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Contemporary clinical conversations about stuttering: Telling parents why their child began to stutter
No full textMeasurement of off-shell Higgs boson production in the H ∗ → Z Z → 4 ℓ decay channel using a neural simulation-based inference technique in 13 TeV pp collisions with the ATLAS detector
No full textAbstract A measurement of off-shell Higgs boson production in the H ∗ → Z Z → 4 ℓ decay channel is presented. The measurement uses 140 fb −1 of proton–proton collisions at s = 13 TeV collected by the ATLAS detector at the Large Hadron Collider and supersedes the previous result in this decay channel using the same dataset. The data analysis is performed using a neural simulation-based inference method, which builds per-event likelihood ratios using neural networks. The observed (expected) off-shell Higgs boson production signal strength in the Z Z → 4 ℓ decay channel at 68% CL is 0.87 − 0.54 + 0.75 ( 1.00 − 0.95 + 1.04 ). The evidence for off-shell Higgs boson production using the Z Z → 4 ℓ decay channel has an observed (expected) significance of 2.5 σ (1.3 σ ). The expected result represents a significant improvement relative to that of the previous analysis of the same dataset, which obtained an expected significance of 0.5 σ . When combined with the most recent ATLAS measurement in the Z Z → 2 ℓ 2 ν decay channel, the evidence for off-shell Higgs boson production has an observed (expected) significance of 3.7 σ (2.4 σ ). The off-shell measurements are combined with the measurement of on-shell Higgs boson production to obtain constraints on the Higgs boson total width. The observed (expected) value of the Higgs boson width at 68% CL is 4.3 − 1.9 + 2.7 ( 4.1 − 3.4 + 3.5 ) MeV
The functionality of telomerase depends on CPF–CF induced 3′end processing of its RNA component TLC1 and a novel Nrd1–Nab3 surveillance mechanism
No full textAbstract Telomere elongation is driven by telomerase, which consists of several proteins and the ncRNA component TLC1 in yeast. While many ncRNAs are terminated via the Nrd1–Nab3–Sen1 (NNS) pathway, we found that TLC1 requires cleavage and polyadenylation factor (CPF)–cleavage factor (CF) mediated 3′end processing and the resulting poly(A) tail to mature into a functional ribozyme. The poly(A) tail is predicted to fold back onto (U)-repeats potentially forming a terminal stem–loop structure that supports Sm-ring binding and thereby re-import into the nucleus after cytoplasmic shuttling. However, longer pre-TLC1 transcripts are predicted to fold differently, resulting in Sm-ring and import receptor binding defects, leaving them unable to overcome this cytoplasmic quality control checkpoint. To prevent cytoplasmic leakage of overlong transcripts, we propose an additional nuclear monitoring system, requiring Nrd1–Nab3 binding sites located between the first PAS motifs. CPF–CF formation might compete with Nrd1–Nab3 releasing them from shorter but not from longer transcripts facilitating their decay. This potential competitive RNA-binding of CPF–CF and Nrd1–Nab3 balances stability and decay
Do Theory of Mind and Mental Time Travel abilities build on joint cognitive foundations?
No full textHigher cognition is special in that it goes beyond representing the here and now. Two relevant forms of such thinking are Theory of Mind (ToM) that enables us to represent others’ perspectives, and Mental Time Travel (MTT) that enables us to represent other points in time. The present studies investigate how these capacities are related in development. Do they build on the same cognitive foundations and thus emerge together? Do higher-order forms of the two abilities rely on analogous recursive embedding and thus progress in parallel and coordinated ways? We addressed these questions in four studies with 3- to 9-year-old children ( N = 395). ToM was operationalized as first-, second- and third-order false belief understanding. MTT was operationalized as reasoning about future possibilities (first-order), counterfactual reasoning (second-order) and anticipating counterfactual emotions (third-order). Study 1 shows a stepwise development of both ToM and MTT and a moderate consistency of performance patterns. However, across all four studies, we did not find robust correlations between first-, second- and third-order tasks of ToM and MTT, respectively. Overall, these results show stepwise and parallel trajectories in ToM and MTT, but do not provide stringent evidence for a joint cognitive foundation of the two capacities.Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659Leibniz Association 50110000166
Real‐Time MRI of the Chest Wall, Diaphragm, and Lungs in Children
No full textABSTRACT Objective To evaluate the clinical applicability and diagnostic potential of real‐time magnetic resonance imaging (rtMRI) as a sedation‐free, radiation‐free imaging modality for assessing the chest wall, diaphragm, and lungs in children. Methods This video‐based narrative review summarizes over four years of clinical experience with rtMRI in pediatric thoracic imaging. Real‐time MRI achieves very high frame rates (up to 50 images per second), effectively minimizing motion artifacts. Representative clinical scenarios—including pneumonia, chest wall tumors, diaphragmatic dysfunction, airway anomalies, and congenital lung malformations—are presented to illustrate the diagnostic capabilities and limitations of rtMRI. Results Real‐time MRI enables reliable imaging of thoracic structures in awake and uncooperative children, minimizing motion artifacts and thus eliminating the need for sedation. It provides diagnostic information on conditions such as pneumonia, abscesses, effusions, and neoplastic lesions, using two basic MR contrasts. Diaphragmatic motion and large airway morphology are clearly visualized. Limitations include reduced sensitivity for detecting interstitial lung disease and small pulmonary metastases. Complete thoracic examinations can be performed within 4 minutes, supporting rapid triage and potentially obviating the need for CT or sedated MRI in selected cases. Conclusion Real‐time MRI is a promising, child‐friendly alternative for thoracic imaging in pediatrics, particularly for evaluating chest wall abnormalities, diaphragmatic disorders, and pneumonia‐related complications. Broader adoption and vendor‐independent implementation may help establish rtMRI as a routine modality in pediatric chest imaging
Thermalization of a closed Sachdev-Ye-Kitaev system in the thermodynamic limit
No full textThe question of thermalization of a closed quantum system is of central interest in nonequilibrium quantum many-body physics. Here we present one such study analyzing the dynamics of a closed coupled Majorana SYK system. We have a large- q SYK model prepared initially at equilibrium quenched by introducing a random hopping term, thus leading to nonequilibrium dynamics. We find that the final stationary state reaches thermal equilibrium with respect to the Green's functions and energy. Accordingly, the final state is characterized by calculating its final temperature and the thermalization rate. We provide a detailed review of analytical methods and derive the required Kadanoff-Baym equations, which are then solved using the algorithm developed in this work. Our results display rich thermalization dynamics in a closed quantum system in the thermodynamic limit.Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/50110000165
Artificial Intelligence‐Based Detection of Central Retinal Artery Occlusion Within 4.5 Hours on Standard Fundus Photographs
No full textBackground Prompt diagnosis of acute central retinal artery occlusion (CRAO) is crucial for therapeutic management and stroke prevention. However, most stroke centers lack onsite ophthalmic expertise before considering fibrinolytic treatment. This study aimed to develop, train, and test a deep learning system to detect hyperacute CRAO on retinal fundus photographs within the critical 4.5‐hour treatment window and up to 24 hours after visual loss to aid in secondary stroke prevention. Methods Our retrospective, cross‐sectional study included 1322 color fundus photographs from 771 patients with acute visual loss due to CRAO, central retinal vein occlusion, nonarteritic anterior ischemic optic neuropathy, and healthy controls. Photographs were collected from 9 expert neuro‐ophthalmology centers in 6 countries, including 3 randomized clinical trials. Training included 1039 photographs (517 patients), followed by testing on 2 data sets: (1) hyperacute CRAO (54 photographs, 54 patients) and (2) CRAO within 24 hours after visual loss (110 photographs, 109 patients). Results The deep learning system achieved an area under the receiver operating characteristic curve of 0.96 (95% confidence interval (CI), 0.95–0.98), a sensitivity of 92.6% (95% CI, 87.0–98.0), and a specificity of 85.0% (95% CI, 81.8–92.8) for detecting CRAO at hyperacute stage, with similar results within 24 hours. The deep learning system outperformed stroke neurologists on a subset of hyperacute testing data set (120 photographs, 120 patients). Conclusions A deep learning system can accurately detect hyperacute CRAO on retinal photographs within a time window compatible with urgent fibrinolysis. If further validated, such systems could improve patient selection for fibrinolytic trials and optimize secondary stroke prevention. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT06390579
Therapeutic Advances in Alzheimer’s Disease: Integrating Natural, Semi-Synthetic, and Synthetic Drug Strategies
No full textAbstract: Alzheimer’s disease (AD) is a neurodegenerative disorder associated with age, marked by progressive memory loss linked to the decline of cholinergic neurons, accumulation of amyloid plaques, and the presence of Neurofibrillary Tangles (NFTs). Neuropil threads in the brain contribute to amyloidosis and dementia. Despite extensive research, AD’s etiology remains unclear, and currently, no promising therapy exists. This review examines the role of natural, semi-synthetic, and synthetic drugs in AD treatment. Natural drugs demonstrate safety and efficacy with minimal adverse effects, while most agents, whether natural or synthetic, target multiple steps or directly counteract amyloidogenesis, tau protein pathology, oxidative stress, NMDA receptor activity, inflammation, acetylcholine (AChE) function, or α, β, γ secretase activity. In pursuit of improved treatment outcomes, we explore the effectiveness and challenges of various therapeutic interventions. Our hypothesis underscores the importance of an integrated approach combining these drug types for tailored symptom relief, suggesting combined therapies may offer greater therapeutic benefits compared to single-drug approaches. The drugs discussed show potential in regulating AD, thereby presenting viable options for its management. However, to obtain more favorable results, additional studies are needed by combining these drugs
