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Resuscitative endovascular balloon oclusion of the aorta (REBOA) in non-traumatic cardiac arrest in a pig-model: Influence on Return of spontaneous circulation (ROSC) with short-term survival, gas exchange and hemodynamics
Background Survival of out-of-hospital cardiac arrest (OHCA) remains poor even when bystander cardiopulmonary resuscitation (CPR) with chest compression is initiated. Chest compressions provide only reduced cardiac output with limited perfusion of heart and brain and therfore may not avoid both death or poor neurological outcome in prolonged CPR. We investigated the impact of resuscitative endovascular balloon occlusion of the aorta (REBOA) on hemodynamics, gas exchange and return of spontanous circulation (ROSC) with short-term survival during mechanical CPR (mCPR) with chest compression synchronized-ventilation (CCSV) in an atraumatic pig model. Methods The study was performed on 20 pigs under general anaesthesia. REBOA catheter was placed in the thoracic aorta at the level of diaphragm beforecardiac arrest (CA) with ventricular fibrillation (VF) was induced. After 3 minutes of CA mCPR was started, CCSV was initiated at t = 5 min. Radomization to REBOA or control group, at t = 7 min inflation of REBOA ballon. CPR was continued until t = 18 min including defibrillation and intravenous epinephrine. Primary endpoint was ROSC with short-term survival, secondary endpoints mean arterial pressures (MAP) and arterial bloodgas analyses. Results ROSC was observed in n = 5 (REBOA) versus n = 1 (control) out of 10 animals, p = 0.141. All these animals remained stable for over an hour and thus also met the criteria for short-term survival. In the REBOA group, MAP was significantly increased following blockage of the ballon. Arterial blood gas analyses (ABG) showed a trend to higher PaO2 (REBOA 375 ± 147 mmHg vs control 277 ± 129 p = 0,220), higher pH-value (REBOA 7,37 ± 0,06 vs control 7,24 ± 0,12 p = 0,052) and less increased PaCO2 (REBOA 38 ± 7 mmHg vs control 59 ± 21 mmHg p = 0,056) at t = 14 min. Conclusion In our animal resuscitation model of non-traumatic CA, REBOA showed a significant increase in MAP and a favourable influence on gasexchange, associated with a trend towards higher ROSC rates and short-term survival. It remains to be seen whether these effects can be replicated in larger experimental and clinical studies.
Correction for Kalakonda et al., Monoallelic loss of tumor suppressor GRIM-19 promotes tumorigenesis in mice
Physical child abuse and self-reported health concerns: A case-control study including police-reported cases and unreported controls
Background Child abuse continues to pose a significant threat to children’s health. The repercussions of abuse are profound, impacting the child’s physical, social, and emotional well-being, with potential long-term effects that may extend into adulthood. To assist in identifying health concerns in children associated with exposure to physical abuse, a health questionnaire was developed to be used in the setting of a forensic examination. Objective This study examines whether children suspected of being exposed to physical violence report more health-related concerns compared to unexposed controls. Participants and setting The case group consists of children suspected of being exposed to physical violence, with reports to the Copenhagen police. Cases were examined from April 1, 2020, to December 31, 2023, at the Child Advocacy Centre (CAC) in Copenhagen, totaling 374 examinations. A control group of children aged 4–14 years with no suspicion of abuse was established through recruitment via social media platforms (Facebook, LinkedIn), posters, and word of mouth. Controls were examined from November 1, 2023, to September 30, 2024, totaling 122 examinations. Methods Children underwent a standardized forensic examination, which included a health interview reviewing health behaviors (e.g., diet, toothbrushing, and sleep patterns) and well-being (liking school/preschool, having friends, and trusted adults). Results Overall, cases reported significantly more concerns than controls on several assessed items. With multivariate logistic regression, adjusted for all significant covariates and stratified by age, two concerns remained significant. Cases aged 8–14 years, had significantly higher odds of brushing their teeth once daily or less (OR: 3.85; CI: 1.47–10.12) and reported low enjoyment of school (OR: 3.74; CI: 1.03–13.53). Conclusions Health interviews may support the identification of children at risk. However, the statistical power was limited, and the findings require validation in larger populations.
Magnetic decoupling as a proofreading strategy for high-yield, time-efficient microscale self-assembly
Life thrives due to its remarkable ability to create complex structures through the self-assembly of proteins, nucleic acids, and other biomolecules. Achieving such complex assemblies with the same level of fidelity, reproducibility, and advanced functionality in synthetic systems, however, has remained a grand challenge. One outstanding problem is the presence of parasitic products and long-lived intermediate states that slow the reaction process and limit the yield of the final product. Biology overcomes this challenge by proofreading to recognize and disassemble parasitic products. Such local checks, however, are currently difficult to implement in available self-assembly platforms. Here, we overcome this challenge by implementing a proofreading mechanism in a self-assembly platform. Specifically, we design intermediate states that strongly couple to an external force but a final product that is decoupled and thus highly stable to external driving, such that application of external forces selectively dissociates parasitic products. To implement this idea, we introduce lithographically patterned magnetic dipoles and an applied magnetic field to drive an assembly process similar to thermal self-assembly, but with additional controls. By applying patterns of magnetic driving that selectively destabilize parasitic states, we effectively implement a proofreading strategy to enable high-yield, time-efficient self-assembly. This realization of a general proofreading mechanism bridges the gap between artificial and biological self-assembly, paving the way for advanced self-assembled materials, with applications in next generation responsive materials, biomimetic devices, and microscale machines.
High-throughput DNA repair monitoring in Saccharomyces cerevisiae suggests SSB- and DSB-induced chromatin reconfiguration
Comparative electron microscopy analysis of internal limiting membrane and epiretinal membrane ultrastructure from vitrectomy surgery: A study protocol
The epiretinal membrane (ERM) is a fibrocellular layer that forms on the inner surface of the retina, often leading to visual impairment and significantly impacting visual function. Understanding the pathophysiology of ERM formation is crucial for advancing ophthalmic care and improving patient outcomes. This research aims to investigate the pathophysiology of ERM by comparing the internal limiting membrane (ILM) pathology in patients with and without ERM. The study involves a comprehensive protocol of ILM and ERM specimens collection during pars plana vitrectomy and membrane peeling procedures. Specimens are assessed using both light microscopy and transmission electron microscopy to evaluate morphological and ultrastructural changes. The study employs a standardized protocol for specimen collection and analysis, focusing on identifying differences in cell counts, extracellular matrix components, and ultrastructural alterations in the ILM. We also investigate the correlation between pathological findings and clinical biomarkers, including fundus photography, optical coherence tomography (OCT), optical coherence tomography angiography (OCT-A), and baseline characteristics such as patient demographics and underlying diseases. These clinical assessments provide a comprehensive understanding of the ocular environment and its relationship to ERM formation. By examining both the ILM and ERM in patients with and without ERM, the study aims to identify distinct pathological features associated with ERM development. We also aimed to elucidate whether changes in the ILM, such as cellular proliferation and extracellular matrix remodeling, are significant contributors to ERM formation. Additionally, the study will explores how these pathological changes correlate with clinical features and biomarkers, offering insights into potential mechanisms driving ERM pathogenesis. Establishing these correlations would support the hypothesis that ILM changes contribute to ERM development, while the absence of significant differences may suggest alternative pathways. Ultimately, this research aims to enhance our understanding of ERM pathophysiology, paving the way for improved prognosis and therapeutic strategies.
Correction for Sun et al., DNA2 protein destruction dictates DNA hyperexcision, cGAS–STING activation, and innate immune response in CDK12-deregulated cancers
Pedestrian flux analysis in a confined university campus network using entropy and accessibility robustness metrics
Correction: Healthcare professionals’ perceptions about implementing accreditation as a strategy to improve healthcare quality and organisational performance: a cross-sectional survey study
CHP1 promotes lipid droplet growth and regulates the localization of key enzymes for triacylglycerol synthesis
The glycerol-3-phosphate (G-3-P) pathway is central to the synthesis of triacylglycerols (TAGs) and glycerophospholipids, essential for membrane biogenesis and lipid storage. The first and rate-limiting step in this pathway is catalyzed by glycerol-3-phosphate acyltransferases (GPATs), with microsomal GPAT3 and GPAT4 being evolutionarily conserved and predominant in most tissues. While previous studies have implicated Calcineurin B homologous protein 1 (CHP1) as a cofactor for GPAT4, the broader role of CHP1 in regulating microsomal GPATs and TAG biosynthesis remains unclear. Here, we demonstrate that CHP1 is a critical regulator of both GPAT3 and GPAT4, essential for their stability, enzymatic activity, and lipid droplet (LD) localization. Structural modeling and mutational analyses identified key hydrophobic interfaces mediating the CHP1–GPAT interaction, which are required for optimal GPAT activity and LD growth. Loss of CHP1 impairs LD expansion and disrupts the localization of GPAT3/4 and downstream enzymes in the TAG synthesis pathway, including 1-acylglycerol-3-phosphate O-acyltransferase 3 (AGPAT3) and diacylglycerol O-acyltransferase 2 (DGAT2). Mechanistically, CHP1 helps circumvent seipin-mediated restriction of late LD-targeting enzymes, facilitating their access to mature LDs. Together, our findings reveal CHP1 as a dual-function regulator that stabilizes and activates microsomal GPATs while enabling the coordinated recruitment of TAG biosynthetic enzymes to LDs. This work uncovers a previously unrecognized mechanism for regulating LD growth and glycerolipid metabolism, with broad implications for lipid homeostasis and metabolic diseases.
Health literacy model integrating health education, health behaviors, self-rated health, and socioeconomic status in the Chinese population
Evaluation of shotgun metagenomics as a diagnostic tool for infectious gastroenteritis
Infectious gastroenteritis is a significant health issue globally. Identifying the causative pathogen is crucial for treatment, infection control and epidemiological surveillance. While PCR-based analyses are fast and sensitive, they only detect known pathogens. Clinical metagenomics can potentially identify novel or unexpected pathogens. This study aimed to evaluate shotgun metagenomics for detecting diarrhoeal pathogens in faecal samples from patients with infectious gastroenteritis and spiked samples from healthy donors, compared to PCR. DNA from clinical faecal samples (n = 12), spiked samples (n = 36), and control samples (n = 7) were analysed by PCR and shotgun metagenomics sequencing. Reads were taxonomically assigned, assembled, and binned into MAGs. MAGs were taxonomically assigned, and virulence genes were detected in bacterial assemblies and MAGs. Pathogens detected by PCR were also identified by taxonomic assignment of reads, though with lower sensitivity. Taxonomic assignment of MAGs identified 50% of bacterial pathogens and HAdV-F. Additional potential pathogens were observed in most samples. More bacterial virulence genes were detected in assemblies than in MAGs. In spiked samples, C. jejuni and HAdV-F were detected by both PCR and metagenomics, with significant correlation between Cq values and reads. Parasites were detected by few reads. Metagenomics has lower sensitivity compared to PCR but can provide supplementary information relevant for treatment. Challenges include additional potential pathogens, background microbiome, and introduced kitome, necessitating optimized extraction methods and strict quality controls.
Echoes in AI: Quantifying lack of plot diversity in LLM outputs
With rapid advances in large language models (LLMs), there has been an increasing application of LLMs in creative content ideation and generation. A critical question emerges: can current LLMs provide ideas that are diverse enough to truly bolster collective creativity? We examine two state-of-the-art LLMs, GPT-4 and LLaMA-3, on story generation and discover that LLM-generated stories often consist of plot elements that are echoed across a number of generations. To quantify this phenomenon, we introduce the Sui Generis score, an automatic metric that measures the uniqueness of a plot element among alternative storylines generated using the same prompt under an LLM. Evaluating on 100 short stories, we find that LLM-generated stories often contain combinations of idiosyncratic plot elements echoed frequently across generations and across different LLMs, while plots from the original human-written stories are rarely recreated or even echoed in pieces. Moreover, our human evaluation shows that the ranking of Sui Generis scores among story segments correlates moderately with human judgment of surprise level, even though score computation is completely automatic without relying on human judgment.
Effectiveness of educational intervention based on the protection motivation theory in promoting brucellosis preventive behaviors in ranchers
Visual processing oscillates differently through time for adults with ADHD
ADHD is a neurodevelopmental disorder affecting 3–4% of Canadian adults and 2.6% of adults worldwide. Its symptoms include inattention, hyperactivity and impulsivity. Though ADHD is known to affect several brain functions and cognitive processes, little is known regarding its impact on perceptual oscillations. This study compared the temporal features of visual processing between ADHD and neurotypical individuals in a visual word recognition task through the use of a temporal sampling technique, the outcome of which are classification images reflecting processing effectiveness according to the temporal properties of the stimulus. These temporal features were sufficiently different across groups while at the same time sufficiently congruent across participants of the same group that a machine learning algorithm classified participants in their respective groups with a 91.8% accuracy using only a small portion of the available features. Secondary findings showed that individuals with ADHD could be classified with high accuracy (91.3%) regarding their use of psychostimulant medication. These findings suggest the existence of strong behavioral markers of ADHD as well as of regular medication usage on visual performance which can be uncovered by random temporal sampling.
Parallel trade-offs in human cognition and neural networks: The dynamic interplay between in-context and in-weight learning
Human learning embodies a striking duality: Sometimes, we can rapidly infer and compose logical rules, benefiting from structured curricula (e.g., in formal education), while other times, we rely on an incremental approach or trial-and-error, learning better from curricula that are randomly interleaved. Influential psychological theories explain this seemingly conflicting behavioral evidence by positing two qualitatively different learning systems—one for rapid, rule-based inferences (e.g., in working memory) and another for slow, incremental adaptation (e.g., in long-term and procedural memory). It remains unclear how to reconcile such theories with neural networks, which learn via incremental weight updates and are thus a natural model for the latter, but are not obviously compatible with the former. However, recent evidence suggests that metalearning neural networks and large language models are capable of in-context learning (ICL)—the ability to flexibly infer the structure of a new task from a few examples. In contrast to standard in-weight learning (IWL), which is analogous to synaptic change, ICL is more naturally linked to activation-based dynamics thought to underlie working memory in humans. Here, we show that the interplay between ICL and IWL naturally ties together a broad range of learning phenomena observed in humans, including curriculum effects on category-learning tasks, compositionality, and a trade-off between flexibility and retention in brain and behavior. Our work shows how emergent ICL can equip neural networks with fundamentally different learning properties that can coexist with their native IWL, thus offering an integrative perspective on dual-process theories of human cognition.
A dual-stream deep learning framework for skin cancer classification using histopathological-inherited and vision-based feature extraction
Exploring the landing speed of digital society PPP projects: A continuous-time event history analysis of 300 projects
The Public-Private Partnership (PPP) model has become a viable alternative or supplement to traditional approaches in the development of a digital society. However, PPP projects in this domain often face significant landing (the launch of project implementation, typically marked by contract signing and the commencement of operational activities) challenges. Understanding the factors that influence the speed of project landing is thus of considerable practical importance. Based on the theoretical framework of Van Meter and Van Horn, we propose a causal mechanism linking the policy implementation system to the landing speed of digital society PPP projects. Using data from 300 projects, the study empirically tests this mechanism through continuous-time event history analysis. The results indicate that, compared with organizational and actor factors, material resources such as government fiscal resources and regional financial resources have a relatively weaker impact on landing speed. In contrast, internal goal consensus on innovation, internal government coordination, government-business relationship quality, leadership performance demand, and corporate social responsibility all significantly promote faster landing. Conversely, due to low project profitability and market barriers to social capital participation, information enterprise development is negatively associated with landing speed. We provide targeted policy recommendations to enhance the efficiency and timeliness of PPP-driven digital society initiatives.