healthy young men in randomized, double-blind, crossover fashion, ingested 160 mg caffeine or placebo in a delayed, pulsatile-release caffeine formula at their habitual bedtime, and initiated a 4-hr sleep opportunity 4.5 hr later. The mean caffeine levels during sleep exhibited high individual variability between 0.2 and 18.4 μmol L1^{-1} . Across the first two non-rapid-eye-movement (NREM)-rapid-eye-movement sleep cycles, electroencephalogram delta (0.75-2.5 Hz) activity and heart rate were reliably modulated by waking and sleep states. Caffeine dose-dependently reduced delta activity and heart rate, and increased high-frequency heart rate variability in NREM sleep when compared with placebo. The average reduction in heart rate equalled 3.24 ± 0.77 beats per minute. Non-linear statistical models suggest that caffeine levels above ~7.4 μmol L1^{-1} decreased electroencephalogram delta activity, whereas concentrations above ~4.3 μmol L1^{-1} and ~ 4.9 μmol L1^{-1} , respectively, reduced heart rate and increased high-frequency heart rate variability. These findings provide quantitative concentration-effect relationships of caffeine, electroencephalogram delta power and cardiac autonomic activity, and suggest increased parasympathetic activity during sleep after intake of caffeine

    Cortical miR-709 links glutamatergic signaling to NREM sleep EEG slow waves in an activity-dependent manner

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    MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression that have been implicated in a plethora of neuronal processes. Nevertheless, their role in regulating brain activity in the context of sleep has so far received little attention. To test their involvement, we deleted mature miRNAs in post-mitotic neurons at two developmental ages, i.e., in early adulthood using conditional Dicer knockout (cKO) mice and in adult mice using an inducible conditional Dicer cKO (icKO) line. In both models, electroencephalographic (EEG) activity was affected and the response to sleep deprivation (SD) altered; while the rapid-eye-movement sleep (REMS) rebound was compromised in both, the increase in EEG delta (1 to 4 Hz) power during non-REMS (NREMS) was smaller in cKO mice and larger in icKO mice compared to controls. We subsequently investigated the effects of SD on the forebrain miRNA transcriptome and found that the expression of 48 miRNAs was affected, and in particular that of the activity-dependent miR-709. In vivo inhibition of miR-709 in the brain increased EEG power during NREMS in the slow-delta (0.75 to 1.75 Hz) range, particularly after periods of prolonged wakefulness. Transcriptome analysis of primary cortical neurons in vitro revealed that miR-709 regulates genes involved in glutamatergic neurotransmission. A subset of these genes was also affected in the cortices of sleep-deprived, miR-709-inhibited mice. Our data implicate miRNAs in the regulation of EEG activity and indicate that miR-709 links neuronal activity during wakefulness to brain synchrony during sleep through the regulation of glutamatergic signaling

    European guidelines for the diagnosis, treatment and follow-up of breast lesions with uncertain malignant potential (B3 lesions) developed jointly by EUSOMA, EUSOBI, ESP (BWG) and ESSO

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    Introduction: Breast lesions of uncertain malignant potential (B3) include atypical ductal and lobular hyperplasias, lobular carcinoma in situ, flat epithelial atypia, papillary lesions, radial scars and fibroepithelial lesions as well as other rare miscellaneous lesions. They are challenging to categorise histologically, requiring specialist training and multidisciplinary input. They may coexist with in situ or invasive breast cancer (BC) and increase the risk of subsequent BC development. Management should focus on adequate classification and management whilst avoiding overtreatment. The aim of these guidelines is to provide updated information regarding the diagnosis and management of B3 lesions, according to updated literature review evidence. Methods: These guidelines provide practical recommendations which can be applied in clinical practice which include recommendation grade and level of evidence. All sections were written according to an updated literature review and discussed at a consensus meeting. Critical appraisal by the expert writing committee adhered to the 23 items in the international Appraisal of Guidelines, Research and Evaluation (AGREE) tool. Results: Recommendations for further management after core-needle biopsy (CNB) or vacuum-assisted biopsy (VAB) diagnosis of a B3 lesion reported in this guideline, vary depending on the presence of atypia, size of lesion, sampling size, and patient preferences. After CNB or VAB, the option of vacuum-assisted excision or surgical excision should be evaluated by a multidisciplinary team and shared decision-making with the patient is crucial for personalizing further treatment. De-escalation of surgical intervention for B3 breast lesions is ongoing, and the inclusion of vacuum-assisted excision (VAE) will decrease the need for surgical intervention in further approaches. Communication with patients may be different according to histological diagnosis, presence or absence of atypia, or risk of upgrade due to discordant imaging. Written information resources to help patients understand these issues alongside with verbal communication is recommended. Lifestyle interventions have a significant impact on BC incidence so lifestyle interventions need to be suggested to women at increased BC risk as a result of a diagnosis of a B3 lesion. Conclusions: These guidelines provide a state-of-the-art overview of the diagnosis, management and prognosis of B3 lesions in modern multidisciplinary breast practice

    The Surgical Algorithm for the AO Spine Sacral Injury Classification System

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    Study design: Global cross-sectional survey. Objective: To establish a surgical algorithm for sacral fractures based on the AO Spine Sacral Injury Classification System. Summary of background data: Although the AO Spine Sacral Injury Classification has been validated across an international audience of surgeons, a consensus on a surgical algorithm has yet to be developed for sacral fractures by using the Sacral AO Spine Injury Score (Sacral AOSIS). Methods: A survey was sent to general orthopedic surgeons, orthopedic spine surgeons, and neurosurgeons across the five AO Spine regions of the world. Descriptions of controversial sacral injuries based on different fracture subtypes were given and surgeons were asked whether the patient should undergo operative or non-operative management. The results of the survey were used to create a surgical algorithm based on each subtypes' Sacral AOSIS. Results: International agreement of 70% was decided on by the AO Spine Knowledge Forum Trauma experts to indicate a recommendation of initial operative intervention. Using this, sacral fracture subtypes of AOSIS 5 or greater were considered operative while those with AOSIS 4 or less were generally non-operative. For subtypes with an AOSIS of 3 or 4, if the sacral fracture was associated with an anterior pelvic ring injury (M3 case-specific modifier), intervention should be left to the surgeons' discretion. Conclusion: The AO Spine Sacral Injury Classification System offers a validated hierarchical system to approach sacral injuries. Through multi-specialty and global surgeon input, a surgical algorithm was developed to determine appropriate operative indications for sacral trauma. Further validation is required, but this algorithm provides surgeons across the world with the basis for discussion and the development of standard of care treatment. Level of evidence: Level IV

    Comparative analysis of late gadolinium enhancement assessment techniques for monitoring fibrotic changes in myocarditis follow-up

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    OBJECTIVES To compare the repeatability and interrelation of various late gadolinium enhancement (LGE) assessment techniques for monitoring fibrotic changes in myocarditis follow-up. MATERIALS AND METHODS LGE extent change between baseline and 3-month cardiovascular magnetic resonance (CMR) was compared in patients with acute myocarditis using the full width at half maximum (FWHM), gray-scale thresholds at 5 and 6 standard deviations (SD5 and SD6), visual assessment with threshold (VAT) and full manual (FM) techniques. In addition, visual presence score (VPS), visual transmurality score (VTS), and a simplified visual change score (VCS) were assessed. Intraclass-correlation (ICC) was used to evaluate repeatability, and methods were compared using Spearman's correlation. RESULTS Forty-seven patients (38 male, median age: 27 [IQR: 21; 38] years) were included. LGE extent change differed among quantitative techniques (p < 0.01), with variability in the proportion of patients showing LGE change during follow-up (FWHM: 62%, SD5: 74%, SD6: 66%, VAT: 43%, FM: 60%, VPS: 53%, VTS: 77%, VCS: 89%). Repeatability was highest with FWHM (ICC: 0.97) and lowest with SD5 (ICC: 0.89). Semiquantitative scoring had slightly lower values (VPS ICC: 0.81; VTS ICC: 0.71). VCS repeatability was excellent (ICC: 0.93). VPS and VTS correlated with quantitative techniques, while VCS was positively associated with VPS, VTS, VAT, and FM, but not with FWHM, SD5, and SD6. CONCLUSION FWHM offers the least observer-dependent LGE follow-up after myocarditis. VPS, VTS, and VCS are practical alternatives, showing reliable correlations with quantitative methods. Classification of patients exhibiting either stable or changing LGE relies on the assessment technique. CLINICAL RELEVANCE STATEMENT This study shows that LGE monitoring in myocarditis is technique-dependent; the FWHM method yields the most consistent fibrotic tracking results, with scoring-based techniques as reliable alternatives. KEY POINTS Recognition of fibrotic changes during myocarditis follow-up is significantly influenced by the choice of the quantification technique employed. The FWHM technique ensures highly repeatable tracking of myocarditis-related LGE changes. Segment-based visual scoring and the simplified visual change score offer practical, reproducible alternatives in resource-limited settings

    FLight Biofabrication Supports Maturation of Articular Cartilage with Anisotropic Properties

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    Tissue engineering approaches that recapitulate cartilage biomechanical properties are emerging as promising methods to restore the function of injured or degenerated tissue. However, despite significant progress in this research area, the generation of engineered cartilage constructs akin to native counterparts still represents an unmet challenge. In particular, the inability to accurately reproduce cartilage zonal architecture with different collagen fibril orientations is a significant limitation. The arrangement of the extracellular matrix (ECM) plays a fundamental role in determining the mechanical and biological functions of the tissue. In this study, it is shown that a novel light-based approach, Filamented Light (FLight) biofabrication, can be used to generate highly porous, 3D cell-instructive anisotropic constructs that lead to directional collagen deposition. Using a photoclick-based photoresin optimized for cartilage tissue engineering, a significantly improved maturation of the cartilaginous tissues with zonal architecture and remarkable native-like mechanical properties is demonstrated

    Central tolerance shapes the neutralizing B cell repertoire against a persisting virus in its natural host

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    Viral mimicry of host cell structures has been postulated to curtail the B cell receptor (BCR) repertoire against persisting viruses through tolerance mechanisms. This concept awaits, however, experimental testing in a setting of natural virus–host relationship. We engineered mouse models expressing a monoclonal BCR specific for the envelope glycoprotein of lymphocytic choriomeningitis virus (LCMV), a naturally persisting mouse pathogen. When the heavy chain of the LCMV-neutralizing antibody KL25 was paired with its unmutated ancestor light chain, most B cells underwent receptor editing, a behavior reminiscent of autoreactive clones. In contrast, monoclonal B cells expressing the same heavy chain in conjunction with the hypermutated KL25 light chain did not undergo receptor editing but exhibited low levels of surface IgM, suggesting that light chain hypermutation had lessened KL25 autoreactivity. Upon viral challenge, these IgM low^{low} cells were not anergic but up-regulated IgM, participated in germinal center reactions, produced antiviral antibodies, and underwent immunoglobulin class switch as well as further affinity maturation. These studies on a persisting virus in its natural host species suggest that central tolerance mechanisms prune the protective antiviral B cell repertoire

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