Functional Components Research Articles

Functional feature extraction and validation from twelve-lead electrocardiograms to identify atrial fibrillation

BackgroundDeep learning methods on standard, 12-lead electrocardiograms (ECG) have resulted in the ability to identify individuals at high-risk for the development of atrial fibrillation. However, the process remains a “black box” and does not help clinicians in understanding the electrocardiographic changes at an individual level. we propose a nonparametric feature extraction approach to identify features that are associated with the development of atrial fibrillation (AF).MethodsWe apply functional principal component analysis to the raw ECG tracings collected in the Chronic Renal Insufficiency Cohort (CRIC) study. We define and select the features using ECGs from participants enrolled in Phase I (2003–2008) of the study. Cox proportional hazards models are used to evaluate the association of selected ECG features and their changes with the incident risk of AF during study follow-up. The findings are then validated in ECGs from participants enrolled in Phase III (2013–2015).ResultsWe identify four features that are related to the P-wave amplitude, QRS complex and ST segment. Both their initial measurement and 3-year changes are associated with the development of AF. In particular, one standard deviation in the 3-year decline of the P-wave amplitude is independently associated with a 29% increased risk of incident AF in the multivariable model (HR: 1.29, 95% CI: [1.16, 1.43]).ConclusionsCompared with deep learning methods, our features are intuitive and can provide insights into the longitudinal ECG changes at an individual level that precede the development of AF.

Ultrasound-enzyme-assisted extraction of flavonoids, polysaccharides, and triterpenes from Gualou and Xiebai: optimization, bioactivity, in vitro digestive stability, and impact on lipid digestion.

Gualou (Trichosanthes kirilowii Maxim) and Xiebai (Allium macrostemon Bunge) have been extensively studied for their diverse active ingredients, which include flavonoids, polysaccharides, and triterpenoids. This study employed a single-factor experiment alongside the Plackett-Burman design and utilized response surface methodology to optimize the ultrasonic-enzyme-assisted extraction (U-EAT) method for the functional components in Gualou and Xiebai (GLXB). The optimal extraction conditionswere identifiedas a solid-to-liquid ratio of 1:11g/mL, an alcohol concentration of 55%, an enzyme concentration of 1.2%, and an extraction temperature of 40°C. The yields of flavonoids, polysaccharides, and triterpenoids obtained were 0.94±0.05, 260.46±1.78, and 118.69±0.71mg/g, respectively, demonstrating increases of 59.19%, 29.03%, and 46.10% compared to HL (HL, the traditional reflux extraction method). Furthermore, in vitro digestion of the GLXB extract demonstrated significant lipid-lowering and hypoglycemic effects. The GLXB extract facilitated the flocculation of lipid droplets during lipid digestion and exhibited the capacity to reduce the rate of fat digestion. These findings indicate that the U-EAT significantly enhanced the content of active ingredients in GLXB and improved the hypoglycemic and lipid-lowering activities of the GLXB extract, highlighting its potential for further development and application in functional foods.

Functional independent component analysis by choice of norm: a framework for near-perfect classification

Functional independent component analysis by choice of norm: a framework for near-perfect classification

Quantifying right ventricular function in tetralogy of fallot: 3D echo into longitudinal, radial, and anteroposterior directions

Abstract Introduction Tetralogy of Fallot (ToF) is a congenital heart disease requiring surgical correction in early childhood. Despite high surgical success rates, patients cope with severe morbidity during adulthood predominantly originating from the right ventricle (RV). Pathophysiological processes underlying these conditions remain largely unknown, but are mostly attributed to RV remodelling. Improved understanding of remodelling patterns is essential for advancements in clinical decision making and treatment planning. Purpose To gain better insight in RV remodelling in patients with ToF, a method for detailed quantification of directional components of RV function was developed using three-dimensional echocardiography (3DE). Methods From RV-focused 3DE studies of 50 ToF patients and 50 healthy controls, three-dimensional dynamic RV meshes were obtained using commercially available software (TomTec 4D RV-Function). Within an in-house developed software application (RV-Dynamics), a technique was realized to decompose RV contraction in longitudinal (LT), radial (RD), and anteroposterior (AP) motion directions (Figure 1). Their relative contributions to RV ejection fraction (RVEF) were calculated as measure for RV function, analysed, and statistically compared within and between ToF patients and healthy controls. Results Decomposed RVEF in the AP motion direction was identified as the largest relative contributor to RVEF in both ToF patients (38% [31 – 42]) and healthy controls (40% [37 – 44]). Moreover, the AP component was significantly reduced in ToF patients compared to healthy controls (p=0.004). Deterioration in AP direction was complemented by a significant increase of the LT RVEF component (p=0.009), with 28% [26 – 33] in ToF patients compared to 26% [23 – 31] in healthy controls. Relative contribution of RD motion remained the same between both groups (p=0.649) (Figure 2). Conclusion RV-Dynamics allowed for effective directional decomposition of RVEF, enabling detailed quantification of RV function in patients with ToF. The AP component proved to be the largest relative contributor to RVEF in both ToF patients and healthy controls, disputing currently applied parameters focussing on LT wall motion for RV function assessment. Deterioration of RV function in ToF patients was mostly assigned to decreased contribution of AP wall motion to RVEF. We hypothesised this relates to the crucial involvement of left ventricular function in RV function, as RV motion in AP direction is largely attributed to left ventricular systolic function. A compensatory increase in LT contraction was observed, suggesting RV remodelling in LT direction in ToF patients.

Left atrial mechanics and left ventricular function in cardiac amyloidosis patients treated with tafamidis

Abstract Introduction and aims Patients with amyloid cardiomyopathy (ATTR-CM) present with a restrictive phenotype characterized by decreased ventricular compliance and increased filling pressures, with progressive loss of atrial function and increased stiffness, which are associated with poor clinical outcomes. Tafamidis improves clinical outcomes and slows disease progression but its effects in left ventricle (LV) and atrium (LA) mechanics are still unclear, with recent studies (reference 1.) suggesting improvement of LA function (as assesses by LA strain [LAS]) in patients with sinus rythm (SR). Our study aimed to characterize the 1-year evolution of LV function and LA mechanics in ATTR-CM patients treated with tafamidis. Methods We prospectively evaluated a cohort of patients with ATTR-CM treated with tafamidis in a single-centre. Results Out of 41 patients treated, 13 were excluded due to incomplete follow-up or poor quality of echocardiographic images that precluded LAS analysis. A total of 28 patients (75% male) were included, with a mean age of 80 ± 10 years at the start of treatment and a median follow up of 14 months. 11 pts (39%) were in sinus rhythm (SR group) and 17 (61%) were not (non-SR group). At the start of the treatment with tafamidis, mean LV ejection fraction (LVEF) was 55.5 ± 11.4%, GLS was -10.7 ± 4.3%, E/e’ 17.2 ± 5.4 and indexed LA volume (LAVi) 47.4 ± 15.3 mL/m2. Median NTproBNP was 2031 (3143) pg/mL and pts walked 313 ± 121m on the 6-minute walk test (6MWT). Regarding LAS, there was significant reduction in all atrial functional components in both SR (LAS reservoir 13.1 ± 12, LAS conduit -6.5 ± 4.2, LA contraction -6.6 ± 3.6) and non-SR groups (LAS reservoir 5.1 ± 3.6) as well as significantly increased LA stiffness (SR – 1.4 ± 0.9, non-SR – 6.1 ±6.0). Our analysis showed stabilization, with no statistically significant differences in LVEF, GLS, diastolic function parameters, LAS or LA stiffness, as well as NTproBNP and 6MWT after 1-year treatment with tafamidis (tables 1 and 2). We found a moderate correlation between LAS contraction and NTproBNP in the SR group (r=0.650, p=0.031) – meaning that worse (less negative) LAS contraction associated with higher NTproBNP values – despite there being no correlation between other echocardiographic variables ante NTproBNP or 6MWT. Conclusions In our cohort of patients, patients presented with significantly reduced atrial function and increased stiffness. 12-month treatment with tafamidis allowed stabilization of LA and LV performance, as well as of NTproBNP and 6MWT. We found a moderate correlation between LA contraction objectively evaluated by strain analysis and NTproBNP in SR patients, highlighting the importance of LA mechanical contraction preservation in patients with a restrictive cardiomyopathy phenotype.

Synthetic embryology of the human heart

The evolution of stem cell-based heart models from cells and tissues to organoids and assembloids and recently synthetic embryology gastruloids, is poised to revolutionize our understanding of cardiac development, congenital to adult diseases, and patient customized therapies. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have already been integrated into transplantable patches and are in preclinical efforts to reverse fibrotic scarring from myocardial infarctions. To inform on the complexity of heart diseases, multi-tissue morphogenic heart models are needed that replicate fundamental components of heart function to heart organogenesis in vitro and which require a deep understanding of heart development. Organoid and assembloid models capture selected multicellular cardiac processes, such as chamber formation and priming events for vascularization. Gastruloid heart models offer deeper insights as synthetic embryology to mimic multi-staged developmental events of in vivo heart organogenesis including established heart fields, crescent formation and heart tube development along with vascular systemic foundation and even further steps. The human Elongating Multi-Lineage Organized Cardiac (EMLOC) gastruloid model captures these stages and additional events including chamber genesis, patterned vascularization, and extrinsic central and intrinsic cardiac nervous system (CNS-ICNS) integration guided by spatiotemporal and morphogenic processes with neural crest cells. Gastruloid synthetic embryology heart models offer new insights into previously hidden processes of development and provide powerful platforms for addressing heart disease that extends beyond cardiomyocytes, such as arrhythmogenic diseases, congenital defects, and systemic injury interactions, as in spinal cord injuries. The holistic view that is emerging will reveal heart development and disease in unprecedented detail to drive transformative state-of-the-art innovative applications for heart health.

Transforming Adsorbate Surface Dynamics in Aqueous Electrocatalysis: Pathways to Unconstrained Performance.

Developing highly efficient catalysts to accelerate sluggish electrode reactions is critical for the deployment of sustainable aqueous electrochemical technologies, yet remains a great challenge. Rationally integrating functional components to tailor surface adsorption behaviors and adsorbate dynamics would divert reaction pathways and alleviate energy barriers, eliminating conventional thermodynamic constraints and ultimately optimizing energy flow within electrochemical systems. This approach has, therefore, garnered significant interest, presenting substantial potential for developing highly efficient catalysts that simultaneously enhance activity, selectivity, and stability. The immense promise and rapid evolution of this design strategy, however, do not overshadow the substantial challenges and ambiguities that persist, impeding the realization of significant breakthroughs in electrocatalyst development. This review explores the latest insights into the principles guiding the design of catalytic surfaces that enable favorable adsorbate dynamics within the contexts of hydrogen and oxygen electrochemistry. Innovative approaches for tailoring adsorbate-surface interactions are discussed, delving into underlying principles that govern these dynamics. Additionally, perspectives on the prevailing challenges are presented and future research directions are proposed. By evaluating the core principles and identifying critical research gaps, this review seeks to inspire rational electrocatalyst design, the discovery of novel reaction mechanisms and concepts, and ultimately, advance the large-scale implementation of electroconversion technologies.

Surgery First Approach to Correct Gummy Smile in an Adult Female

Abstract Vertical maxillary excess associated with long face syndrome or a hyperdivergent growth pattern gives patients an excessive gummy smile with overexposure of the upper anterior teeth. This results in a very unesthetic gummy smile and facial profile for the patient. Hyperdivergent growth patterns also affect the normal maxilla-mandibular relationship, as there is a presence of mandibular clockwise rotation, which compromises the functional component. Hence, this condition leads to poor aesthetics and function. This condition is treated by a non-surgical approach using Temporary anchorage device (TAD) s in recent years. However, for an excessive gummy smile, the ideal treatment option is orthognathic surgery combined with orthodontic treatment to correct the dental irregularities. In this case report, we will discuss gummy smile correction in a young adult female using a surgery-first approach, with a combined orthodontic and orthognathic surgical treatment, highlighting absolutely no forward movement of the mandible after the maxillary impaction, thus maintaining perfect Class I molar and canine relations.

Concurrent Validity and Reliability of In-Person and Supervised Remote STEADI Fall Risk Assessment in Community-Dwelling Older Adults.

Physical therapists play a vital role in preventing and managing falls in older adults. With advancements in digital health and technology, community fall prevention programs need to adopt valid and reliable telehealth-based assessments. The purpose of this study was to evaluate the validity and reliability of the telehealth-based timed up and go (TUG) test, 30-second chair stand test (30s-CST), and four-stage (4-stage) balance test as functional components of the Stopping Elderly Accidents, Deaths, and Injuries (STEADI) fall risk assessment. This cross-sectional study was conducted using a convenience sample of community-dwelling older adults. The TUG, 30s-CST, and 4-stage balance test were administered in random order in 1 session in the participant's own environment. Performance was scored concurrently by an in-person and synchronous telehealth rater. The video recordings of the performances were scored by an asynchronous telehealth rater on days 1 and 30 for inter- and intra-rater reliability. Additionally, participants performed the TUG test twice, using the distance measured by the participant and the distance measured by the in-person rater. To establish the validity of telehealth-based STEADI fall risk assessments, the Intraclass Correlation Coefficient (ICC), Pearson correlation coefficient, and 95% limits of agreement were derived. Inter- and intra-rater reliability were established by calculating ICC using a 2-way mixed model. Bland-Altman plots were created for nonsignificant proportional bias tests. Thirty community-dwelling older adults participated. Based on the STEADI algorithm, 13 participants were classified as having a moderate fall risk. A comparison of in-person and synchronous telehealth ratings showed excellent ICCs (0.97-0.99) and relationships (r=0.94-0.98). Bland-Altman plots were created for all tests except for the 30s-CST (t=-2.168, P =.04). All tests had good to excellent inter-rater reliability (ICC=0.84-1.00) and intra-rater reliability (0.77-1.00). No adverse events were reported. This study suggests that telehealth-administered functional tests in the STEADI fall risk assessment are valid and reliable when technology, environment, camera view, and angle are optimally managed.

Working Memory as the Focus of the Bilingual Effect in Executive Functions

The bilingual effect on executive functions (EFs) has garnered considerable attention, with most studies focusing on the visual domain and largely overlooking the auditory domain. Furthermore, research has predominantly concentrated on specific subcomponents of executive functions, with few studies systematically examining all three key subcomponents. This raises two important questions: (a) Is the bilingual effect specific to certain modalities (modality-specific), or a more general phenomenon (modality-general)? (b) Is the bilingual effect concentrated in a specific component of executive functions (process-specific), or does it extend to all three components (process-general)? To explore these questions, this study recruited monolingual Chinese and bilingual Chinese–English participants, using matched visual and auditory Stroop, N-back, and task-switching tasks to assess inhibitory control, working memory, and cognitive flexibility in both groups. The results showed that, after controlling for variables like intelligence, socioeconomic status, and age, bilingualism significantly predicted performance in both auditory and visual working memory tasks, explaining 34% and 19% of the variance, respectively. However, no evidence was found to support a bilingual effect in inhibitory control or cognitive flexibility. In conclusion, these results suggest that bilingual effects are not only process-specific (affecting only working memory) but also modality-general (providing advantages in both visual and auditory modalities).

Effect of Porosity on Tribological Properties of Medical-Grade 316L Stainless Steel Manufactured by Laser-Based Powder Bed Fusion

The potential of laser-based powder bed fusion (L-PBF) technology for producing functional components relies on its capability of maintaining or even improving the mechanical properties of the processed material. This improvement is associated with the microstructure resulting from the high thermal gradient and fast cooling rate. However, this microstructural advantage may be counterbalanced by the lack of full density, which could be tolerated to a certain degree for applications such as biomedical implants and medical equipment. In this study, medical-grade 316L stainless steel specimens with porosities ranging from 1.7 to 9.1% were additively manufactured by L-PBF using different combinations of laser power and scanning speeds. Tribological properties were evaluated by pin-on-disc testing in dry conditions against a silicon nitride test body and analyzed in the context of microstructural characterization by optical and electron microscopy. The results reveal that higher porosity allows for a diminishing wear rate, which is explained by the capacity of the pores to retain wear debris related with the three-body abrasion. This research provides practical insights into the design of medical wear-resistant components, thereby enhancing our understanding of the potential of L-PBF in the fields of materials science and biomedical engineering.

The Role of Internal Audit in Enhancing Performance: A Case Study of Mirwais Neeka Institute of Higher Education, Kandahar, Afghanistan

The Internal Audit is a systematic process of analyzing risk, its likelihood and impact and taking necessary steps to avoid and control risks by its various control measures particularly in educational institutions. The prime objective of this research is to study and explore the specific impact of the internal audit function on the performance of Mirwais Neeka Institute of Higher Education in Kandahar. This study investigates how the internal audit function at Mirwais Neeka Institute contributes to the institution’s overall performance by examining audit processes, stakeholder perceptions, and tangible outcomes. The population for this study consists of administrators, faculty, students, and relevant staff of Mirwais Neeka Institute of Higher Education involved in or affected by internal audit processes and purposive sampling technique has been used for selecting representative sample of 40 respondents from the population. The analysis employs descriptive statistics, correlations, and Ordinary Least Squares Regression to determine the relationships between internal audit functions and organizational performance. The study concludes that internal audit functions are crucial in enhancing risk mitigation, operational efficiency, and performance measurement, thus significantly impacting the performance of Mirwais Neeka Institute. The research provides valuable insights for administrators and policymakers, emphasizing the need for robust internal audit practices to improve institutional performance. Future research could explore additional factors influencing organizational performance and delve deeper into the specific components of internal audit functions driving performance improvements.

Effects of consuming S-allyl-L-cysteine enriched garlic extract on sleep quality in Japanese adults: A randomized, double-blind, placebo-controlled, parallel-group comparative study

Introduction: Sleep promotes well-being, which includes physical and mental health, but many people suffer from sleep deprivation. One of the functional components of garlic, S-allyl-L-cysteine (SAC), can reportedly improve mental fatigue and is expected to regulate the autonomic nervous system and improve sleep quality. This study investigated the effects of SAC-enriched garlic extract intake on sleep quality in healthy Japanese adults. Methods: This was a single center, stratified (male and female with balanced randomization [1:1]), double-blind, placebo-controlled, parallel-group study conducted from September 12, 2023, to February 25, 2024. Participants consumed either the SAC-enriched garlic extract tablet (2 mg/day as SAC) or placebo (22 participants per group) for 12 weeks. The assessment items included the Oguri-Shirakawa-Azumi sleep inventory middle-aged version (OSA-MA), the Japanese version of the Pittsburgh Sleep Quality Index (PSQI-J), and St. Mary’s Hospital sleep questionnaire (SMH). The primary outcome was the initiation and maintenance of sleep as measured by the OSA-MA after the 12-week intervention. Results: The final analysis included 19 and 22 participants in the SAC and Placebo groups, respectively. An additional subgroup analysis explored the effect of SAC intake on sleep quality, with 14 and 19 participants in the SAC and Placebo groups, respectively. After the 12-week intervention, the overall analysis showed no significant differences between groups for the primary outcome. In the subgroup analysis, however, the “Initiation and maintenance of sleep” and “Sleepiness on rising” scores in the OSA-MA significantly increased in the SAC group versus placebo. Both the overall and subgroup analyses revealed a decreased total score, subjective sleep quality (C1), and sleep latency (C2) of PSQI-J in the SAC group versus placebo. Regarding the question “How much difficulty did you have in falling asleep last night?” in the SMH, more participants in the SAC group reported “none or very little” in the overall analysis, while all participants reported “none or very little” in the subgroup analysis after the intervention. Conclusions: SAC-enriched garlic extract relieves difficulties associated with initiating and maintaining sleep. Keywords: garlic, S-Allyl-L-Cysteine, sleep quality, falling asleep, sleep maintenance Trial registration number: UMIN000052187

Euclid: Relativistic effects in the dipole of the two-point correlation function

Gravitational redshift and Doppler effects give rise to an antisymmetric component of the galaxy correlation function when cross-correlating two galaxy populations or two different tracers. In this paper, we assess the detectability of these effects in the spectroscopic galaxy survey. We model the impact of gravitational redshift on the observed redshift of galaxies in the Flagship mock catalogue using a Navarro--Frenk--White profile for the host haloes. We isolate these relativistic effects, largely subdominant in the standard analysis, by splitting the galaxy catalogue into two populations of faint and bright objects and estimating the dipole of their cross-correlation in four redshift bins. In the simulated catalogue, we detect the dipole signal on scales below $ Mpc $, with detection significances of $4,σ$ and $3,σ$ in the two lowest redshift bins, respectively. At higher redshifts, the detection significance drops below $2,σ$. Overall, we estimate the total detection significance in the spectroscopic sample to be approximately $6,σ$. We find that on small scales, the major contribution to the signal comes from the nonlinear gravitational potential. Our study on the Flagship mock catalogue shows that this observable can be detected in Euclid Data Release 2 and beyond.

MEGA-GO: Functions prediction of diverse protein sequence length using Multi-scalE Graph Adaptive neural network.

The increasing accessibility of large-scale protein sequences through advanced sequencing technologies has necessitated the development of efficient and accurate methods for predicting protein function. Computational prediction models have emerged as a promising solution to expedite the annotation process. However, despite making significant progress in protein research, graph neural networks face challenges in capturing long-range structural correlations and identifying critical residues in protein graphs. Furthermore, existing models have limitations in effectively predicting the function of newly sequenced proteins that are not included in protein interaction networks. This highlights the need for novel approaches integrating protein structure and sequence data. We introduce MEGA-GO, highlighting the capability of capturing diverse protein sequence length features from multiple scales. The unique graph adaptive neural network architecture of MEGA-GO enables a more nuanced extraction of graph structure features, effectively capturing intricate relationships within biological data. Experimental results demonstrate that MEGA-GO outperforms mainstream protein function prediction models in the accuracy of Gene Ontology (GO) term classification, yielding 33.4%, 68.9%, and 44.6% of Area Under the Precision-Recall Curve (AUPR) on Biological Process (BP), Molecular Function (MF), and Cellular Component (CC) domains respectively. The rest of the experimental results reveal that our model consistently surpasses the state-of-the-art methods. The source code and implementation of MEGA-GO are available at https://github.com/Cheliosoops/MEGA-GO. The supplementary file can be found at Supplementary.

Influence of the Oscillation Parameters Amplitude and Frequency on the Microstructure of Laser-Welded Thin Nitinol Foils

Laser welding has become well established for joining Ni-Ti-based shape memory alloys and extends the manufacturability of highly functional components with complex geometries. Published studies on the effect of laser welding on alterations to microstructure and properties of these alloys, however, mainly deal with conventional component dimensions and linear laser beam movement. In view of the increasing importance of microtechnology, research into joining of thin-walled Ni-Ti components is therefore of interest. At the same time, studies comparing oscillating and linear beam movement on other materials and the authors’ own work on Ni-Ti materials suggest that oscillating beam movement has a more favorable effect on alterations in material properties and microstructure. Therefore, laser welding of foils made of Ni55/Ti45 with 125 µm thickness was systematically analyzed using a fiber laser and circular oscillation. Amplitude A and frequency f were varied from 0 to 200 µm and 0 to 2000 Hz, respectively. Microstructural analysis showed that by increasing the frequency, grain refinement could be achieved up to a certain value of f. An increasing amplitude led to decreasing hardness values of the weld seam, while the influence of f was less pronounced. The analysis of the weld material using chip calorimetry (Flash DSC) revealed that the beam oscillation had fewer effects on the change in transformation points compared to a linear beam movement.

P0162 Distinct mucin RNA isoform expression in the blood of Inflammatory Bowel Disease patients with variable degree of inflammation

Abstract Background Mucosal healing is considered as a key therapeutic endpoint in inflammatory bowel diseases (IBD) and comprises endoscopic improvement of inflammation without taking barrier healing into account. Mucins are critical components of the intestinal mucosal barrier function that give rise to structurally diverse isoforms. In a recent study, we demonstrated that intestinal region-specific mucin RNA isoform expression captured the heterogeneity of the IBD patient population and showed great potential to indicate barrier function enhancing IBD management [1]. Given that epithelial cells can enter the bloodstream because of epithelial barrier injury upon inflammation, we further investigated whether intestinal-type mucin RNA isoforms have the potential as non-invasive biomarkers for IBD disease monitoring. Methods Using bulk RNA sequencing data (Illumina) mapped to our recently designed mucin RNA isoform landscape [1], we assessed mucin RNA isoform expression in the blood from 45 IBD patients (22 UC, 23 CD) and 19 controls and correlated the data to clinical outcome parameters (i.e. endoscopic activity (Mayo or SES-CD), inflamed intestinal region, histological activity (Geboes score), C-reactive protein level). Additionally, random forest-based feature selection, using a publicly available dataset (PRJNA774251), was carried out to select peripheral mucin RNA isoforms that accurately stratified UC patients (n=79) from controls (n=209). Results Overall, expression of MUC1, MUC4, MUC6, MUC12, MUC12-AS1, MUC16, MUC20, MUC20P1, and MUC20-OT1 mRNA was identified in the blood of IBD and control patients, with MUC1, MUC20 and MUC20-OT1 being abundantly present in both cohorts. At mucin RNA isoform level, 50 originated from the intestinal mucin RNA isoform landscape [1] with RNA isoforms derived from MUC20 and MUC20-OT1 classified as the top 10 most predominantly expressed isoforms. Interestingly, expression of several MUC20-OT1 RNA isoforms was decreased in UC or CD patients with moderate to severe inflammation compared to controls (Figure 1). In addition, four MUC20-OT1 isoforms and two MUC20 were correlated to the endoscopic inflammation score. Feature selection based on random forest modeling to distinguish UC patients with moderate to severe inflammation from controls unveiled a panel of 5 mucin RNA isoforms (MUC6 (ENST00000421673.7), MUC20-OT1(ENST00000429897.5), MUC4(ENST00000467235.1), MUC20-OT1(ENST00000626852.2) and MUC5AC(PB.2811.15); area under the curve of 75.7% (train set) and 60.3% (test set); Figure 2). Conclusion Peripheral blood mucin RNA isoform expression can be monitored in IBD patients, with MUC20-OT1 RNA isoforms as potential non-invasive biomarkers for intestinal barrier dysfunction.

Терапия благополучия: обзор исследований, оценивающих эффективность и перспективы развития позитивной психотерапевтической стратегии

<p style="text-align: justify;">Well-being therapy was developed in the 1990s on the basis of a model of psychological well-being describing the components of positive psychological functioning, and then revised within the framework of the concept of euthymia, defending the idea of a balance of positive and negative psychological characteristics. Being a short-term psychotherapeutic strategy, well-being therapy includes from 8 to 20 sessions grouped into three stages: the preparatory stage of therapy is aimed at identifying and integrating episodes of well-being into daily life; the main stage consists in identifying thoughts, beliefs, and behaviors that lead to a decrease in well-being; the final stage consists in cognitive restructuring using specific models of psychological well-being. A review showed that well-being therapy is effective in the treatment of generalized anxiety disorder, depressive and cyclothymic disorders, post-traumatic stress disorder, as well as in lifestyle changes in somatic diseases, prevention of relapses of depressive disorders, therapeutic resistance to antidepressants, antidepressant discontinuation syndrome, adaptation to learning, reduction of death anxiety in the elderly, and prevention of addictive behaviors in adolescents. The prospects for the development of well-being therapy include its introduction into other psychotherapeutic approaches, expanding the scope of its clinical and nonclinical implication, using it as a method of prevention and treatment of somatic and psychosomatic diseases.</p>

Mixed-trust Computing: Safe and Secure Real-time Systems

Verifying complex Cyber-physical Systems (CPSs) is increasingly important given the push to deploy safety-critical autonomous features. Unfortunately, traditional verification methods do not scale to the complexity of these systems and do not provide systematic methods to protect verified properties when not all the components can be verified. To address these challenges, this article proposes a real-time mixed-trust computing framework that combines verification and protection. The framework introduces a new task model, where an application task can have both an untrusted and a trusted part. The untrusted part allows complex computations supported by a full OS with a real-time scheduler running in a VM hosted by a trusted hypervisor. The trusted part is executed by another scheduler within the hypervisor and is thus protected from the untrusted part. If the untrusted part fails to finish by a specific time, the trusted part is activated to preserve safety (e.g., prevent a crash) including its timing guarantees. This framework is the first allowing the use of untrusted components for CPS critical functions while preserving logical and timing guarantees, even in the presence of malicious attackers. We present the framework, its schedulability analysis, and the coordination protocol between the trusted and untrusted parts. Our implementation on a Raspberry Pi 3 is also discussed along with experiments showing the behavior of the system under failures of untrusted components and a drone application to demonstrate its practicality.

Intestinal Effects of Brewers’ Spent Grain Extract In Ovo (Gallus gallus)—A Pilot Study

Upcycling brewers’ spent grain (BSG) into poultry feed needs to be optimized. Since broiler chickens inefficiently digest fiber, we created a water-soluble BSG extract (BSGE) to explore this fraction’s potential nutritional benefits. We utilized intra-amniotic administration (in ovo) to target the gastrointestinal tract of broiler embryos. BSGE increased villus surface area and goblet cell quantity and size, implying improved duodenal development. The extract also changed cecal Escherichia coli (E. coli) and Clostridium abundances. Synchrotron X-ray fluorescence microscopy, along with zinc and iron transporter relative expression, did not reveal significant changes by BSGE. These findings highlight the potential for BSGE to be a functional feed component, underscoring the potential value of upcycling this byproduct. This pilot study supports future work exploring the impact of BSGE within feed and its effects over long-term consumption.